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

HRID 2169418Notes

Reaction equation

HRID 2169418 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]([F: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]([OH:35])=[C:10]3[C:9]([OH:8])=[C:14]([OH:15])[N:13]=2)=[C:18]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH:19]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260499-benzyloxy-6-(5-chloro-4'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260506-(5-chloro-4'-fluoro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-diolYield 80,107.102%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (385) (30 mg, 0.056 mmol) in acetic acid (1 mL), concentrated H2SO4 (0.001 mL, 0.011 mmol) was added and the reaction mixture was stirred for 4 h at room temperature (monitored by LC-MS). From the reaction, volatiles was removed and the residue was quenched with ice cold water (5 mL). Aqueous saturated NaHCO3 was added to adjust the pH up to 8. The quenched mass was extracted with ethyl acetate (2×15 mL). The combined organic part was dried, concentrated and purified by preparative HPLC to get 6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-diol (386) (11.2 mg, 44.86 mmol) as an off-white solid.

Workup

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

Sources & evidence

ORD record
ord-ad8b5cbc36ee42c9b8582d16282dd79b
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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