Hydrochloric Acid → 6-((1-(4-chlorophenyl)cyclopentyl)methyl)-9-hydroxy-2-(1-phenylethyl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione

HRID 2169180Notes

Reaction equation

HRID 2169180 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]2[CH2:29][CH2:30][N:31]([CH:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH3:35])[C:32](=[O:33])[C:10]=12)C1C=CC=CC=1.Cl.C([O-])(O)=O.[Na+]>CO>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C:17]2([CH2:16][C:12]3[N:11]4[CH2:29][CH2:30][N:31]([CH:34]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[CH3:35])[C:32](=[O:33])[C:10]4=[C:9]([OH:8])[C:14](=[O:15])[N:13]=3)[CH2:18][CH2:19][CH2:20][CH2:21]2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 867258319-(benzyloxy)-6-((1-(4-chlorophenyl)cyclopentyl)methyl)-2-(1-phenylethyl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione

Product 1

HCID 867258326-((1-(4-chlorophenyl)cyclopentyl)methyl)-9-hydroxy-2-(1-phenylethyl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dioneYield 79.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 9-(benzyloxy)-6-((1-(4-chlorophenyl)cyclopentyl)methyl)-2-(1-phenylethyl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione (37) (76 mg, 134 μmol, Eq: 1.00) in methanol (5 ml) was added HCl (conc) (195 mg, 163 μl, 5.35 mmol, Eq: 40) and the reaction mixture was heated at 70° C. for 48 hrs. The reaction mixture was neutralized with saturated aqueous NaHCO3 solution, extracted with dichloromethane, dried (MgSO4), concentrated, and chromatographed (silica gel, gradient 0 to 5% methanol-dichloromethane) to obtain an off-white solid. The solid was triturated with diethyl ether, filtered, and dried to obtain 6-((1-(4-chlorophenyl)cyclopentyl)methyl)-9-hydroxy-2-(1-phenylethyl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione (38) (off-white powder, 51 mg, 107 μmol, 79.8% yield).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customchromatographed (silica gel, gradient 0 to 5% methanol-dichloromethane)
  5. customto obtain an off-white solid
  6. customThe solid was triturated with diethyl ether
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-2e3f9a3acc554e149e0a2a16665e6033
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

Loading…