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【结 构 式】

【分子编号】53510

【品名】4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid

【CA登记号】77716-11-1

【 分 子 式 】C11H16N2O4

【 分 子 量 】240.25912

【元素组成】C 54.99% H 6.71% N 11.66% O 26.64%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

The condensation of 4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxylic acid (I) with 4-amino-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (II) by means of DCC, HOBT and TEA in hot DMF gives the dimeric amide (III), which is hydrolyzed with NaOH in hot methanol/water to yield the carboxylic acid (IV). The condensation of (IV) with methyl ester (II) by means of HBTU and TEA in hot DMF affords the trimeric diamide (V), which is hydrolyzed with NaOH in methanol/water to provide the carboxylic acid (VI). The deprotection of the carbamate group of (VI) with HCl in ethyl acetate gives the trimeric amino acid (VII), which is condensed with 4,5-dichloroisothiazole-3-carboxylic acid (VIII) by means of HBTU and DIEA in DMF to yield the tetrameric carboxylic acid (IX). The condensation of (IX) with 3-aminopropionitrile (X) by means of HBTU and TEA in DMF affords the corresponding tetrameric tetraamide (XI), which is treated with gaseous HCl in methanol to provide the iminoester (XII). Finally, this compound is treated with NH3 in methanol to furnish the target carboxamidine.

1 Burli, R.; et al.; HARP: A novel class of antibiotics. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1685.
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) 53510 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid 77716-11-1 C11H16N2O4 详情 详情
(II) 53511 methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate 180258-45-1 C7H10N2O2 详情 详情
(III) 53512 methyl 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate n/a C18H24N4O5 详情 详情
(IV) 53513 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid n/a C17H22N4O5 详情 详情
(V) 53514 methyl 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate n/a C24H30N6O6 详情 详情
(VI) 53515 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid n/a C23H28N6O6 详情 详情
(VII) 53516 4-{[(4-{[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylic acid n/a C18H20N6O4 详情 详情
(VIII) 53517 4,5-Dichloroisothiazole-3-carboxylic acid 131947-13-2 C4HCl2NO2S 详情 详情
(IX) 53518 4-{[(4-{[(4-{[(4,5-dichloro-3-isothiazolyl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylic acid n/a C22H19Cl2N7O5S 详情 详情
(X) 38094 3-aminopropanenitrile 151-18-8 C3H6N2 详情 详情
(XI) 53519 4,5-dichloro-N-(5-{[(5-{[(5-{[(2-cyanoethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-3-isothiazolecarboxamide n/a C25H23Cl2N9O4S 详情 详情
(XII) 53520 methyl 3-{[(4-{[(4-{[(4-{[(4,5-dichloro-3-isothiazolyl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}propanimidoate n/a C26H27Cl2N9O5S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VIII)

Friedel-Crafts acylation of N-methylpyrrole (I) with trichloroacetyl chloride (II) affords the pyrrolyl ketone (III), which is subsequently subjected to electrophilic nitration with in situ generated acetyl nitrate, producing nitropyrrole (IV). Cleavage of the trichloroketone group of (IV) under alkaline conditions, followed by Fischer esterification leads to methyl ester (V). The nitro group of (V) is then reduced to amine (VI) by catalytic hydrogenation over Pd/C. After protection of amine (VI) as the corresponding N-Boc derivative (VII), saponification of the methyl ester group of (VII) yields acid (VIII). Coupling between the pyrrolecarboxylic acid (VIII) and amino ester (VI) provides the amide adduct (IX). After alkaline ester hydrolysis in (IX), the resultant carboxylic acid (X) is coupled with a further moiety of methyl 4-amino-1-methylpyrrole-2-carboxylate (VI) to furnish the tripyrrolyl compound (XI). Subsequent methyl ester saponification in (XI) provides acid (XII).

1 Ge, Y.; Taylor, M.J.; Baird, E.E.; Moser, H.E.; Burli, R.W. (GeneSoft, Inc.); Charged cpds. comprising a nucleic acid binding moiety and uses therefor. JP 2003529609; WO 0174898 .
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) 11285 1-Methyl-1H-pyrrole; Methylpyrrole 96-54-8 C5H7N 详情 详情
(II) 47015 2,2,2-trichloroacetyl chloride 76-02-8 C2Cl4O 详情 详情
(III) 47020 2,2,2-trichloro-1-(1-methyl-1H-pyrrol-2-yl)-1-ethanone C7H6Cl3NO 详情 详情
(IV) 47021 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1-ethanone C7H5Cl3N2O3 详情 详情
(V) 58474 methyl 1-methyl-4-nitro-1H-pyrrole-2-carboxylate C7H8N2O4 详情 详情
(VI) 53511 methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate 180258-45-1 C7H10N2O2 详情 详情
(VII) 58475 methyl 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate C12H18N2O4 详情 详情
(VIII) 53510 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid 77716-11-1 C11H16N2O4 详情 详情
(IX) 53512 methyl 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate n/a C18H24N4O5 详情 详情
(X) 53513 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid n/a C17H22N4O5 详情 详情
(XI) 53514 methyl 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate n/a C24H30N6O6 详情 详情
(XII) 53515 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid n/a C23H28N6O6 详情 详情
Extended Information