Ammonia → 2-(3-Fluorophenyl)pyrimidine-5-carboxylic acid-[5-fluoro-3-sulfamoylindol-1-yl)amide

HRID 2381935Notes

Reaction equation

HRID 2381935 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[CH:15]=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[C:5]2[S:27](Cl)(=[O:29])=[O:28].[NH3:31].Cl>C(Cl)Cl.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[CH:15]=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[C:5]2[S:27](=[O:29])(=[O:28])[NH2:31]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 866393645-fluoro-1-{[2-(3-fluorophenyl)pyrimidine-5-carbonyl]amino}-1H-indole-3-sulfonyl chloride

Product 1

HCID 250995892-(3-Fluorophenyl)pyrimidine-5-carboxylic acid-[5-fluoro-3-sulfamoylindol-1-yl)amideYield 8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-fluoro-1-{[2-(3-fluorophenyl)pyrimidine-5-carbonyl]amino}-1H-indole-3-sulfonyl chloride (0.14 g) in DCM (20 mL) is treated with a solution of aqueous ammonia solution (28%-5 mL) in water (15 mL) and stirred at rt for 24 h. The reaction mixture is acidified with 10 N aqueous HCl to pH ˜3 and extracted with DCM. The organic layer is washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 50% EtOAc in heptane to afford 2-(3-fluorophenyl)pyrimidine-5-carboxylic acid-[5-fluoro-3-sulfamoylindol-1-yl)amide (10 mg, 8%) as a solid. MS: 430 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 7.20-7.30 (m, 1H), 7.40-7.50 (m, 2H), 7.60-7.72 (m, 2H), 8.10 (s, 1H), 8.19-8.22 (d, 1H), 8.33-8.37 (d, 1H), 9.44 (s, 1H), 12.45 (s, 1H).

Workup

  1. extractionextracted with DCM
  2. washThe organic layer is washed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with 50% EtOAc in heptane

Sources & evidence

ORD record
ord-d3d80bcf9ce74e049fdc80e8ca592556
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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