1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 58266320, compound

HRID 1506050Notes

Reaction equation

HRID 1506050 reaction equation
Br[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[C@H:27]([CH3:28])[CH2:26][CH2:25][CH2:24][C@@H:23]5[CH3:29])=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.C(OCC)(=O)C>[CH3:29][C@H:23]1[CH2:24][CH2:25][CH2:26][C@@H:27]([CH3:28])[N:22]1[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[N:11][C:6]3[NH:7][C:8]4[CH:9]=[N:10][C:2]([C:34]5[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=5)=[CH:3][C:4]=4[C:5]=3[CH:14]=2)=[CH:16][CH:17]=1

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266836HCID 58266836, compound

Product 1

HCID 58266320HCID 58266320, compoundYield 31.1%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A degassed mixture of 6-bromo-3-[4-((2S,6R)-2,6-dimethyl-piperidin-1-ylmethyl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (223 mg, 0.50 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (208 mg, 1.0 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (41 mg, 0.05 mmol) in 2N aqueous sodium carbonate solution (6 mL) and acetonitrile (6 mL) was heated under microwave irradiation at 130° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and 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, 25 g column, Biotage, 0-15% methanol in DCM) to afford the title compound as a white solid (70 mg, 31%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.85 (d, J=1.1 Hz, 1H), 8.82-8.77 (m, 2H), 8.33 (d, J=1.1 Hz, 1H), 8.08 (s, 1H), 8.06 (d, J=0.8 Hz, 1H), 7.71-7.65 (m, 2H), 7.56-7.51 (m, 2H), 4.00 (d, J=1.9 Hz, 5H), 2.65-2.52 (m, 2H), 1.72-1.60 (m, 3H), 1.47-1.30 (m, 3H), 1.25 (d, J=6.2 Hz, 6H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed 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, 25 g column, Biotage, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-d18e58a6bac3410c8b052ebf83e6e7f3
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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