Ethanol → HCID 69480274, compound

HRID 2364440Notes

Reaction equation

HRID 2364440 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([NH:20][CH2:21][CH2:22][N:23]([CH3:34])[C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:13][CH:14]=2)=[CH:4][CH:3]=1.C([CH:37]([C:41](Cl)=[O:42])[C:38](Cl)=[O:39])C.[CH3:44][CH2:45][OH:46]>ClCCCl>[CH2:45]([O:46][C:41](=[O:42])[CH2:37][C:38]([N:20]([CH2:21][CH2:22][N:23]([CH3:34])[C:24]([O:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:25])[C:11]1[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:13][CH:14]=[C:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH:10]=1)=[O:39])[CH3:44]

Participants

5

Reactant 3

HCID 702EthanolHCID 109209242-Ethylpropanedioyl dichloride2×HCID 69482688HCID 69482688, compound

Product 1

HCID 69480274HCID 69480274, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of ethyl 5-[(4-fluorophenyl)methyl]-3-{[2-(methyl {[(phenylmethyl)oxy]carbonyl}amino)ethyl]amino}-2-pyridinecarboxylate (1.62 g, 3.5 mmol) and ethyl malonyl chloride (1.24 mL, 8.7 mmol) in DCE (50 mL) was heated under nitrogen at reflux for 2 hrs. An additional 0.5 mL of the ethyl malonyl chloride was added and the reaction was stirred at reflux an additional ½ hour. The mixture was cooled, treated with EtOH (25 mL), and then concentrated in vacuo. The residue was purified on silica gel eluting with a gradient between 0 and 100% EtOAc in CH2Cl2 to provide after combination and concentration in vacuo of pure fractions the product as an yellow viscous oil: 1H NMR (400 MHz, DMSO-d6@90° C.) δ ppm 1.11 (t, J=6.77 Hz, 2 H), 1.28 (t, J=7.14 Hz, 3 H), 2.82 (s, 3 H), 3.03 (s, 3 H), 3.34-3.43 (m, 2 H), 3.96 (d, J=5.85 Hz, 2 H), 4.02-4.07 (m, 4 H), 4.27-4.35 (m, 2 H), 5.02 (s, 2H), 7.08 (t, J=8.87 Hz, 2 H), 7.23-7.34 (m, 7 H), 7.70 (s, 1 H), 8.59 (s, 1 H); ES+ MS: 580 (M+H+).

Workup

  1. temperatureat reflux for 2 hrs
  2. temperatureat reflux an additional ½ hour
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on silica gel eluting with a gradient between 0 and 100% EtOAc in CH2Cl2
  6. customto provide
  7. concentrationafter combination and concentration in vacuo of pure fractions the product as an yellow viscous oil

Sources & evidence

ORD record
ord-06b4cf1d49434d26a4f76fcf5218fc83
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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