4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one -Drug Synthesis Database

【结构式】

【分子编号】60048

【品名】4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

【CA登记号】

【分子式】C₆H₄ClN₃O

【分子量】169.57008

【元素组成】C 42.5% H 2.38% Cl 20.91% N 24.78% O 9.44%

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：(VII)

Condensation of 2-cyano-4,4-diethoxybutyric acid ethyl ester (I) with formamidine hydrochloride (II) in the presence of NaOEt provides the pyrimidine derivative (III). Subsequent hydrolysis of the diethyl acetal of (III) under acidic conditions leads to the pyrrolopyrimidinone (IV). This is converted to the 4-chloro derivative (V) upon treatment with POCl3. Then, oxidation of (V) by means of pyridinium bromide perbromide furnishes the dibromo pyrrolopyridinone (VI), which is further debrominated to (VII) employing zinc dust in AcOH

参考文献中间体

合成目标

【1】 Wei, C.C.; Tang, P.C.; McMahon, G.; Sun, L.; Hirth, K.P.; Liang, C.; Cui, J. (Sugen, Inc.); 4-Substd. 7-aza-indolin-2-ones and their use as protein kinase inhibitors. EP 1244672; WO 0146196 .

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)	14789	ethyl 2-cyano-4,4-diethoxybutanoate		C₁₁H₁₉NO₄	详情	详情
(II)	15369	Iminoformamide; Methanimidamide	463-52-5	CH₄N₂	详情	详情
(III)	60044	6-amino-5-(2,2-diethoxyethyl)-4(3H)-pyrimidinone		C₁₀H₁₇N₃O₃	详情	详情
(IV)	60045	3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one		C₆H₅N₃O	详情	详情
(V)	60046	4-chloro-7H-pyrrolo[2,3-d]pyrimidine；6-Chloro-7-deazapurine；4-chloropyrrolo[2,3-d]pyrimidine；4-Chloro-1H-pyrrolo[2,3-d]pyrimidine	3680-69-1	C₆H₄ClN₃	详情	详情
(VI)	60047	5,5-dibromo-4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one		C₆H₂Br₂ClN₃O	详情	详情
(VII)	60048	4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one		C₆H₄ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Vilsmeier formylation of ethyl 4-methylpyrrole-2-carboxylate (VIII) affords aldehyde (IX). The ethyl ester group of (IX) is subsequently hydrolyzed under alkaline conditions to provide acid (X). Coupling of (X) with 4-(2-aminoethyl)morpholine (XI) gives amide (XII). Then, condensation between aldehyde (XII) and lactam (VII) in the presence of piperidine leads to adduct (XIII). The 4-chloro group of (XIII) is finally displaced with 3-chloro-4-fluoroaniline (XIV) in hot NMP to provide the title compound

参考文献中间体

合成目标

【1】 Wei, C.C.; Tang, P.C.; McMahon, G.; Sun, L.; Hirth, K.P.; Liang, C.; Cui, J. (Sugen, Inc.); 4-Substd. 7-aza-indolin-2-ones and their use as protein kinase inhibitors. EP 1244672; WO 0146196 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	60048	4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one		C₆H₄ClN₃O	详情	详情
(VIII)	60049	ethyl 4-methyl-1H-pyrrole-2-carboxylate		C₈H₁₁NO₂	详情	详情
(IX)	60050	ethyl 5-formyl-4-methyl-1H-pyrrole-2-carboxylate		C₉H₁₁NO₃	详情	详情
(X)	60051	5-formyl-4-methyl-1H-pyrrole-2-carboxylic acid		C₇H₇NO₃	详情	详情
(XI)	12880	4-(2-Aminoethyl)morpholine; 2-(4-Morpholinyl)ethylamine; 2-(4-Morpholinyl)-1-ethanamine; N-(2-Aminoethyl)morpholine; N-Morpholine ethanamide	2038-03-1	C₆H₁₄N₂O	详情	详情
(XII)	59999	5-formyl-4-methyl-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide		C₁₃H₁₉N₃O₃	详情	详情
(XIII)	59998	5-[(4-chloro-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-ylidene)methyl]-4-methyl-N-[2-(4-morpholinyl)ethyl]-1H-pyrrole-2-carboxamide		C₁₉H₂₁ClN₆O₃	详情	详情
(XIV)	18688	3-Chloro-4-fluorophenylamine; 3-Chloro-4-fluoroaniline	367-21-5	C₆H₅ClFN	详情	详情

Extended Information