Potassium Carbonate → HCID 89924175, compound

HRID 1505697Notes

Reaction equation

HRID 1505697 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]=[CH:35][C:34](B(O)O)=[CH:33]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>CCOC(C)=O.O>[O:32]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[C:4]([C:8]3[N:9]=[CH:10][C:11]([C:14]4[CH:15]=[N:16][N:17]([CH:19]5[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH2:21][CH2:20]5)[CH:18]=4)=[CH:12][N:13]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:33]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734358Furan-3-boronic acidHCID 89924531HCID 89924531, compound2×

Product 1

HCID 89924175HCID 89924175, compoundYield 102.7%

Reagents, catalysts & solvents 2

HCID 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; 100 mg; 0.19 mmol; 1.0 eq.), furan-3-boronic acid (25 mg; 0.23 mmol; 1.2 eq.), Pd(Ph3)4 (11 mg; 0.01 mmol; 0.05 eq.) and potassium carbonate (78 mg; 0.56 mmol; 3.0 eq.) were flushed with nitrogen before the addition of dioxane: water (1.5:0.75 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 (three times) and combined organic phases were dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (heptane:EtOAc, gradient from 80:20 to 50:50 afforded the title compound as a white solid (92 mg; 100%). 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 2H), 8.57-8.54 (m, 2H), 8.30-8.27 (m, 2H), 8.15 (s, 1H), 7.75 (t, J=1.7 Hz, 1H), 7.78-7.74 (m, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.03 (dd, J=1.7 Hz, 1.0 Hz, 1H), 4.47-4.40 (m, 1H), 4.09-4.05 (m, 2H), 2.94 (m, 2H), 2.09-2.05 (m, 2H), 1.88-1.74 (m, 2H), 1.43 (s, 9H). HPLC (Condition A): Rt 5.13 min (purity 92.1%). MS (ESI+): 472.3.

Workup

  1. extractionAqueous phase was extracted with EtOAc (three times)
  2. dry with materialwere dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography (heptane

Sources & evidence

ORD record
ord-d858cc95b10b4531a2634b1f2c66b4ad
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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