Triethylamine → 5,6-dimethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 2064208Notes

Reaction equation

HRID 2064208 reaction equation
[CH3:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.C(N(CC)CC)C.[O:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH4-].C([BH3-])#N.[Na+]>ClCCl.CO>[CH3:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:11][CH2:12][N:13]([CH:29]4[CH2:30][CH2:31][O:26][CH2:27][CH2:28]4)[CH2:14][CH2:15]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 28123Borohydride2×HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 204466955,6-dimethyl-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

Product 1

HCID 160710195,6-dimethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

5,6-Dimethyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D32) (330 mg, 0.6 mmol) as suspension in dichloromethane (10 ml) was treated under argon at room temperature with triethylamine (4.2 mmol, 425 mg, 7 eq) and tetrahydro-4H-pyran-4-one (4.2 mmol, 420 mg, 7 eq). Then sodium triacetoxyborohydride (4.2 mmol, 890 mg, 7 eq) was added and the mixture was stirred overnight. Then 7 eq of fresh borohydride and the ketone were added again and stirred for 2 h 15 min. Methanol (3 mL) was added and stirred for 2 h. 7 eq of borohydride and the ketone were added again and stirred for 3.5 h. Then sodium cyanoborohydride (3 mmol, 188 mg, 5 eq) was added and the mixture was allowed to stand overnight. The mixture was loaded on an SCX cartridge, washed with methanol and eluted with 2M ammonia in methanol and dichloromethane. The eluate was concentrated under reduced pressure and chromatographed to give 5,6-dimethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one as a white solid, which was transformed into the corresponding HCl salt. M+H=330.10,

Workup

  1. stirringstirred for 2 h 15 min
  2. stirringstirred for 2 h
  3. stirringstirred for 3.5 h
  4. waitto stand overnight
  5. washwashed with methanol
  6. washeluted with 2M ammonia in methanol and dichloromethane
  7. concentrationThe eluate was concentrated under reduced pressure
  8. customchromatographed

Sources & evidence

ORD record
ord-bb9e09856a65474695bd08e69807c338
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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