Hydrochloric Acid → HCID 69128659, compound

HRID 2064221Notes

Reaction equation

HRID 2064221 reaction equation
[CH3:1][C:2]1[C:3]([C:18]#[N:19])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:6]=2[CH:17]=1.[O:20]1[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[ClH:50]>ClCCl.CO>[ClH:50].[CH3:1][C:2]1[C:3]([C:18]#[N:19])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:12][CH2:13][N:14]([CH:23]4[CH2:24][CH2:25][O:20][CH2:21][CH2:22]4)[CH2:15][CH2:16]3)[C:6]=2[CH:17]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 69128036HCID 69128036, compound

Product 1

HCID 69128659HCID 69128659, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 6-methyl-2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile (D94) (μmol, 256 mg) in dichloromethane (10 mL) was treated with tetrahydro-4H-pyran-4-one (10 mmol, 1.0 g, 10 eq) and triethylamine (3 mmol, 303.6 mg, 3 eq) at room temperature under argon, then sodium triacetoxyborohydride (10 mmol, 2.12 g, 10 eq) was added and the mixture was allowed to stir for 6.5 h and to stand overnight. The mixture was diluted with dichloromethane and treated with aqueous sodium hydroxide so that the pH was maintained around 12. The aqueous phase was extracted with dichloromethane and the organics were combined, washed with an aqueous sodium hydroxide solution (pH ˜12), dried and concentrated under reduced pressure. The residue was purified by chromatography (methanol/dichloromethane) to give a gum which was dissolved in dichloromethane and methanol, treated with hydrogen chloride (in ether, 2M) then concentrated under reduced pressure to give the title compound as its hydrochloride salt-beige solid (0.22 mmol, 83 mg, 22% yield). M+H 341.1.

Workup

  1. waitto stand overnight
  2. temperaturewas maintained around 12
  3. extractionThe aqueous phase was extracted with dichloromethane
  4. washwashed with an aqueous sodium hydroxide solution (pH ˜12)
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography (methanol/dichloromethane)
  8. customto give a gum which
  9. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-d5df922f48cd4556b658fceddc3d84dc
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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