methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】52016

【品名】methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate

【CA登记号】

【分子式】C₁₅H₁₀BrNO₃S

【分子量】364.21934

【元素组成】C 49.47% H 2.77% Br 21.94% N 3.85% O 13.18% S 8.8%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VII)

The formylation of 3,5-dichloropyridine (I) with methyl formate (II), BuLi and DIEA in THF gives 3,5-dichloropyridine-4-carbaldehyde (III), which is treated with 4-bromophenol (IV) and potassium tert-butoxide in hot THF to yield the adduct (V). This compound, without isolation is cyclized with methyl 2-mercaptoacetate (VI) by means of Cs2CO3 to afford 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylic acid methyl ester (VII), which is hydrolyzed with LiOH in THF/water to provide the corresponding carboxylic acid (VIII). Finally, this compound is condensed with methylamine (IX) by means of EDC and HOBt in DMF to give the target amide. Alternatively, the target amide can also be obtained by direct reaction of methyl ester (VII) with methylamine (IX) in hot methanol in a sealed tube.

参考文献中间体

合成目标

【1】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)theino[2,3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 2001, 44, 21, 3469.
【2】 Lartey, K.; Gunawardana, I.W.; Stout, D.M.; Bhatia, P.; Patel, M.V.; Staeger, M.A.; Boyd, S.A.; Mort, N.A.; Zhu, G.-D.; McCarty, C.M.; Stewart, A.O.; Arendsen, D.L.; Condroski, K.R.; Freeman, J.C. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory cpds.. WO 9962908 .

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)	35535	3,5-dichloropyridine	2457-47-8	C₅H₃Cl₂N	详情	详情
(II)	45474	methyl formate	107-31-3	C₂H₄O₂	详情	详情
(III)	35536	3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde	136590-83-5	C₆H₃Cl₂NO	详情	详情
(IV)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(V)	52015	3-(4-bromophenoxy)-5-chloroisonicotinaldehyde		C₁₂H₇BrClNO₂	详情	详情
(VI)	18838	methyl 2-sulfanylacetate	2365-48-2	C₃H₆O₂S	详情	详情
(VII)	52016	methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate		C₁₅H₁₀BrNO₃S	详情	详情
(VIII)	52017	4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylic acid		C₁₄H₈BrNO₃S	详情	详情
(IX)	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

参考文献中间体

合成目标

【1】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)theino[2,3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 2001, 44, 21, 3469.
【2】 Lartey, K.; Gunawardana, I.W.; Stout, D.M.; Bhatia, P.; Patel, M.V.; Staeger, M.A.; Boyd, S.A.; Mort, N.A.; Zhu, G.-D.; McCarty, C.M.; Stewart, A.O.; Arendsen, D.L.; Condroski, K.R.; Freeman, J.C. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory cpds.. WO 9962908 .

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)	35535	3,5-dichloropyridine	2457-47-8	C₅H₃Cl₂N	详情	详情
(II)	45474	methyl formate	107-31-3	C₂H₄O₂	详情	详情
(III)	35536	3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde	136590-83-5	C₆H₃Cl₂NO	详情	详情
(IV)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(V)	52015	3-(4-bromophenoxy)-5-chloroisonicotinaldehyde		C₁₂H₇BrClNO₂	详情	详情
(VI)	18838	methyl 2-sulfanylacetate	2365-48-2	C₃H₆O₂S	详情	详情
(VII)	52016	methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate		C₁₅H₁₀BrNO₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

The formylation of 3,5-dichloropyridine (I) with methyl formate (II), BuLi and DIEA in THF gives 3,5-dichloropyridine-4-carbaldehyde (III), which is treated with 4-bromophenol (IV) and potassium tert-butoxide in hot THF to yield the adduct (V). This compound, without isolation is cyclized with methyl 2-mercaptoacetate (VI) by means of Cs2CO3 to afford 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylic acid methyl ester (VII), which is hydrolyzed with LiOH in THF/water to provide the corresponding carboxylic acid (VIII). Finally, this compound is condensed with ethanolamine (IX) by means of EDC and HOBt in DMF to give the target ethanolamide. Alternatively, the target amide can also be obtained by direct reaction of methyl ester (VII) with ethanolamine (IX) in refluxing methanol.

参考文献中间体

合成目标

【1】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)theino[2,3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 2001, 44, 21, 3469.
【2】 Lartey, K.; Gunawardana, I.W.; Stout, D.M.; Bhatia, P.; Patel, M.V.; Staeger, M.A.; Boyd, S.A.; Mort, N.A.; Zhu, G.-D.; McCarty, C.M.; Stewart, A.O.; Arendsen, D.L.; Condroski, K.R.; Freeman, J.C. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory cpds.. WO 9962908 .

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)	35535	3,5-dichloropyridine	2457-47-8	C₅H₃Cl₂N	详情	详情
(II)	45474	methyl formate	107-31-3	C₂H₄O₂	详情	详情
(III)	35536	3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde	136590-83-5	C₆H₃Cl₂NO	详情	详情
(IV)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(V)	52015	3-(4-bromophenoxy)-5-chloroisonicotinaldehyde		C₁₂H₇BrClNO₂	详情	详情
(VI)	18838	methyl 2-sulfanylacetate	2365-48-2	C₃H₆O₂S	详情	详情
(VII)	52016	methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate		C₁₅H₁₀BrNO₃S	详情	详情
(VIII)	52017	4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylic acid		C₁₄H₈BrNO₃S	详情	详情
(IX)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情

Extended Information