5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】60386

【品名】5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

【CA登记号】356068-93-4

【分子式】C₁₆H₁₃FN₂O₃

【分子量】300.2893032

【元素组成】C 64% H 4.36% F 6.33% N 9.33% O 15.98%

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：(XII)

5-Fluoroisatin (IX) is heated with neat hydrazine hydrate to produce 2-amino-5-fluorophenylacetic hydrazide (X), which, upon acidic treatment cyclizes to 5-fluorooxindole (XI). Subsequent condensation of oxindole (XI) with the formylpyrrole carboxamide (VIII) in the presence of piperidine in hot EtOH leads to the title compound. In an alternative procedure, oxindole (XI) is condensed with the formylpyrrole carboxylic acid (VI) giving (XII), which is further coupled with 2-(diethylamino)ethylamine (VII) in the presence of EDC/HOBt to yield the target carboxamide.

参考文献中间体

合成目标

【1】 Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Ciu, J.; Fukuda, J.Y.; Chu, J.-Y.; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.; Luu, T.C.; Tang, F.; Wei, J.; Tang, C.; Discovery of 5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine. J Med Chem 2003, 46, 7, 1116.
【2】 Wei, C.C.; Miller, T.; Tang, P.C.; Nematalla, A.S.; Li, X.; Liang, C.; Shirazian, S.; Su, L.; Vojkovsky, T. (Sugen, Inc.); Pyrrole substd. 2-indolinone protein kinase inhibitors. EP 1255752; US 2002156292; US 6573293; WO 0160814 .
【3】 Shenoy, N.; Sorasuchart, W. (Sugen, Inc.); Formulations for pharmaceutical agents ionizable as free acids or free bases. JP 2003514851; WO 0137820 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	60382	5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid	253870-02-9	C₈H₉NO₃	详情	详情
(VII)	12420	N-(2-Aminoethyl)-N,N-diethylamine; N,N-Diethylethylene-diamine; N(1),N(1)-Diethyl-1,2-ethanediamine	100-36-7	C₆H₁₆N₂	详情	详情
(VIII)	63355	N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide	356068-86-5	C₁₄H₂₃N₃O₂	详情	详情
(IX)	21552	5-fluoro-1H-indole-2,3-dione	443-69-6	C₈H₄FNO₂	详情	详情
(X)	63356	2-(2-amino-5-fluorophenyl)acetohydrazide	356068-89-8	C₈H₁₀FN₃O	详情	详情
(XI)	60384	5-fluoro-1,3-dihydro-2H-indol-2-one	56341-41-4	C₈H₆FNO	详情	详情
(XII)	60386	5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid	356068-93-4	C₁₆H₁₃FN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

In a related, scale-up procedure, 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (I) is condensed to 5-fluorooxindole (II) in the presence of pyrrolidine and AcOH to furnish adduct (III). This is then condensed with N-(2-aminoethyl)pyrrolidine (IV) in the presence of BOP to produce the target amide

参考文献中间体

合成目标

【1】 Wei, C.C.; Miller, T.; Tang, P.C.; Nematalla, A.S.; Li, X.; Liang, C.; Shirazian, S.; Su, L.; Vojkovsky, T. (Sugen, Inc.); Pyrrole substd. 2-indolinone protein kinase inhibitors. EP 1255752; US 2002156292; US 6573293; WO 0160814 .

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)	60382	5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid	253870-02-9	C₈H₉NO₃	详情	详情
(II)	60384	5-fluoro-1,3-dihydro-2H-indol-2-one	56341-41-4	C₈H₆FNO	详情	详情
(III)	60386	5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid	356068-93-4	C₁₆H₁₃FN₂O₃	详情	详情
(IV)	18161	2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine	7154-73-6	C₆H₁₄N₂	详情	详情

Extended Information