1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 58266417, compound

HRID 1506046Notes

Reaction equation

HRID 1506046 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:32])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([CH2:23][N:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)=[C:17]([O:30][CH3:31])[CH:16]=3)[CH:14]=2)[CH:3]=1.[CH3:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1>[F-].[K+].C(#N)C.C(OCC)(=O)C>[CH3:31][O:30][C:17]1[CH:16]=[C:15]([C:13]2[CH:14]=[C:9]([C:4]3[CH:3]=[C:2]([C:37]4[CH:36]=[N:35][N:34]([CH3:33])[CH:38]=4)[N:7]=[CH:6][C:5]=3[NH2:8])[C:10]([F:32])=[N:11][CH:12]=2)[CH:20]=[C:19]([O:21][CH3:22])[C:18]=1[CH2:23][N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266813HCID 58266813, compound

Product 1

HCID 58266417HCID 58266417, compoundYield 70.2%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of 6′-chloro-5-(3,5-dimethoxy-4-piperidin-1-ylmethylphenyl)-2-fluoro-[3,4]bipyridinyl-3′-ylamine (830 mg, 1.40 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (577 mg, 2.78 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (151 mg, 0.19 mmol) in 1N aqueous potassium fluoride solution (10 mL) and acetonitrile (6 mL) was heated under microwave irradiation at 100° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (100 mL) then washed with water (75 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 20 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a white solid (494 mg, 54%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.55 (dd, J=2.5, 1.0 Hz, 1H), 8.22 (dd, J=8.8, 2.5 Hz, 1H), 8.16 (d, J=0.6 Hz, 1H), 7.92 (s, 1H), 7.85 (d, J=0.8 Hz, 1H), 7.37 (s, 1H), 6.95 (s, 2H), 4.35 (s, 2H), 4.01 (s, 6H), 3.95 (s, 3H), 3.61-3.22 (br m, 2H), 3.19-2.90 (br m, 2H), 2.02-1.47 (br m, 6H).

Workup

  1. customThe cooled reaction mixture
  2. washthen washed with water (75 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 20 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-1a2aa81fb862446db81f457bf3b87bd2
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

Loading…