Cesium carbonate → 4-[4-(4-Fluorophenyl)-1-[1-(1-isoxazol-3-ylethyl)piperidin-4-yl]-1H-imidazol-5-yl}-N-methylpyrimidin-2-amine

HRID 1896646Notes

Reaction equation

HRID 1896646 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][CH3:20])[N:14]=2)=[CH:4][CH:3]=1.CS(O[CH:32]([C:34]1[CH:38]=[CH:37][O:36][N:35]=1)[CH3:33])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:21]3[CH2:26][CH2:25][N:24]([CH:32]([C:34]4[CH:38]=[CH:37][O:36][N:35]=4)[CH3:33])[CH2:23][CH2:22]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][CH3:20])[N:14]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 99284384-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]-N-methylpyrimidin-2-amineHCID 574617131-Isoxazol-3-ylethyl methanesulfonate

Product 1

HCID 582351144-[4-(4-Fluorophenyl)-1-[1-(1-isoxazol-3-ylethyl)piperidin-4-yl]-1H-imidazol-5-yl}-N-methylpyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]-N-methylpyrimidin-2-amine (C8, which can be prepared by the method of J. Sisko, U.S. Pat. No. 6,239,279 B1, May 29, 2001) (75 mg, 0.21 mmol), 1-isoxazol-3-ylethyl methanesulfonate (C7) (60 mg, 0.31 mmol) and cesium carbonate (139 mg, 0.43 mmol) in acetonitrile (2 mL) was heated at 70° C. for 24 hours. Removal of solvent under reduced pressure provided a residue, which was purified by silica gel chromatography (Eluants: 0%, then 5%, then 15% methanol in ethyl acetate). The resulting colorless oil was dissolved in ethyl acetate/heptane, then concentrated in vacuo to provide the product as a white solid. Yield: 57 mg, 0.13 mmol, 62%. APCI m/z 448.3 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.46 (d, J=6.9 Hz, 3H), 1.93-2.07 (m, 2H), 2.12-2.24 (m, 4H), 2.98-3.08 (m, 2H), 3.02 (d, J=5.0 Hz, 3H), 3.94 (q, J=6.9 Hz, 1H), 4.59 (br m, 1H), 5.14 (br d, J=5 Hz, 1H), 6.35 (d, J=1.7 Hz, 1H), 6.40 (d, J=5.0 Hz, 1H), 7.00 (dd, J=8.8, 8.8 Hz, 2H), 7.46 (dd, J=9.0, 5.5 Hz, 2H), 7.77 (s, 1H), 8.15 (br d, J=5 Hz, 1H), 8.38 (dd, J=1.7, 0.6 Hz, 1H).

Workup

  1. customcan be prepared by the method of J
  2. customRemoval of solvent under reduced pressure
  3. customprovided a residue, which
  4. customwas purified by silica gel chromatography (Eluants
  5. dissolutionThe resulting colorless oil was dissolved in ethyl acetate/heptane
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab79f7a821164d8ba496fb9af04be248
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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