Methanol → 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropylmethyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169368Notes

Reaction equation

HRID 2169368 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]([CH2:34][CH:35]3[CH2:37][CH2:36]3)[C:32](=[O:33])[C:10]=12)C1C=CC=CC=1.OS(O)(=O)=O.CO.CCCCCC>C(O)(=O)C.ClCCl>[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]([CH2:34][CH:35]5[CH2:36][CH2:37]5)[C:32](=[O:33])[C:10]4=[C:9]([OH:8])[C:14](=[O:15])[N:13]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 8058HexaneHCID 867259989-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropylmethyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867259996-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropylmethyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 52.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 9-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropylmethyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (331) (200 mg, 0.38 mmol) in acetic acid (6.0 mL) was added H2SO4 (0.05 mL) at 0° C. and the reaction mixture was stirred at room temperature for 2 h (TLC; 5% methanol in dichloromethane/UV/SiO2, Rf=0.3). The reaction mixture was quenched with NaHCO3 solution, diluted with water and extracted with ethyl acetate (2×50 mL). The organic part was washed with water (40 mL) and brine (40 mL). The organic phase was thereafter dried and concentrated in vacuo to get a brownish gummy mass which was dissolved in dichloromethane (1 mL). 5 mL of hexane was added to the solution and the solid formed was allowed to settle down. The liquid phase was removed by decantation and the solid was triturated with diethyl ether and n-pentane to get pure 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropylmethyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (332) (86 mg, 52%) as a light brown solid.

Workup

  1. customThe reaction mixture was quenched with NaHCO3 solution
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe organic part was washed with water (40 mL) and brine (40 mL)
  5. customThe organic phase was thereafter dried
  6. concentrationconcentrated in vacuo
  7. customto get a brownish gummy mass which
  8. customthe solid formed
  9. customThe liquid phase was removed by decantation
  10. customthe solid was triturated with diethyl ether and n-pentane

Sources & evidence

ORD record
ord-848a2996666345fa9687fd3a4bf6b8df
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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