Hydrochloric Acid → HCID 67973582, compound

HRID 2046204Notes

Reaction equation

HRID 2046204 reaction equation
[O:1]([CH2:8][C:9]1[CH:18]=[C:12]2[C:13](=[O:17])[NH:14][CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.Cl>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:19]1([N:14]2[CH2:15][CH2:16][N:11]3[N:10]=[C:9]([CH2:8][O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH:18]=[C:12]3[C:13]2=[O:17])[CH2:21][CH2:20]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 2760897Cyclopropylboronic acidHCID 57411799HCID 57411799, compound

Product 1

HCID 67973582HCID 67973582, compoundYield 16.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 165397Cupric acetate monohydrateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Copper(II) acetate monohydrate (83 mg, 041 mmol) was added to a mixture of 2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.1 g, 0.41 mmol), cyclopropylboronic acid (35 mg, 0.41 mmol) and DMAP (75 mg, 0.617 mmol) in toluene (1 mL). The mixture was stirred at 95° C. for 16 hours. The mixture was stirred at 95° C. for 24 hours more. The reaction was allowed to room temperature and was poured into a 1N solution of HCl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo. The desired product was triturated with diethyl ether to yield 5-cyclopropyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (19 mg, 16% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 0.68-0.79 (m, 2H), 0.89-1.00 (m, 2H), 2.74-2.82 (m, 1H), 3.74-3.82 (m, 2H), 4.30-4.37 (m, 2H), 5.08 (s, 2H), 6.93 (s, 1H), 6.94-6.97 (m, 1H), 6.98-7.02 (m, 2H), 7.26-7.31 (m, 2H).

Workup

  1. stirringThe mixture was stirred at 95° C. for 24 hours more
  2. customwas allowed to room temperature
  3. extractionextracted with AcOEt
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo
  11. customThe desired product was triturated with diethyl ether

Sources & evidence

ORD record
ord-5ad8d904dbea430a81c28dc32f3aa904
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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