Hydrochloric Acid → 3-(aminomethyl)-4-cyclohexyl-6-methyl-2(1H)-pyridinone

HRID 85533Notes

Reaction equation

HRID 85533 reaction equation
[CH:1]1([C:7]2[CH:12]=[C:11]([CH3:13])[NH:10][C:9](=[O:14])[C:8]=2[C:15]#[N:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+].II.Cl>C1COCC1>[NH2:16][CH2:15][C:8]1[C:9](=[O:14])[NH:10][C:11]([CH3:13])=[CH:12][C:7]=1[CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 807IodineHCID 4311764Sodium borohydrideHCID 152536744-Cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile

Product 1

HCID 671243593-(aminomethyl)-4-cyclohexyl-6-methyl-2(1H)-pyridinoneYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-bath cooled THF (100 mL) solution of the product from step 1 (2 g, 9.26 mmol) were added NaBH4 (0.81 g, 21.3 mmol), and I2 (2.3 g, 9.26 mmol), and the mixture stirred for 30 min. The reaction mixture was then heated at reflux for 3 h, and then allowed to cool to room temperature. After cooling to 0° C., the reaction mixture was acidified by slow addition of 3 N HCl (1 mL). The reaction mixture was concentrated in vacuo and the crude product purified by reverse phase HPLC to give the title compound as a solid (0.5 g, 25%). LCMS E-S (M+H)=221.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.8-11.9 (br s, 1H), 7.80-7.93 (br s, 3H), 6.07 (s, 1H), 3.69 (s, 2H), 2.67-2.75 (m, 1H), 2.17 (s, 3H), 1.58-1.72 (m, 5H), 1.19-1.41 (m, 5H).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 3 h
  3. temperatureAfter cooling to 0° C.
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe crude product purified by reverse phase HPLC

Sources & evidence

ORD record
ord-fac9cf2ecd464b9281d1c683dfc649a4
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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