Potassium Carbonate → HCID 178480055, compound

HRID 1505714Notes

Reaction equation

HRID 1505714 reaction equation
FC(F)(F)C(N1C[CH2:9][CH:8]([N:11]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]5[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=5)[CH:23]=4)=[N:20][CH:21]=3)[CH:13]=[N:12]2)[CH2:7][CH2:6]1)=O.[CH3:36][C:37]1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)[O:38]1.C([O-])(=O)C.[K+].IC1C=NN([C@H]2CC[C@H](O)CC2)C=1.C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O.C1OCCOC1>[CH3:33][N:31]1[CH:32]=[C:28]([C:24]2[CH:23]=[C:22]([C:19]3[N:18]=[CH:17][C:16]([C:14]4[CH:13]=[N:12][N:11]([C@H:8]5[CH2:7][CH2:6][C@H:37]([OH:38])[CH2:36][CH2:9]5)[CH:15]=4)=[CH:21][N:20]=3)[CH:27]=[CH:26][CH:25]=2)[CH:29]=[N:30]1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 899359682,2,2-Trifluoro-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone2×HCID 178521568HCID 178521568, compound2×

Product 1

HCID 178480055HCID 178480055, compoundYield 62%

Reagents, catalysts & solvents 4

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)Catalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine (intermediate 2; 700 mg; 2.22 mmol; 1.0 eq.), 4,4,5,5,4′,4′,5′,5′-Octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl](620 mg; 2.44 mmol; 1.1 eq.), Potassium acetate (327 mg; 3.33 mmol; 1.5 eq.) and trans-Dichlorobis(tricyclohexylphosphine)palladium(II), 99% (16.4 mg; 0.02 mmol; 0.01 eq.) were flushed with nitrogen for 10 min before the addition of Dioxane-1,4 (15 mL). The reaction mixture was then heated at reflux under nitrogen for 4 h. The temperature was reduced to 70° C. before the addition of trans-4-(4-Iodo-pyrazol-1-yl)-cyclohexanol (intermediate 22; 714 mg; 2.44 mmol; 1.10 eq.), potassium carbonate (921 mg; 6.66 mmol; 3.0 eq.), trans-Dichlorobis(tricyclohexylphosphine)palladium(II), 99% (16.4 mg; 0.02 mmol; 0.01 eq.) and water (5 mL). The new reaction mixture was heated again at 100° C. for 30 min. It was allowed to cool to RT and diluted with EtOAc. Organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica (THF: EtOAc, 50:50) followed by a recrystallisation in THF afforded the tittle compound as an off-white powder (550 mg, 62%). 1H NMR (300 MHz, DMSO) δ 9.14 (s, 2H), 6.51 (m, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 8.20 (m, 1H), 8.11 (s, 1H), 7.91 (s, 1H), 7.69 (m, 1H), 7.50 (t, J=8.1 Hz, 1H), 4.70 (d, J=4.2 Hz, 1H), 4.18 (m, 1H), 3.88 (s, 3H), 3.50 (m, 1H), 1.73-2.08 (m, 6H), 1.36 (m, 2H). HPLC (Condition A): Rt 3.21 min (purity 98.6%). MS (ESI+): 459.4.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux under nitrogen for 4 h
  3. temperatureto cool to RT
  4. washOrganic phase was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography on silica (THF: EtOAc, 50:50)
  9. customfollowed by a recrystallisation in THF

Sources & evidence

ORD record
ord-d5429a5cd7304be4b1218eac71d7be17
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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