HCID 86726108, compound → HCID 86726107, compound

HRID 2169483Notes

Reaction equation

HRID 2169483 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][CH:25]=[CH:24][N:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]2[CH2:28][CH2:29][N:30]([CH:33]3[CH2:35][CH2:34]3)[C:31](=[O:32])[C:10]=12)C1C=CC=CC=1>C(O)(=O)C.OS(O)(=O)=O>[CH:33]1([N:30]2[CH2:29][CH2:28][N:11]3[C:12]([CH2:16][C:17]4([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=5)[CH2:21][CH2:20][CH2:19][CH2:18]4)=[N:13][C:14](=[O:15])[C:9]([OH:8])=[C:10]3[C:31]2=[O:32])[CH2:34][CH2:35]1

Participants

4

Reactant 1

HCID 86726108HCID 86726108, compound

Product 1

HCID 86726107HCID 86726107, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1118Sulfuric AcidSolvent

Procedure

To a stirred solution of 9-benzyloxy-2-cyclopropyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (452) (250 mg, crude) in acetic acid (4 mL), concentrated H2SO4 (0.001 mL) was added and the reaction mixture was stirred for 2 h at room temperature (monitored by LC-MS). Volatiles were removed from the reaction mixture ant the residue was quenched with ice water (10 mL). The pH of the mixture was adjusted to 8 using NaHCO3 and extracted with 10% methanol in dichloromethane (2×40 mL). The crude product obtained after drying and concentrating the organic part was purified by preparative HPLC to get 2-cyclopropyl-9-hydroxy-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (453) (17.3 mg, 30% 2 steps) as an off-white solid.

Workup

  1. customVolatiles were removed from the reaction mixture ant the residue
  2. customwas quenched with ice water (10 mL)
  3. extractionextracted with 10% methanol in dichloromethane (2×40 mL)
  4. customThe crude product obtained
  5. customafter drying
  6. concentrationconcentrating the organic part
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-cb67ea9e844c44529770d75e375ed911
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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