Potassium Carbonate → 2-(2-Fluorophenyl)-5-[(2'-methyl-3,3'-bipyridin-6-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3one

HRID 341059

Reaction equation

HRID 341059 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[F:29])[C:21](=[O:22])[C:11]3=[CH:10]2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:64][C:65]1[C:70](B(O)O)=[CH:69][CH:68]=[CH:67][N:66]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[CH:10][N:9]([CH2:8][C:5]3[N:6]=[CH:7][C:2]([C:70]4[C:65]([CH3:64])=[N:66][CH:67]=[CH:68][CH:69]=4)=[CH:3][CH:4]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 201116472-Methylpyridine-3-boronic acidHCID 681544925-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Product 1

HCID 681535342-(2-Fluorophenyl)-5-[(2'-methyl-3,3'-bipyridin-6-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

5-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (51 mg, 0.11 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (16 mg, 0.034 mmol, 0.3 equiv), (2-methylpyridin-3-yl)boronic acid (26 mg, 0.19 mmol, 1.7 equiv), palladium(II) acetate (2.6 mg, 0.011 mmol, 0.1 equiv) and an aqueous solution (0.1 mL) of potassium carbonate (39 mg, 0.28 mmol, 2.5 equiv) were combined in dimethylsulfoxide (0.5 mL) and placed into a preheated oil bath at 85° C. for 90 minutes. The mixture was cooled to ambient temperature, stirred with Quadrapure® (50 mg, 1 wt equiv) for 1 hour, filtered and purified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (500 MHz, d6-DMSO) δ 9.10 (1H, s), 8.57 (1H, d, J=2.1 Hz), 8.55 (1H, d, J=4.6 Hz), 8.21 (1H, dd, J=7.9, 1.4 Hz), 7.96 (1H, dd, J=8.1, 2.4 Hz), 7.84 (1H, d, J=8.7 Hz), 7.80 (1H, br s), 7.72 (1H, d, J=8.3 Hz), 7.65 (1H, ddd, J=8.6, 7.3, 1.5 Hz), 7.61 (1H, td, J=7.8, 1.6 Hz), 7.54 (1H, br t, J=7.6 Hz), 7.48-7.38 (3H, m), 7.34 (1H, td, J=7.6, 1.5 Hz), 5.92 (2H, s), 2.44 (3H, s) ppm; low resolution mass spectrometry (ES+) m/z 462.1709 [(M+H)+; calculated for C28H21FN5O: 462.1725].

Workup

  1. filtrationfiltered
  2. custompurified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-b0464dfc0e8d4ea1a11b9aad8cd03096
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Linked notes

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