Ammonia → HCID 66825610, compound

HRID 1912470Notes

Reaction equation

HRID 1912470 reaction equation
[NH3:1].[Br:2][C:3]1[CH:4]=[C:5]([C@@:9]2([CH3:19])[NH:14][C:13](=S)[CH2:12][N:11]3[N:16]=[CH:17][CH:18]=[C:10]23)[CH:6]=[CH:7][CH:8]=1.CO>O.C([O-])([O-])=O.[Na+].[Na+]>[Br:2][C:3]1[CH:4]=[C:5]([C@@:9]2([CH3:19])[N:14]=[C:13]([NH2:1])[CH2:12][N:11]3[N:16]=[CH:17][CH:18]=[C:10]23)[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 222Ammonia2×HCID 887MethanolHCID 86690809HCID 86690809, compound

Product 1

HCID 66825610HCID 66825610, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
60 °C

Procedure

32% aqueous ammonia solution (11.9 mL, 201.1 mmol) was added to a stirred mixture of (R)-4-(3-bromo-phenyl)-4-methyl-4,5-dihydro-pyrazolo[1,5-a]pyrazine-6-thione (1.8 g, 5.59 mmol) in 7 N solution of ammonia in methanol (11.97 mL, 83.79 mmol) in a sealed tube. The mixture was stirred at 60° C. for 90 minutes. After cooling to room temperature the mixture was diluted with water and Na2CO3 (aq. sat. solution) and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 7 M solution of ammonia in methanol in DCM 0/100 to 2/98 to 3/97 to 10/90). The desired fractions were collected and concentrated in vacuo to yield (R)-4-(3-bromo-phenyl)-4-methyl-4,7-dihydro-pyrazolo[1,5-a]pyrazin-6-ylamine (1.4 g, 82% yield) as a yellow solid.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica gel; 7 M solution of ammonia in methanol in DCM 0/100 to 2/98 to 3/97 to 10/90)
  8. customThe desired fractions were collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a747c58991784e498b51eb7a760493f2
Source dataset
uspto-grants-2013_12
Patent number
US08609660B2

Reaction notes

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