Sodium hydride → HCID 86680471, compound

HRID 240461Notes

Reaction equation

HRID 240461 reaction equation
[OH:1][CH:2]1[C:23](=[O:24])[N:5]2[CH2:6][CH2:7][N:8]([S:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)(=[O:12])=[O:11])[CH2:9][CH:4]2[CH2:3]1.[H-].[Na+].Br[C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][N:29]=1>CN(C)C=O>[F:20][C:19]([F:21])([F:22])[C:15]1[CH:14]=[C:13]([S:10]([N:8]2[CH2:7][CH2:6][N:5]3[C:23](=[O:24])[CH:2]([O:1][C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][N:29]=4)[CH2:3][CH:4]3[CH2:9]2)(=[O:12])=[O:11])[CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 86680472HCID 86680472, compound

Product 1

HCID 86680471HCID 86680471, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product from Example 217B (23 mg, 0.063 mmol) in anhydrous N,N-dimethylformamide (0.6 mL) at 0° C. was added sodium hydride (60% suspension in mineral oil, 2.78 mg, 0.069 mmol). The resulting mixture was stirred at 0° C. for 10 minutes, and 2-bromo-5-(trifluoromethyl)pyridine (21 mg, 0.095 mmol) was added. The resulting mixture was allowed to warm to room temperature and stirred for 3 hours. The mixture was partitioned between water and ethyl acetate (3×), and the combined organic layers were concentrated in vacuo and purified on C18 silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid). The title compound was obtained as a colorless solid (22 mg, 68%). 1H NMR (300 MHz, CDCl3) δ ppm 1.58-1.68 (m, 0.5H) 2.03-2.49 (m, 3H) 2.88-3.21 (m, 1.5H) 3.72-4.08 (m, 3H) 4.21 (dd, J=13.39, 3.22 Hz, 1H) 5.50-5.74 (m, 1H) 6.88 (t, J=8.82 Hz, 1H) 7.69-7.85 (m, 2H) 7.88-8.00 (m, 2H) 8.02 (s, 1H) 8.26-8.43 (m, 1H); MS (ESI) m/z 510 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 3 hours
  3. customThe mixture was partitioned between water and ethyl acetate (3×)
  4. concentrationthe combined organic layers were concentrated in vacuo
  5. custompurified on C18 silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-32a1eb9884d9444699dee6e696a93458
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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