Potassium Phosphate, Tribasic → HCID 178519564, compound

HRID 2177599Notes

Reaction equation

HRID 2177599 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2[C:20](I)=[N:21][N:22](C3CCCCO3)[C:16]=2[CH2:15]1)=[O:13].[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[N:35][CH:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2=[C:20]([C:33]3[CH:34]=[N:35][CH:36]=[C:31]([F:30])[CH:32]=3)[NH:21][N:22]=[C:16]2[CH2:15]1)=[O:13]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 90409420HCID 90409420, compound

Product 1

HCID 178519564HCID 178519564, compoundYield 42.3%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (90 mg, 0.167 mmol) in 1,4-dioxane (1 mL) was added 5-fluoropyridine-3-boronic acid (70 mg, 0.50 mmol), potassium phosphate (106 mg, 0.50 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.025 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (6 mg, 0.010 mmol). The reaction was stirred at 100° C. overnight under an atmosphere of N2. The reaction was filtered through Celite© and the Celite© was washed with EtOAc. The solvent was concentrated and the residue was purified by HPLC (Agilent prep system, Waters XBridge, C18, 5 μm, 30×100 mm column, 5-99% MeOH/20 mM NH4OH over 18 min at 30 mL/min) followed by THP deprotection as described in Example 94 to provide the desired product (30 mg, 42%). MS (ESI) mass calcd. C19H13ClF4N4O, 424.1. m/z found, 425.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.73-8.64 (d, J=6.1 Hz, 1H), 8.48-8.39 (m, 1H), 7.83-7.74 (m, 1H), 7.72-7.60 (m, 1H), 7.56-7.44 (m, 2H), 5.15 (d, J=16.6 Hz, 0.7H), 4.88 (d, J=16.6 Hz, 0.7H), 4.50 (d, J=15.9 Hz, 0.3H), 4.39 (d, J=15.9 Hz, 0.3H), 4.25 (dt, J=12.8, 5.5 Hz, 0.3H), 4.04-3.95 (m, 0.3H), 3.54 (t, J=5.7 Hz, 1.4H), 2.99 (t, J=5.7 Hz, 0.7H), 2.92-2.73 (m, 1.3H).

Workup

  1. filtrationThe reaction was filtered through Celite©
  2. washthe Celite© was washed with EtOAc
  3. concentrationThe solvent was concentrated
  4. customthe residue was purified by HPLC (Agilent prep system, Waters XBridge, C18, 5 μm, 30×100 mm column, 5-99% MeOH/20 mM NH4OH over 18 min at 30 mL/min)

Sources & evidence

ORD record
ord-965bf6e74ab34512a0e83a5d7d542e64
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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