• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】11285

【品名】1-Methyl-1H-pyrrole; Methylpyrrole

【CA登记号】96-54-8

【 分 子 式 】C5H7N

【 分 子 量 】81.11732

【元素组成】C 74.03% H 8.7% N 17.27%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(I)

The synthesis of [14C]-labeled prinomide has been described: The carboxylation of 1-methylpyrrole (I) with 14CO2 and butyllithium in THF gives labeled 1-methylpyrrole-2-carboxylic acid (II), which is esterified with diazomethane to the methyl ester (III). The reaction of (III) with acetonitrile by means of NaH in DMF affords 3-(1-methylpyrrol-2-yl)-3-oxopropanenitrile (IV) labeled in the carbonyl group. Finally, this compound is condensed with phenylisocyanate (V) by means of triethylamine in toluene, affording the prinomide labeled in the carbonyl group. The condensation of unlabeled (IV) with (V) labeled in the phenyl ring yields the corresponding prinomide labeled in the aromatic ring.

1 Chaudhuri, N.K.; Markus, B.; Synthesis of two 14C-labeled forms of prinomide, a potential anti-inflammatory compound and its hydroxy metabolite, labeled with 14C. J Label Compd Radiopharm 1990, 28, 3, 321.
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) 11286 1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid 6973-60-0 C6H7NO2 详情 详情
(II) 45058 1-methyl-1H-pyrrole-2-carboxylic acid C6H7NO2 详情 详情
(III) 11287 methyl 1-methyl-1H-pyrrole-2-carboxylate 37619-24-2 C7H9NO2 详情 详情
(III) 45059 methyl 1-methyl-1H-pyrrole-2-carboxylate C7H9NO2 详情 详情
(IV) 11288 3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile C8H8N2O 详情 详情
(IV) 45060 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile C8H8N2O 详情 详情
(V) 11289 1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate 103-71-9 C7H5NO 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IX)

Alkylation of imidazole (I) with 1,7-dibromoheptane (II) by means of potassium (metal) in refluxing THF furnishes N,N'-bis-(1-imidazolyl)heptane (III), which is treated with trichloroacetyl chloride (IV) in CH2Cl2 to provide derivative (V). Nitration of (V) by means of nitric acid/sulfuric acid in Ac2O/CH2Cl2 yields compound (VI), which is then converted into intermediate (VIII) by coupling in DMF/THF with substituted pyrrole (VII). In turn, (VII) can be obtained as follows: Treatment of N-methylpyrrole (IX) with trichloroacetyl chloride (IV) in CH2Cl2 affords derivative (X), which is nitrated to yield compound (XI) in the same conditions as for nitration of (V). The last step involves coupling of (XI) with 3-(dimethylamino)propylamine (XII), followed by reduction of the nitro moiety by hydrogenation over Pd/C in DMF/MeOH. Finally, the target product can be obtained by first hydrogenation of intermediate (VIII) over Pd/C in DMF/MeOH, followed by reaction with DCC and HOBt in DMF to allow coupling with carboxylic acid (XIV), which can be obtained by saponification of ethyl ester (XIII) in EtOH.

1 Sharma, S.K.; et al.; Design and synthesis of novel thiazole-containing cross-linked polyamides related to tha antiviral antibiotic distamycin. J Org Chem 2000, 65, 4, 1102.
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) 10255 Imidazole; 1H-Imidazole 288-32-4 C3H4N2 详情 详情
(II) 47013 1,7-dibromoheptane 4549-31-9 C7H14Br2 详情 详情
(III) 47014 1-[7-(1H-imidazol-1-yl)heptyl]-1H-imidazole C13H20N4 详情 详情
(IV) 47015 2,2,2-trichloroacetyl chloride 76-02-8 C2Cl4O 详情 详情
(V) 47016 2,2,2-trichloro-1-(1-[7-[2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone C17H18Cl6N4O2 详情 详情
(VI) 47017 2,2,2-trichloro-1-(4-nitro-1-[7-[4-nitro-2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone C17H16Cl6N6O6 详情 详情
(VII) 47018 4-amino-N-[3-(dimethylamino)propyl]-1-methyl-1H-pyrrole-2-carboxamide C11H20N4O 详情 详情
(VIII) 47019 N-[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]-1-[7-[2-([[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]amino]carbonyl)-4-nitro-1H-imidazol-1-yl]heptyl]-4-nitro-1H-imidazole-2-carboxamide C37H54N14O8 详情 详情
(IX) 11285 1-Methyl-1H-pyrrole; Methylpyrrole 96-54-8 C5H7N 详情 详情
(X) 47020 2,2,2-trichloro-1-(1-methyl-1H-pyrrol-2-yl)-1-ethanone C7H6Cl3NO 详情 详情
(XI) 47021 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1-ethanone C7H5Cl3N2O3 详情 详情
(XII) 25248 N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine 109-55-7 C5H14N2 详情 详情
(XIII) 47022 ethyl 2-amino-4-methylthiazole-5-carboxylate; ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate 7210-76-6 C7H10N2O2S 详情 详情
(XIV) 47023 2-amino-4-methyl-1,3-thiazole-5-carboxylic acid C5H6N2O2S 详情 详情

合成路线3

该中间体在本合成路线中的序号:(I)

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