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

HRID 2169470Notes

Reaction equation

HRID 2169470 reaction equation
O[CH2:2][CH2:3][N:4]([CH:34]([CH3:36])[CH3:35])[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.C(OCC)(=O)C.O>ClCCl>[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)[CH2:24][CH2:25][CH2:26][CH2:27]2)[N:8]2[CH2:2][CH2:3][N:4]([CH:34]([CH3:35])[CH3:36])[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 962WaterHCID 8857Ethyl AcetateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178457444HCID 178457444, compound

Product 1

HCID 867260979-benzyloxy-2-isopropyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 90.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylicacid (2-hydroxyethyl)-isopropylamide (439) (70 mg, 0.143 mmol), in dichloromethane (10 mL), TPP (131 mg, 0.5 mmol) diisopropyl azodicarboxylate (0.084 mL, 0.429 mmol) were added and stirring was continued for 1 h at room temperature while silica thin layer chromatography was performed (100% ethyl acetate, Rf=0.2). After completion of the reaction, water (10 mL) was added and the mixture was extracted with dichloromethane (2×30 mL). The organic part was dried over sodium sulfate, then concentrated and the resulting crude product was purified by normal silica gel (100-200 mesh) column chromatography using 70-80% ethyl acetate in hexane as gradient polarity mobile phase to get 9-benzyloxy-2-isopropyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (440) (60.0 mg, 90.2%) as a white sticky liquid.

Workup

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

Sources & evidence

ORD record
ord-e39bf30f1c08494ca4c45b86aef211eb
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

Loading…