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

HRID 2067533Notes

Reaction equation

HRID 2067533 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[C:14](=[O:15])[N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[N:12]=[CH:11]2)[S:5][C:6]=1[C:7]([OH:9])=O.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.[NH2:58][CH2:59][C:60]1[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[C:14](=[O:15])[N:13]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=3)[N:12]=[CH:11]2)[S:5][C:6]=1[C:7]([NH:58][CH2:59][C:60]1[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=1)=[O:9]

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580316664-methyl-2-(5-oxo-1-(4-(trifluoromethyl)benzyl)-1H-1,2,4-triazol-4(5H)-yl)thiazole-5-carboxylic acid

Product 1

HCID 580314474-methyl-2-(5-oxo-1-(4-(trifluoromethyl)benzyl)-1H-1,2,4-triazol-4(5H)-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-methyl-2-(5-oxo-1-(4-(trifluoromethyl)benzyl)-1H-1,2,4-triazol-4(5H)-yl)thiazole-5-carboxylic acid (0.15 g, 0.39 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.97 g, 0.51 mmol) and N,N-diisopropylethylamine (0.09 mL, 0.51 mmol) in N,N-dimethylformamide (3 mL) was added 1-hydroxybenzotriazole (0.07 g, 0.51 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes and followed by the addition of 3-(aminomethyl)pyridine (0.05 mL, 0.05 mmol). The reaction mixture was stirred for 17 hours at ambient temperature, diluted with ethyl acetate (30 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 as a white powder in 59% yield (0.11 g): mp 156-158° C.; 1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.51 (s, 1H), 8.27 (s, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.59 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 7.31-7.19 (m, 1H), 6.46 (t, J=5.8 Hz, 1H), 5.04 (s, 2H), 4.59 (d, J=5.8 Hz, 2H), 2.63 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 161.4, 153.4, 150.9, 149.9, 149.3, 149.2, 138.9, 135.7, 131.2, 128.7, 125.8, 123.7, 121.8, 49.1, 41.6, 17.2; MS (ES+) m/z 475.3 (M+1).

Workup

  1. stirringThe reaction mixture was stirred for 17 hours at ambient temperature
  2. washwashed with water and brine
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-1c350f795e1e4c7f81747c6f433add0b
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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