1,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one → 1-[1-(2-Methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl)-piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 2414843Notes

Reaction equation

HRID 2414843 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[O:27]=[C:28]1[N:32]([CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[C:31]2[CH:39]=[CH:40][CH:41]=[CH:42][C:30]=2[NH:29]1>CS(C)=O>[CH3:24][C:21]1[O:22][C:23]2=[C:15]3[C:16](=[CH:17][CH:18]=[C:19]2[N:20]=1)[O:25][CH2:26][CH:13]([CH2:12][N:36]1[CH2:35][CH2:34][CH:33]([N:32]2[C:31]4[CH:39]=[CH:40][CH:41]=[CH:42][C:30]=4[NH:29][C:28]2=[O:27])[CH2:38][CH2:37]1)[O:14]3

Participants

4

Reactant 2

HCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate

Product 1

HCID 102736431-[1-(2-Methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl)-piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
82 °C

Procedure

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.43 g, 1.14 mmole) and 4-(2-keto-1-benzimidazolinyl)-piperidine (0.77 g, 3.54 mmole) were combined in 10 mL of DMSO under nitrogen. This solution was heated to 82° C. under nitrogen for 4 hours. After completion, the reaction was allowed to cool to room temperature and was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over sodium sulfate and concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 1% methanol/methylene chloride to elute 0.4 g of the (S)-enantiomer of the title compound, m.p. 218-220° C.

Workup

  1. temperatureto cool to room temperature
  2. customwas partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. wash1% methanol/methylene chloride to elute 0.4 g of the (S)-enantiomer of the title compound, m.p. 218-220° C.

Sources & evidence

ORD record
ord-609df4b1b85449e18e096324bcfac36f
Source dataset
uspto-grants-2004_11
Patent number
US06815448B2

Reaction notes

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