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

HRID 475944Notes

Reaction equation

HRID 475944 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-327ffb9e0af04408a6e17e2743d2b004
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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