4-Methylmorpholine → (1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

HRID 1061683Notes

Reaction equation

HRID 1061683 reaction equation
CN1CCOCC1.[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24](O)=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9].ClC(OCC(C)C)=O.Cl.[NH2:40][C@@H:41]([CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[CH:42]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[OH:43]>O1CCCC1.CS(C)=O.O>[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24]([NH:40][C@@H:41]([CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:42]([C:44]2[S:45][CH:46]=[CH:47][N:48]=2)[OH:43])=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9]

Participants

8

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 22284314{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acidHCID 69748243(1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride

Product 1

HCID 60073849(1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

N-Methylmorpholine (66.4 μl) is added to a solution of {(3RS)-4-acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acid (162 mg, Reference compound No. 51-1) in tetrahydrofuran (2.5 ml). The mixture is cooled to −10° C., isobutyl chloroformate (65.4 μl) is added to the mixture, and the whole is stirred for 15 minutes. A mixed solution of (1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride (150 mg, Reference compound No. 10-2) and N-methylmorpholine (132.6 μl) in tetrahydrofuran (2.5 ml) and dimethyl sulfoxide (1 ml) is added thereto, and the whole is stirred overnight. Water is added to the reaction mixture, and the whole is extracted with ethyl acetate. The extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively and dried over magnesium sulfate. The extract is concentrated under reduced pressure, and the resulting residue is purified by column chromatography to give the titled compound (162.9 mg).

Workup

  1. stirringthe whole is stirred overnight
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe extract is concentrated under reduced pressure
  6. customthe resulting residue is purified by column chromatography

Sources & evidence

ORD record
ord-20062eec12b94237b3f5613ebb52f1fa
Source dataset
uspto-grants-2005_11
Patent number
US06960575B2

Reaction notes

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