Sulfuric Acid → 6-(4-chloro-2-pyridin-4-yl-benzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169420Notes

Reaction equation

HRID 2169420 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][N:27]=[CH:26][CH:25]=2)[N:11]2[CH2:30][CH2:31][N:32]([CH:35]([CH3:37])[CH3:36])[C:33](=[O:34])[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[CH2:30][CH2:31][N:32]([CH:35]([CH3:37])[CH3:36])[C:33](=[O:34])[C:10]3=[C:9]([OH:8])[C:14](=[O:15])[N:13]=2)=[C:18]([C:24]2[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=2)[CH:19]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260519-benzyloxy-6-(4-chloro-2-pyridin-4-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260526-(4-chloro-2-pyridin-4-yl-benzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 34.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-(4-chloro-2-pyridin-4-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (387) (50 mg, 0.097 mmol) in acetic acid (2 mL), concentrated H2SO4 (0.001 mL, 0.019 mmol) was added and the reaction mixture was stirred for 4 h at room temperature (monitored by LC-MS). From the reaction, volatiles were removed and the residue was quenched with ice c old 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 and concentrated and the resulting residue was purified by preparative HPLC to get 6-(4-chloro-2-pyridin-4-yl-benzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (388) (14.3 mg, 31.45%) as an off-white solid.

Workup

  1. customFrom the reaction, volatiles
  2. customwere removed
  3. customthe residue was quenched with ice c old 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. customthe resulting residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c5daa574054849cfafab82e9e111cd57
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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