Hydrochloric Acid → HCID 59850191, compound

HRID 2064203Notes

Reaction equation

HRID 2064203 reaction equation
[CH3:1][C:2]1[C:25]([CH3:26])=[CH:24][C:5]2[N:6]([C:10]3[CH2:11][CH2:12][N:13]([C:16]4([C:22]#N)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:14][CH:15]=3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.C[Mg]Br.[Cl-].[NH4+].Cl>O1CCCC1.ClCCl.CCOCC>[CH3:1][C:2]1[C:25]([CH3:26])=[CH:24][C:5]2[N:6]([C:10]3[CH2:11][CH2:12][N:13]([C:16]4([CH3:22])[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)[CH2:14][CH:15]=3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 59850133HCID 59850133, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 59850191HCID 59850191, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 4-[4-(5,6-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-3,6-dihydro-1(2H)-pyridinyl]tetrahydro-2H-pyran-4-carbonitrile (D101) (0.32 mmol, 113 mg) in tetrahydrofuran (10 mL) was treated at room temperature under argon with methyl magnesium bromide (0.96 mmol, 0.32 mL of 3M solution in tetrahydrofuran, 3 eq) dropwise over 2 min. The mixture became a solution and was stirred for 45 min. Then 6 more equivalents of methyl magnesium bromide were added and stirred for 3 h. The mixture was cooled down to 0° C. and 1M aqueous ammonium chloride solution was added until everything was solubilised. Tetrahydrofuran was removed under reduced pressure and the mixture was diluted with water and extracted 3 times with ethyl acetate. The organics were combined, dried and concentrated to give a white solid (0.26 mmol, 89 mg, 81% crude yield). This solid was dissolved in 3 mL of dichloromethane and treated with 1 mL 1M ethereal hydrogen chloride. A yellow gum crashed out of the mixture. More ether was added and the gum turned into crystals upon trituration. The crystals were filtered off and dried to give the title compound as its hydrochloride salt (0.2 mmol, 75 mg, 62% yield) still containing hydrogenated compound (no double C═C bond in the piperidine core). M+H 342.1, 344.1, M−H 340.3.

Workup

  1. stirringstirred for 3 h
  2. customTetrahydrofuran was removed under reduced pressure
  3. additionthe mixture was diluted with water
  4. extractionextracted 3 times with ethyl acetate
  5. customdried
  6. concentrationconcentrated
  7. customto give a white solid (0.26 mmol, 89 mg, 81% crude yield)
  8. filtrationThe crystals were filtered off
  9. customdried

Sources & evidence

ORD record
ord-74e8dcc9fbd0436db462b52879652178
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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