Sodium hydride → HCID 24898953, compound

HRID 910257Notes

Reaction equation

HRID 910257 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[C:5]([CH3:9])[N:4]=[CH:3]1.[H-].[Na+].[CH2:12]([C:16]1[N:20]([C:21]2[N:26]=[C:25]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)[C:24]([CH3:32])=[CH:23][N:22]=2)[N:19]=[CH:18][C:17]=1[CH2:33]Cl)[CH2:13][CH2:14][CH3:15]>CN(C=O)C>[CH2:12]([C:16]1[N:20]([C:21]2[N:26]=[C:25]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)[C:24]([CH3:32])=[CH:23][N:22]=2)[N:19]=[CH:18][C:17]=1[CH2:33][O:8][CH2:7][C:6]1[N:2]([CH3:1])[CH:3]=[N:4][C:5]=1[CH3:9])[CH2:13][CH2:14][CH3:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 20568532(1,4-dimethyl-1H-imidazol-5-yl)methanolHCID 60207813HCID 60207813, compound

Product 1

HCID 24898953HCID 24898953, compoundYield 1.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 20 mL vial was added (1,4-dimethyl-1H-imidazol-5-yl)methanol (32 mg, 0.26 mmol), NaH (10 mg, 60% in oil, 0.12 mmol) and 4 mL of DMF. The reaction mixture was stirred at room temperature for 30 minutes, at which time the reaction was cooled to 0° C., the crude intermediate 2-(5-butyl-4-(chloromethyl)-1H-pyrazol-1-yl)-5-methyl-4-(thiophen-2-yl)pyrimidine (60 mg, 0.17 mmol) was added, warmed to room temperature and stirred for an additional 2 hours. The crude reaction was partitioned between water and EtOAc, the organic layer was concentrated and was purified by reverse phase preparative HPLC to provide 1.4 mg of 24 as a clear film. 1H NMR (400 MHz, MeOD-d3) δ 0.851 (t, J=5.9 Hz, 3H), 1.35 (q, J=5.9 Hz, 2H), 1.57 (t, J=6.2 Hz, 2H), 2.38 (s, 3H), 2.67 (s, 3H), 3.35 (t, J=4.8 Hz, 2H), 3.91 (s, 3H), 4.61 (s, 2H), 4.67 (s, 2H) 7.31 (t, J=3.6 Hz, 1H), 7.76 (s, 1H), 7.78 (d, J=4.1 Hz, 1H), 7.96 (d, J=3.1 Hz, 1H), 8.71 (s, 1H), 8.81 (s, 1H). LCMS (ES+) m/z 437 (M+1).

Workup

  1. temperaturewas cooled to 0° C.
  2. temperaturewarmed to room temperature
  3. stirringstirred for an additional 2 hours
  4. customThe crude reaction
  5. customwas partitioned between water and EtOAc
  6. concentrationthe organic layer was concentrated
  7. customwas purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-36609aa444784fd98421a4c1f242a9df
Source dataset
uspto-grants-2011_09
Patent number
US08022061B2

Reaction notes

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