3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】39112

【品名】3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone

【CA登记号】2835-78-1

【分子式】C₁₃H₁₁NO

【分子量】197.23648

【元素组成】C 79.17% H 5.62% N 7.1% O 8.11%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The acetylation of 4-aminobenzophenone (I) with acetic anhydride in hot benzene gives 4-acetamidobenzophenone (II), which is nitrated with 90% HNO3 in acetic acid-acetic anhydride yielding 4-acetamido-3-nitrobenzophenone (III). The hydrolysis of (III) with H2SO4 affords 4-amino-3-nitrobenzophenone (IV), which is reduced with H2 over Raney-Ni in THF to give 3,4-diaminobenzophenone (V). The cyclization of (V) with cyanogen bromide in methanol-water gives rise to 2-amino-5-benzoylbenzimidazol (VI), which is treated with isopropylsulfonyl chloride (A) and NaH in dimethoxyethane affording 2-amino-1-isopropylsulfonyl-6-benzoylbenzimidazol (VII). Finally, this compound is treated with hydroxylamine hydrochloride in refluxing methanol.

参考文献中间体

合成目标

【1】 Paget, C.J.; et al.; DE 2638551 .
【2】 Castaner, J.; Hopkins, S.J.; AR-336. Drugs Fut 1980, 5, 3, 120.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	18477	2-propanesulfonyl chloride	10147-37-2	C₃H₇ClO₂S	详情	详情
(I)	39112	3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone	2835-78-1	C₁₃H₁₁NO	详情	详情
(II)	39113	N-(3-benzoylphenyl)acetamide	58202-86-1	C₁₅H₁₃NO₂	详情	详情
(III)	39114	N-(5-benzoyl-2-nitrophenyl)acetamide		C₁₅H₁₂N₂O₄	详情	详情
(IV)	39115	(3-amino-4-nitrophenyl)(phenyl)methanone		C₁₃H₁₀N₂O₃	详情	详情
(V)	12830	(3,4-Diaminophenyl)phenylmethanone; 3,4-Diaminobenzophenone	39070-63-8	C₁₃H₁₂N₂O	详情	详情
(VI)	39116	(2-amino-1H-benzimidazol-6-yl)(phenyl)methanone		C₁₄H₁₁N₃O	详情	详情
(VII)	39117	[2-amino-1-(isopropylsulfonyl)-1H-benzimidazol-6-yl](phenyl)methanone		C₁₇H₁₇N₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The cyclization of pyridine-3-carbaldehyde (II) with L-cysteine (I) in ethanol gives the thiazolidine derivative (III), which is treated with formic acid, yielding a diastereomeric mixture of formyl derivatives from which the desired (2R,4R)-(IV) is isolated by crystallization. The cyclization of (2R,4R)-(IV) with ethyl 2,3-dichloropropionate (V) by means of TsCl and Et3N affords (2R)-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylic acid ethyl ester (VI), which is hydrolyzed with NaOH to the corresponding free acid (VII). Finally, this compound is condensed with 3-aminobenzophenone (VIII) by means of SOCl2 to provide the target amide.

参考文献中间体

合成目标

【1】 (Aventis SA); 1H,3H-pyrrolo[1,2-c]thiazole derivs.. EP 0253711; FR 2601015; JP 1988022589 .
【2】 Rajoharison, H.G. (Aventis Pharma SA); Process for the preparation of dextrorotatory 3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]-7-thiazolecarboxylic acid. EP 0297987; US 4906757 .
【3】 Lavé, D.; James, C.; Rajoharison, H.; Bost, P.E.; Cavero, I.; PYRROLO[1,2-c]THIAZOLE DERIVATIVES: POTENT PAF RECEPTOR ANTAGONISTS. Drugs Fut 1989, 14, 9, 891.

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)	14643	L-cysteine; (R)-2-Amino-3-mercaptopropionic acid	52-90-4	C₃H₇NO₂S	详情	详情
(II)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(III)	38634	(4R)-2-(3-pyridinyl)-1,3-thiazolidine-4-carboxylic acid		C₉H₁₀N₂O₂S	详情	详情
(IV)	43713	(2R,4R)-3-formyl-2-(3-pyridinyl)-1,3-thiazolidine-4-carboxylic acid		C₁₀H₁₀N₂O₃S	详情	详情
(V)	43714	ethyl 2,3-dichloropropanoate	6628-21-3	C₅H₈Cl₂O₂	详情	详情
(VI)	43715	ethyl (3R)-3-(3-pyridinyl)-1H-pyrrolo[1,2-c][1,3]thiazole-7-carboxylate		C₁₄H₁₄N₂O₂S	详情	详情
(VII)	43716	(3R)-3-(3-pyridinyl)-1H-pyrrolo[1,2-c][1,3]thiazole-7-carboxylic acid		C₁₂H₁₀N₂O₂S	详情	详情
(VIII)	39112	3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone	2835-78-1	C₁₃H₁₁NO	详情	详情

Extended Information