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

HRID 2169422Notes

Reaction equation

HRID 2169422 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:25]=[N:26][CH:27]=[CH:28][CH:29]=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]=[N:26][CH:27]=[CH:28][CH:29]=2)[CH:19]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867260539-benzyloxy-6-(4-chloro-2-pyridin-3-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867260546-(4-chloro-2-pyridin-3-yl-benzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 32.26%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-6-(4-chloro-2-pyridin-3-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (389) (45 mg, 0.088 mmol) in acetic acid (2 mL), concentrated H2SO4 (0.001 mL, 0.018 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 col d 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-(4-chloro-2-pyridin-3-yl-benzyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (390) (12.0 mg, 32.26%) as an off-white solid.

Workup

  1. customFrom the reaction, volatiles
  2. customwere removed
  3. customthe residue was quenched with ice col
  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-19bc0da260ba4980a1c9034b64a03877
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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