Triethylamine → HCID 16071020, compound

HRID 2064209Notes

Reaction equation

HRID 2064209 reaction equation
[Br: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.[O:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCl>[Br: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:22]4[CH2:23][CH2:24][O:19][CH2:20][CH2:21]4)[CH2:14][CH2:15]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59850173HCID 59850173, compound

Product 1

HCID 16071020HCID 16071020, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-Bromo-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D37) (1.16 mmol, 359 mg) was dissolved in dichloromethane (20 mL) and tetrahydropyran-4-one (8.12 mmol, 7 eq, 813 mg), sodium triacetoxyborohydride (8.12 mmol, 1.72 g, 7 eq) and triethylamine (3.48 mmol, 352 mg, 3 eq, 0.48 ml) added. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with dichloromethane, washed with aqueous NaOH (pH 12), and the product extracted with dichloromethane (×2). The combined organic layers were washed with aqueous NaOH (pH 12), dried (MgSO4) and the solvent removed under reduced pressure to afford the crude product. The product was purified by chromatography, eluting with 12+M, DCM/50% MeOH in DCM, 00%-50%, 8CVs), to afford 5-bromo-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one as a pale yellow solid (0.3 mmol, 111 mg, 26%). This was dissolved in dichloromethane (5 mL) and HCl (1M solution in ether) was added. The mixture was stirred at room temperature for 15 minutes. The solvents were removed under reduced pressure to afford the title compound as a white solid (0.02 mmol, 9 mg, 7%)

Workup

  1. washwashed with aqueous NaOH (pH 12)
  2. extractionthe product extracted with dichloromethane (×2)
  3. washThe combined organic layers were washed with aqueous NaOH (pH 12)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed under reduced pressure
  6. customto afford the crude product
  7. customThe product was purified by chromatography
  8. washeluting with 12+M, DCM/50% MeOH in DCM, 00%-50%

Sources & evidence

ORD record
ord-ed8fa35b41f94a3e9dc9bbe0e0a21a3a
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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