Triethylamine → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amide

HRID 2381949Notes

Reaction equation

HRID 2381949 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)(=O)=O.CCN(CC)CC>C1COCC1.[Cl-].[Na+].O>[C:33]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[N:7]([NH:11][C:12]([C:14]2[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]=2)=[O:13])[CH:6]=1)#[N:32]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 25099831HCID 25099831, compound

Product 1

HCID 250996952-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amideYield 38%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 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 THF (8 mL) is cooled to 0° C., treated with chlorosulfonyl isocyanate (86 μL, 0.99 mmol) and the mixture is stirred at rt for 1 h. The mixture is treated with Et3N (138 μL, 0.99 mmol) and stirred for 1 h. The mixture is diluted with brine, extracted with EtOAc. The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 25% -35% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amide (120 mg, 38%). MS: 390 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.78 (s, 3H), 7.32 (m, 1H), 7.46 (m, 1H), 7.55 (m, 1H), 7.66 (m, 1H), 7.77 (m, 1H), 8.20 (m, 1H), 8.35 (m, 1H), 8.65 (s, 1H), 9.28 (s, 1H).

Workup

  1. stirringstirred for 1 h
  2. extractionextracted with EtOAc
  3. customThe organic layer is separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 25% -35% EtOAc in heptane

Sources & evidence

ORD record
ord-50fd6f9cc36b4cd39756ac4e49e86c57
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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