Potassium Carbonate → HCID 68978422, compound

HRID 1396543Notes

Reaction equation

HRID 1396543 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[C:7]2[N:9]([CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[C:16]([F:18])[C:15]([OH:19])=[C:14]([Br:20])[CH:13]=3)[C:6]2=[CH:5][N:4]=1.C([O-])([O-])=O.[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.O[CH2:62][CH2:63][N:64]1[CH2:68][CH2:67][CH2:66][CH2:65]1>C1COCC1.O>[Br:20][C:14]1[CH:13]=[C:12]([C:11]2[C:6]3[C:7](=[N:8][C:3]([NH2:2])=[N:4][CH:5]=3)[N:9]([CH3:21])[N:10]=2)[CH:17]=[C:16]([F:18])[C:15]=1[O:19][CH2:62][CH2:63][N:64]1[CH2:68][CH2:67][CH2:66][CH2:65]1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 762881-PyrrolidineethanolHCID 5363146Diisopropyl azodicarboxylateHCID 136387218HCID 136387218, compound

Product 1

HCID 68978422HCID 68978422, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-bromo-6-fluoro-phenol hydrochloride (Example 42b) (30 mg, 0.08 mmol) is dissolved in anhydrous THF (10 ml), K2CO3 (12 mg, 0.09 mmol) is added and the reaction mixture is stirred at room temperature for 10 minutes. Triphenylphosphine (116 mg, 0.44 mmol), DIAD (0.076 ml, 0.40 mmol) and 1-(2-hydroxyethyl)pyrrolidine (0.048 ml, 0.40 mmol) are added and the reaction mixture is heated to reflux for 20 hours. After cooling to room temperature the reaction mixture is diluted with water (˜15 ml) and extracted with EtOAc (3×50 ml). The combined organic portions are dried over MgSO4, filtered and concentrated in vacuo Purification of the crude residue by flash chromatography on silica firstly eluting the non-polar impurities with iso-hexanes:EtOAc (4:1 to 1:4) then eluting the product with EtOAc:MeOH:Et3N (4:1:0.01) affords the title compound.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux for 20 hours
  3. temperatureAfter cooling to room temperature the reaction mixture
  4. extractionextracted with EtOAc (3×50 ml)
  5. dry with materialThe combined organic portions are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo Purification of the crude residue by flash chromatography on silica
  8. washfirstly eluting the non-polar impurities with iso-hexanes:EtOAc (4:1 to 1:4)
  9. washthen eluting the product with EtOAc:MeOH:Et3N (4:1:0.01)

Sources & evidence

ORD record
ord-945b8515043f40bd8f324a049460e75e
Source dataset
uspto-grants-2014_12
Patent number
US08901134B2

Reaction notes

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