4-Chloropyridine-3-boronic acid, pinacol ester → HCID 58266814, compound

HRID 1506072Notes

Reaction equation

HRID 1506072 reaction equation
I[C:2]1[N:10]=[CH:9][C:8]2[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]3[N:19]=[CH:20][C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)=[CH:22][C:5]=3[C:4]=2[CH:3]=1.[Cl:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1B1OC(C)(C)C(C)(C)O1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.O>[Cl:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[C:2]1[N:10]=[CH:9][C:8]2[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:16])([CH3:17])[CH3:18])[C:6]3[N:19]=[CH:20][C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)=[CH:22][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 120670644-Chloropyridine-3-boronic acid, pinacol esterHCID 58266395HCID 58266395, compound

Product 1

HCID 58266814HCID 58266814, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

6-Iodo-3-(1-methyl-1H-pyrazol-4-yl)-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (0.21 g, 0.41 mmol), 4-chloro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (0.15 g, 0.615 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloro palladium(II) (17 mg, 0.021 mmol) in saturated aqueous sodium carbonate solution (1 mL) and acetonitrile (4 mL) were placed under an atmosphere of argon and heated with microwave irradiation at 100° C. for 45 minutes. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered and evaporated to afford a residue which was purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a yellow oil (0.13 g, 66%). 1H NMR (CDCl3, 400 MHz): 9.22 (d, J=1.1 Hz, 1H), 8.91 (d, J=0.5 Hz, 1H), 8.79 (d, J=2.1 Hz, 1H), 8.53 (d, J=5.4 Hz, 1H), 8.48 (d, J=2.1 Hz, 1H), 8.32 (d, J=1.1 Hz, 1H), 7.86 (d, J=0.8 Hz, 1H), 7.73 (s, 1H), 7.48 (dd, J=5.4, 0.5 Hz, 1H), 6.01 (s, 2H), 4.01 (s, 3H), 3.70-3.63 (m, 2H), 1.02-0.94 (m, 2H), −0.06 (s, 9H). LCMS (Method G): RT=4.8 min, M+H+=491.

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a residue which
  8. customwas purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-2b4b6d94e7284b99b84d3067d30c40db
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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