4-Methylmorpholine → N-benzyl-2-(4-bromobutanamido)-4-methylthiazole-5-carboxamide

HRID 883133Notes

Reaction equation

HRID 883133 reaction equation
[Br:1][CH2:2][CH2:3][CH2:4][C:5]([OH:7])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:23][C:24]1[S:25][C:26]([C:30]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])=[C:27]([CH3:29])[N:28]=1>O1CCCC1>[CH2:33]([NH:32][C:30]([C:26]1[S:25][C:24]([NH:23][C:5](=[O:7])[CH2:4][CH2:3][CH2:2][Br:1])=[N:28][C:27]=1[CH3:29])=[O:31])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 758094-Bromobutyric acidHCID 210824N-Benzyl-2-imino-4-methyl-2,3-dihydro-1,3-thiazole-5-carboximidic acid

Product 1

HCID 86638730N-benzyl-2-(4-bromobutanamido)-4-methylthiazole-5-carboxamideYield 90.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-bromobutyric acid (0.94 g, 5.50 mmol) and 4-methylmorpholine (0.70 mL, 6.20 mmol) in tetrahydrofuran (40 mL) was added isobutyl chloroformate (0.75 mL, 5.60 mmol) at 0° C. The resulting reaction mixture was stirred at 0° C. for 2 hours and then 2-amino-N-benzyl-4-methylthiazole-5-carboxamide (1.24 g, 5.00 mmol) was added. After 14 hours at ambient temperature, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate (200 mL), washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by column chromatography to yield the title compound (1.80 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 5H), 5.99 (s, 1H), 4.57-4.55 (m, 2H), 4.34-4.27 (m, 2H), 3.38-3.44 (m, 2H), 2.64-2.18 (m, 5H); MS (ES+) m/z 396.3 (M+1) and 398.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. waitAfter 14 hours at ambient temperature
  3. customthe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-338dc72db0c54705abec33ceab07e44b
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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