2-amino-5-chloro-N-(5-chloro-2-pyridinyl)benzamide -Drug Synthesis Database

【结构式】

【分子编号】44135

【品名】2-amino-5-chloro-N-(5-chloro-2-pyridinyl)benzamide

【CA登记号】

【分子式】C₁₂H₉Cl₂N₃O

【分子量】282.12848

【元素组成】C 51.09% H 3.22% Cl 25.13% N 14.89% O 5.67%

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：(IV)

The condensation between 5-chloro-2-nitrobenzoyl chloride (I) and 2-amino-5-chloropyridine (II) produced the corresponding amide (III). Subsequent catalytic hydrogenation of the nitro group of (III) gave aniline (IV). Acid chloride (VI), prepared from N-Boc-isonipecotic acid (V) and oxalyl chloride, was then coupled to aniline (IV) to furnish amide (VII). Further trifluoroacetic acid-promoted cleavage of the Boc protecting group of (VII) yielded piperidine (VIII). Finally, reductive alkylation with acetone in the presence of sodium triacetoxyborohydride gave rise to the target N-isopropyl piperidine.

参考文献中间体

合成目标

【1】 Kyle, J.A.; et al.; SAR investigations of N-aryl-2-[(piperidin-4-ylcarbonyl)amino]benzamide factor Xa inhibitors. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 288.
【2】 Aromatic amides. WO 0039118 .

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)	44133	5-chloro-2-nitrobenzoyl chloride		C₇H₃Cl₂NO₃	详情	详情
(II)	18559	5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine	1072-98-6	C₅H₅ClN₂	详情	详情
(III)	44134	5-chloro-N-(5-chloro-2-pyridinyl)-2-nitrobenzamide		C₁₂H₇Cl₂N₃O₃	详情	详情
(IV)	44135	2-amino-5-chloro-N-(5-chloro-2-pyridinyl)benzamide		C₁₂H₉Cl₂N₃O	详情	详情
(V)	17404	1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid	84358-13-4	C₁₁H₁₉NO₄	详情	详情
(VI)	44136	tert-butyl 4-(chlorocarbonyl)-1-piperidinecarboxylate		C₁₁H₁₈ClNO₃	详情	详情
(VII)	44137	tert-butyl 4-[(4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]anilino)carbonyl]-1-piperidinecarboxylate		C₂₃H₂₆Cl₂N₄O₄	详情	详情
(VIII)	44138	N-(4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]phenyl)-4-piperidinecarboxamide		C₁₈H₁₈Cl₂N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

An alternative preparation for the title compound consisted in the reductive alkylation of ethyl isonipecotate (IX) with acetone to afford the N-isopropyl isonipecotate (X). After basic hydrolysis of the ethyl ester group of (X), the resulting carboxylic acid (XI) was activated as the mixed anhydride (XII) with isobutyl chloroformate. Anhydride (XII) was finally coupled to aniline (IV) to generate the required amide.

参考文献中间体

合成目标

【1】 Aromatic amides. WO 0039118 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(X)	44139	ethyl 1-isopropyl-4-piperidinecarboxylate		C₁₁H₂₁NO₂	详情	详情
(XI)	44140	1-isopropyl-4-piperidinecarboxylic acid		C₉H₁₇NO₂	详情	详情
(XII)	44141			C₁₄H₂₅NO₄	详情	详情
(XIII)	44135	2-amino-5-chloro-N-(5-chloro-2-pyridinyl)benzamide		C₁₂H₉Cl₂N₃O	详情	详情

Extended Information