2-(Chloromethyl)pyridine -Drug Synthesis Database

【结构式】

【分子编号】26187

【品名】2-(Chloromethyl)pyridine

【CA登记号】4377-33-7

【分子式】C₆H₆ClN

【分子量】127.57308

【元素组成】C 56.49% H 4.74% Cl 27.79% N 10.98%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

This compound can be obtained in two different ways: 1) By reaction of 2-(p-isobutylphenyl)propionic acid sodium salt (I) with 2-pyridylmethyl chloride (II) in refluxing benzene. 2) By reaction of 2-(p-isobutylphenyl)propionyl chloride (III) with 2-pyridylmethanol (IV) by means of triethylamine in THF.

参考文献中间体

合成目标

【1】 Noda, K.; Nakagawa, A.; Ishikura, Y.; Tosu, S.; Ide, H. (Hisamitsu Pharmaceutical Co., Ltd.); Pyridylalkyl esters of 2-(p-isobutylphenyl)acetic acid and propionic acids and use. US 4150137 .
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Pineprofen. Drugs Fut 1982, 7, 6, 401.

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)	31961	sodium 2-(4-isobutylphenyl)propanoate		C₁₃H₁₇NaO₂	详情	详情
(II)	26187	2-(Chloromethyl)pyridine	4377-33-7	C₆H₆ClN	详情	详情
(III)	22117	2-(4-isobutylphenyl)propanoyl chloride		C₁₃H₁₇ClO	详情	详情
(IV)	30208	2-pyridinylmethanol；pyridin-2-ylmethanol；2-pyridylmethanol	586-98-1	C₆H₇NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The compound was obtained by condensation of 2-(chloromethyl)pyridine (I) with 2-methylimidazole (II) in hot DMF. The free base (III) was then treated with fumaric acid in EtOH to produce the title fumarate salt.

参考文献中间体

合成目标

【1】 Giger, R.K.A. (Novartis AG; Novartis Deutschland GmbH); Imidazolylmethyl-pyridines. DE 4131584; EP 0534904; JP 1993194491; US 5635521 .

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)	26187	2-(Chloromethyl)pyridine	4377-33-7	C₆H₆ClN	详情	详情
(II)	15670	2-Methylimidazole; 2-Methyl-1H-imidazole	693-98-1	C₄H₆N₂	详情	详情
(III)	37793	2-[(2-methyl-1H-imidazol-1-yl)methyl]pyridine		C₁₀H₁₁N₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Protection of ethyl piperidine-3-carboxylate (I) with di tert-butyl dicarbonate gave carbamate (II), which was alkylated with 2-(chloromethyl)pyridine chloride (III) in the presence of potassium hexamethyldisilazide to afford racemic (IV). Acid deprotection of the Boc group of (IV) yielded amine (V). This was resolved by coupling with (R)-O-acetyl mandelic acid (VI), followed by chromatographic separation of the diastereoisomers. Then, acid hydrolysis of the desired isomer (VII) provided the (S)-piperidine (VIII). Subsequent coupling of (VIII) with N-Boc-D-tryptophan (IX) in the presence of EDC and HOBt gave amide (X). After Boc deprotection of (X), the resulting amine (XI) was coupled with N-Boc-2-aminoisobutyric acid (XII) to produce (XIII). Finally, acid removal of the Boc group of (XIII) furnished the title compound.

参考文献中间体

合成目标

【1】 Schleim, K.D.; Leung, K.; Cheng, K.; Patchent, A.A.; Morriello, G.; Smith, R.; Jacks, T.; Yang, L.; Thiazole-derived potent, highly bioavailable short duration growth hormone secretagogues. Bioorg Med Chem Lett 1999, 9, 13, 1761.

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)	25693	ethyl 3-piperidinecarboxylate	5006-62-2	C₈H₁₅NO₂	详情	详情
(II)	26186	1-(tert-butyl) 3-ethyl 1,3-piperidinedicarboxylate		C₁₃H₂₃NO₄	详情	详情
(III)	26187	2-(Chloromethyl)pyridine	4377-33-7	C₆H₆ClN	详情	详情
(IV)	26188	1-(tert-butyl) 3-ethyl 3-(2-pyridinylmethyl)-1,3-piperidinedicarboxylate		C₁₉H₂₈N₂O₄	详情	详情
(V)	26189	ethyl 3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₁₄H₂₀N₂O₂	详情	详情
(VI)	26190	(2R)-2-(acetoxy)-2-phenylethanoic acid		C₁₀H₁₀O₄	详情	详情
(VII)	26191	ethyl (3S)-1-[(2R)-2-(acetoxy)-2-phenylethanoyl]-3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₂₄H₂₈N₂O₅	详情	详情
(VIII)	26192	ethyl (3S)-3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₁₄H₂₀N₂O₂	详情	详情
(IX)	16114	N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid	13139-14-5	C₁₆H₂₀N₂O₄	详情	详情
(X)	26193	ethyl (3S)-1-[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propanoyl]-3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₃₀H₃₈N₄O₅	详情	详情
(XI)	26194	ethyl (3S)-1-[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]-3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₂₅H₃₀N₄O₃	详情	详情
(XII)	18471	N-(tert-butoxycarbonyl)-2-methylalanine	30992-29-1	C₉H₁₇NO₄	详情	详情
(XIII)	26195	ethyl (3S)-1-[(2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-3-(1H-indol-3-yl)propanoyl]-3-(2-pyridinylmethyl)-3-piperidinecarboxylate		C₃₄H₄₅N₅O₆	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XIII)

Hydrogenolytic removal of the O-benzyl group provided phenol (XII), which was subsequently alkylated with 2-picolyl chloride (XIII) to produce ether (XIV). The Boc protecting group of (XIV) was finally cleaved by treatment with HCl in EtOAc.

参考文献中间体

合成目标

【1】 Ikeo, T.; Ukita, T.; Omori, K. (Tanabe Seiyaku Co., Ltd.); Isoquinolinone derivs., process for preparing the same, and their use as phosphodiesterase inhibitors. JP 1998298164; WO 9838168 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	43974	methyl 7-(benzyloxy)-2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate		C₃₈H₃₈N₂O₉	详情	详情
(XII)	43975	methyl 2-[4-[(tert-butoxycarbonyl)amino]phenyl]-7-hydroxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate		C₃₁H₃₂N₂O₉	详情	详情
(XIII)	26187	2-(Chloromethyl)pyridine	4377-33-7	C₆H₆ClN	详情	详情
(XIV)	43976	methyl 2-[4-[(tert-butoxycarbonyl)amino]phenyl]-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-1,2-dihydro-3-isoquinolinecarboxylate		C₃₇H₃₇N₃O₉	详情	详情

Extended Information