Methylamine → Dimethyl 2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

HRID 11315

Reaction equation

HRID 11315 reaction equation
CN.[CH3:3][O:4][C:5]([C:7]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:11]([C:20]([O:22][CH3:23])=[O:21])=[C:10]([CH3:24])[NH:9][C:8]=1[CH2:25][O:26][CH2:27][CH2:28][N:29]1C(=O)C2C(=CC=CC=2)C1=O)=[O:6]>O>[CH3:3][O:4][C:5]([C:7]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:11]([C:20]([O:22][CH3:23])=[O:21])=[C:10]([CH3:24])[NH:9][C:8]=1[CH2:25][O:26][CH2:27][CH2:28][NH2:29])=[O:6]

Participants

4

Reactant 2

HCID 6329MethylamineHCID 112609924-(2-Chlorophenyl)-2-[[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy]methyl]-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic Acid 3,5-Dimethyl Ester

Product 1

HCID 11200267Dimethyl 2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of methylamine (40 wt % in water, 125 mL, 1.45 mol) at ambient temperature was added 4-(2-chloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester (dimethylamlodipine phthalimide) (4, 6.30 g, 12.0 mmol). The reaction mixture was stirred at ambient temperature for 18 hours, then diluted with water (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with saturated brine (100 mL), dried over MgSO4 and concentrated under reduced pressure to give 5 a yellow oil (4.0 g, 84% yield, 90% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.15 (m, 1H); 7.02–7.00 (m, 3H); 4.43 (m, 1H); 4.04 (s, 2H); 3.76 (singlets, 6H total); 3.63 (m, 2H); 2.82 (m, 2H); 1.71 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. washThe combined organic extracts were washed with saturated brine (100 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customto give 5 a yellow oil (4.0 g, 84% yield, 90% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.15 (m, 1H); 7.02–7.00 (m, 3H); 4.43 (m, 1H); 4.04 (s, 2H); 3.76 (singlets, 6H total); 3.63 (m, 2H); 2.82 (m, 2H); 1.71 (s, 3H)

Sources & evidence

ORD record
ord-86bb6c1c56cf4becacfd08467622ce3d
Source dataset
uspto-grants-2006_08
Patent number
US07098211B2

Linked notes

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