Hydrochloric Acid → HCID 71208757, compound

HRID 2280247Notes

Reaction equation

HRID 2280247 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.[NH:24]1[CH2:28][CH2:27][C@H:26](O)[CH2:25]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.Cl>C1COCC1>[O:17]([C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C@@H:26]3[CH2:27][CH2:28][NH:24][CH2:25]3)[N:9]=2)=[CH:16][CH:15]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 2733874(3S)-pyrrolidin-3-olHCID 5363146Diisopropyl azodicarboxylateHCID 178508717HCID 178508717, compound

Product 1

HCID 71208757HCID 71208757, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine (45.50 g, 150 mmol, 1.0 eq), (S)-pyrrolidin-3-ol (bought from CNH, 51.95 g, 277.5 mmol, 1.85 eq) and Ph3P (72.79 g, 277.5 mmol, 1.85 eq) in THF (400 mL) at rt was added DIAD (57.6 mL, 292.5 mmol, 1.95 eq) dropwise over 1.5 h. The mixture was stirred another 30 min and concentrated HCl solution (100 mL) was added dropwise over 30 min. The mixture was stirred overnight at rt. The mixture was then heated to 50° C. for 1 h to push the de-Boc to completion. THF was removed by rotavap. The crude was diluted with toluene and water. The aqueous solution was further washed with EtOAc and toluene. MeOH (70 mL, 10% v/v to the aqueous solution) was added followed by KOH solution (100 g in 100 ml, water). The mixture became warm and precipitate immediately formed. The mixture was cooled in a 4° C. fridge for 2 h and filtered. The solid was washed with water, air-dried and then dried under high-vac for 3 days. Yield 49.45 g (89%), HPLC purity 95%.

Workup

  1. stirringThe mixture was stirred overnight at rt
  2. customTHF was removed by rotavap
  3. additionThe crude was diluted with toluene and water
  4. washThe aqueous solution was further washed with EtOAc and toluene
  5. additionMeOH (70 mL, 10% v/v to the aqueous solution) was added
  6. temperatureThe mixture became warm
  7. customprecipitate immediately
  8. customformed
  9. temperatureThe mixture was cooled in a 4° C. fridge for 2 h
  10. filtrationfiltered
  11. washThe solid was washed with water
  12. customair-dried
  13. customdried under high-vac for 3 days

Sources & evidence

ORD record
ord-28cbf249ad33439b9845e7a012337035
Source dataset
uspto-grants-2015_09
Patent number
US09138436B2

Reaction notes

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