4-Methylmorpholine → HCID 59369652, compound

HRID 45377

Reaction equation

HRID 45377 reaction equation
[C:1]([NH:9][C:10]1[S:11][C:12]([C:16]([OH:18])=O)=[C:13]([CH3:15])[N:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[C:34]([NH:42][NH2:43])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(OCC)(=O)C>[C:34]([NH:42][NH:43][C:16]([C:12]1[S:11][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[N:14][C:13]=1[CH3:15])=[O:18])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 11955BenzoylhydrazineHCID 62365Isobutyl chloroformateHCID 8568022-Benzoylamino-4-methyl-thiazole-5-carboxylic acid

Product 1

HCID 59369652HCID 59369652, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-benzamido-4-methylthiazole-5-carboxylic acid (0.30 g, 1.14 mmol) in tertahydrofuran (28 mL) was added N-methylmorpholine (0.23 mL, 0.21 g, 2.09 mmol) under nitrogen atmosphere, followed by the addition of isobutyl chloroformate (0.2 mL, 0.21 g, 1.54 mmol) dropwise at ambient temperature. The mixture was stirred at ambient temperature for 7 hours. Benzhydrazide (0.23 g, 1.71 mmol) and 4-methylmorpholine (0.15 mL, 0.14 g, 1.36 mmol) were added to the reaction mixture. After being stirred at ambient temperature for 18 hours, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (3×10 mL). The organic phase was separated and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The crude product was purified by column chromatography eluted with ethyl acetate/hexanes (20/80 to 30/70) to afford the title compound as a white solid (0.059 g, 14% yield); m.p. 258-260° C.; 1H NMR (DMSO-d6, 300 MHz) δ 12.90 (br, 1H), 10.46 (s, 1H), 10.10 (s, 1H), 8.09 (d, J=7.4 Hz, 2H), 7.93 (d, J=6.9 Hz, 2H), 7.65-7.47 (m, 6H), 2.56 (s, 3H); MS (ES+) m/z 381.4 (M+1).

Workup

  1. stirringAfter being stirred at ambient temperature for 18 hours
  2. washwashed with water (3×10 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe crude product was purified by column chromatography
  8. washeluted with ethyl acetate/hexanes (20/80 to 30/70)

Sources & evidence

ORD record
ord-d31cf82d68bb44b7ba94b65dc8ba2bd1
Source dataset
uspto-grants-2013_09
Patent number
US08541457B2

Linked notes

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