Potassium Acetate → tert-butyl 1-(5-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1774987Notes

Reaction equation

HRID 1774987 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:5]2=[CH:6][N:7]=1.CC1(C)C(C)(C)OB([C:26]2[CH:27]=[C:28]([N:32]3[CH2:37][CH2:36][CH:35]([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:34][CH2:33]3)[CH:29]=[N:30][CH:31]=2)O1.C([O-])(=O)C.[K+]>C(#N)C.O.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:26]3[CH:27]=[C:28]([N:32]4[CH2:33][CH2:34][CH:35]([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:43])([CH3:42])[CH3:44])[CH2:36][CH2:37]4)[CH:29]=[N:30][CH:31]=3)=[N:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:5]2=[CH:6][N:7]=1

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 67959870Tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamateHCID 726984825-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 86676686tert-butyl 1-(5-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamateYield 45%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

5-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (0.0736 g, 0.180 mmol), tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate (0.080 g, 0.20 mmol) and 1,1′-Bis(diphenylphosphino)ferrocenepalladium (II) chloride (0.0221 g, 0.0270 mmol) were dissolved in Acetonitrile (3.00 mL), followed by the addition of 1.0 M of Potassium acetate in Water (0.270 mL) and 1.0 M of Sodium carbonate in Water (0.270 mL). The reaction was stirred at 80° C. for 1 h. After filtration, the crude was evaporated and purified by silica gel column using (EtOAc/Hep eluted at 75% EtOAc) to give tert-butyl 1-(5-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (45 mg, 45% yield). ESI MS m/z=558.1 (M+1).

Workup

  1. filtrationAfter filtration
  2. customthe crude was evaporated
  3. custompurified by silica gel column
  4. wash(EtOAc/Hep eluted at 75% EtOAc)

Sources & evidence

ORD record
ord-0bab04dc06e645efa08e890c2d602393
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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