Ammonium Chloride → (2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-1-(2,3-dihydrofuran-5-yl)-1-oxo-3-phenylpropane

HRID 1061693Notes

Reaction equation

HRID 1061693 reaction equation
[O:1]1[CH:5]=[CH:4][CH2:3][CH2:2]1.C([Li])(C)(C)C.CCCCC.CON(C)[C:19](=[O:51])[C@@H:20]([NH:28][C:29]([CH2:31][N:32]1[C:37]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:36][N:35]([C:44](=[O:46])[CH3:45])[CH:34]([CH:47]([CH3:49])[CH3:48])[C:33]1=[O:50])=[O:30])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Cl-].[NH4+]>O1CCCC1>[C:44]([N:35]1[CH:36]=[C:37]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:32]([CH2:31][C:29]([NH:28][C@@H:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([C:2]2[O:1][CH2:5][CH2:4][CH:3]=2)=[O:51])=[O:30])[C:33](=[O:50])[CH:34]1[CH:47]([CH3:49])[CH3:48])(=[O:46])[CH3:45]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 709342,3-DihydrofuranHCID 86592307N1-methoxy-N1-methyl-(2S)-2-{(3RS)-4-acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenylpropionamideHCID 178446069HCID 178446069, compound

Product 1

HCID 60073841(2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-1-(2,3-dihydrofuran-5-yl)-1-oxo-3-phenylpropane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2,3-dihydrofuran (80 μl) in anhydrous tetrahydrofuran (2 ml) is cooled to −78° C., a 1.55 N tert-butyllithium/pentane solution (660 μl) is added thereto, and the mixture is stirred for one hour. The mixture is added to a solution of N1-methoxy-N1-methyl-(2S)-2-{(3RS)-4-acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenylpropionamide (295 mg, Compound No. 1-51) in anhydrous tetrahydrofuran (3 ml) cooled at −78° C., and the whole is stirred for two hours. The temperature is raised to 0° C., and the reaction mixture is stirred for 30 minutes. A saturated aqueous ammonium chloride solution is added to the reaction mixture, and the whole is extracted with ethyl acetate. The extract is washed with saturated brine and dried over anhydrous magnesium sulfate. The extract is concentrated under reduced pressure, and the resulting residue is purified by silica gel column chromatography to give the titled compound (38.4 mg).

Workup

  1. stirringthe whole is stirred for two hours
  2. temperatureThe temperature is raised to 0° C.
  3. stirringthe reaction mixture is stirred for 30 minutes
  4. extractionthe whole is extracted with ethyl acetate
  5. washThe extract is washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationThe extract is concentrated under reduced pressure
  8. customthe resulting residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-271c3acf861343eeba6891f75838872b
Source dataset
uspto-grants-2005_11
Patent number
US06960575B2

Reaction notes

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