(1S)-2,2-dimethylcyclopropanecarbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】57427

【品名】(1S)-2,2-dimethylcyclopropanecarbonyl chloride

【CA登记号】

【分子式】C₆H₉ClO

【分子量】132.58956

【元素组成】C 54.35% H 6.84% Cl 26.74% O 12.07%

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：(V)

Coupling between 2-chloro-5-nitropyridine (I) and 4-nitrophenol (II) affords the diaryl ether (III). Subsequent catalytic hydrogenation of both nitro groups of (III) gives rise to diamine (IV). This is finally acylated with (S)-2,2-dimethylcyclopropanecarbonyl chloride (V) to furnish the title diamide.

参考文献中间体

合成目标

【1】 Yamamoto, T.; Iino, Y.; Kobayashi, T.; Fujita, K.; Hatanaka, T.; Kodaira, A.; Takehana, K.; Konishi, A. (Ajinomoto Co., Inc.); Heterocyclic cpds. and medicinal use thereof. EP 1193255; WO 0102359 .

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)	29610	2-chloro-5-nitropyridine	4548-45-2	C₅H₃ClN₂O₂	详情	详情
(II)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(III)	57425	4-nitrophenyl 5-nitro-2-pyridinyl ether; 5-nitro-2-(4-nitrophenoxy)pyridine		C₁₁H₇N₃O₅	详情	详情
(IV)	57426	6-(4-aminophenoxy)-3-pyridinamine; 6-(4-aminophenoxy)-3-pyridinylamine		C₁₁H₁₁N₃O	详情	详情
(V)	57427	(1S)-2,2-dimethylcyclopropanecarbonyl chloride		C₆H₉ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Reduction of (R)-ethyl nipecotate (VII) with LiAlH4 yields 3-piperidinemethanol (VIII), which is further protected as the N-Boc derivative (IX) by using Boc2O. Treatment of the piperidine alcohol (IX) with p-toluenesulfonyl chloride and pyridine leads to tosylate (X). Condensation of the sodium derivative of 4-methylimidazole (XI) with tosylate (X) gives rise to a mixture of regioisomeric N-alkylated imidazoles, which are chromatographically separated after derivatization with trityl chloride. The desired isomer (XII) is then deprotected under acidic conditions, giving piperidine (XIII). Finally, EDC-mediated coupling between piperidine (XIII) and the piperazinecarboxylic acid (VI) furnishes the title amide.

参考文献中间体

合成目标

【1】 Cooper, A.B.; Girijavallabhan, V.M.; Mallams, A.K.; Doll, R.J.; Kelly, J.M.; Rane, D.F.; Taveras, A.G.; Guzi, T.; Strickland, C.; Chao, J. (Schering Corp.); Farnesyl protein transferase inhibitors. EP 1140904; JP 2002533335; WO 0037458 .
【2】 Cooper, A.B.; Girijavallabhan, V.M.; Mallams, A.K.; Doll, R.J.; Kelly, J.M.; Rane, D.F.; Taveras, A.G.; Guzi, T.; Strickland, C.; Chao, J. (Schering Corp.); Farnesyl protein transferase inhibitors. US 6362188 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	51595	(2R)-4-[(11S)-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-[(cyclohexyloxy)carbonyl]-2-piperazinecarboxylic acid		C₂₆H₃₀ClN₃O₄	详情	详情
(VII)	12453	ethyl (3R)hexahydro-3-pyridinecarboxylate		C₈H₁₅NO₂	详情	详情
(VIII)	57427	(1S)-2,2-dimethylcyclopropanecarbonyl chloride		C₆H₉ClO	详情	详情
(IX)	35221	tert-butyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate		C₁₁H₂₁NO₃	详情	详情
(X)	57428	ethyl 3-ethyl-2-pentenoate		C₉H₁₆O₂	详情	详情
(XI)	51586	4-Methylimidazole; 4-Methyl-1H-imidazole; 4-Methyl Imidazole	822-36-6	C₄H₆N₂	详情	详情
(XII)	58429	tert-butyl (3S)-3-[(4-methyl-1H-imidazol-1-yl)methyl]-1-piperidinecarboxylate		C₁₅H₂₅N₃O₂	详情	详情
(XIII)	58430	(3R)-3-[(4-methyl-1H-imidazol-1-yl)methyl]piperidine		C₁₀H₁₇N₃	详情	详情

Extended Information