4-Methylmorpholine → 3-Ethyl 5-methyl 2-amino-6-methyl-4-(p-tolyl)-1,4-dihydropyridine-3,5-dicarboxylate

HRID 1912527Notes

Reaction equation

HRID 1912527 reaction equation
[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6]=[C:7]([C:12](=O)[CH3:13])[C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.Cl.[NH2:18][C:19]([NH2:26])=[CH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].CN1CCOCC1>C(O)(C)C>[NH2:18][C:19]1[NH:26][C:12]([CH3:13])=[C:7]([C:8]([O:10][CH3:11])=[O:9])[CH:6]([C:5]2[CH:15]=[CH:16][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:20]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 124946853,3-Diamino-acrylic acid ethyl ester hydrochlorideHCID 54176673Methyl 2-(4-methylbenzylidene)-3-oxobutanoate

Product 1

HCID 712091963-Ethyl 5-methyl 2-amino-6-methyl-4-(p-tolyl)-1,4-dihydropyridine-3,5-dicarboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of (E and Z) methyl 2-(4-methylbenzylidene)-3-oxobutanoate (887 mg, 4.06 mmol), ethyl 3,3-diaminoacrylate, hydrochloride (677 mg, 4.06 mmol), and N-methylmorpholine (447 μl, 4.06 mmol) in Isopropanol (7682 μl) was refluxed overnight. The reaction was then concentrated and purified with column chromatography (0-100% EtOAc/Hexane) to afford 3-ethyl 5-methyl 2-amino-6-methyl-4-(p-tolyl)-1,4-dihydropyridine-3,5-dicarboxylate (1.1349 g, 3.44 mmol, 85% yield) as pale yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.15 (d, J=8.0 Hz, 2 H), 7.01 (d, J=7.8 Hz, 2 H), 5.90 (br. s., 2 H), 5.64 (s, 1 H), 4.86 (s, 1 H), 4.07 (q, J=7.1 Hz, 2 H), 3.64 (s, 3 H), 2.32 (s, 3 H), 2.27 (s, 3 H), 1.23 (t, 3 H); LCMS (m/z) ES+=331 (M+1).

Workup

  1. temperaturewas refluxed overnight
  2. concentrationThe reaction was then concentrated
  3. custompurified with column chromatography (0-100% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c78bd4e441ec40c6a0b1736f36695cb8
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

Loading…