1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 6-(1-Methyl-1H-pyrazol-4-yl)-3-(4-morpholin-4-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506052Notes

Reaction equation

HRID 1506052 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][O:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.[CH3:28][N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.C(OCC)(=O)C>[CH3:28][N:29]1[CH:33]=[C:32]([C:2]2[N:10]=[CH:9][C:8]3[NH:7][C:6]4[N:11]=[CH:12][C:13]([C:15]5[CH:20]=[CH:19][C:18]([CH2:21][N:22]6[CH2:23][CH2:24][O:25][CH2:26][CH2:27]6)=[CH:17][CH:16]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)[CH:31]=[N:30]1

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 582667156-Bromo-3-(4-morpholin-4-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 582665726-(1-Methyl-1H-pyrazol-4-yl)-3-(4-morpholin-4-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 25%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A degassed mixture of 6-bromo-3-(4-morpholin-4-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (245 mg, 0.58 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (241 mg, 1.16 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (47 mg, 0.06 mmol) in 2N aqueous sodium carbonate solution (7 mL) and acetonitrile (7 mL) was heated under microwave irradiation at 130° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (75 mL) and washed with water (50 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, 10 g column, Biotage, 0-10% methanol in DCM) to afford the title compound as a white solid (61 mg, 25%). 1H NMR (CDCl3, 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), 8.31 (d, J=1.1 Hz, 1H), 8.07 (s, 1H), 8.05 (d, J=0.8 Hz, 1H), 7.73-7.67 (m, 2H), 7.54-7.48 (m, 2H), 4.01 (s, 3H), 3.80-3.73 (m, 4H), 3.63 (s, 2H), 2.60-2.52 (m, 4H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (50 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, 10 g column, Biotage, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-16de1e0b384b4b9c8bfce86ed8b78dc4
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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