Benzylamine → 2-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

HRID 1879174Notes

Reaction equation

HRID 1879174 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[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>[CH2:11]([NH:18][C:8]([C:4]1[S:3][C:2]([Br:1])=[N:6][C:5]=1[CH3:7])=[O:10])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 28240582-Bromo-4-methyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamideYield 83.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (3.00 g, 13.5 mmol) in methylene chloride (20 mL) was added benzyl amine (1.60 mL, 14.9 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 6.57 g, 14.86 mmol) and N,N-diisopropylethylamine (4.71 mL; 27.02 mmol) and the mixture was stirred under nitrogen at room temperature for 16 hr. The reaction mixture was diluted with methylene chloride (100 mL), washed with water (100 mL) and brine (2×100 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (hexanes:ethyl acetate, 1:1) to provide 2-bromo-4-methyl-thiazole-5-carboxylic acid benzyl amide (3.50 g, 83% yield) as a yelloW solid. 1H NMR (400 MHz, CDCl3) δ 7.47-7.55 (m, 5H), 6.25 (bs, 1H), 4.75 (d, J=8.0 Hz, 2H), 2.79 (s, 3H); MS (M+H)+=312.1; Rt=1.31 min.

Workup

  1. washwashed with water (100 mL) and brine (2×100 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by flash chromatography (hexanes:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-edf78a7b286d4a389ff3f6e3e045425b
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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