Cesium carbonate → 2-[3-Fluoro-4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline

HRID 33900

Reaction equation

HRID 33900 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:20])[CH:5]=[CH:6][C:7]=1[C:8]1[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:11][N:10]([CH3:19])[N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1.[OH-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[C:8]1[C:12]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:11][N:10]([CH3:19])[N:9]=1)[O:20][CH2:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 203942-(Chloromethyl)quinolineHCID 1363758353-Fluoro-4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenol

Product 1

HCID 115896242-[3-Fluoro-4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-Fluoro-4-(1-methyl-4-pyridin4-yl-1H-pyrazol-3-yl)-phenol (450 mg) in dimethylformamide (10 ml) was added cesium carbonate (2 g) and 2-chloro methyl quinoline (481 mg) and the reaction mixture was heated at 60° C. for 18 h. The reaction mixture was poured into 1N NaOH, extracted with methylene chloride, dried magnesium sulfate, filtered and concentrated. Biotage MPLC purification eluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes provided the title compound. The free base was stirred in ethyl acetate and 1.1 equivalents of succinic acid was added. The white precipitate was filtered and dried to provide the title compound as the succinate salt (280 mg). 1H NMR (400 MHz, DMSO) δ 8.43 (d, J=8.3 Hz, 1 H), 8.37 (d, J=6.2 Hz, 2H), 8.26 (s, 1H), 8.00 (m, 2H), 7.78 (t, J=7.1 Hz, 1H), 7.70 (d, J=8.3 Hz, 1 H), 7.61 (t, J=6.6 Hz, 1 H), 7.38 (t, J=8.3, Hz, 1 H), 7.10 (d, J=6.2 Hz, 2H), 7.00 (m, 2H), 5.40 (s, 2H), 3.88 (s, 3 H), 2.38 (s, 4H), MS: (M+H m/z=411.1).

Workup

  1. extractionextracted with methylene chloride, dried magnesium sulfate
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customBiotage MPLC purification
  5. washeluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-85f8e56f8b9c4a0d87acb77ae7fd109a
Source dataset
uspto-grants-2008_09
Patent number
US07429665B2

Linked notes

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