1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 44545619, compound

HRID 1888593Notes

Reaction equation

HRID 1888593 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[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]5)=[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(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:29][O:28][CH:25]1[CH2:26][CH2:27][N:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:13]3[CH:12]=[N:11][C:6]4[NH:7][C:8]5[CH:9]=[N:10][C:2]([C:34]6[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=6)=[CH:3][C:4]=5[C:5]=4[CH:14]=3)=[CH:16][CH:17]=2)[CH2:23][CH2:24]1

Participants

5

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266391HCID 58266391, compound

Product 1

HCID 44545619HCID 44545619, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A degassed mixture of 6-bromo-3-[4-(4-methoxypiperidin-1-ylmethyl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (0.16 g, 0.36 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.15 g, 0.72 mmol) and 1,1′-[bis(diphenyl phosphino)ferrocene]dichloropalladium(II) (29 mg, 0.036 mmol) in acetonitrile (3.6 mL) and saturated aqueous sodium carbonate solution (3.6 mL). The reaction mixture was heated under microwave irradiation at 130° C. for 20 minutes. The cooled reaction mixture was partitioned between DCM and water. The organic phase was dried over sodium sulfate, filtered and evaporated and the resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-15% methanol in DCM) to afford the title compound as a yellow solid (68 mg, 42%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.86 (d, J=1.1 Hz, 1H), 8.81 (d, J=2.2 Hz, 1H), 8.77 (d, J=2.2 Hz, 1H), 8.30 (d, J=1.1 Hz, 1H), 8.06-8.04 (m, 2H), 7.71 (d, J=7.9 Hz, 2H), 7.52 (d, J=2.0 Hz, 2H), 4.01 (s, 3H), 3.74-3.63 (m, 2H), 2.94-2.79 (m, 2H), 2.47-2.25 (m, 2H), 2.04-1.90 (m, 2H), 1.78-1.58 (m, 2H). LCMS (Method A): RT=4.76 min, M+H+=453.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between DCM and water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customthe resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-c217cfbf77684843933f7b6fe6dd9cb1
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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