4-Methylmorpholine → 2-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 2067340Notes

Reaction equation

HRID 2067340 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:26][CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>O1CCCC1>[Br:1][C:2]1[S:3][C:4]([C:8]([NH:26][CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[O:10])=[C:5]([CH3:7])[N:6]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 310183-PyridinemethanamineHCID 62365Isobutyl chloroformateHCID 28240582-Bromo-4-methyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 666315502-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-4-methylthiazole-5-carboxylic acid (10.00 g, 45.00 mmol) and 4-methylmorpholine (6.5 mL, 59.0 mmol) in tetrahydrofuran (150 mL) was added isobutyl chloroformate (6.5 mL, 49.6 mmol) at 0° C. The resulting mixture was stirred at room temperature for 1 hour and 3-(aminomethyl)pyridine (5.2 mL, 51.4 mmol) was added. The reaction mixture was stirred at ambient temperature for 17 hours, and then concentrated in vacuo. The residue was purified by column chromatography to afford 2-bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide in 52% yield (7.3 g): 1H NMR (300 MHz, CDCl3) δ 8.39-8.80 (m, 2H), 7.80-7.72 (m, 1H), 7.40-7.35 (m, 1H), 6.47 (br s, 1H), 4.60 (d, J=6.0 Hz, 2H), 2.64 (s, 3H); MS (ES+) m/z 312.1 (M+1), 314.1 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 17 hours
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-eaa2a243e63b483c95e46ee748209bb6
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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