6-Chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one → 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3-dihydro-benzoimidazol-2-one

HRID 967370Notes

Reaction equation

HRID 967370 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:21][CH:22]3[CH2:24][O:23]3)[N:9]=2)=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]2[NH:33][C:32](=[O:34])[N:31]([CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[C:30]=2[CH:41]=1>CCO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:21][CH:22]([OH:23])[CH2:24][N:38]3[CH2:37][CH2:36][CH:35]([N:31]4[C:30]5[CH:41]=[C:26]([Cl:25])[CH:27]=[CH:28][C:29]=5[NH:33][C:32]4=[O:34])[CH2:40][CH2:39]3)[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 137921086-Chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-oneHCID 222937413-(4-bromo-phenyl)-5-methanesulfonyl-1-oxiranylmethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 102118161-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3-dihydro-benzoimidazol-2-oneYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred solution of 25.0 mg (0.061 mmol) of 3-(4-bromo-phenyl)-5-methanesulfonyl-1-oxiranylmethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine and 19.0 mg (0.073 mmol) of 6-chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one in EtOH (0.5 mL) was heated to 80° C. in a sealed vessel for 16 h. The reaction was cooled and the solvent was removed under reduced pressure. The crude product was purified by column chromatography (silica, 0-5% MeOH/CH2Cl2) to afford 0.025 g (63%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.4. MS (electrospray): m/z calculated for C28H32BrClN6O4S [M++H] 663.11, observed 663.0. 1H NMR (400 MHz, CDCl3): 10.2 (s, 1H), 7.52 and 7.46 (A and B of AA′BB′, J=8.6 Hz, 4H), 7.15 (br d, J=1.5 Hz, 1H), 7.04-6.95 (m, 2H), 4.52 and 4.49 (A and B of AB quartet, Jab=14.5 Hz, 2H), 4.33-4.14 (m, 3H), 4.07-3.97 (m, 1H), 3.74-3.58 (m, 2H), 3.17-2.89 (m, 4H), 2.86 (s, 3H), 2.57-2.30 (m, 5H), 2.20 (t, J=11.1 Hz, 1H), 1.87-1.73 (m, 2H).

Workup

  1. temperatureThe reaction was cooled
  2. customthe solvent was removed under reduced pressure
  3. customThe crude product was purified by column chromatography (silica, 0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7050d74813ba4081bc320cdeee76c40a
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

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