Cyclohexane → HCID 72944334, compound

HRID 1505704Notes

Reaction equation

HRID 1505704 reaction equation
[N:1]1([C:6](=[O:34])[CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:14]=[N:15][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21](B5OC(C)(C)C(C)(C)O5)[CH:20]=4)=[N:17][CH:18]=3)[CH:10]=[N:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:36]1[N:40]([CH3:41])[CH:39]=[N:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].C1CCCCC1>O.C(Cl)Cl>[CH3:41][N:40]1[C:36]([C:21]2[CH:20]=[C:19]([C:16]3[N:15]=[CH:14][C:13]([C:11]4[CH:10]=[N:9][N:8]([CH2:7][C:6]([N:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)=[O:34])[CH:12]=4)=[CH:18][N:17]=3)[CH:24]=[CH:23][CH:22]=2)=[CH:37][N:38]=[CH:39]1

Participants

7

Reactant 4

HCID 8078CyclohexaneHCID 11430Potassium CarbonateHCID 15152585-Bromo-1-methyl-1H-imidazole2×HCID 89923991HCID 89923991, compound2×

Product 1

HCID 72944334HCID 72944334, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-Pyrrolidin-1-yl-2-(4-{2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone (4 mL of the solution obtained in step 1), 5-bromo-1-methyl-1H-imidazole (35 mg; 0.22 mmol; 1.0 eq.), Pd(Ph3)4 (13 mg; 0.01 mmol; 0.05 eq.) and potassium carbonate (90 mg; 0.65 mmol; 3.0 eq.) in water (0.73 mL) was heated at 120° C. in MW for 30 min. Addition of 5-bromo-1-methyl-1H-imidazole (35 mg; 0.22 mmol; 1.0 eq.) and heating at 120° C. for 30 min had to be repeated twice to complete the reaction. The reaction mixture was then diluted with water and extracted twice with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 80:20) gave a black gum which was redissolved in DCM. Addition of cyclohexane afforded a brown precipitate which was filtered and dried under vacuum to give the title compound as a beige solid (40 mg, 44%). 1H NMR (300 MHz, DMSO-d6) δ 9.20 (s, 2H), 8.47-8.46 (m, 1H), 8.41-8.37 (m, 2H), 8.14 (d, J=0.6 Hz, 1H), 7.76 (s, 1H), 7.68-7.60 (m, 2H), 7.15 (s, 1H), 5.12 (s, 2H), 3.74 (s, 3H), 3.52 (t, J=6.8 Hz, 2H), 3.32 (t, J=6.8 Hz, 2H), 1.93 (quint., J=6.8 Hz, 2H), 1.80 (quint., J=6.8 Hz, 2H). HPLC (Condition A): Rt 2.21 min (purity 96.2%). MS (ESI+): 414.4.

Workup

  1. temperatureheating at 120° C. for 30 min
  2. customthe reaction
  3. extractionextracted twice with EtOAc
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 80:20)
  9. customgave a black gum which
  10. customafforded a brown precipitate which
  11. filtrationwas filtered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-6222140862e0409dada88aed300ff99f
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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