1-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine → {3-[4-(4-Methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-methanol

HRID 1888552Notes

Reaction equation

HRID 1888552 reaction equation
Br[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([CH2:13][OH:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH3:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)[CH2:20][CH2:19]1>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:25]=[CH:26][C:27]([C:2]3[CH:16]=[N:15][C:5]4[NH:6][C:7]5[CH:12]=[N:11][C:10]([CH2:13][OH:14])=[CH:9][C:8]=5[C:4]=4[CH:3]=3)=[CH:28][CH:29]=2)[CH2:20][CH2:19]1

Participants

7

Reactant 2

HCID 179989051-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazineHCID 582664323-Bromo-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-methanol

Product 1

HCID 58266339{3-[4-(4-Methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-methanol

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-methanol (40.7 mg, 0.146 mmol), 4-(4-methylpiperazin-1-yl)phenylboronic acid pinacol ester (46.4 mg, 0.154 mmol) and bis(triphenylphosphine)palladium(II) dichloride (5.1 mg, 7.3 mmol) in acetonitrile (0.73 mL) and 2N aqueous sodium carbonate solution (0.73 mL) was heated at 150° C. under microwave irradiation for 20 minutes. The cooled reaction mixture was diluted with THF, the solid removed by filtration, and washed with THF and DCM. The combined filtrate was concentrated in vacuo and the resultant residue purified by flash chromatography (silica, 1-15% (2N ammonia methanol) in DCM) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.46 (s, 1H), 9.76 (s, 1H), 9.07 (d, J=1.8 Hz, 1H), 8.97 (d, J=1.8 Hz, 1H), 8.50 (s, 1H), 7.76 (d, J=8.7 Hz, 2H), 7.17 (d, J=8.7 Hz, 2H), 4.13 (s, 2H), 3.38-3.30 (m, 8H), 2.89 (s, 3H). LCMS (Method D): RT=5.24 min, M+H+=374.

Workup

  1. customThe cooled reaction mixture
  2. customthe solid removed by filtration
  3. washwashed with THF and DCM
  4. concentrationThe combined filtrate was concentrated in vacuo
  5. customthe resultant residue purified by flash chromatography (silica, 1-15% (2N ammonia methanol) in DCM)

Sources & evidence

ORD record
ord-69bc1ba7b8c845ffae47688fcb7c9fb0
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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