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

HRID 2169386Notes

Reaction equation

HRID 2169386 reaction equation
O[CH2:2][CH2:3][N:4]([CH3:38])[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[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:27][CH2:26][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:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]2[CH2:2][CH2:3][N:4]([CH3:38])[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 178484637HCID 178484637, compound

Product 1

HCID 867260169-benzyloxy-2-methyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 101.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-methyl-amide (351) (85 mg, 0.17 mmol) in dichloromethane (20 mL) was added triphenyl phosphine (174 mg, 0.67 mmol) and the reaction mixture was cooled to 0° C., followed by the addition of diisopropyl azodicarboxylate (0.2 mL, 0.1 mmol). The reaction mixture was stirred for 15 min at the same temperature (silica TLC, 5% methanol in ethyl acetate; Rf=0.3). The dichloromethane was removed in vacuum and the crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography using a gradient eluent mixture of 50% ethyl acetate in hexane to 100% ethyl acetate to get 9-benzyloxy-2-methyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (352) (85 mg, semi pure) as a white sticky solid.

Workup

  1. customThe dichloromethane was removed in vacuum
  2. customthe crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography
  3. additiona gradient eluent mixture of 50% ethyl acetate in hexane to 100% ethyl acetate

Sources & evidence

ORD record
ord-3cd9d41a808c4a5eae38cc73cbe1fd64
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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