Potassium Carbonate → 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide

HRID 2382011Notes

Reaction equation

HRID 2382011 reaction equation
[CH3:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:3]=1.[F:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([NH2:27])[CH:22]=[CH:21]2.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.O>[F:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([NH:27][C:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[N:5][CH:6]=1)=[O:9])[CH:22]=[CH:21]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 450786905-Fluoro-1H-indol-1-amineHCID 874952714-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid chloride

Product 1

HCID 591999524-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amideYield 35.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid chloride (1 mmol) in EtOAc (20 mL) is added to a stirred solution of 5-fluoro-indol-1-ylamine (1.20 mmol) and K2CO3 (2 mmol) in EtOAc (10 mL) and H2O (20 mL) at rt, and the reaction mixture is stirred at rt overnight. The reaction mixture is extracted with EtOAc. The organic layer is washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-10% MeOH in DCM to give a solid. The solid is triturated with EtOAc/heptane to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide (122 mg, 35%) as a solid. MS: 348 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.77 (s, 3H), 6.55 (m, H) 7.06 (m, H), 7.32-7.66 (m, 4H), 8.02 (m, H), 8.45 (d, H), 8.79 (s, H), 9.26 (s, H), 12.00 (s, N—H). IC50=17 nM.

Workup

  1. extractionThe reaction mixture is extracted with EtOAc
  2. washThe organic layer is washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with 0-10% MeOH in DCM
  8. customto give a solid
  9. customThe solid is triturated with EtOAc/heptane

Sources & evidence

ORD record
ord-be7dad4f4afa4bc590dfe07632c86f6d
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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