Sodium Hydroxide → 5-fluoro-1-{[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-1H-indole-3-carboxylic acid amide

HRID 2382034Notes

Reaction equation

HRID 2382034 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[C:15]([CH3:27])=[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]=[CH:5]2.ClS([N:32]=[C:33]=[O:34])(=O)=O.[OH-].[Na+]>[Cl-].[Na+].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[C:15]([CH3:27])=[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[C:33]([NH2:32])=[O:34]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 70918Chlorosulfonyl isocyanateHCID 25099831HCID 25099831, compound

Product 1

HCID 591999775-fluoro-1-{[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-1H-indole-3-carboxylic acid amideYield 83%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide (300 mg, 0.82 mmol) in 2-Me-THF (7 mL) is treated with chlorosulfonyl isocyanate (CSI) (85 uL, 2.0 mmol) at 0° C., and the mixture is warmed to rt for 2 h. The mixture is then cooled to 0° C., treated with 1 M NaOH (1 mL), diluted with brine (20 mL), and extracted with EtOAc (3×20 mL). The combined organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo to afford 5-fluoro-1-{[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-1H-indole-3-carboxylic acid amide (275 mg, 83%). MS: 408 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.27 (s, 1H), 8.35 (d, 1H), 8.26 (s, 1H), 8.20 (d, 1H), 7.95 (d, 1H), 7.59 (m, 3H), 7.15 (m, 1H), 2.78 (s, 3H). IC50=8 nM.

Workup

  1. temperatureThe mixture is then cooled to 0° C.
  2. extractionextracted with EtOAc (3×20 mL)
  3. customThe combined organic layer is separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dbb8de5e04154424812fe4368abc4bd1
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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