Potassium Carbonate → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid pyrrolo[2,3-b]pyridin-1-ylamide

HRID 2382010Notes

Reaction equation

HRID 2382010 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15](Cl)=[O:16])=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:18]1([NH2:27])[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]=[CH:19]1.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.O>[N:18]1([NH:27][C:15]([C:11]2[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:16])[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]=[CH:19]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 52239501H-Pyrrolo[2,3-b]pyridin-1-amineHCID 874957952-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid chloride

Product 1

HCID 250998332-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid pyrrolo[2,3-b]pyridin-1-ylamideYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid chloride (1 mmol) in EtOAc (10 mL) is added to a stirred solution of pyrrolo[2,3-b]pyridin-1-ylamine (1 mmol) and K2CO3 (1 mmol) in EtOAc (20 mL) and H2O (20 mL) at rt, then stirred at rt overnight. EtOAc is evaporated in vacuo, and the resulting solid is collected by filtration. The solid is purified by silica gel chromatography eluting with 20-80% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid pyrrolo[2,3-b]pyridin-1-ylamide (162 mg, 47%) as a solid. MS: 348 (M+H); 1H NMR (300 MHz, CDCl3): δ 2.78 (s, 3H), 6.59 (m, H) 7.09-7.58 (m, 4H), 7.96 (m, H), 8.22 (m, H), 8.31 (d, 2H), 9.14 (s, 2H). IC50=12 nM.

Workup

  1. customEtOAc is evaporated in vacuo
  2. filtrationthe resulting solid is collected by filtration
  3. customThe solid is purified by silica gel chromatography
  4. washeluting with 20-80% EtOAc in heptane

Sources & evidence

ORD record
ord-504c587fc3f1474db59b7554cde5fdff
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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