Sulfuric Acid → 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169364Notes

Reaction equation

HRID 2169364 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]2[CH2:29][CH2:30][N:31]([CH:34]3[CH2:36][CH2:35]3)[C:32](=[O:33])[C:10]=12)C1C=CC=CC=1.OS(O)(=O)=O>C(O)(=O)C>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C:17]2([CH2:16][C:12]3[N:11]4[CH2:29][CH2:30][N:31]([CH:34]5[CH2:35][CH2:36]5)[C:32](=[O:33])[C:10]4=[C:9]([OH:8])[C:14](=[O:15])[N:13]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 867259949-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867259956-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 57%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

9-benzyloxy-6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (327) (30 mg, 0.06 mmol) was taken up in acetic acid (1 mL) and H2SO4 (0.2 mL) was added slowly to the reaction at 0° C. and stirring was continued at room temperature for 1 h. The reaction was quenched with aqueous saturated NaHCO3 and extracted with ethyl acetate (2×15 ml). The combined extracts were dried and concentrated under reduced pressure. The obtained crude product was purified by preparative HPLC to get 6-[1-(4-chlorophenyl)-cyclopentylmethyl]-2-cyclopropyl-9-hydroxy-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (328) as an off-white solid (14 mg, 57%).

Workup

  1. customThe reaction was quenched with aqueous saturated NaHCO3
  2. extractionextracted with ethyl acetate (2×15 ml)
  3. customThe combined extracts were dried
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained crude product
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-ac2b0b2613104c14a892f0648277415a
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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