Butyl vinyl ether → 6-(4-Acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

HRID 1693513Notes

Reaction equation

HRID 1693513 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[C:10](=[O:23])[C:11]3[CH:16]=[N:15][N:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:12]=3[N:13]=2)=[CH:4][CH:3]=1.[CH2:31]([O:35][CH:36]=[CH2:37])[CH2:32][CH2:33][CH3:34].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:31]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:24]3[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[C:10](=[O:23])[C:11]3[CH:16]=[N:15][N:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:12]=3[N:13]=2)=[CH:4][CH:3]=1)(=[O:35])[CH3:32].[CH2:31]([O:35][CH:36]=[CH:37][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[C:10](=[O:23])[C:11]3[CH:16]=[N:15][N:14]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:12]=3[N:13]=2)=[CH:6][CH:7]=1)[CH2:32][CH2:33][CH3:34]

Participants

9

Reactant 4

HCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 20472026-(4-Bromophenyl)-5-(4-chlorophenyl)-1-phenyl-1H,4H,5H-pyrazolo[3,4-D]pyrimidin-4-one

Product 2

HCID 116765606-(4-Acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-oneHCID 672814696-[4-(2-Butoxy-vinyl)-phenyl]-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a reaction tube charged with 6-(4-bromo-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (20 mg, 0.042 mmol), butylvinyl ether (21 mg, 0.21 mmol), Pd(OAc)2 (1.0 mg, 0.004 mmol), 1,3-bis(diphenylphosphino)propane (3.5 mg, 0.008 mmol) and K2CO3 (7 mg, 0.05 mmol) is added water (0.05 mL) in DMF (0.5 mL). The system is purged with N2, sealed and heated to 100° C. for 14 h. After cooling down to room temperature, the mixture is hydrolyzed by adding 1 mL of 1 N HCl for 30 min. The mixture is then treated with H2O (5 mL) and extracted with EtOAc (3×2 mL). The combined extracts is concentrated and purified by preparative LC/MS to provide the title compound 6-(4-acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one and 6-[4-(2-butoxy-vinyl)-phenyl]-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (example 360) as a by product (ratio about 1:2). Example 86: HPLC-MS calculated for C25H17ClNO2 (M+1+): 441.1. Found: 441.1. Example 360: HPLC-MS calculated C29H25ClN4O2 (M+1+): 497.2. Found: 497.2.

Workup

  1. customThe system is purged with N2
  2. customsealed
  3. temperatureAfter cooling down to room temperature
  4. additionby adding 1 mL of 1 N HCl for 30 min
  5. additionThe mixture is then treated with H2O (5 mL)
  6. extractionextracted with EtOAc (3×2 mL)
  7. concentrationThe combined extracts is concentrated
  8. custompurified by preparative LC/MS

Sources & evidence

ORD record
ord-fefe230070d94f8093ca0fa7ac7156a9
Source dataset
uspto-grants-2012_04
Patent number
US08158634B2

Reaction notes

Loading…