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【结 构 式】

【分子编号】65396

【品名】1-benzyl-3-(methoxycarbonylamino)-4-methylpyridinium chloride

【CA登记号】 

【 分 子 式 】C15H17ClN2O2

【 分 子 量 】292.76496

【元素组成】C 61.54% H 5.85% Cl 12.11% N 9.57% O 10.93%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

An enantioselective synthesis of the (3R,4R)-isomer has also been reported. Quaternization of 3-(methoxycarbonylamino)-4-methylpyridine (VII) with benzyl chloride in toluene at 80 °C, followed by reduction of the resulting pyridinium salt (VIII) with NaBH4 in ethanol, yields the tetrahydropyridine (IX). Enantioselective hydrogenation of (IX) in the presence of chiral rhodium catalyst in ethanol, and subsequent purification of the obtained piperidine by crystallization as the corresponding di-p-toluoyltartrate salt, provides the pure (3R,4R)-enantiomer (X). This is then condensed with 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (XI) by means of K2CO3 in boiling water to give the tertiary amine (XII), which is subjected to simultaneous debenzylation and dechlorination by means of H2 and Pd(OH)2/C to yield the deprotected piperidine (XIII) (2). This compound is finally condensed with cyanoacetyl chloride (VI) (prepared from cyanoacetic acid [XIV] and oxalyl chloride) by means of triethylamine in dichloromethane to obtain the chiral CP-690550 (2, 3). Scheme 2.

2 Hawkins, J.M., Makowski, T.M., Ruggeri, S.G., Rutherford, J.L., Urban, F.J. (Pfizer Products Inc.). Pyrrolo[2,3-d]pyrimidine derivatives; their intermediates and synthesis. JP 2007039455, WO 2007012953.
3 Flanagan, M.E., Li, Z.J. (Pfizer, Inc.). Novel crystalline cpd. JP 2005511696, US 2003130292, WO 03048162.
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) 65394 cyanoacetyl chloride   C3H2ClNO 详情 详情
(VII) 65395 3-(methoxycarbonylamino)-4-methylpyridine   C8H10N2O2 详情 详情
(VIII) 65396 1-benzyl-3-(methoxycarbonylamino)-4-methylpyridinium chloride   C15H17ClN2O2 详情 详情
(IX) 65397     C15H20N2O2 详情 详情
(X) 65398 (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine 477600-70-7 C14H22N2 详情 详情
(XI) 65399 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine; 2,4-Dichloro-1H-pyrrolo[2,3-d]pyrimidine 90213-66-4 C6H3Cl2N3 详情 详情
(XII) 65400     C20H24ClN5 详情 详情
(XIII) 65401 N-Methyl-N-[(3R,4R)-4-methyl-3-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine 477600-74-1 C13H19N5 详情 详情
(XIV) 12591 Cyanoacetic Acid; 2-Cyanoacetic acid 372-09-8 C3H3NO2 详情 详情
Extended Information