Methanol → 9-benzyloxy-2-isopropyl-6-(4-oxo-1-phenyl-cyclohexylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169307Notes

Reaction equation

HRID 2169307 reaction equation
O[CH2:2][CH2:3][N:4]([CH:36]([CH3:38])[CH3:37])[C:5]([C:7]1[C:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:11]([OH:21])[N:10]=[C:9]([CH2:22][C:23]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]2)[N:8]=1)=[O:6].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.CO>ClCCl.C(OCC)(=O)C>[CH2:14]([O:13][C:12]1[C:11](=[O:21])[N:10]=[C:9]([CH2:22][C:23]2([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]2)[N:8]2[CH2:2][CH2:3][N:4]([CH:36]([CH3:38])[CH3:37])[C:5](=[O:6])[C:7]=12)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178457438HCID 178457438, compound

Product 1

HCID 867259549-benzyloxy-2-isopropyl-6-(4-oxo-1-phenyl-cyclohexylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 72.53%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-benzyloxy-6-hydroxy-2-(4-oxo-1-phenyl-cyclohexylmethyl)-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-isopropylamide (272) (200 mg, 0.39 mmol) in dichloromethane (25.0 mL) was added triphenyl phosphine (152 mg, 0.58 mmol) and diisopropyl azodicarboxylate (0.12 mL, 0.58 mmol) at room temperature and stirred for 30 min (silica TLC, 5% methanol in ethyl acetate, Rf=0.5). The reaction mixture was concentrated under reduced pressure and purified by normal silica gel (100-200 mesh) column chromatography using gradient polarity mobile phase (50% ethyl acetate in hexane to 5% methanol in dichloromethane) to get pure 9-benzyloxy-2-isopropyl-6-(4-oxo-1-phenyl-cyclohexylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (273) (140 mg, 72.53%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. custompurified by normal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-25dbed0c7f524d6ca0529a883f23d90f
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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