Sulfuric Acid → 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-9-hydroxy-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169372Notes

Reaction equation

HRID 2169372 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]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[C:32](=[O:33])[C:10]=12)C1C=CC=CC=1.OS(O)(=O)=O>C(O)(=O)C>[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]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[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

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260029-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260036-[1-(4-chlorophenyl)-cyclopentylmethyl]-9-hydroxy-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 41%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (335) in acetic acid (1 mL), concentrated H2SO4 (0.001 mL, 0.02 mmol) was added and stirred for 4 h at room temperature (monitored by LC-MS). After completion of the reaction, volatiles were removed from the reaction mixture, and the mixture was quenched with ice-cold water (5 mL). Saturated aqueous NaHCO3 (adjusted pH to 8) was added and the quenched mixture was extracted with ethyl acetate (2×15 mL). The combined extracts were dried and concentrated. The resulting residue was washed with 10% dichloromethane in ether to get 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-9-hydroxy-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (336) (19 mg, 41%) as an off-white solid.

Workup

  1. customAfter completion of the reaction, volatiles
  2. customwere removed from the reaction mixture
  3. customthe mixture was quenched with ice-cold water (5 mL)
  4. additionwas added
  5. extractionthe quenched mixture was extracted with ethyl acetate (2×15 mL)
  6. customThe combined extracts were dried
  7. concentrationconcentrated
  8. washThe resulting residue was washed with 10% dichloromethane in ether

Sources & evidence

ORD record
ord-61e75718ee464fa5b0c6af76cf4c2810
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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