Dimethyl Sulfoxide → (5-Fluoro-2-trifluoromethylphenyl)-{4-[5-(5-propyl-1H-imidazol-2-YL)pyridin-2-YL]piperazin-1-YL}methanone

HRID 499182Notes

Reaction equation

HRID 499182 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:40]([F:43])([F:42])[F:41])=[C:16]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[NH:33][CH:34]([CH2:37][CH2:38][CH3:39])[CH2:35][N:36]=4)=[CH:28][N:27]=3)[CH2:22][CH2:21]2)=[O:19])[CH:17]=1.C(N(CC)CC)C>C(Cl)Cl>[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:40]([F:43])([F:41])[F:42])=[C:16]([C:18]([N:20]2[CH2:21][CH2:22][N:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[NH:33][C:34]([CH2:37][CH2:38][CH3:39])=[CH:35][N:36]=4)=[CH:28][N:27]=3)[CH2:24][CH2:25]2)=[O:19])[CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67523309(5-Fluoro-2-trifluoromethylphenyl)-{4-[5-(5-propyl-4,5-dihydro-1H-imidazol-2-YL)pyridin-2-YL]piperazin-1-YL}methanone

Product 1

HCID 67523335(5-Fluoro-2-trifluoromethylphenyl)-{4-[5-(5-propyl-1H-imidazol-2-YL)pyridin-2-YL]piperazin-1-YL}methanoneYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of oxalyl chloride (0.029 g, 0.228 mmol) in CH2Cl2 (1.5 mL) was added dropwise DMSO (0.028 g, 0.358 mmol) at −78° C. under nitrogen. The resulting mixture was stirred for 10 minutes. To this mixture was added dropwise a solution of (5-fluoro-2-trifluoromethylphenyl)-{4-[5-(5-propyl-4,5-dihydro-1H-imidazol-2-yl)pyridin-2-yl]piperazin-1-yl}methanone (0.052 g, 0.112 mmol) in dichloromethane (1.5 mL). The resulting mixture was stirred for 10 minutes followed by the addition of triethylamine (0.056 g, 0.553 mmol). The reaction mixture was stirred at −78° C. for 1 h, and then allowed to warm to ambient temperature and quenched with water. The aqueous phase was extracted with dichloromethane. The combined organic layers were dried over Na2SO4 and then concentrated. The crude product was purified by preparative TLC to afford the title compound in 10% yield (0.005 g). 1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.07 (dd, J=1.0, 9.0 Hz, 1H), 7.75 (dd, J=5.1, 8.8 Hz, 1H), 7.08 (dd, J=2.3, 7.9 Hz, 1H), 6.81 (s, 1H), 6.67 (d, J=9.0 Hz, 1H), 4.01-3.64 (m, 4H), 3.58-3.51 (m, 2H), 3.35-3.27 (m, 2H), 2.64-2.55 (m, 2H), 1.74-1.61 (m, 2H), 0.96 (t, J=7.3 Hz, 3H). MS (ES+) m/z 462 (M+1).

Workup

  1. stirringThe resulting mixture was stirred for 10 minutes
  2. stirringThe reaction mixture was stirred at −78° C. for 1 h
  3. customquenched with water
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-6378cacbeb7742028d233a753be14348
Source dataset
uspto-grants-2010_08
Patent number
US07767677B2

Reaction notes

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