Phosphinic Acid → 6-Bromo-3-(morpholin-4-ylsulfonyl)-1H-indole-2-carboxamide

HRID 227505Notes

Reaction equation

[Br:1][C:2]1[C:10](N)=[C:9]2[C:5]([C:6]([S:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)(=[O:17])=[O:16])=[C:7]([C:12]([NH2:14])=[O:13])[NH:8]2)=[CH:4][CH:3]=1.[PH2](O)=O.N([O-])=O.[Na+]>O1CCCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([S:15]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)(=[O:16])=[O:17])=[C:7]([C:12]([NH2:14])=[O:13])[NH:8]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

6-Bromo-7-amino-3-(morpholin-4-ylsulfonyl)-1H-indole-2-carboxamide (25 mg, 0.062 mmol, 1.0 equiv) was dissolved in 5 ml of tetrahydrofuran and cooled to 0° C. 1.3 mL of hypophosphorous acid (50% weight in water) was added, immediately followed by Cu2O (0.9 mg, 0.01 mmol, 0.1 equiv) and NaNO2 (21.4 mg, 0.31 mmol), and the reaction was stirred for 90 minutes. The reaction mixture was partitioned between dichloromethane and water and extracted four times with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by preparative reversed phase HPLC provided the titled compound. Proton NMR for the product was consistent with the titled compound. ESI+MS: 388.1 M+H]+.

Workup

customThe reaction mixture was partitioned between dichloromethane and water
extractionextracted four times with dichloromethane
dry with materialThe combined organic layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by preparative reversed phase HPLC

Sources & evidence

ORD record: ord-59bbda793d17455d87323b149a116d88
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560546B2

Reaction notes

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