3-Chloro-4-fluorophenyl isocyanate → N-(3-chloro-4-fluorophenyl)-4-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine-1-carboxamide

HRID 603160Notes

Reaction equation

HRID 603160 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH2:17][C@@H:16]([CH2:20][N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH2:15]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[Cl:27][C:28]1[CH:29]=[C:30]([N:35]=[C:36]=[O:37])[CH:31]=[CH:32][C:33]=1[F:34]>C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:29]=[C:30]([NH:35][C:36]([N:24]2[CH2:25][CH2:26][N:21]([CH2:20][C@@H:16]3[CH2:17][CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=4)[CH2:15]3)[CH2:22][CH2:23]2)=[O:37])[CH:31]=[CH:32][C:33]=1[F:34]

Participants

4

Reactant 2

HCID 27346323-Chloro-4-fluorophenyl isocyanate2×HCID 576567341-[((3R)-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine

Product 1

HCID 57656769N-(3-chloro-4-fluorophenyl)-4-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine-1-carboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine (215 mg, 0.57 mmol) in toluene (15 ml) was added 3-chloro-4-fluorophenyl isocyanate (107 mg, 0.62 mmol) and the solution stirred for 18 hours. A further portion of 3-chloro-4-fluorophenyl isocyanate (54.0 mg, 0.31 mmol) was added and stirred for 30 minutes. The reaction was evaporated to an oil and flash column chromatography (silica, CH2Cl2 to 10% MeOH/CH2Cl2) gave N-(3-chloro-4-fluorophenyl)-4-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine-1-carboxamide as a white foam (155 mg, 50%).

Workup

  1. stirringstirred for 30 minutes
  2. customThe reaction was evaporated to an oil and flash column chromatography (silica, CH2Cl2 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-dce14645859d414b858e348fd49e4fcf
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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