Sulfuric Acid → 6-(5,4'-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169414Notes

Reaction equation

HRID 2169414 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=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.OS(O)(=O)=O>C(O)(=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:12]2[N:11]3[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34](=[O:35])[C:10]3=[C:9]([OH:8])[C:14](=[O:15])[N:13]=2)=[C:18]([C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[CH:19]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260449-benzyloxy-6-(5,4'-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260466-(5,4'-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 61.72%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-(5,4′-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (10a) (35 mg, 0.064 mmol) in acetic acid (1 mL), concentrated H2SO4 (0.001 mL, 0.013 mmol) was added and the reaction mixture was stirred for 4 h at room temperature (reaction was monitored by LC/MS). Volatiles were removed from the reaction mixture and the residue was quenched with ice cold water (5 mL). The pH of this mixture was adjusted to pH 8 using NaHCO3. After extraction with ethyl acetate (2×15 mL), the organic part was dried and concentrated. The resulting crude product was purified by prep HPLC to get 6-(5,4′-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (P046-03-EB-01) (18.1 mg, 61.72%) as an off-white solid.

Workup

  1. custom(reaction was monitored by LC/MS)
  2. customVolatiles were removed from the reaction mixture
  3. customthe residue was quenched with ice cold water (5 mL)
  4. extractionAfter extraction with ethyl acetate (2×15 mL)
  5. customthe organic part was dried
  6. concentrationconcentrated
  7. customThe resulting crude product was purified by prep HPLC

Sources & evidence

ORD record
ord-9bf5683f7e8a44699adf059fb45d752e
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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