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

HRID 1879136Notes

Reaction equation

HRID 1879136 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:47]([NH2:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>ClCCl>[CH2:47]([NH:54][C:8]([C:4]1[S:3][C:2]([Br:1])=[N:6][C:5]=1[CH3:7])=[O:10])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=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 64.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Part A. To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (10.0 g, 45.0 mmol, 1.0 equiv) and diisopropylethylamine (15.6 mL, 90.0 mmol, 2.0 equiv) in anhydrous dichloromethane (400 mL) was added benzotriazol-1-yloxytris-(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 22.0 g, 49.5 mmol, 1.1 equiv) and benzylamine (5.4 mL, 49.5 mmol, 1.1 equiv). The resulting mixture was stirred at ambient temperature for 12 hr. The reaction was diluted with dichloromethane, washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 10:90 to 35:65, v/v]. Further purification by stirring in pentane then filtration afforded 2-bromo-4-methyl-thiazole-5-carboxylic acid benzylamide (9.0 g, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.84 (bs, 1H), 7.23-7.36 (m, 5H), 4.42 (d, J=8.0 Hz, 2H), 2.55 (s, 3H); MS (M+H)+=312.1, Rt=1.32 min.

Workup

  1. washwashed with water, brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 10:90 to 35:65, v/v]
  6. customFurther purification
  7. stirringby stirring in pentane
  8. filtrationfiltration

Sources & evidence

ORD record
ord-222c616c5a784c798978cce21bae799e
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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