Sodium Carbonate → (+/-)-1,3-dihydro-1-(1-{1-[1-(2-pyrazinyl)-1-ethyl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-one

HRID 2294938Notes

Reaction equation

HRID 2294938 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH:7]([N:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1)[CH3:8].[O:16]=[C:17]1[N:21]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[C:20]2[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=2[NH:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>ClCCl.C(O)(=O)C.ClCCCl>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH:7]([N:9]1[CH2:14][CH2:13][CH:12]([N:25]2[CH2:24][CH2:23][CH:22]([N:21]3[C:20]4[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=4[NH:18][C:17]3=[O:16])[CH2:27][CH2:26]2)[CH2:11][CH2:10]1)[CH3:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 5049666Sodium triacetoxyborohydrideHCID 214716861-(1-(2-Pyrazinyl)-ethyl)-4-oxopiperidine

Product 1

HCID 21471585(+/-)-1,3-dihydro-1-(1-{1-[1-(2-pyrazinyl)-1-ethyl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-oneYield 47.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(1-(2-pyrazinyl)-ethyl)-4-oxopiperidine (37 mg), 4-(2-oxo-1-benzimidazolinyl)piperidine (41 mg), 1,2-dichloroethane (0.75 mL), glacial acetic acid (0.011 mL) and sodium triacetoxyborohydride (60 mg) was stirred at room temperature for 48 h. The reaction mixture was poured into dichloromethane (5 mL) and saturated aqueous Na2CO3 (3 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (2×5 mL) and the combined organic layers dried over Na2SO4 and concentrated under reduced pressure. Purification by preparative TLC, eluting with chloroform; 10% methanol; 1% NH4OH, followed by trituration with diethyl ether gave 35 mg of (±)-1,3-dihydro-1-(1-{1-[1-(2-pyrazinyl)-1-ethyl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-one as a colorless solid: 1H NMR (400 MHz, CDCl3) 9.77 (br s, 1H), 8.69 (d, 1H), 8.54 (dd, 1H), 8.46 (d, 1H), 7.35 (m, 1H), 7.11-7.03 (m, 3H), 4.39 (m, 1H), 3.73 (q, 1H), 3.11 (m, 3H), 2.90 (m, 1H), 2.35-2.55 (m, 5H), 2.11 (m, 2H), 1.92-1.61 (m, 6H), 1.44 (d, 3H). Analysis calculated for C23H30N6O.0.1 H2O.0.3 CHCl3 : C: 63.01, H: 6.92, N: 18.92 found C: 63.07, H: 6.96, N: 18.76.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with dichloromethane (2×5 mL)
  3. dry with materialthe combined organic layers dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by preparative TLC
  6. washeluting with chloroform

Sources & evidence

ORD record
ord-8a0575a1c8fd4fdc84ed6bb98f172348
Source dataset
uspto-grants-1997_11
Patent number
US05691323

Reaction notes

Loading…