methyl 1H-pyrrole-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】45616

【品名】methyl 1H-pyrrole-2-carboxylate

【CA登记号】

【分子式】C₆H₇NO₂

【分子量】125.12712

【元素组成】C 57.59% H 5.64% N 11.19% O 25.57%

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：(I)

Treatment of methyl pyrrole-2-carboxylate (I) with KOtBu and 18-crown-6 in Et2O, followed by reaction with ethyl iodide (II) in Et2O, yields methyl 1-ethylpyrrole-2-carboxylate (III), which is then subjected to saponification with NaOH to afford carboxylic acid (IV). Condensation of (IV) with beta-alanine benzyl ester p-toluene sulfonate (V) in the presence of diethyl phosphorocyanidate (DEPC) and Et3N in DMF provides benzyl ester (VI), which is then hydrogenated over Pd/C in THF, furnishing carboxylic acid (VII). Cyclization of (VII) with polyphosphoric acid (PPA) affords derivative (VIII), which is then treated with NaH in DMF and alkylated with chloro derivative (IX) in DMF to produce compound (X). Finally, treatment of (X) with hydroxylamine hydrochloride and NaOAc affords the target compound.

参考文献中间体

合成目标

【1】 Mizuno, A.; Miya, M.; Inomata, N.; Tatsuoka, T.; Ishihara, T. (Suntory Ltd.); Pyrroloazepine cpd.. EP 0557526; JP 1993503481; US 5399557; WO 9303032 .
【2】 Yamaki, A.; Tatsuoka, T.; Miya, M.; Nakanishi, K.; Mizuno, A.; Takiguchi, C.; Hidaka, T.; Kamei, T.; Shibata, M.; Inomata, N.; Studies on antihypertensive agents with antithrombotic activity. 2. Syntheses and pharmacological evaluation of pyrrolo[2,3-c]azepine derivatives. Chem Pharm Bull 2000, 48, 8, 1129.

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)	45616	methyl 1H-pyrrole-2-carboxylate		C₆H₇NO₂	详情	详情
(II)	10925	Iodoethane;ethyl iod	75-03-6	C₂H₅I	详情	详情
(III)	45617	methyl 1-ethyl-1H-pyrrole-2-carboxylate		C₈H₁₁NO₂	详情	详情
(IV)	45618	1-ethyl-1H-pyrrole-2-carboxylic acid		C₇H₉NO₂	详情	详情
(V)	30194	benzyl 3-aminopropanoate	27019-47-2	C₁₀H₁₃NO₂	详情	详情
(VI)	45619	benzyl 3-[[(1-ethyl-1H-pyrrol-2-yl)carbonyl]amino]propanoate		C₁₇H₂₀N₂O₃	详情	详情
(VII)	45620	N-[(1-ethyl-1H-pyrrol-2-yl)carbonyl]-beta-alanine		C₁₀H₁₄N₂O₃	详情	详情
(VIII)	45621	1-ethyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₁₀H₁₂N₂O₂	详情	详情
(IX)	45622	1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine		C₁₃H₁₈ClFN₂	详情	详情
(X)	45623	1-ethyl-7-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₂₃H₂₉FN₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Esterification of pyrrole-2-carboxylic acid (I) by treatment with TMSCl in MeOH yields methyl carboxylate (II), which is then condensed with tert-butyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide methyl 5-tert-butyl pyrrole-2-carboxylate (IV). Nitration of pyrrolic derivative (IV) by reaction with HNO3/H2SO4 affords a mixture of compounds from which 3-nitropyrrole derivative (V) is cromatographically separated. Hydrogenation of (V) over Pd/C in MeOH allows conversion of the nitro group into an amino group to furnish methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (VI), which is finally coupled to 2,3-dichlorophenyl isocyanate (VII) in dichloromethane to afford the desired compound.

参考文献中间体

合成目标

【1】 Johnson, J.S.; Dally, R.; Redman, A.M.; et al.; p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: Thienyl, furyl, and pyrrolyl ureas. Bioorg Med Chem Lett 2001, 11, 1, 9.
【2】 Gunn, D.; Ranges, G.; Chen, J.; Bombara, M.; Scott, W.; Rauner, D.; Redman, A.; Paulsen, H.; Smith, R.; Renick, J. (Bayer Corp.); Inhibition of p38 kinase activity by aryl ureas. WO 9852558 .

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)	31796	Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid	634-97-9	C₅H₅NO₂	详情	详情
(II)	45616	methyl 1H-pyrrole-2-carboxylate		C₆H₇NO₂	详情	详情
(III)	47128	2-chloro-2-methylpropane	507-20-0	C₄H₉Cl	详情	详情
(IV)	47129	methyl 5-(tert-butyl)-1H-pyrrole-2-carboxylate		C₁₀H₁₅NO₂	详情	详情
(V)	47130	methyl 5-(tert-butyl)-3-nitro-1H-pyrrole-2-carboxylate		C₁₀H₁₄N₂O₄	详情	详情
(VI)	47131	methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylate		C₁₀H₁₆N₂O₂	详情	详情
(VII)	29667	N-(2-chloroethyl)-N-[2-(3-methoxyphenyl)-1-methylethyl]-N-methylamine; N-(2-chloroethyl)-1-(3-methoxyphenyl)-N-methyl-2-propanamine		C₁₃H₂₀ClNO	详情	详情

Extended Information