1,2-Dichloroethane → N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamide

HRID 1908863Notes

Reaction equation

HRID 1908863 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9](O)=[O:10])[CH:6]=[C:5]([CH3:12])[N:4]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)C(C)C)C.Cl.Cl.[CH2:38]([O:40][C:41]([O:55][CH2:56][CH3:57])([C:44]1[CH:49]=[C:48]([CH3:50])[N:47]=[C:46]([CH2:51][CH:52]([CH3:54])[CH3:53])[CH:45]=1)[CH2:42][NH2:43])[CH3:39]>CN(C=O)C.CC(=O)OCC>[CH2:56]([O:55][C:41]([O:40][CH2:38][CH3:39])([C:44]1[CH:49]=[C:48]([CH3:50])[N:47]=[C:46]([CH2:51][CH:52]([CH3:53])[CH3:54])[CH:45]=1)[CH2:42][NH:43][C:9](=[O:10])[C:7]1[CH:6]=[C:5]([CH3:12])[N:4]=[C:3]([CH3:2])[CH:8]=1)[CH3:57]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 533934312,6-Dimethylisonicotinic acid hydrochlorideHCID 670269622,2-Diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethylamine dihydrochloride

Product 1

HCID 67027093N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamideYield 126.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,6-dimethyl-4-pyridine carboxylic acid hydrochloride (159 mg, 0.849 mmol) in DMF (6 mL), EDC (244 mg, 1.27 mmol) and HOBt (172 mg, 1.27 mmol) is added. The mixture is stirred at rt for 15 min before ethyl diisopropylamine (439 mg, 3.37 mmol) and a solution of 2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethylamine dihydrochloride (300 mg, 0.849 mmol) in DMF (0.5 mL) is added. The mixture is stirred at rt for 4 h, diluted with EA (30 mL), and washed with sat. aq. NaHCO3 (15 mL) and brine (15 mL). The org. extract is dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC plates with DCM containing 5% of methanol to give N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamide (444 mg) as a colourless resin; LC-MS: tR=0.89*, [M+1]+=414.11; 1H NMR (CDCl3): δ 0.91 (d, J=6.5 Hz, 6H), 1.26 (t, J=6.8 Hz, 6H), 2.01-2.13 (m, 1H), 2.55 (s, 6H), 2.59 (s, 3H), 2.67 (d, J=7.3 Hz, 2H), 3.40-3.49 (m, 2H), 3.52-3.61 (m, 2H), 3.86 (d, J=5.5 Hz, 2H), 5.80 (s br, 1H), 7.04 (s, 2H), 7.10 (s, 1H), 7.16 (s, 1H).

Workup

  1. washwashed with sat. aq. NaHCO3 (15 mL) and brine (15 mL)
  2. extractionextract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-c69f3a76de044be0870fd8a4d1661bd0
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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