Ammonium Chloride → 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxamide

HRID 554933Notes

Reaction equation

HRID 554933 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:14][C:15]([C:19](O)=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1.O[N:25]1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>CN(C)C=O>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:14][C:15]([C:19]([NH2:25])=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579198022-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 441936012-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxamideYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid (0.35 g, 1.05 mmol) in anhydrous N,N-dimethylformamide (10.0 mL) was added 1-hydroxybenzotriazole (0.28 g, 2.09 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (0.80 g, 2.09 mmol), N,N-diisopropylethylamine (1.09 mL, 6.28 mmol) and ammonium chloride (0.22 g, 4.19 mmol). The resulting solution was stirred at ambient temperature for 72 h and concentrated in vacuo. The residue was suspended in saturated aqueous sodium bicarbonate solution (100 mL). The crude product was filtered and washed with water (50 mL). The crude solid was recrystallized in ethanol to afford the title compound as an off-white solid (0.27 g, 73%): mp 232-233° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.75 (s, 1H), 7.64 (br, 2H), 7.40-7.36 (m, 2H), 7.22-7.16 (m, 2H), 5.00 (s, 2H), 2.55 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.7, 161.69 (d, 1JC-F=243.5 Hz), 151.3, 150.9, 149.7, 132.2 (d, 4JC-F=3.0 Hz), 132.0, 129.9 (d, 3JC-F=8.4 Hz), 123.0, 115.4 (d, 2JC-F=21.5 Hz), 47.7, 16.8; MS (ES+) m/z 334.3 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. filtrationThe crude product was filtered
  3. washwashed with water (50 mL)
  4. customThe crude solid was recrystallized in ethanol

Sources & evidence

ORD record
ord-998d8950e75e40b79584b3b9235dbbb4
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

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