3-Amino-4-pyrazolecarboxylic acid ethyl ester; Ethyl 3-aminopyrazole-4-carboxylate; 3-Amino-4-carbethoxypyrazole -Drug Synthesis Database

【结构式】

【分子编号】51140

【品名】3-Amino-4-pyrazolecarboxylic acid ethyl ester; Ethyl 3-aminopyrazole-4-carboxylate; 3-Amino-4-carbethoxypyrazole

【CA登记号】6994-25-8

【分子式】C₆H₉N₃O₂

【分子量】155.15648

【元素组成】C 46.45% H 5.85% N 27.08% O 20.62%

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：(XXI)

Cyclization of 5-aminopyrazole-4-carboxylic acid ethyl ester (XXI) with either, 3,3-diethoxypropionic acid ethyl ester (XXII) or 3-oxopropionic acid ethyl ester (XXIII) in refluxing AcOH gives 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester (XXIV), which is treated with POCl3 to yield the corresponding chloro derivative (XXV). Condensation of compound (XXV) with 3-(N-methylacetamido)phenylboronic acid (XXVI) by means of Pd(PPh3)4 and Na2CO3 in ethanol affords the pyrazolo-[1,5-a]pyrimidine-carboxylic acid ethyl ester (XXVII), which is finally condensed with 2-bromothiophene (XX) and Mg.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739.
【2】 Wilcoxen, K.M.; Gross, R.S. (Neurocrine Biosciences Inc.); Synthesis of substd. pyrazolopyrimidines. WO 0110868 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XX)	13681	2-Bromothiophene	1003-09-4	C₄H₃BrS	详情	详情
(XXI)	51140	3-Amino-4-pyrazolecarboxylic acid ethyl ester; Ethyl 3-aminopyrazole-4-carboxylate; 3-Amino-4-carbethoxypyrazole	6994-25-8	C₆H₉N₃O₂	详情	详情
(XXII)	17901	Ethyl 3,3-diethoxypropanoate	10601-80-6	C₉H₁₈O₄	详情	详情
(XXIII)	62966	ethyl 3-oxopropanoate		C₅H₈O₃	详情	详情
(XXIV)	62967	ethyl 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate		C₉H₉N₃O₃	详情	详情
(XXV)	62968	ethyl 7-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate		C₉H₈ClN₃O₂	详情	详情
(XXVI)	62969	3-[acetyl(methyl)amino]phenylboronic acid		C₉H₁₂BNO₃	详情	详情
(XXVII)	62970	ethyl 7-{3-[acetyl(methyl)amino]phenyl}pyrazolo[1,5-a]pyrimidine-3-carboxylate		C₁₈H₁₈N₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

3-Amino-4-carbethoxypyrazole (I) was protected with p-methoxybenzyl chloride (II) in the presence of NaH to give two alkylated regioisomers (III) and (IV). This mixture was subjected to condensation with diethyl malonate under basic conditions to furnish the respective pyrazolopyridines (V) and (VI). Only isomer (VI) could be converted to its corresponding dichloro derivative (VII) under reflux in POCl3. Regioselective displacement of one chloride group from (VII) with ethanolic ammonia afforded amine (VIII). The ester group of (VIII) was then hydrolyzed by LiOH to the carboxylic acid (IX), which was converted to amide (X) via activation as the pentafluorophenyl ester.

参考文献中间体

合成目标

【1】 Bi, Y.; et al.; The discovery of novel, potent and selective PDE5 inhibitors. Bioorg Med Chem Lett 2001, 11, 18, 2461.

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)	51140	3-Amino-4-pyrazolecarboxylic acid ethyl ester; Ethyl 3-aminopyrazole-4-carboxylate; 3-Amino-4-carbethoxypyrazole	6994-25-8	C₆H₉N₃O₂	详情	详情
(II)	11910	4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether	824-94-2	C₈H₉ClO	详情	详情
(III)	51141	ethyl 5-amino-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate		C₁₄H₁₇N₃O₃	详情	详情
(IV)	51142	ethyl 3-amino-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate		C₁₄H₁₇N₃O₃	详情	详情
(V)	51143	ethyl 4,6-dihydroxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₇H₁₇N₃O₅	详情	详情
(VI)	51144	ethyl 4,6-dihydroxy-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₇H₁₇N₃O₅	详情	详情
(VII)	51145	ethyl 4,6-dichloro-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₇H₁₅Cl₂N₃O₃	详情	详情
(VIII)	51146	ethyl 4-amino-6-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₇H₁₇ClN₄O₃	详情	详情
(IX)	51147	4-amino-6-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine-5-carboxylic acid		C₁₅H₁₃ClN₄O₃	详情	详情
(X)	51148	4-amino-6-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine-5-carboxamide		C₁₅H₁₄ClN₅O₂	详情	详情

Extended Information