Cesium fluoride → HCID 89924280, compound

HRID 1505698Notes

Reaction equation

HRID 1505698 reaction equation
N[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]3[CH:15]=[N:16][N:17]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)[CH:18]=3)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[O:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.[F-].[Cs+].O1CCOCC1>CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[O:32]1[CH:36]=[C:35]([C:2]2[CH:3]=[C:4]([C:8]3[N:13]=[CH:12][C:11]([C:14]4[CH:15]=[N:16][N:17]([CH:19]5[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]5)[CH:18]=4)=[CH:10][N:9]=3)[CH:5]=[CH:6][CH:7]=2)[CH:34]=[N:33]1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 164141804-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazoleHCID 89924531HCID 89924531, compound2×

Product 1

HCID 89924280HCID 89924280, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Tert-butyl 4-4-[2-(3-iodophenyl)pyrimidin-5-yl]-1H-pyrazol-1-ylpiperidine-1-carboxylate (intermediate 5, 150 mg; 0.24 mmol; 1.0 eq.), 4-Isoxazoleboronic acid pinacol ester (47 mg; 0.24 mmol; 1.0 eq.), bis(triphenylphosphine)palladium(II)chloride (17 mg; 0.02 mmol; 0.10 eq.) and cesium fluoride (109 mg; 0.72 mmol; 3.0 eq.) were flushed with nitrogen before the addition of dioxane: water (2.25:1.1 mL). The reaction mixture was heated in MW at 120° C. for 30 min. It was then diluted with EtOAc and water. Aqueous phase was extracted with EtOAc and combined organic phases were dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (cyclohexane:EtOAc, gradient from 80:20 to 30:70) afforded the title compound as a white beige solid (70 mg; 62%). 1H NMR (300 MHz, DMSO-d6) δ 9.60 (s, 1H), 9.27 (s, 1H), 9.17 (s, 2H), 8.64 (t, J=1.5 Hz, 1H), 8.56 (s, 1H), 8.35 (dt, J=8.0 Hz, 1.5 Hz, 1H), 8.16 (s, 1H), 7.87-7.83 (m, 1H), 7.61 (t, J=8.0 Hz, 1H), 4.47-4.35 (m, 1H), 4.09-4.04 (m, 2H), 2.95 (m, 2H), 2.09-2.06 (m, 2H), 1.87-1.72 (m, 2H), 1.43 (s, 9H). HPLC (Condition A): Rt 4.70 min (purity 97.4%). MS (ESI+): 473.5.

Workup

  1. extractionAqueous phase was extracted with EtOAc
  2. dry with materialwere dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography (cyclohexane:EtOAc, gradient from 80:20 to 30:70)

Sources & evidence

ORD record
ord-92ec2279202740a6803f63f1602b1fbb
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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