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

HRID 1887246Notes

Reaction equation

HRID 1887246 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 then 3-(aminomethyl)pyridine (5.2 mL, 51.4 mmol) was added. The reaction mixture was stirred at ambient temperature for 17 hours, 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, 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-3132a29dc67a4a16bd5b985797b165c9
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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