Triphenylphosphine → 9-benzyloxy-6-(2,6-dichlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169204Notes

Reaction equation

HRID 2169204 reaction equation
O[CH2:2][CH2:3][N:4]([CH:31]([CH3:33])[CH3:32])[C:5]([C:7]1[NH:8][C:9]([CH2:22][C:23]2[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:30])=[N:10][C:11](=[O:21])[C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.ClCCl.CO>ClCCl>[CH2:14]([O:13][C:12]1[C:11](=[O:21])[N:10]=[C:9]([CH2:22][C:23]2[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:30])[N:8]2[CH2:2][CH2:3][N:4]([CH:31]([CH3:33])[CH3:32])[C:5](=[O:6])[C:7]=12)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 21226129Dichloromethane methanolHCID 178457457HCID 178457457, compound

Product 1

HCID 867258549-benzyloxy-6-(2,6-dichlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 42.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Benzyloxy-2-(2,6-dichlorobenzyl)-6-oxo-3,6-dihydro-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-isopropylamide (64) (0.11 g, 224 μmol, Eq: 1.00) was dissolved in dichloromethane (1.5 ml) and Ph3P (88.3 mg, 336 μmol, Eq: 1.5) was added. The clear colorless solution was stirred at room temperature for approx. 10 min and then diisopropyl azodicarboxylate (diisopropylazodicarboxylate) (71.6 mg, 68.9 μl, 336 μmol, Eq: 1.5) was added. Stirring was continued at room temperature for 1 h. The solvent was removed and the remaining oil was purified by SiO2 flash chromatography (12 g SiO2, dichloromethane/methanol 0-3% methanol). SiO2 flash chromatography was repeated (12 g SiO2, hexanes/ethyl acetate 7-50% ethyl acetate, then dichloromethane/methanol 0-3% methanol) to afford 9-benzyloxy-6-(2,6-dichlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (65) (0.045 g, 95.3 μmol, 42.5% yield) as a white solid.

Workup

  1. stirringStirring
  2. waitwas continued at room temperature for 1 h
  3. customThe solvent was removed
  4. customthe remaining oil was purified by SiO2 flash chromatography (12 g SiO2, dichloromethane/methanol 0-3% methanol)

Sources & evidence

ORD record
ord-04460def4a3745d9823001ca2d215851
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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