Isonicotinoyl chloride hydrochloride → [4-[6-Fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-pyridin-4-yl-methanone

HRID 131229

Reaction equation

HRID 131229 reaction equation
[F:1][C:2]1[C:30]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:29][C:5]2[N:6]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[C:7]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:8][C:4]=2[CH:3]=1.Cl.[C:38](Cl)(=[O:45])[C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1>ClCCl>[F:1][C:2]1[C:30]([N:31]2[CH2:36][CH2:35][N:34]([C:38]([C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[O:45])[CH2:33][CH2:32]2)=[CH:29][C:5]2[N:6]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][C:25]([F:26])([F:27])[F:28])=[CH:22][CH:23]=3)[C:7]([CH2:9][O:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[N:8][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 12262826Isonicotinoyl chloride hydrochlorideHCID 684671025-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole

Product 1

HCID 68463787[4-[6-Fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-pyridin-4-yl-methanoneYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

80 mg of 5-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole (0.16 mmol) and 0.06 ml TEA (0.44 mmol) were dissolved in 1.5 ml dichloromethane and treated with 36 mg isonicotinic acid chloride hydrochloride (0.2 mmol). After 22 h of stirring at rt, the reaction mixture was diluted with dichloromethane, washed with water, saturated sodium bicarbonate and brine, dried with magnesium sulfate, filtered and concentrated in vacuo, leading to 86 mg yellow solid which was purified by column chromatography (9.5 g silicagel, dichloromethane/methanol 24:1). 46 mg product as a light yellow solid (48%) was obtained. MS (ISP) 606.3 (M+H)+.

Workup

  1. washwashed with water, saturated sodium bicarbonate and brine
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customwas purified by column chromatography (9.5 g silicagel, dichloromethane/methanol 24:1)

Sources & evidence

ORD record
ord-6271d692e05a43c0917dada1b431ac04
Source dataset
uspto-grants-2008_06
Patent number
US07384945B2

Linked notes

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