Methanol → HCID 178506148, compound

HRID 419748Notes

Reaction equation

HRID 419748 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.Cl.[F:12][C:13]([F:32])([F:31])[C:14]1[CH:15]=[C:16]([C:20]2[N:21]=[C:22]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[NH:23][CH:24]=2)[CH:17]=[CH:18][CH:19]=1.CO.C(N(CC)CC)C>O>[F:31][C:13]([F:12])([F:32])[C:14]1[CH:15]=[C:16]([C:20]2[N:21]=[C:22]([CH:25]3[CH2:26][CH2:27][N:28]([C:2]4[N:7]=[CH:6][N:5]=[C:4]5[NH:8][N:9]=[CH:10][C:3]=45)[CH2:29][CH2:30]3)[NH:23][CH:24]=2)[CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 178478963HCID 178478963, compound

Product 1

HCID 178506148HCID 178506148, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

Charge 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine (93.3 g; 1.00 equiv; 603.66 mmoles; 93.30 g), (4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine)-, Hydrochloride (1:1) (200.1 g; 1.00 equiv; 603.13 mmoles), and Methanol (1800 mL) to a 5000 mL 4-necked round bottom flask (fitted with nitrogen blanket, rubber septum, mechanical stirrer, heating mantle, condenser and thermocouple probe). Add Triethylamine (280 mL; 2.01 moles) via addition funnel over approximately 15 min. Heat the resulting clear orange solution to 50° C. and hold at 50° C. for 15 min. When reaction is deemed complete by HPLC, add Water (2000 mL) via an addition funnel at 50° C. Add seed crystals during this water addition and the product crystallizes. On completion of addition, heat the slurry to reflux for 1 hour. Cool to room temperature then filter and wash solids with 20% MeOH in water (2×250 mL). Dry the solids in a vacuum oven at 45° C. overnight to afford 4-{4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine as a tan solid (211.5 g, 0.603 mol, 85%).

Workup

  1. custom(fitted with nitrogen blanket, rubber septum, mechanical stirrer, heating mantle, condenser and thermocouple probe)
  2. customWhen reaction
  3. additionAdd seed crystals
  4. customthe product crystallizes
  5. additionOn completion of addition
  6. temperatureheat the slurry
  7. temperatureto reflux for 1 hour
  8. temperatureCool to room temperature
  9. filtrationthen filter
  10. washwash solids with 20% MeOH in water (2×250 mL)
  11. customDry the solids in a vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-3073d3e804724fb9be2feffecde1cc60
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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