Cesium carbonate → 1-({5-[1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl)-3-methylimidazolidine-2,4-dione

HRID 2281044Notes

Reaction equation

HRID 2281044 reaction equation
CS(O[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:25]=[CH:24][C:16]3[N:17]([CH2:20][CH:21]4[CH2:23][CH2:22]4)[N:18]=[N:19][C:15]=3[C:14]=2[C:26]([F:29])([F:28])[F:27])=[C:9]([F:30])[N:8]=1)(=O)=O.[CH3:31][N:32]1[C:36](=[O:37])[CH2:35][NH:34][C:33]1=[O:38].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH:21]1([CH2:20][N:17]2[C:16]3[CH:24]=[CH:25][C:13]([C:10]4[CH:11]=[CH:12][C:7]([CH2:6][N:34]5[CH2:35][C:36](=[O:37])[N:32]([CH3:31])[C:33]5=[O:38])=[N:8][C:9]=4[F:30])=[C:14]([C:26]([F:29])([F:27])[F:28])[C:15]=3[N:19]=[N:18]2)[CH2:23][CH2:22]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1388512,4-Imidazolidinedione, 3-methyl-HCID 86711980{5-[1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl methanesulfonate

Product 1

HCID 709796071-({5-[1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl)-3-methylimidazolidine-2,4-dione

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

{5-[1-(Cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl methanesulfonate (25 mg, 0.056 mmol) was dissolved in acetonitrile (0.56 mL) and treated with 3-methylimidazolidine-2,4-dione (9.6 mg, 0.084 mmol), cesium carbonate (55 mg, 0.17 mmol) and tetra-n-butylammonium iodide (4.2 mg, 0.011 mmol). The mixture was placed into a preheated oil bath at 85° C. for 30 minutes. The mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with sodium bicarbonate (2×5 mL, aqueous saturated). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (85:15 to 36:64; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid) to afford the titled compound as a white solid. H1-NMR (400 MHz, CDCl3): δ 7.84 (1H, d, J=8.5 Hz), 7.77 (1H, dd, J=9.2, 7.6 Hz), 7.39 (1H, d, J=8.6 Hz), 7.30 (1H, dd, J=7.5, 1.5 Hz), 4.77 (1H, d, J=16.4 Hz), 4.67 (1H, d, J=16.2 Hz), 4.61 (2H, d, J=7.1 Hz), 4.16 (1H, d, J=17.4 Hz), 4.07 (1H, d, J=17.1 Hz), 3.32 (3H, s), 1.49-1.39 (1H, m), 0.78-0.66 (2H, m), 0.61-0.11 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 463.1514 [(M+H)+; calculated for C21H19F4N6O2: 463.1500].

Workup

  1. washwashed with sodium bicarbonate (2×5 mL, aqueous saturated)
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative reverse phase HPLC (85:15 to 36:64; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-fdafe7c5507d4a6a86e3dc0b78c48b79
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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