Cesium carbonate → HCID 52914606, compound

HRID 341058Notes

Reaction equation

HRID 341058 reaction equation
ClC1N=CC([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)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1>O1CCCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)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:12]3[CH:13]=[C:18]([C:40]4[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=4)[N:9]=[CH:10][CH:11]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 52914605HCID 52914605, compound

Product 1

HCID 52914606HCID 52914606, compound

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

5-[(6-Chloropyridin-3-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 225, 40 mg, 0.10 mmol), bis(tri-tert-butylphosphine)palladium(0) (5.0 mg, 0.010 mmol, 0.1 equiv), cesium carbonate (0.20 mL, 1 M aqueous, 0.20 mmol, 2 equiv) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (35 mg, 0.17 mmol, 1.7 equiv) were suspended in tetrahydrofuran (1 mL) and the mixture was irradiated (high setting) for 10 minutes at 140° C. The mixture was cooled to ambient temperature, the organic layer removed, stirred with Quadrapure® (40 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 (400 MHz, d6-DMSO) δ 9.16 (1H, s), 8.65 (1H, d, J=2.2 Hz), 829 (1H, s), 8.20 (1H, dd, J=7.8, 1.4 Hz), 7.99 (1H, s), 7.83 (1H, d, J=8.7 Hz), 7.76 (1H, dd, J=8.2, 2.0 Hz), 7.66-7.58 (3H, m), 7.54 (1H, t, J=7.5 Hz), 7.48-7.37 (2H, m), 7.34 (1H, td, J=7.7, 1.5 Hz), 5.76 (2H, s), 3.87 (3H, s) ppm; low resolution mass spectrometry (ES+) m/z 451.0 [(M+H)+; calculated for C26H20FN6O: 451.2].

Workup

  1. customthe mixture was irradiated (high setting) for 10 minutes at 140° C
  2. customthe organic layer removed
  3. filtrationfiltered
  4. 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-1edaa44da1434cf9bc9703840340593b
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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