Sodium hydride → 5-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

HRID 1505700Notes

Reaction equation

HRID 1505700 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+].Cl[CH2:27][CH2:28][CH2:29][O:30][CH3:31]>CN(C=O)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][N:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[N:18][C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=3)=[N:14][CH:15]=2)[CH:23]=[N:22]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1189271-Chloro-3-methoxypropaneHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

Product 1

HCID 729442235-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

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, 130 mg; 0.43 mmol; 1.0 eq.) in dry DMF (1 mL) was added over a suspension of NaH (60% in oil, 21 mg; 0.86 mmol; 2.0 eq.) in dry DMF (1 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 1-chloro-3-methoxypropane (47 mg; 0.43 mmol; 1.0 eq.) in DMF (2 mL). Reaction mixture was then cooled down to RT, quenched with water and extracted with EtOAc (three times). Combined organic phases were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. The resulting solid was dried O/N at 60° C. under reduced pressure to give the title compound a beige powder (165 mg; 75%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 2H), 8.58-8.49 (m, 1H), 8.46 (s, 1H), 8.30-8.17 (m, 2H), 8.17-8.11 (m, 1H), 7.96-7.89 (m, 1H), 7.75-7.68 (m, 1H), 7.51 (t, J=7.8 Hz, 1H), 4.22 (t, J=7.0 Hz, 2H), 3.90 (s, 3H), 3.39-3.30 (m, 2H), 3.25 (s, 3H), 2.15-1.97 (m, 2H). HPLC (Condition A): Rt 3.34 min (purity 97.1%). MS (ESI+): 375.5.

Workup

  1. temperaturethen heated at 100° C
  2. customReaction mixture
  3. temperaturewas then cooled down to RT
  4. customquenched with water
  5. extractionextracted with EtOAc (three times)
  6. washCombined organic phases were washed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting solid was dried O/N at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-55f9c2401fef4908a4809f7fa2a96d7e
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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