Cesium carbonate → 2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-pyridin-4-yl-ethyl)-1H-pyrazol-4-yl]-pyrimidine

HRID 1505705Notes

Reaction equation

HRID 1505705 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([C:13]3[N:18]=[CH:17][C:16]([C:19]4[CH:20]=[N:21][NH:22][CH:23]=4)=[CH:15][N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:4]=[N:3]1.[H-].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].Br.Br[CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=1>CC(N(C)C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([C:13]3[N:14]=[CH:15][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH2:34][CH2:35][C:36]5[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=5)[CH:23]=4)=[CH:17][N:18]=3)[CH:10]=[CH:11][CH:12]=2)[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 219962524-(2-Bromoethyl)pyridine hydrobromideHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

Product 1

HCID 729445422-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-pyridin-4-yl-ethyl)-1H-pyrazol-4-yl]-pyrimidine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine (example 3, 120 mg; 0.40 mmol; 1.0 eq.) in dry DMA (1 mL) was added over a suspension of NaH (60% in oil, 28 mg; 1.19 mmol; 3.0 eq.) in dry DMA (2 mL) maintained at 0° C. under nitrogen atmosphere. The resulting mixture was stirred for one hour at 0° C. then heated at 100° C. O/N after the addition of a solution of 14-(2-Bromo-ethyl)-pyridine hydrobromide (159 mg; 0.60 mmol; 1.5 eq.) in DMA (2 mL). Cesium carbonate (388 mg; 1.19 mmol; 3.00 eq.) and 4-(2-Bromo-ethyl)-pyridine hydrobromide (159 mg; 0.60 mmol; 1.5 eq.) were added and the reaction mixture was heated again at 100° C. O/N. Reaction mixture was then cooled down to RT and quenched with water and extracted with DCM (three times). Combined organic phases were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. The resulting oil was purified by autopreparative LC/MS to give the title compound a white foam (80 mg, 49%). 1H NMR (300 MHz, DMSO-d6) δ 9.12 (s, 2H), 8.56-8.50 (m, 1H), 8.50-8.41 (m, 2H), 8.38 (s, 1H), 8.26 (s, 1H), 8.24-8.17 (m, 1H), 8.15 (s, 1H), 7.92 (s, 1H), 7.77-7.66 (m, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.29-7.19 (m, 2H), 4.48 (t, J=7.1 Hz, 2H), 3.89 (s, 3H), 3.21 (t, J=7.0 Hz, 2H). HPLC (Condition A): Rt 2.47 min (purity 99.6%). MS (ESI+): 408.4.

Workup

  1. temperaturethen heated at 100° C
  2. temperaturethe reaction mixture was heated again at 100° C
  3. customReaction mixture
  4. temperaturewas then cooled down to RT
  5. customquenched with water
  6. extractionextracted with DCM (three times)
  7. washCombined organic phases were washed with water, brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting oil was purified by autopreparative LC/MS

Sources & evidence

ORD record
ord-7b87731a01b5487cb83913d7e3108ba4
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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