4-Methyl-2-(pyridin-2-yl)pyrimidine-5-carboxylic acid → 5-PyriMidinecarboxaMide, N-(5-fluoro-3-Methyl-1H-indol-1-yl)-4-Methyl-2-(2-pyridinyl)-

HRID 2381901Notes

Reaction equation

HRID 2381901 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH2:11])[CH:6]=[C:5]2[CH3:12].[CH3:13][C:14]1[C:19]([C:20](O)=[O:21])=[CH:18][N:17]=[C:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[N:15]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:20]([C:19]1[C:14]([CH3:13])=[N:15][C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[N:17][CH:18]=1)=[O:21])[CH:6]=[C:5]2[CH3:12]

Participants

4

Reactant 2

HCID 617020254-Methyl-2-(pyridin-2-yl)pyrimidine-5-carboxylic acidHCID 68554957HCID 68554957, compound

Product 1

HCID 250994745-PyriMidinecarboxaMide, N-(5-fluoro-3-Methyl-1H-indol-1-yl)-4-Methyl-2-(2-pyridinyl)-Yield 83.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-3-methyl-indol-1-ylamine (10.6 mmol) is treated with 4-methyl-2-pyridin-2-ylpyrimidine-5-carboxylic acid (2.75 g, 12.8 mmol) in DMF (75 mL) and the mixture is stirred at rt for 10 min. The mixture is then treated with 2,4-dimethoxy-6-(4-methylmorpholin-4-yl)-[1,3,5]triazine chloride (3.82 g, 13.85 mmol) and stirred at 60° C. for 1 h. The mixture is concentrated in vacuo. The residue is diluted with Et2O (50 mL) and 10% NaHCO3 (50 mL), and the mixture is stirred at rt for 20 min. The resulting solid is filtered, washed, and dried to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)amide (3.2 g, 83%). The solid is crystallized with MeOH:water (4:1) to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)amide as a crystal. MS: 362 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.27 (s, 3H), 2.78 (s, 3H), 7.06 (m, 1H), 7.34 (m, 1H), 7.37 (s, 1H), 7.44 (m, 1H), 7.59 (m, 1H), 8.05 (m, 1H), 8.45 (m, 1H), 8.80 (m, 1H), 9.25 (s, 1H). IC50=7 nM.

Workup

  1. stirringstirred at 60° C. for 1 h
  2. concentrationThe mixture is concentrated in vacuo
  3. additionThe residue is diluted with Et2O (50 mL) and 10% NaHCO3 (50 mL)
  4. stirringthe mixture is stirred at rt for 20 min
  5. filtrationThe resulting solid is filtered
  6. washwashed
  7. customdried

Sources & evidence

ORD record
ord-6b52eeb8d902485baf18f60620b622da
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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