4-Benzylpiperidine boronic acid → 6-Fluoro-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888560Notes

Reaction equation

HRID 1888560 reaction equation
Br[C:2]1[CH:15]=[N:14][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([F:13])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH2:16](C1CCN(B(O)O)CC1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(#N)C.[F-].[K+]>[F:13][C:10]1[N:11]=[CH:12][C:7]2[NH:6][C:5]3[N:14]=[CH:15][C:2]([C:20]4[CH:19]=[CH:18][C:17]([CH2:16][N:11]5[CH2:12][CH2:7][CH2:8][CH2:9][CH2:10]5)=[CH:22][CH:21]=4)=[CH:3][C:4]=3[C:8]=2[CH:9]=1

Participants

5

Reactant 2

HCID 536988504-Benzylpiperidine boronic acidHCID 582668313-Bromo-6-fluoro-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 582664146-Fluoro-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-bromo-6-fluoro-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (100 mg, 0.38 mmol), 4-benzylpiperidine boronic acid (123 mg, 0.56 mmol) and 1,1′-[bis(diphenylphosphino) ferrocene]dichloropalladium(II) (31 mg, 0.038 mmol) in acetonitrile (1.5 mL) and 2N aqueous potassium fluoride solution (1.5 mL) was degassed with nitrogen for 20 minutes. The reaction mixture was then heated under microwave irradiation at 150° C. for 30 minutes, allowed to cool to ambient temperature and diluted with water (3 mL). The resultant precipitate was collected by filtration, washed with water (5 mL) and ethyl acetate (10 mL). The resultant solid residue was purified by flash chromatography (silica, 4 g column, ISCO, 0-20% methanol in DCM) to afford the title compound as an off white solid (90 mg, 67%). 1H NMR (DMSO-D6, 300 MHz): 12.27 (s, 1H), 9.00 (d, J=2.3 Hz, 1H), 8.93 (d, J=2.3 Hz, 1H), 8.49 (d, J=1.5 Hz, 1H), 7.98 (d, J=2.3 Hz, 1H), 7.74 (d, J=8.0 Hz, 2H), 7.43 (d, J=7.9 Hz, 2H), 3.48 (s, 2H), 2.42-2.29 (m, 4H), 1.54-1.47 (m, 4H), 1.44-1.34 (m, 2H). LCMS (Method A): RT=5.87 min, M+H+=361.

Workup

  1. customwas degassed with nitrogen for 20 minutes
  2. temperatureto cool to ambient temperature
  3. additiondiluted with water (3 mL)
  4. filtrationThe resultant precipitate was collected by filtration
  5. washwashed with water (5 mL) and ethyl acetate (10 mL)
  6. customThe resultant solid residue was purified by flash chromatography (silica, 4 g column, ISCO, 0-20% methanol in DCM)

Sources & evidence

ORD record
ord-a33d212962b64180b415e119e22d6bad
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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