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

HRID 1522337Notes

Reaction equation

HRID 1522337 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)-pyridinone

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 3N 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 (TFA salt), 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-6007642d6f644ae59ace0412406b6e09
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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