4-Fluorobenzylamine → 2-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 1879208Notes

Reaction equation

HRID 1879208 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH2:17])=[CH:14][CH:13]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH:17][C:8]([C:4]2[S:3][C:2]([Br:1])=[N:6][C:5]=2[CH3:7])=[O:10])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 28240582-Bromo-4-methyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 666314052-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 91.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (10.0 g, 45.0 mmol) in methylene chloride (200 mL) was added 4-fluoro-benzylamine (6.19 g, 49.5 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (21.9 g, 49.5 mmol) and N,N-diisopropylethylamine (15.7 mL, 90.1 mmol) and the mixture was stirred under nitrogen at room temperature for 16 hr. The reaction mixture was diluted with methylene chloride (300 mL), washed with water (300 mL) and brine (2×200 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by flash chromatography over silica gel (methylene chloride:methanol, 95:5) to provide 2-bromo-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide as a beige solid (13.5 g, 90% yield). MS (M+H)+=330; Rt=136 min.

Workup

  1. washwashed with water (300 mL) and brine (2×200 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by flash chromatography over silica gel (methylene chloride:methanol, 95:5)

Sources & evidence

ORD record
ord-866c3c41b7fa4601b90a55878728d959
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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