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【结 构 式】 
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【分子编号】22296 【品名】2-fluorophenylamine; 2-fluoroaniline 【CA登记号】348-54-9 |
【 分 子 式 】C6H6FN 【 分 子 量 】111.1187832 【元素组成】C 64.85% H 5.44% F 17.1% N 12.61% |
合成路线1
该中间体在本合成路线中的序号：(X)By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II). The starting products are obtained as follows: a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V), which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I). b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII), which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX). The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI), which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).
| 【1】 Fukuchi, I.; et al.; Neurochemical study of mafoprazine, a new phenylpiperazine derivative. Jpn Pharmacol 1988, 47, 9, 51. |
| 【2】 Kanno, T.; Gaino, M.; Yamamura, M.; Ishida, R.; Shintomi, K. (Tanabe Seiyaku Co., Ltd.); N-Aryl-N-phenoxy-alkyl-piperazine compounds useful in decreasing intracranial presssure. EP 0034284; JP 156115769; US 4413006 . |
| 【3】 Prous, J.; Castaner, J.; Mafoprazine mesylate. Drugs Fut 1988, 13, 10, 920. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 23114 | 3-[4-(acetamido)-2-methoxyphenoxy]propyl 4-methylbenzenesulfonate | C19H23NO6S | 详情 | 详情 | |
| (II) | 23115 | 1-(2-fluorophenyl)piperazine | 1011-15-0 | C10H13FN2 | 详情 | 详情 |
| (III) | 23116 | N-(4-hydroxy-3-methoxyphenyl)acetamide | C9H11NO3 | 详情 | 详情 | |
| (IV) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (IV) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (V) | 23118 | ethyl 3-[4-(acetamido)-2-methoxyphenoxy]propanoate | C14H19NO5 | 详情 | 详情 | |
| (VI) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (VIII) | 23121 | ethyl 2-[benzyl(2-ethoxy-2-oxoethyl)amino]acetate | C15H21NO4 | 详情 | 详情 | |
| (IX) | 23122 | N-benzyl-2-chloro-N-(2-chloroethyl)-1-ethanamine; N-Benzylbis(2-chloroethyl)amine | 10429-82-0 | C11H15Cl2N | 详情 | 详情 |
| (X) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (XI) | 23124 | 1-benzyl-4-(2-fluorophenyl)piperazine | C17H19FN2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Condensation of 1-benzyl-4-piperidone (I) with 2-fluoroaniline (II) affords imine (III). Addition of phenyllithium (IV) to imine (III) gives amine (V), which is acylated with propionyl chloride and the resultant amide (VI) is debenzylated via 1-chloroethyl chloroformate in refluxing 1,2-dichloroethane followed by methanolysis to give (VII). Amine (VII)) is alkylated with 1-(2-bromoethyl)-4-ethyl-4,5-dihydro-1H-tetrazol-5-one(VIII) to yield A-3665. A-3665 hydrochloride is precipitated with dry HCl gas in ethyl ether.
| 【1】 Kudzma, L.V.; Spencer, H.K.; Severnak, S.A. (BOC Health Care, Inc.); 4-Phenyl-4-[N-(phenyl)amido]piperidine derivs. and methods employing such cpds. AU 8824558; EP 0315405; JP 1990015061; JP 1990152963; US 4791121; US 4921864 . |
| 【2】 Kudzma, L.V.; Ossipov, M.H.; Benvenga, M.J.; Spaulding, T.C.; Rudo, F.G.; A-3665. Drugs Fut 1990, 15, 6, 559. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 15750 | (6R,7R)-3-[(acetoacetoxy)methyl]-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C17H18N6O8S2 | 详情 | 详情 | |
| (II) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (III) | 13865 | N-(1-Benzyl-4-piperidinylidene)-N-(2-fluorophenyl)amine; N-(1-Benzyl-4-piperidinylidene)-2-fluoroaniline | C18H19FN2 | 详情 | 详情 | |
| (IV) | 24014 | Phenyllithium | 591-51-5 | C6H5Li | 详情 | 详情 |
| (V) | 13866 | N-(1-Benzyl-4-phenyl-4-piperidinyl)-N-(2-fluorophenyl)amine; 1-Benzyl-N-(2-fluorophenyl)-4-phenyl-4-piperidinamine | C24H25FN2 | 详情 | 详情 | |
| (VI) | 13867 | N-(1-Benzyl-4-phenyl-4-piperidinyl)-N-(2-fluorophenyl)propanamide | C27H29FN2O | 详情 | 详情 | |
| (VII) | 13868 | N-(2-Fluorophenyl)-N-(4-phenyl-4-piperidinyl)propanamide | C20H23FN2O | 详情 | 详情 | |
| (VIII) | 14721 | 1-(2-bromoethyl)-4-ethyl-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one | C5H9BrN4O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Condensation of the piperidone (I) with 2-fluoroaniline (II), followed by reduction of the Schiff base with sodium borohydride afforded 1-benzyl-3-methyl-4-phenylaminopiperidine (III). Intermediate (III) was produced in an approximate 7:3 (cis/trans) isomeric ratio. Acylation of (III) with methoxyacetyl chloride gave compound (IV) and subsequent catalytic debenzylation gave the compound (V), which was N-alkylated in acetonitrile with 1-(2-bromoethyl)-4-ethyl-1,4-dihydro-5H-tetrazol-5-one (VI). Brifentanil is the cis-isomer obtained by the chromatographic separation of the isomeric mixture.
| 【1】 Huang, B.-S.; Deutsche, K.H.; Lalinde, N.L.; Terrell, R.C.; Kudzma, L.V. (BOC Health Care, Inc.); (BOC, Inc.). N-Aryl-N-(4-piperidinyl)amides and pharmaceutical compsns. and method employing such cpds. EP 0160422; ES 8609251; ES 8705387; JP 1985248670; US 4584303 . |
| 【2】 Ossipov, M.H.; Wright, D.; Spencer, K.H.; Spaulding, T.C.; Lalinde, N.; Moliterni, J.; Rufo, F.G.; Synthesis and pharmacological evaluation of a series of new 3-methyl-1,4-disubstituted-piperidine analgesics. J Med Chem 1989, 33, 10, 2876-82. |
| 【3】 Moliterni, J.; Spencer H.K.; Rudo, F.G.; Ossipov, M.H.; Spaulding, T.C.; Lalinde, N.; Wright, D.; Waters, S.J.; Brifentanil Hydrochloride. Drugs Fut 1991, 16, 8, 706. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 14714 | 1-Benzyl-3-methyl-4-piperidone; 1-benzyl-3-methyltetrahydro-4(1H)-pyridinone | 34737-89-8 | C13H17NO | 详情 | 详情 |
| (II) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (III) | 14715 | N-(1-benzyl-3-methyl-4-piperidinyl)-N-(2-fluorophenyl)amine; 1-benzyl-N-(2-fluorophenyl)-3-methyl-4-piperidinamine | C19H23FN2 | 详情 | 详情 | |
| (IV) | 14716 | N-(1-benzyl-3-methyl-4-piperidinyl)-N-(2-fluorophenyl)-2-methoxyacetamide | C22H27FN2O2 | 详情 | 详情 | |
| (V) | 14717 | N-(2-fluorophenyl)-2-methoxy-N-(3-methyl-4-piperidinyl)acetamide | C15H21FN2O2 | 详情 | 详情 | |
| (VI) | 14421 | (2R,3S)-2,3-bis([[tert-butyl(dimethyl)silyl]oxy]methyl)cyclobutanone O-methyloxime | C19H41NO3Si2 | 详情 | 详情 | |
| (VII) | 14718 | N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-1,2,3,4-tetraazol-1-yl)ethyl]-3-methyl-4-piperidinyl]-N-(2-fluorophenyl)-2-methoxyacetamide | C20H29FN6O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IX)Michael addition of acrylonitrile (II) to 4-fluoro-2-nitroaniline (I) in the presence of Triton B provided nitrile (III). The nitro group of (III) was then reduced to the amine (IV) by hydrogenation over Pd/C. Further cyclization of amine (IV) with ethyl (ethoxycarbonyl)acetimidate (V) furnished the benzimidazole (VI). Diester (VII) (prepared by refluxing the nitrile (VI) with ethanolic HCl), was submitted to Dieckmann cyclization in the presence of NaOEt to produce the pyridobenzimidazole (VIII). Reaction of the ester group of (VIII) with 2-fluoroaniline (IX) in boiling xylene yielded the corresponding anilide (X), which was finally alkylated with ethoxymethyl chloride (XI) in the presence of NaH and crown ether.
| 【1】 Sanfilippo, P.J.; Reitz, A.B.; Kordik, C.P.; Dubinsky, B.; Rosenthal, D.I.; Vaidya, A.H.; Jordan, A.D.; Wu, W.-N.; Potential anxiolytic agents. Part 4: Novel orally-active N(5)-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity. Bioorg Med Chem Lett 2002, 12, 17, 2381. |
| 【2】 Cohen, J.H.; et al.; Process research for the synthesis of RWJ-51204, a novel anxiolytic agent. Org Process Res Dev 1999, 3, 4, 260. |
| 【3】 Reitz, A.B.; Jordan, A.D.; Sanfilippo, P.J.; Scott, M.K. (Ortho-McNeil Pharmaceutical, Inc.); 5-Heteroatom-containing alkyl substd.-3-oxo-pyrido(1,2-a)benzimidazole-4-carboxamide derivs. useful in treating central nervous system disorders. EP 0935598; US 5817668; WO 9815553 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22288 | 4-fluoro-2-nitrophenylamine; 4-fluoro-2-nitroaniline | 364-78-3 | C6H5FN2O2 | 详情 | 详情 |
| (III) | 22290 | 3-(4-fluoro-2-nitroanilino)propanenitrile | C9H8FN3O2 | 详情 | 详情 | |
| (IV) | 22291 | 3-(2-amino-4-fluoroanilino)propanenitrile | C9H10FN3 | 详情 | 详情 | |
| (VI) | 22293 | ethyl 2-[1-(2-cyanoethyl)-5-fluoro-1H-benzimidazol-2-yl]acetate | C14H14FN3O2 | 详情 | 详情 | |
| (VII) | 22294 | ethyl 3-[2-(2-ethoxy-2-oxoethyl)-5-fluoro-1H-benzimidazol-1-yl]propanoate | C16H19FN2O4 | 详情 | 详情 | |
| (VIII) | 22295 | ethyl 7-fluoro-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxylate | C14H13FN2O3 | 详情 | 详情 | |
| (IX) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (X) | 22297 | 7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide | C18H13F2N3O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)The condensation of 2-fluoroaniline (I) with diethyl ethoxymethylene malonate (II) at 130 C afforded enamine (III), which was further cyclized to ethyl 8-fluoro-4-hydroxy-3-quinolinecarboxylate (IV) upon heating at 250 C. Condensation of (III) with neat 4-chlorobenzylamine (V) then provided the desired carboxamide.
| 【1】 Cudahy, M.M.; Clayton, T.L.; Vailancourt, V.A.; et al.; 4-Hydroxyquinoline-3-carboxamides as inhibitors of herpes virus DNA polymerases. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 135. |
| 【2】 Schnute, M.E.; Turner, S.R.; Cudahy, M.M.; Vaillancourt, V.A.; Thaisrivongs, S.; Strohbach, J.W.; Romines, K.R.; Tucker, J.A. (Pharmacia Corp.); 4-Hydroxyquinoline-3-carboxamides and hydrazides as antiviral agents. EP 1042295; US 6093732; WO 9932450 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (II) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (III) | 40763 | diethyl 2-[(2-fluoroanilino)methylene]malonate | C14H16FNO4 | 详情 | 详情 | |
| (IV) | 40764 | ethyl 8-fluoro-4-hydroxy-3-quinolinecarboxylate | C12H10FNO3 | 详情 | 详情 | |
| (V) | 23378 | (4-chlorophenyl)methanamine; 4-chlorobenzylamine | 104-86-9 | C7H8ClN | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)Clauson-Kaas reaction between 2-fluoroaniline (I) and 2,5-dimethoxytetrahydrofuran (II) in refluxing HOAc affords pyrrolic compound (III), which is then converted into cyanopyrrole derivative (IV) through a one-pot sequence involving formylation with oxalyl chloride, oximation with NH2OH.HCl and dehydration with Ac2O. Cyclization of nitrile (IV) by treatment with KOH in ethylene glycol or in tert-butyl alcohol yields quinoxalinone derivative (V), which is then transformed into the hydrazine derivative (VI) by refluxing with POCl3 and catalytic N,N-dimethylaniline followed by treatment with hydrazine in MeOH. Finally, the desired product is obtained by reaction of (VI) with pyrazinecarboxylic acid (VII) in the presence of PPh3 and 2,2'-dipyridyl disulfide (Aldrithiol-2) in CH2Cl2.
| 【2】 Campiani, G.; et al.; Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure. J Med Chem 1997, 40, 22, 3670. |
| 【1】 Campiani, G.; Fabbrini, M.; Aiello, F.; et al.; Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent. J Med Chem 2001, 44, 3, 305. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (II) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (III) | 48110 | 1-(2-fluorophenyl)-1H-pyrrole | C10H8FN | 详情 | 详情 | |
| (IV) | 48111 | 1-(2-fluorophenyl)-1H-pyrrole-2-carbonitrile | C11H7FN2 | 详情 | 详情 | |
| (V) | 48112 | pyrrolo[1,2-a]quinoxalin-4(5H)-one | C11H8N2O | 详情 | 详情 | |
| (VI) | 48113 | 4-hydrazinopyrrolo[1,2-a]quinoxaline | C11H10N4 | 详情 | 详情 | |
| (VII) | 37256 | 2-pyrazinecarboxylic acid; Pyrazinoic acid | 98-97-5 | C5H4N2O2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(V)Nitration of 2,3,4-trifluorobenzoic acid (I) using HNO3 and H2SO4 gives 2,3,4-trifluoro-5-nitrobenzoic acid (II), which by displacement with NH4OH in H2O at 0 °C yields 4-amino-2,3-difluoro-5-nitrobenzoic acid (III). Fisher esterification of acid (III) with Me3SiCHN2 in THF/MeOH at 0 °C affords 4-amino-2,3-difluoro-5-nitrobezoic acid methyl ester (IV), which is condensed with 2-fluoroaniline (V) in xylene at 140 °C to provide methyl 4-amino-3-fluoro-2-(2-fluorophenylamino)-5-nitrobenzoic acid methyl ester (VI). Reduction and cyclization of intermediate (VI) using formic acid and Pd(OH)2/C in EtOH at 95 °C generates methyl 4-fluoro-5-(2-fluorophenylamino)-benzimidazole-6-carboxylate (VII), which by bromination with NBS and p-TsOH in DMF produces the bromo derivative (VIII). N-Methylation of compound (VIII) with methyl iodide by means of K2CO3 in DMF at 75 °C gives compound (IX), which is hydrolyzed with NaOH in THF/H2O to yield the free carboxylic acid (X). Condensation of carboxylic acid (X) with O-[2-(vinyloxy)ethyl]hydroxylamine (XI) using HOBt, Et3N and EDC in DMF affords amide (XII), which is finally treated with HCl in EtOH (1).
Intermediate O-[2-(vinyloxy)ethyl]hydroxylamine (XI) is prepared by Mitsnoubu reaction of 2-(vinyloxy)ethanol (XIII) with N-hydroxy - phthalimide (XIV) using PPh3 and DEAD in THF at 0 °C to give 2-[2-(vinyloxy)ethoxy]-1H-isoindole-1,3(2H)-dione (XV), which is finally treated with MeNHNH2 in CH2Cl2 .
| 【1】 Barrett, S.D., Biwersi, C., Warmus, J.S., Tecle, H., Kaufman, M. (Pfizer, Inc.). Oxygenated esters of 4-iodo phenylamino benzhydroxamic acids. WO 2002006213; EP 1301472; CA 2416685; US 2004054172; US 6960614. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 34622 | 2,3,4-trifluorobenzoic acid | 61079-72-9 | C7H3F3O2 | 详情 | 详情 |
| (II) | 67510 | 2,3,4-trifluoro-5-nitrobenzoic acid | C7H2F3NO4 | 详情 | 详情 | |
| (III) | 67511 | 4-amino-2,3-difluoro-5-nitrobenzoic acid | C7H4F2N2O4 | 详情 | 详情 | |
| (IV) | 67512 | 4-amino-2,3-difluoro-5-nitrobezoic acid methyl ester | 284030-58-6 | C8H6F2N2O4 | 详情 | 详情 |
| (V) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (VI) | 67513 | methyl 4-amino-3-fluoro-2-(2-fluorophenyl-amino)-5-nitrobenzoic acid methyl ester | C15H13F2N3O4 | 详情 | 详情 | |
| (VII) | 67514 | methyl 4-fluoro-5-(2-fluorophenylamino)-benzimidazole-6-carboxylate | C15H11F2N3O2 | 详情 | 详情 | |
| (VIII) | 67515 | methyl 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-1H-benzo[d]imidazole-6-carboxylate | C15H10BrF2N3O2 | 详情 | 详情 | |
| (IX) | 67516 | methyl 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate | C16H12BrF2N3O2 | 详情 | 详情 | |
| (X) | 67517 | 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylic acid | C15H10BrF2N3O2 | 详情 | 详情 | |
| (XI) | 67518 | O-[2-(vinyloxy)ethyl]hydroxylamine | 391212-29-6 | C4H9NO2 | 详情 | 详情 |
| (XII) | 67519 | 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-1-methyl-N-(2-(vinyloxy)ethoxy)-1H-benzo[d]imidazole-6-carboxamide | C19H17BrF2N4O3 | 详情 | 详情 | |
| (XIII) | 67520 | 2-(vinyloxy)ethanol | 764-48-7 | C4H8O2 | 详情 | 详情 |
| (XIV) | 13505 | N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione | 524-38-9 | C8H5NO3 | 详情 | 详情 |
| (XV) | 67521 | 2-[2-(vinyloxy)ethoxy]-1H-isoindole-1,3(2H)-dione | C12H11NO4 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XIV)Condensation of 2-fluoroaniline (XIV) or 2-bromo-6-fluoroaniline (I) with 2-methoxy-5-(trifluoromethyl)phenyl isocyanate (V) in refluxing acetonitrile yields the corresponding diaryl ureas (XV) or (XVI), respec-tively. The N-(2-Fluorophenyl)urea derivative (XV) is then condensed with methyl acrylate (II) by means of Pd(OAc)2 and H2S2O7 in AcoH to give the corresponding (E)-cinnamate (XVII), which finally undergoes intramolecular Michael addition in the presence of DBU in refluxing acetone .
Alternatively, intermediate (XI) is obtained by Heck coupling of aryl bromide (XVI) with methyl acrylate (II) in the presence of Pd(MeCn)2Cl2, (o-tol)3P and Et3n in isobutyronitrile at 90-102 °C .
| 【1】 Goossen, K., Kuhn, o., Berwe, M., Krueger, J., Militzer, H.-C. (Bayer HealthCare AG). Method for producing dihydroquinazolines. Cn 101863843, DE 10227517, EP 1893587, JP 2008543797, US 2009221822, US 8084604, US 2012130072, US 8372972, Wo 2006133822. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 68030 | 2-bromo-6-fluoroaniline | 65896-11-9 | C6H5BrFN | 详情 | 详情 |
| (II) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (V) | 68033 | 2-methoxy-5-(trifluoromethyl)phenyl isocyanate | 16588-75-3 | C9H6F3NO2 | 详情 | 详情 |
| (XI) | 68037 | methyl 2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetate | C19H16F4N2O4 | 详情 | 详情 | |
| (XIV) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (XV) | 68040 | 1-(2-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea | C15H12F4N2O2 | 详情 | 详情 | |
| (XVI) | 68041 | 1-(2-bromo-6-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea | C15H11BrF4N2O2 | 详情 | 详情 | |
| (XVII) | 68042 | (E)－methyl 3-(3-fluoro-2-(3-(2-methoxy-5-(trifluoromethyl)phenyl)ureido)phenyl)acrylate | C19H16F4N2O4 | 详情 | 详情 |