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

HRID 2169412Notes

Reaction equation

HRID 2169412 reaction equation
O[CH2:2][CH2:3][N:4]([CH:31]([CH3:33])[CH3:32])[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[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[Br:30])[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.O>[CH2:14]([O:13][C:12]1[C:11](=[O:21])[N:10]=[C:9]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[Br:30])[N:8]2[CH2:2][CH2:3][N:4]([CH:31]([CH3:32])[CH3:33])[C:5](=[O:6])[C:7]=12)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178457452HCID 178457452, compound

Product 1

HCID 867260459-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 41.95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylicacid(2-hydroxyethyl)-isopropylamide (379) (1.0 g, 1.873 mmol) and triphenyl phosphine (1.717 g, 6.554 mmol) in dichloromethane (120 mL), diisopropyl azodicarboxylate (1.114, 5.618 mmol) was added over 10 h (dilution 0.19 M; rate 3 ml/h) at 0° C. The reaction was monitored by silica thin layer chromatography (3% methanol in dichloromethane; Rf=0.4). After completion of the reaction, 50 mL water were added and the mixture was extracted with dichloromethane (2×100 mL). The organic part was dried over sodium sulphate and concentrated. The resulting crude product was column purified (using amine bound silica) to get 9-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (380) (0.406 g, 41.95%) as a white solid.

Workup

  1. additionwere added
  2. extractionthe mixture was extracted with dichloromethane (2×100 mL)
  3. dry with materialThe organic part was dried over sodium sulphate
  4. concentrationconcentrated
  5. custompurified (using amine bound silica)

Sources & evidence

ORD record
ord-314bd41b48a746348d32e42cb165ee6b
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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