Dimethylformamide → HCID 178509669, compound

HRID 1098114Notes

Reaction equation

HRID 1098114 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2=[N:13][CH:14]=[N:15][C:16]([OH:17])=[C:11]2[CH:10]=[N:9]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:60][N:61](C=O)C>CCOC(C)=O.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[C:60]#[N:61])[N:9]=[CH:10][C:11]=12

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 178517917HCID 178517917, compound

Product 1

HCID 178509669HCID 178509669, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

1-(2-bromophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol B17b (1.456 g, 5 mmol) and zinc cyanide (0.528 g, 4.50 mmol) were dissolved in DMF (15 mL) and sealed into a microwave tube. The tube was evacuated and back flushed with nitrogen several times. 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.289 g, 0.50 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.229 g, 0.25 mmol) were added. The reaction was heated to 160° C. for 10 minutes in the microwave reactor and cooled to RT. This was repeated on exactly the same scale. The two reaction mixtures were combined and diluted with EtOAc (200 mL) and water (30 mL). The biphasic mixture was filtered, and the organic phase separated and washed with brine (20 mL) then dried over MgSO4, filtered and evaporated. The residue was purified by hot filtration, then crystallization from MeOH, providing 2-(4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzonitrile (1.225 g). 1H NMR (400 MHz, DMSO-d6) δ 7.70-7.75 (1H, m), 7.86-7.88 (1H, m), 7.91-7.95 (1H, m), 8.08-8.10 (1H, m), 8.17 (1H, s), 8.43 (1H, s), 12.49 (1H, s), m/z (ESI+) (M+H)+=238; HPLC tR=1.15 min.

Workup

  1. customsealed into a microwave tube
  2. customThe tube was evacuated
  3. customback flushed with nitrogen several times
  4. temperaturecooled to RT
  5. customThe two reaction mixtures
  6. filtrationThe biphasic mixture was filtered
  7. customthe organic phase separated
  8. washwashed with brine (20 mL)
  9. dry with materialthen dried over MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. filtrationThe residue was purified by hot filtration
  13. customcrystallization from MeOH

Sources & evidence

ORD record
ord-3f86c2bd3a3d4a4bb6ff175fa354aed0
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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