3-cyanobenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】34921

【品名】3-cyanobenzoyl chloride

【CA登记号】1711-11-1

【分子式】C₈H₄ClNO

【分子量】165.5786

【元素组成】C 58.03% H 2.43% Cl 21.41% N 8.46% O 9.66%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

Regioselective coupling of methyl 3,4-diaminobenzoate (I) with 3-cyanobenzoyl chloride (II) afforded benzamide (III). Further coupling of (III) with 4-tert-butylbenzoyl chloride (IV) gave diamide (V). Conversion of the methyl ester group of (V) into the benzyl ester analogue (VII) was effected by hydrolysis with LiOH, followed by treatment of the resulting carboxylic acid (VI) with benzyl bromide. Addition of hydroxylamine to the cyano group of (VII) gave rise to amidoxime (VIII). Subsequent hydrogenation of (VIII) over Pd/C produced the title amidine.

参考文献中间体

合成目标

【1】 Briggs, S.; Weir, L.C.; Wiley, M.R.; et al.; Structure-based design of potent, amidine-derived inhibitors of factor Xa: Evaluation of selectivity, anticoagulant activity, and antithrombotic activity. J Med Chem 2000, 43, 5, 883.

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)	34920	methyl 3,4-diaminobenzoate	36692-49-6	C₈H₁₀N₂O₂	详情	详情
(II)	34921	3-cyanobenzoyl chloride	1711-11-1	C₈H₄ClNO	详情	详情
(III)	34922	methyl 4-amino-3-[(3-cyanobenzoyl)amino]benzoate		C₁₆H₁₃N₃O₃	详情	详情
(IV)	34923	4-(tert-butyl)benzoyl chloride	1710-98-1	C₁₁H₁₃ClO	详情	详情
(V)	34924	methyl 4-[[4-(tert-butyl)benzoyl]amino]-3-[(3-cyanobenzoyl)amino]benzoate		C₂₇H₂₅N₃O₄	详情	详情
(VI)	34925	4-[[4-(tert-butyl)benzoyl]amino]-3-[(3-cyanobenzoyl)amino]benzoic acid		C₂₆H₂₃N₃O₄	详情	详情
(VII)	34926	benzyl 4-[[4-(tert-butyl)benzoyl]amino]-3-[(3-cyanobenzoyl)amino]benzoate		C₃₃H₂₉N₃O₄	详情	详情
(VIII)	34927	benzyl 4-[[4-(tert-butyl)benzoyl]amino]-3-([3-[(hydroxyamino)(imino)methyl]benzoyl]amino)benzoate		C₃₃H₃₂N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Acylation of amino derivative (I) with 3-cyanobenzoyl chloride (II) provides amide (III) which is then cyclized to give phenanthridine (IV) by refluxing with phosphoryl chloride in nitrobenzene and catalysis of SnCl4. Hydrolysis of the nitrile derivative (IV) in H2SO4 gives carboxylic acid derivative (V). Quaternization of (V) is carried out using dimethyl sulfate and after refluxing in a HCl solution, derivative (VI) is obtained. Reduction of (VI) using iron powder in a mixture of HCl-ethanol yields the ethidium chloride derivative (VII) which is coupled to the protected arginine-linking chain (VIII) (see below) in presence of DCC and HOBt. Last step is the deprotection of the arginine moiety with TFA and separation of the obtained products.

参考文献中间体

合成目标

【1】 Guedj, R.; Peytou, V.; Aubertin, A.-M.; Terreux, R.; Bailly, C.; Patino, N.; Condom, R.; Cabrol-Bass, D.; Gelus, N.; Synthesis and antiviral activity of ethidium - Arginine conjugates directed against the TAR RNA of HIV-1. J Med Chem 1999, 42, 20, 4042.

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)	41160	4,4'-dinitro[1,1'-biphenyl]-2-amine; 4,4'-dinitro[1,1'-biphenyl]-2-ylamine		C₁₂H₉N₃O₄	详情	详情
(II)	34921	3-cyanobenzoyl chloride	1711-11-1	C₈H₄ClNO	详情	详情
(III)	41161	3-cyano-N-(4,4'-dinitro[1,1'-biphenyl]-2-yl)benzamide		C₂₀H₁₂N₄O₅	详情	详情
(IV)	41162	3-(3,8-dinitro-6-phenanthridinyl)benzonitrile		C₂₀H₁₀N₄O₄	详情	详情
(V)	41163	3-(3,8-dinitro-6-phenanthridinyl)benzoic acid		C₂₀H₁₁N₃O₆	详情	详情
(VI)	41164	6-(3-carboxyphenyl)-5-methyl-3,8-dinitrophenanthridinium chloride		C₂₁H₁₄ClN₃O₆	详情	详情
(VII)	41165	3,8-diamino-6-(3-carboxyphenyl)-5-methylphenanthridinium chloride		C₂₁H₁₈ClN₃O₂	详情	详情
(VIII)	41166	methyl (2S)-2-([3-[(6-aminohexanoyl)amino]propanoyl]amino)-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoate		C₃₀H₅₂N₆O₇S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Treatment of 2-chloroquinoline-3-carboxylic acid (I) with oxalyl chloride affords acid chloride (II), which is subsequently coupled with methyl 3,4-diaminobenzoate (III) to yield amide (IV). Intramolecular cyclization of amino amide (IV) with Burgess reagent in refluxing THF produces the benzimidazole (V). Then, acidic hydrolysis of both methyl ester and chloroquinoline functions of (V) gives rise to the carboxylic acid (VI). Coupling of (VI) with N-Boc-piperazine (VII) furnishes amide (VIII). The N-Boc protecting group of (VIII) is finally removed by treatment with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Hungate, R.W.; Fraley, M.E.; Hambaugh, S.R. (Merck & Co., Inc.); Tyrosine kinase inhibitors. JP 2003512353; US 6479512; WO 0128993 .

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)	61948	2-chloro-3-quinolinecarboxylic acid		C₁₀H₆ClNO₂	详情	详情
(II)	61950	2-chloro-3-quinolinecarbonyl chloride		C₁₀H₅Cl₂NO	详情	详情
(III)	34921	3-cyanobenzoyl chloride	1711-11-1	C₈H₄ClNO	详情	详情
(IV)	61951	methyl 3-amino-4-{[(2-chloro-3-quinolinyl)carbonyl]amino}benzoate		C₁₈H₁₄ClN₃O₃	详情	详情
(V)	61952	methyl 2-(2-chloro-3-quinolinyl)-1H-benzimidazole-5-carboxylate		C₁₈H₁₂ClN₃O₂	详情	详情
(VI)	61953	2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-benzimidazole-5-carboxylic acid		C₁₇H₁₁N₃O₃	详情	详情
(VII)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(VIII)	61954	tert-butyl 4-{[2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-benzimidazol-5-yl]carbonyl}-1-piperazinecarboxylate		C₂₆H₂₇N₅O₄	详情	详情

Extended Information