Sodium hydride → HCID 21099461, compound

HRID 2376945Notes

Reaction equation

HRID 2376945 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].[H-].[Na+].[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1/[CH:18]=[CH:19]/[C:20]1[CH:25]=[CH:24][C:23]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2F)(=[O:28])=[O:27])=[CH:22][N:21]=1>CN(C)C=O.C(OCC)(=O)C>[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1/[CH:18]=[CH:19]/[C:20]1[CH:25]=[CH:24][C:23]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[O:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])(=[O:28])=[O:27])=[CH:22][N:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 766463-(Dimethylamino)-1-propanolHCID 21099465HCID 21099465, compound

Product 1

HCID 21099461HCID 21099461, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3-(dimethylamino)-1-propanol (17 μL, 0.14 mmol) was dissolved in N,N-dimethylformamide (1 mL) and sodium hydride (60% dispersion in mineral oil; 6 mg, 0.14 mmol) added. After stirring at room temperature under nitrogen for 10 minutes, a solution of 2-[(E)-2-(2,4-difluorophenyl)vinyl]-5-[(2-fluorophenyl)sulfonyl]pyridine (Example 1, 50 mg, 0.13 mmol) in N,N-dimethylformamide (1 mL) was added and the reaction stirred at room temperature under nitrogen for 3.5 days. The reaction was diluted with ethyl acetate and washed with water (×4) and brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 5% methanol/0.5% ammonia/dichloromethane, to give the title compound which was dissolved in ethyl acetate and treated with ethereal HCl to give the hydrochloride salt (42 mg, 66%). δH (400 MHz, MeOD): 9.10 (1H, d, J=2.2 Hz), 8.29 (1H, dd, J=2.3, 8.4 Hz), 8.12 (1H, dd, J=1.6, 7.9 Hz), 7.98 (1H, d, J=16.2 Hz), 7.83 (2H, q, J=7.9 Hz), 7.75-7.67 (1H, m), 7.38 (1H, d, J=16.3 Hz), 7.23 (1H, t, J=7.7 Hz), 7.18 (1H, d, J=8.3 Hz), 7.08-7.02 (2H, m), 4.22 (2H, t, J=5.7 Hz), 3.40 (2H, t, J=7.8 Hz), 2.97 (6H, s), 2.28-2.22 (2H, m); m/z (ES+) 459 [MH+].

Workup

  1. stirringthe reaction stirred at room temperature under nitrogen for 3.5 days
  2. washwashed with water (×4) and brine
  3. dry with materialdried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was purified by flash column chromatography on silica
  6. washeluting with 5% methanol/0.5% ammonia/dichloromethane

Sources & evidence

ORD record
ord-f720095279dc4a2db9993c2f55f67240
Source dataset
uspto-grants-2008_12
Patent number
US07468393B2

Reaction notes

Loading…