Potassium Carbonate → 2-(1-((2,2-difluorocyclopropyl)methyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 555007Notes

Reaction equation

HRID 555007 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:17]2[C:21](=[O:22])[NH:20][N:19]=[CH:18]2)[S:5][C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=[O:8].C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:34][CH:35]1[CH2:37][C:36]1([F:39])[F:38])(=O)=O>CN(C)C=O.C(OCC)(=O)C>[F:38][C:36]1([F:39])[CH2:37][CH:35]1[CH2:34][N:20]1[C:21](=[O:22])[N:17]([C:4]2[S:5][C:6]([C:7]([NH:9][CH2:10][C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[O:8])=[C:2]([CH3:1])[N:3]=2)[CH:18]=[N:19]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 58198163Cyclopropanemethanol, 2,2-difluoro-, 1-methanesulfonateHCID 594812404-methyl-2-(5-oxo-1H-1,2,4-triazol-4(5H)-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

Product 1

HCID 579199232-(1-((2,2-difluorocyclopropyl)methyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-methyl-2-(5-oxo-1H-1,2,4-triazol-4(5H)-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (0.15 g, 0.47 mmol) and potassium carbonate (0.10 g, 1.47 mmol) in N,N-dimethylformamide (2 mL) was added (2,2-difluorocyclopropyl)-methyl methanesulfonate (0.13 g, 0.70 mmol). The reaction mixture was kept stirring at ambient temperature for 20 hours, diluted with ethyl acetate (100 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography to afford the title compound in 41% yield (0.08 g): mp 160-161° C.; 1H NMR (300 MHz, CDCl3) δ 8.53-8.41 (m, 2H), 8.24 (s, 1H), 7.69-7.62 (m, 1H), 7.27-7.16 (m, 2H), 4.54 (d, J=5.8 Hz, 2H), 4.00-3.81 (m, 2H), 2.58 (s, 3H), 2.08-1.91 (m, 1H), 1.56-1.41 (m, 1H), 1.40-1.10 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 161.8, 153.3, 150.9, 149.8, 149.1, 148.7, 135.8, 133.9, 131.1, 123.7, 121.8, 112.7, 43.2, 41.5, 20.8, 17.2, 15.4; MS (ES+) m/z 407.1 (M+1).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e44200c01f6146239225fbcf4cb13d1c
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

Loading…