NO313236B1 - Asymmetrisk syntese av benzoksazinoner - Google Patents

Asymmetrisk syntese av benzoksazinoner Download PDF

Info

Publication number: NO313236B1
Authority: NO; Norway
Prior art keywords: compound; formula; acid; agent; alkyl
Prior art date: 1996-12-16

Application number

NO19992914A

Other languages

English (en)

Norwegian (no)

Other versions

NO992914D0 (no

NO992914L (no

Inventor

Michael Ernest Pierce

Anusuya Choudhury

Jr Rodney Lawrence Parsons

Lilian Alicia Radesca

Original Assignee

Du Pont Pharm Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-12-16

Filing date

1999-06-15

Publication date

2002-09-02

1999-06-15 Application filed by Du Pont Pharm Co filed Critical Du Pont Pharm Co

1999-06-15 Publication of NO992914D0 publication Critical patent/NO992914D0/no

1999-06-15 Publication of NO992914L publication Critical patent/NO992914L/no

2002-09-02 Publication of NO313236B1 publication Critical patent/NO313236B1/no

Links

238000011914 asymmetric synthesis Methods 0.000 title claims abstract description 8
HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 title abstract description 29
238000000034 method Methods 0.000 claims abstract description 95
239000003795 chemical substances by application Substances 0.000 claims abstract description 90
239000000203 mixture Substances 0.000 claims abstract description 50
239000003377 acid catalyst Substances 0.000 claims abstract description 38
-1 alkyl lithium Chemical compound 0.000 claims abstract description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 33
NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical group C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 claims abstract description 26
125000000217 alkyl group Chemical group 0.000 claims abstract description 19
229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
229910052744 lithium Inorganic materials 0.000 claims abstract description 11
125000006242 amine protecting group Chemical group 0.000 claims abstract description 9
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
125000002757 morpholinyl group Chemical group 0.000 claims abstract description 6
125000003386 piperidinyl group Chemical group 0.000 claims abstract description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 301
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 82
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 66
238000002360 preparation method Methods 0.000 claims description 55
239000002904 solvent Substances 0.000 claims description 50
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 44
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 36
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 32
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 30
150000004703 alkoxides Chemical class 0.000 claims description 26
239000007800 oxidant agent Substances 0.000 claims description 26
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 25
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 24
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 23
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 23
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
229940098779 methanesulfonic acid Drugs 0.000 claims description 22
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
MJASWWFHVAFXPM-UHFFFAOYSA-N lithium;ethynylcyclopropane Chemical compound [Li+].[C-]#CC1CC1 MJASWWFHVAFXPM-UHFFFAOYSA-N 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 11
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 10
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 10
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 10
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 10
235000011116 calcium hydroxide Nutrition 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
CETVQRFGPOGIQJ-UHFFFAOYSA-N lithium;hexane Chemical compound [Li+].CCCCC[CH2-] CETVQRFGPOGIQJ-UHFFFAOYSA-N 0.000 claims description 10
239000011591 potassium Substances 0.000 claims description 10
229910052700 potassium Inorganic materials 0.000 claims description 10
239000012279 sodium borohydride Substances 0.000 claims description 10
229910000033 sodium borohydride Inorganic materials 0.000 claims description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 9
239000000920 calcium hydroxide Substances 0.000 claims description 9
229910001861 calcium hydroxide Inorganic materials 0.000 claims description 9
239000011734 sodium Substances 0.000 claims description 9
229910052708 sodium Inorganic materials 0.000 claims description 9
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 9
ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 claims description 8
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 8
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 8
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 8
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
239000003125 aqueous solvent Substances 0.000 claims description 8
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 8
229940092714 benzenesulfonic acid Drugs 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 8
ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims description 7
239000012351 deprotecting agent Substances 0.000 claims description 7
LZTRCELOJRDYMQ-UHFFFAOYSA-N triphenylmethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1=CC=CC=C1 LZTRCELOJRDYMQ-UHFFFAOYSA-N 0.000 claims description 7
229960004838 phosphoric acid Drugs 0.000 claims description 6
229940032330 sulfuric acid Drugs 0.000 claims description 6
MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 claims description 3
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 3
238000003776 cleavage reaction Methods 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
230000007017 scission Effects 0.000 claims description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 3
229960004319 trichloroacetic acid Drugs 0.000 claims description 3
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000003944 tolyl group Chemical group 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
229940005561 1,4-benzoquinone Drugs 0.000 claims 1
238000010511 deprotection reaction Methods 0.000 claims 1
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims 1
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 1
125000004448 alkyl carbonyl group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 56
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 31
230000015572 biosynthetic process Effects 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
238000005481 NMR spectroscopy Methods 0.000 description 29
238000003786 synthesis reaction Methods 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
239000000047 product Substances 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
150000002374 hemiaminals Chemical class 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
239000007787 solid Substances 0.000 description 17
239000002002 slurry Substances 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
108010078851 HIV Reverse Transcriptase Proteins 0.000 description 14
241000725303 Human immunodeficiency virus Species 0.000 description 14
239000006227 byproduct Substances 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
239000003153 chemical reaction reagent Substances 0.000 description 12
150000002576 ketones Chemical class 0.000 description 12
239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 12
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
150000001412 amines Chemical class 0.000 description 11
239000000460 chlorine Substances 0.000 description 11
238000010626 work up procedure Methods 0.000 description 11
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
QJDSIBXBBGLAOW-UHFFFAOYSA-N [Li]C#CC1CC1 Chemical compound [Li]C#CC1CC1 QJDSIBXBBGLAOW-UHFFFAOYSA-N 0.000 description 9
150000003934 aromatic aldehydes Chemical group 0.000 description 9
239000002585 base Substances 0.000 description 9
XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 8
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 8
230000035484 reaction time Effects 0.000 description 8
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
230000006698 induction Effects 0.000 description 7
238000007363 ring formation reaction Methods 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
239000000538 analytical sample Substances 0.000 description 6
238000006264 debenzylation reaction Methods 0.000 description 6
238000004821 distillation Methods 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
229960000395 phenylpropanolamine Drugs 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000000523 sample Substances 0.000 description 5
KEMUGFRERPPUHB-LBPRGKRZSA-N (2s)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol Chemical compound NC1=CC=C(Cl)C=C1[C@](O)(C(F)(F)F)C#CC1CC1 KEMUGFRERPPUHB-LBPRGKRZSA-N 0.000 description 4
FUYMYLYDBVWEHG-UHFFFAOYSA-N 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone;hydrate;hydrochloride Chemical compound O.Cl.NC1=CC=C(Cl)C=C1C(=O)C(F)(F)F FUYMYLYDBVWEHG-UHFFFAOYSA-N 0.000 description 4
QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000012458 free base Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
230000001939 inductive effect Effects 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000002955 isolation Methods 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
239000007858 starting material Substances 0.000 description 4
NOKSRMDODJGCPZ-UHFFFAOYSA-N 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C(F)(F)F NOKSRMDODJGCPZ-UHFFFAOYSA-N 0.000 description 3
LEFWQCCBPBNBBO-UHFFFAOYSA-N 1-[5-chloro-2-(tritylamino)phenyl]-2,2,2-trifluoroethanone Chemical compound FC(F)(F)C(=O)C1=CC(Cl)=CC=C1NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LEFWQCCBPBNBBO-UHFFFAOYSA-N 0.000 description 3
BLTYAJPHEPYMJK-UHFFFAOYSA-N 1-[5-chloro-2-[(4-methoxyphenyl)methylamino]phenyl]-2,2,2-trifluoroethanone Chemical compound C1=CC(OC)=CC=C1CNC1=CC=C(Cl)C=C1C(=O)C(F)(F)F BLTYAJPHEPYMJK-UHFFFAOYSA-N 0.000 description 3
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102100034343 Integrase Human genes 0.000 description 3
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
238000005574 benzylation reaction Methods 0.000 description 3
125000001743 benzylic group Chemical group 0.000 description 3
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
239000002777 nucleoside Substances 0.000 description 3
150000003833 nucleoside derivatives Chemical class 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
238000010979 pH adjustment Methods 0.000 description 3
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 3
238000012545 processing Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
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208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000009413 insulation Methods 0.000 description 1
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
QCYIFDAFIXZTQO-UHFFFAOYSA-N lithium;diphenylmethylbenzene Chemical compound [Li+].C1=CC=CC=C1[C-](C=1C=CC=CC=1)C1=CC=CC=C1 QCYIFDAFIXZTQO-UHFFFAOYSA-N 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
238000006263 metalation reaction Methods 0.000 description 1
239000010814 metallic waste Substances 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
MBHINSULENHCMF-UHFFFAOYSA-N n,n-dimethylpropanamide Chemical compound CCC(=O)N(C)C MBHINSULENHCMF-UHFFFAOYSA-N 0.000 description 1
LIJJGMDKVVOEFT-UHFFFAOYSA-N n-benzyl-4-methoxyaniline Chemical compound C1=CC(OC)=CC=C1NCC1=CC=CC=C1 LIJJGMDKVVOEFT-UHFFFAOYSA-N 0.000 description 1
229940073569 n-methylephedrine Drugs 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
238000010915 one-step procedure Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000005457 optimization Methods 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000007243 oxidative cyclization reaction Methods 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000003908 quality control method Methods 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
230000010076 replication Effects 0.000 description 1
210000000582 semen Anatomy 0.000 description 1
238000000926 separation method Methods 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
239000010959 steel Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
STOSPPMGXZPHKP-UHFFFAOYSA-N tetrachlorohydroquinone Chemical compound OC1=C(Cl)C(Cl)=C(O)C(Cl)=C1Cl STOSPPMGXZPHKP-UHFFFAOYSA-N 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
210000002268 wool Anatomy 0.000 description 1
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
229960002555 zidovudine Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Virology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Engineering & Computer Science (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Catalysts (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

NO19992914A 1996-12-16 1999-06-15 Asymmetrisk syntese av benzoksazinoner NO313236B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US3298096P	1996-12-16	1996-12-16
US08/838,838 US5932726A (en)	1996-12-16	1997-04-11	Asymmetric synthesis of benzoxazinones
PCT/US1997/022674 WO1998027073A1 (en)	1996-12-16	1997-12-15	Asymmetric synthesis of benzoxazinones

Publications (3)

Publication Number	Publication Date
NO992914D0 NO992914D0 (no)	1999-06-15
NO992914L NO992914L (no)	1999-06-15
NO313236B1 true NO313236B1 (no)	2002-09-02

Family

ID=26709131

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19992914A NO313236B1 (no)	1996-12-16	1999-06-15	Asymmetrisk syntese av benzoksazinoner

Country Status (27)

Country	Link
US (1)	US5932726A (ja)
EP (1)	EP0944610B1 (ja)
JP (1)	JP4232911B2 (ja)
KR (1)	KR100498665B1 (ja)
CN (1)	CN1075063C (ja)
AT (1)	ATE289296T1 (ja)
AU (1)	AU750047B2 (ja)
BR (1)	BR9714031A (ja)
CA (1)	CA2275323C (ja)
CZ (1)	CZ297168B6 (ja)
DE (1)	DE69732525T2 (ja)
EA (1)	EA002987B1 (ja)
EE (1)	EE03920B1 (ja)
ES (1)	ES2235265T3 (ja)
HR (1)	HRP970688A2 (ja)
HU (1)	HU225655B1 (ja)
IL (2)	IL130684A (ja)
LV (1)	LV12432B (ja)
NO (1)	NO313236B1 (ja)
NZ (1)	NZ336163A (ja)
PL (1)	PL192661B1 (ja)
PT (1)	PT944610E (ja)
RO (1)	RO120844B1 (ja)
SI (1)	SI20071A (ja)
SK (1)	SK285258B6 (ja)
UA (1)	UA66773C2 (ja)
WO (1)	WO1998027073A1 (ja)

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US5874430A (en) *	1996-10-02	1999-02-23	Dupont Pharmaceuticals Company	4,4-disubstitued-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same
US6673372B1 (en)	1998-06-11	2004-01-06	Bristol-Myers Squibb Pharma Company	Crystalline Efavirenz
TWI326283B (en) *	2002-07-31	2010-06-21	Du Pont	Method for preparing fused oxazinones
WO2004087628A1 (fr) *	2003-04-04	2004-10-14	Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences	Ligand amino-alcool et son utilisation dans la preparation d'alcools tertiaires propargyliques et d'amines tertiaires par le biais d'une reaction d'addition eniantioselective
EP2313379B1 (en) *	2008-05-30	2015-03-11	Emcure Pharmaceuticals Limited	Process for the preparation of efavirenz
US8080655B2 (en) *	2009-07-20	2011-12-20	Apotex Pharmachem Inc.	Methods of making efavirenz and intermediates thereof
CN101844990B (zh) *	2010-05-27	2013-03-20	浙江沙星医药化工有限公司	中间体4-氯-2-(三氟乙酰基)苯胺盐酸盐水合物的合成方法
EP2441759A1 (en)	2010-10-14	2012-04-18	Lonza Ltd.	Process for the synthesis of cyclic carbamates
EP2447255A1 (en)	2010-10-14	2012-05-02	Lonza Ltd.	Process for the synthesis of cyclic carbamates
CN102584801B (zh) *	2011-01-06	2015-02-18	中国科学院上海有机化学研究所	Hiv逆转录酶抑制剂依法韦伦类化合物的一锅法不对称合成工艺
WO2015118515A1 (en) *	2014-02-10	2015-08-13	Discovery Intermediates Private Limited	An improved process for the preparation of a non-nucleoside reverse transcriptase inhibitor
EP2944631A1 (en) *	2014-05-12	2015-11-18	F.I.S.- Fabbrica Italiana Sintetici S.p.A.	Improved process for the preparation of Efavirenz
CN104016936B (zh) *	2014-06-18	2016-08-17	中国科学院上海有机化学研究所	手性氨基酚配体在依法韦仑不对称合成中的应用
CN105801442A (zh) *	2015-10-16	2016-07-27	浙江沙星医药化工有限公司	4-氯-2-(三氟乙酰基)苯胺盐酸盐水合物的制备方法
EP3388460A4 (en) *	2015-12-08	2019-05-22	DIC Corporation	OXAZINE COMPOUND, COMPOSITION AND CURED PRODUCT
CN108368217B (zh) *	2015-12-08	2021-05-07	Dic株式会社	恶嗪化合物、组合物及固化物
US11117873B2 (en) *	2015-12-08	2021-09-14	Dic Corporation	Oxazine compound, composition, and cured product
NL2018412B1 (en) *	2017-02-23	2018-09-17	Univ Nelson Mandela Metropolitan	Method for the manufacture of efavirenz

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DE343057C (de) *	1914-06-21	1921-10-25	Kalle & Co Aktien Ges	Verfahren zur Darstellung von 1-Arylamino-4-oxynaphthalinen
US3280120A (en) *	1964-03-09	1966-10-18	Rexall Drug Chemical	Substituted benzoxazines, process therefor and intermediates
US3526621A (en) *	1966-08-03	1970-09-01	Farmaceutical Italia Soc	Substituted 3,1-benzoxazin-2-one
US3513166A (en) *	1967-05-22	1970-05-19	Robins Co Inc A H	3-(omega-aminoalkyl)-4-substituted-1,3-benzoxazine-2-ones
AU5960380A (en) *	1979-08-30	1981-03-05	A. Ehrenreich G.m.b.H. & Co. KG	Bellows seal and retaining ring
DE3622262A1 (de) *	1986-07-02	1988-01-07	Bayer Ag	Chromogene 3,1-benzoxazine
JPH0436252A (ja) *	1990-05-30	1992-02-06	Nippon Alkyl Alum Kk	光学活性アルキニルアルコールの製造方法
US5519021A (en) *	1992-08-07	1996-05-21	Merck & Co., Inc.	Benzoxazinones as inhibitors of HIV reverse transcriptase
IL106507A (en) *	1992-08-07	1997-11-20	Merck & Co Inc	Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type
AU1694295A (en) *	1994-01-28	1995-08-15	Merck & Co., Inc.	Benzoxazinones as inhibitors of hiv reverse transcriptase
US5663467A (en) *	1995-01-23	1997-09-02	Merck & Co., Inc.	Synthesis of cyclopropylacetylene
US5633405A (en) *	1995-05-25	1997-05-27	Merck & Co., Inc.	Asymmetric synthesis of (-)-6-chloro-4-cyclopropyl-ethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxanzin-2-one

1997
- 1997-04-11 US US08/838,838 patent/US5932726A/en not_active Expired - Lifetime
- 1997-12-15 HU HU0000168A patent/HU225655B1/hu unknown
- 1997-12-15 KR KR10-1999-7005331A patent/KR100498665B1/ko active IP Right Grant
- 1997-12-15 EA EA199900552A patent/EA002987B1/ru not_active IP Right Cessation
- 1997-12-15 BR BR9714031-7A patent/BR9714031A/pt not_active Application Discontinuation
- 1997-12-15 PT PT97953140T patent/PT944610E/pt unknown
- 1997-12-15 NZ NZ336163A patent/NZ336163A/en not_active IP Right Cessation
- 1997-12-15 AU AU56944/98A patent/AU750047B2/en not_active Expired
- 1997-12-15 AT AT97953140T patent/ATE289296T1/de active
- 1997-12-15 PL PL334281A patent/PL192661B1/pl unknown
- 1997-12-15 UA UA99063227A patent/UA66773C2/uk unknown
- 1997-12-15 WO PCT/US1997/022674 patent/WO1998027073A1/en active IP Right Grant
- 1997-12-15 IL IL13068497A patent/IL130684A/xx active IP Right Grant
- 1997-12-15 ES ES97953140T patent/ES2235265T3/es not_active Expired - Lifetime
- 1997-12-15 CA CA002275323A patent/CA2275323C/en not_active Expired - Lifetime
- 1997-12-15 CZ CZ0212899A patent/CZ297168B6/cs not_active IP Right Cessation
- 1997-12-15 EE EEP199900243A patent/EE03920B1/xx unknown
- 1997-12-15 CN CN97181746A patent/CN1075063C/zh not_active Expired - Lifetime
- 1997-12-15 JP JP52781198A patent/JP4232911B2/ja not_active Expired - Lifetime
- 1997-12-15 SK SK803-99A patent/SK285258B6/sk not_active IP Right Cessation
- 1997-12-15 DE DE69732525T patent/DE69732525T2/de not_active Expired - Lifetime
- 1997-12-15 RO RO99-00672A patent/RO120844B1/ro unknown
- 1997-12-15 SI SI9720079A patent/SI20071A/sl unknown
- 1997-12-15 EP EP97953140A patent/EP0944610B1/en not_active Expired - Lifetime
- 1997-12-16 HR HR08/838,838A patent/HRP970688A2/hr not_active Application Discontinuation
1999
- 1999-06-15 NO NO19992914A patent/NO313236B1/no not_active IP Right Cessation
- 1999-07-30 LV LVP-99-96A patent/LV12432B/en unknown
- 1999-12-15 IL IL13068499A patent/IL130684A0/xx unknown

Also Published As

Publication number	Publication date
KR20000057574A (ko)	2000-09-25
EP0944610A1 (en)	1999-09-29
WO1998027073A1 (en)	1998-06-25
CZ297168B6 (cs)	2006-09-13
CN1245493A (zh)	2000-02-23
HUP0000168A2 (hu)	2000-09-28
WO1998027073A8 (en)	1999-11-04
UA66773C2 (uk)	2004-06-15
EA199900552A1 (ru)	2000-02-28
SK285258B6 (sk)	2006-10-05
CA2275323A1 (en)	1998-06-25
US5932726A (en)	1999-08-03
SK80399A3 (en)	2000-03-13
AU750047B2 (en)	2002-07-11
NZ336163A (en)	2001-04-27
LV12432A (lv)	2000-02-20
IL130684A (en)	2003-12-10
EE03920B1 (et)	2002-12-16
LV12432B (en)	2000-07-20
CN1075063C (zh)	2001-11-21
NO992914D0 (no)	1999-06-15
ATE289296T1 (de)	2005-03-15
EE9900243A (et)	1999-12-15
HRP970688A2 (en)	1998-10-31
DE69732525D1 (de)	2005-03-24
RO120844B1 (ro)	2006-08-30
DE69732525T2 (de)	2006-01-12
NO992914L (no)	1999-06-15
SI20071A (sl)	2000-04-30
AU5694498A (en)	1998-07-15
HU225655B1 (en)	2007-05-29
CZ212899A3 (cs)	1999-11-17
PL192661B1 (pl)	2006-11-30
PT944610E (pt)	2005-04-29
JP4232911B2 (ja)	2009-03-04
IL130684A0 (en)	2000-06-01
PL334281A1 (en)	2000-02-14
BR9714031A (pt)	2000-05-09
HUP0000168A3 (en)	2001-02-28
JP2001507684A (ja)	2001-06-12
ES2235265T3 (es)	2005-07-01
EA002987B1 (ru)	2002-12-26
EP0944610B1 (en)	2005-02-16
KR100498665B1 (ko)	2005-07-01
CA2275323C (en)	2003-04-08

Publication	Publication Date	Title
NO313236B1 (no)	2002-09-02	Asymmetrisk syntese av benzoksazinoner
US6040480A (en)	2000-03-21	Asymmetric synthesis of benzoxazinones
US6028237A (en)	2000-02-22	Synthesis of cyclopropylacetylene
US6049019A (en)	2000-04-11	Process for the preparation of cyclopropylacetylene
US6348616B1 (en)	2002-02-19	Practical synthesis of benzoxazinones useful as HIV reverse transcriptase inhibitors
CA2260922A1 (en)	1998-02-05	A practical synthesis of benzoxazinones useful as hiv reverse transcriptase inhibitors
MXPA99008913A (en)	2000-01-01	Asymmetric synthesis of benzoxazinones via new intermediates
LT4646B (lt)	2000-04-25	Benzoksazinonų asimetrinė sintezė
CZ349099A3 (cs)	2000-05-17	Asymetrické syntézy benzoxazinonů přes nové meziprodukty
MXPA99005410A (es)	2000-04-24	Sintesis asimetrica de benzoxazinonas
JP4032593B2 (ja)	2008-01-16	４−アミノテトラヒドロピラン誘導体の製法
MXPA00003328A (en)	2001-05-07	Preparation of asymmetric cyclic ureas through a monoacylated diamine intermediate

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2018-01-08	MK1K	Patent expired