Sulfuric Acid → 9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169416Notes

Reaction equation

HRID 2169416 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12](CC2C=CC(Cl)=CC=2C2C=CC=C(F)C=2)[N:11]2[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34](=[O:35])[C:10]=12)C1C=CC=CC=1.S(=O)(=O)(O)O>C(O)(=O)C>[OH:8][C:9]1[C:14](=[O:15])[N:13]=[CH:12][N:11]2[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34](=[O:35])[C:10]=12

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260479-benzyloxy-6-(5-chloro-3'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260489-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 79.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-(5-chloro-3′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (383) (60 mg, 0.113 mmol) in acetic acid (1 mL), concentrated sulfuric acid (0.001 mL, 0.023 mmol) was added. The reaction mixture was stirred for 4 h, at room temperature (monitored by LC-MS). Volatiles were removed from the reaction and the residue was quenched with ice cold water (5 mL). Aqueous saturated NaHCO3 was added to adjust the pH to 8. The quenched mass was extracted with ethyl acetate (2×15 mL) and the combined organic part was dried, concentrated and purified by preparative HPLC to get 6-(5-chloro-3% fluoro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (384) (20.0 mg, 40.06%) as an off-white solid.

Workup

  1. customVolatiles were removed from the reaction
  2. customthe residue was quenched with ice cold water (5 mL)
  3. additionAqueous saturated NaHCO3 was added
  4. extractionThe quenched mass was extracted with ethyl acetate (2×15 mL)
  5. customthe combined organic part was dried
  6. concentrationconcentrated
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f6c18261c8334bc4a2121f27464bb22c
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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