Sodium Hydroxide → N-[2-(2-isobutyl-6-methyl-pyridin-4-yl)-2-oxo-ethyl]-2,6-dimethyl-isonicotinamide

HRID 1908864Notes

Reaction equation

HRID 1908864 reaction equation
C([O:3][C:4](OCC)([C:17]1[CH:22]=[C:21]([CH3:23])[N:20]=[C:19]([CH2:24][CH:25]([CH3:27])[CH3:26])[CH:18]=1)[CH2:5][NH:6][C:7](=[O:16])[C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([CH3:15])[CH:9]=1)C.[OH-].[Na+]>C1COCC1.Cl>[CH2:24]([C:19]1[CH:18]=[C:17]([C:4](=[O:3])[CH2:5][NH:6][C:7](=[O:16])[C:8]2[CH:9]=[C:10]([CH3:15])[N:11]=[C:12]([CH3:14])[CH:13]=2)[CH:22]=[C:21]([CH3:23])[N:20]=1)[CH:25]([CH3:27])[CH3:26]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 67027093N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamide

Product 1

HCID 67027016N-[2-(2-isobutyl-6-methyl-pyridin-4-yl)-2-oxo-ethyl]-2,6-dimethyl-isonicotinamideYield 15%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamide (60 mg, 0.177 mmol) in THF (4 mL), 25% aq. HCl (50 μL) is added and the mixture is stirred at 65° C. for 2 h. Another portion of 25% aq. HCl (50 μL) is added and stirring is continued at 65° C. for 3 h. The mixture is cooled to 0° C., neutralized by adding 1 N aq. NaOH solution and extracted twice with EA. The combined org. extracts are dried over Na2SO4, filtered and concentrated to give crude N-[2-(2-isobutyl-6-methyl-pyridin-4-yl)-2-oxo-ethyl]-2,6-dimethyl-isonicotinamide (48 mg) as an orange oil. Part of this material (22 mg) is purified on prep. TLC plates using DCM containing 10% of methanol to give N-[2-(2-isobutyl-6-methyl-pyridin-4-yl)-2-oxo-ethyl]-2,6-dimethyl-isonicotinamide (9 mg) as a pale yellow oil; LC-MS: tR=0.75*, [M+1]+=330.13; 1H NMR (CDCl3): δ 0.97 (d, J=6.5 Hz, 6H), 2.09-2.21 (m, 1H), 2.64 (s, 6H), 2.67 (s, 3H), 2.75 (d, J=7.3 Hz, 2H), 4.94 (d, J=3.8 Hz, 2H), 7.23 (s br, 1H), 7.38 (s, 2H), 7.42 (s, 1H), 7.49 (s, 1H).

Workup

  1. stirringstirring
  2. waitis continued at 65° C. for 3 h
  3. temperatureThe mixture is cooled to 0° C.
  4. extractionextracted twice with EA
  5. dry with materialextracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude N-[2-(2-isobutyl-6-methyl-pyridin-4-yl)-2-oxo-ethyl]-2,6-dimethyl-isonicotinamide (48 mg) as an orange oil
  9. customPart of this material (22 mg) is purified on prep

Sources & evidence

ORD record
ord-667ad2999e3640349823912b02dc2d92
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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