4-Methylmorpholine → 2-Benzoylamino-4-methylthiazole-5-carboxylic Acid (1-Phenylpropyl)amide

HRID 45367

Reaction equation

HRID 45367 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.C(OC(Cl)=O)C(C)C.[CH2:34]([CH:36]([NH2:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH3:35]>O1CCCC1>[C:37]1([CH:36]([NH:43][C:16]([C:12]2[S:11][C:10]([NH:9][C:1](=[O:8])[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[N:14][C:13]=2[CH3:15])=[O:18])[CH2:34][CH3:35])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 180541-Phenylpropan-1-amineHCID 62365Isobutyl chloroformateHCID 8568022-Benzoylamino-4-methyl-thiazole-5-carboxylic acid

Product 1

HCID 593696422-Benzoylamino-4-methylthiazole-5-carboxylic Acid (1-Phenylpropyl)amideYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-benzoylamino-4-methylthiazole-5-carboxylic acid (0.13 g, 0.50 mmol) and 4-methylmorpholine (0.08 mL, 0.70 mmol) in tetrahydrofuran (20 mL) at 0° C. was added iso-butylchloroformate (0.08 mL, 0.60 mmol). The reaction mixture was stirred for 15 minutes, then warmed to ambient temperature and stirred for another hour before α-ethylbenzylamine (0.1 mL, 0.70 mmol) was added. The reaction mixture was kept stirring at ambient temperature overnight and then concentrated. Purification of the residue by column chromatography afforded the title compound in 19% yield (0.037 g); m. p. 87-89° C.; 1H NMR (CDCl3, 300 MHz) δ 7.89-7.86 (m, 2H), 7.61-7.22 (m, 8H), 5.91 (d, J=7.5 Hz, 1H), 5.02-4.94 (m, 1H), 2.33 (s, 3H), 2.27-1.78 (m, 2H), 0.92 (t, J=7.5 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ 165.1, 161.4, 157.0, 152.1, 141.8, 133.3, 131.4, 129.1, 128.7, 127.6, 127.5, 126.6, 118.8, 55.6, 29.3, 16.7, 10.8. MS (ES+) m/z 380.5 (M+1).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was kept stirring at ambient temperature overnight
  3. concentrationconcentrated
  4. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-2feb64882ea748ea87061f021f6721bf
Source dataset
uspto-grants-2013_09
Patent number
US08541457B2

Linked notes

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