ethyl 7-(2,6-difluorobenzyl)-3-methyl-4-oxo-2-phenyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】23151

【品名】ethyl 7-(2,6-difluorobenzyl)-3-methyl-4-oxo-2-phenyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate

【CA登记号】

【分子式】C₂₄H₁₉F₂NO₃S

【分子量】439.4826064

【元素组成】C 65.59% H 4.36% F 8.65% N 3.19% O 10.92% S 7.3%

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：(IX)

Aminothiophene (III) was prepared by condensation of phenylacetone (I) with ethyl cyanoacetate (II), followed by treatment with sulfur and diethylamine. Subsequent condensation of (III) with diethyl ethoxymethylenemalonate (IV) at 120 C provided the enaminomalonate (V). the partial hydrolysis of (V) with KOH in EtOH-dioxan provided monoacid (VI), which was cyclized by means of PPE to the thienopyridine (VII). Alkylation of (VII) with 2,6-difluorobenzyl chloride (VIII) and K2CO3 yielded predominantly the N-benzylated compound (IX), which was selectively nitrated at the phenyl ring to produce (X) (2). Radical bromination of the 3-methyl group of (X) gave bromomethyl compound (XI).

参考文献中间体

合成目标

【1】 Cho, N.; Harada, M.; Imaeda, T.; Imada, T.; Matsumoto, H.; Hayase, Y.; Sasaki, S,; Furuya, S.; Suzuki, N.; Okubo, S.; Ogi, K.; Endo, S.; Onda, H.; Fujino, M.; Discovery of a novel, potent, and orally active no. J Med Chem 1998, 41, 22, 4190.

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)	23143	1-Phenylacetone; Methyl benzyl ketone; Benzyl methyl ketone; phenylacetone; Phenyl-2-propanone	103-79-7	C₉H₁₀O	详情	详情
(II)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(III)	23145	ethyl 2-amino-4-methyl-5-phenyl-3-thiophenecarboxylate		C₁₄H₁₅NO₂S	详情	详情
(IV)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(V)	23147	diethyl 2-([[3-(ethoxycarbonyl)-4-methyl-5-phenyl-2-thienyl]amino]methylene)malonate		C₂₂H₂₅NO₆S	详情	详情
(VI)	23148	2-[[3-ethoxy-2-(ethoxycarbonyl)-3-oxo-1-propenyl]amino]-4-methyl-5-phenyl-3-thiophenecarboxylic acid		C₂₀H₂₁NO₆S	详情	详情
(VII)	23149	ethyl 4-hydroxy-3-methyl-2-phenylthieno[2,3-b]pyridine-5-carboxylate		C₁₇H₁₅NO₃S	详情	详情
(VIII)	23150	2-(chloromethyl)-1,3-difluorobenzene	697-73-4	C₇H₅ClF₂	详情	详情
(IX)	23151	ethyl 7-(2,6-difluorobenzyl)-3-methyl-4-oxo-2-phenyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate		C₂₄H₁₉F₂NO₃S	详情	详情
(X)	23152	ethyl 7-(2,6-difluorobenzyl)-3-methyl-2-(4-nitrophenyl)-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate		C₂₄H₁₈F₂N₂O₅S	详情	详情
(XI)	23153	ethyl 3-(bromomethyl)-7-(2,6-difluorobenzyl)-2-(4-nitrophenyl)-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate		C₂₄H₁₇BrF₂N₂O₅S	详情	详情

Extended Information