Hydrochloric Acid → 3-(5-acetyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester

HRID 2078702Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:12][C:11]2[C:10]([C:13]3[N:14](C(OC(C)(C)C)=O)[C:15]4[C:20]([CH:21]=3)=[CH:19][C:18]([C:22](=[O:24])[CH3:23])=[CH:17][CH:16]=4)=[N:9][N:8](C(OC(C)(C)C)=O)[C:7]=2[CH:6]=1)=[O:4].Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[S:12][C:11]2[C:10]([C:13]3[NH:14][C:15]4[C:20]([CH:21]=3)=[CH:19][C:18]([C:22](=[O:24])[CH3:23])=[CH:17][CH:16]=4)=[N:9][NH:8][C:7]=2[CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 3-(5-acetyl-1-tert-butoxycarbonyl-1H-indol-2-yl)-thieno[3,2-c]pyrazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-methyl ester (115 mg, 0.213 mmol, Example 35) in tetrahydrofuran (5 mL) is treated with 2N hydrochloric acid (aqueous, 3 mL) and heated at 70° C. for 17 hours. The reaction is cooled to room temperature and neutralized with Na2CO3 (aqueous). The aqueous phase is extracted three times with ether (10 mL). Combined ether phases are washed with brine and dried over sodium sulfate. Purification by chromatography on 10 g silica gel cartridge (50-70% ethyl acetate gradient in heptane) afforded 3-(5-acetyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester (15 mg, Example 36) as white solid; 1H NMR [(CD3)2SO)]: δ 13.82 (1H, s), 12.13 (1H, s), 8.34 (1H, s), 7.97 (1H, s), 7.78 (1H, d), 7.50 (1H, d), 6.90 (1H, s), 3.91 (3H, s), 2.61 (3H, s); LC/MS: 340 (M+H).

Workup

extractionThe aqueous phase is extracted three times with ether (10 mL)
washCombined ether phases are washed with brine
dry with materialdried over sodium sulfate
customPurification by chromatography on 10 g silica gel cartridge (50-70% ethyl acetate gradient in heptane)

Sources & evidence

ORD record: ord-f42e2b6c3b494bf7abcf6e2200adbb96
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928231B2

Reaction notes

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