Methanol → 9-benzyloxy-2-methyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169474Notes

Reaction equation

HRID 2169474 reaction equation
O[CH2:2][CH2:3][N:4]([CH3:34])[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:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]=1)=[O:6].N(C(OC(C)C)=O)=NC(OC(C)C)=O.CO.O>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:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]2[CH2:2][CH2:3][N:4]([CH3:34])[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 962WaterHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178484640HCID 178484640, compound

Product 1

HCID 867261029-benzyloxy-2-methyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 82%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-methyl-amide (443) (90 mg, 0.195 mmol), in dichloromethane (10 mL), TPP (178.64 mg, 0.682 mmol) and diisopropyl azodicarboxylate (0.115 mL, 0.584 mmol) were added and stirring was continued for 1 h at room temperature while silica thin layer chromatography was performed (3% methanol in ethyl acetate; Rf=0.2). After completion of the reaction, water (5 mL) was added and the mixture was extracted with dichloromethane (2×30 mL). The organic part was dried and concentrated. The resulting crude product was purified by normal silica gel (100-200 mesh) column chromatography using 60-70% ethyl acetate in hexane as gradient polarity mobile phase to get 9-benzyloxy-2-methyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (444) (71 mg, 82%) as a white solid.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with dichloromethane (2×30 mL)
  3. customThe organic part was dried
  4. concentrationconcentrated
  5. customThe resulting crude product was purified by normal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-f5dc9b7c295d4c7aba0613a146157431
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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