1-Methyl-3-(piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one → (S)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one

HRID 1371011Notes

Reaction equation

HRID 1371011 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][C@@H:25]3[CH2:27][O:26]3)[N:12]=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[C:7]=2[CH2:6]1)(=[O:4])=[O:3].[CH3:28][N:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[C:30]1=[O:44]>CCO.ClC(Cl)C>[OH:26][C@H:25]([CH2:24][N:11]1[C:8]2[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][C:7]=2[C:13]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:23])[F:22])=[CH:18][CH:19]=2)=[N:12]1)[CH2:27][N:41]1[CH2:40][CH2:39][CH:38]([N:31]2[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[N:29]([CH3:28])[C:30]2=[O:44])[CH2:43][CH2:42]1

Participants

5

Reactant 2

HCID 149244491-Methyl-3-(piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 53348235(R)-5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 59071356(S)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-oneYield 86%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of (R)-5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (134 mg, 0.334 mmol) and 1-methyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one (110 mg, 0.476 mmol) in EtOH (0.8 mL) and dichloroethane (0.8 mL) was heated to 80° C. for 18 h. The mixture was then concentrated and the residue purified by column chromatography (silica, 0-50% acetone/CH2Cl2) to give the title compound (134 mg, 86%). TLC (20% acetone/CH2Cl2) Rf=0.3. MS (electrospray): calculated for C30H36F3N6O4S, [M +H]+ 633.24; m/z found, 633.3. 1H NMR (CDCl3, 400 MHz): 7.72 and 7.66 (A and B of M′BB′, Jab=8.3 Hz, 4H), 7.15 (dd, J=7.0, 1.7 Hz, 1H ), 7.08 (m, 2H), 6.98 (dd, J=6.6, 1.8 Hz, 1H), 4.60 and 4.55 (A and B of AB, Jab=14.5 Hz, 2H), 4.34 (m, 1H), 4.23 (dd, J=13.8, 2.8 Hz, 1H), 4.15 (m, 1H), 4.23 (dd, J=13.8, 6.6 Hz, 1H), 3.71 (m, 2H), 3.40 (s, 3H), 3.08 (m, 2H), 2.96 (m, 2H), 2.89 (s, 3H), 2.56-2.36 (m, 4H), 2.23 (d, J=11.6 Hz, 1H), 1.81 (m, 2H).

Workup

  1. concentrationThe mixture was then concentrated
  2. customthe residue purified by column chromatography (silica, 0-50% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-f39ed69346ae4fc2bb82df9e08dd61de
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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