3-Pyridinemethanamine → 2-(1-(2,2-difluoro-2-phenylethyl)-1H-1,2,3-triazol-4-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 2381865Notes

Reaction equation

HRID 2381865 reaction equation
[F:1][C:2]([F:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:3][N:4]1[CH:8]=[C:7]([C:9]2[S:10][C:11]([C:15](O)=[O:16])=[C:12]([CH3:14])[N:13]=2)[N:6]=[N:5]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.[NH2:56][CH2:57][C:58]1[CH:59]=[N:60][CH:61]=[CH:62][CH:63]=1>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]([F:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:3][N:4]1[CH:8]=[C:7]([C:9]2[S:10][C:11]([C:15]([NH:56][CH2:57][C:58]3[CH:59]=[N:60][CH:61]=[CH:62][CH:63]=3)=[O:16])=[C:12]([CH3:14])[N:13]=2)[N:6]=[N:5]1

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 591797042-(1-(2,2-difluoro-2-phenylethyl)-1H-1,2,3-triazol-4-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 249578532-(1-(2,2-difluoro-2-phenylethyl)-1H-1,2,3-triazol-4-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(1-(2,2-difluoro-2-phenylethyl)-1H-1,2,3-triazol-4-yl)-4-methylthiazole-5-carboxylic acid (0.10 g, 0.28 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.07 g, 0.34 mmol) and N,N-diisopropylethylamine (0.09 mL, 0.51 mmol) in N,N-dimethylformamide (2 mL) was added 1-hydroxy-benzotriazole (0.10 g, 0.74 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes and 3-(aminomethyl)pyridine (0.04 mL, 0.04 mmol) was added. The reaction mixture was stirred at ambient temperature for 17 hours, then diluted with ethyl acetate (30 mL), washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to the title compound as a white solid (0.03 g, 7%): mp 150-151° C.; 1H NMR (300 MHz, CDCl3) δ 8.57 (br s, 1H), 8.53-8.47 (m, 1H), 8.23 (s, 1H), 7.74-7.64 (m, 1H), 7.55-7.39 (m, 5H), 7.32-7.22 (m, 1H), 6.56 (t, J=5.6 Hz, 1H), 5.02-4.93 (m, 2H), 4.60 (d, J=5.6 Hz, 2H), 2.70 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 161.8, 157.6, 157.3, 149.2, 149.1, 143.1, 135.7, 133.7, 132.8, 131.2, 129.0, 125.0, 124.6, 123.7, 122.9, 118.6, 56.1, 41.6, 17.3; MS (ES+) m/z 441.4 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 17 hours
  2. washwashed with water and brine
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography to the title compound as a white solid (0.03 g, 7%)

Sources & evidence

ORD record
ord-027765c01b2f457593044a3c53a31c58
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

Loading…