Beta-Alanine → (E)-3-(6-Bromopyridin-2-yl)-2-cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acrylamide

HRID 2406583Notes

Reaction equation

HRID 2406583 reaction equation
[C:1]([CH2:3][C:4]([NH:6][CH:7]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:13][CH:12]=1)[CH2:8][CH2:9][CH3:10])=[O:5])#[N:2].NCCC(O)=O.O.[Br:32][C:33]1[N:38]=[C:37]([CH:39]=O)[CH:36]=[CH:35][CH:34]=1>C(O)C.C(OCC)(=O)C>[Br:32][C:33]1[N:38]=[C:37](/[CH:39]=[C:3](\[C:1]#[N:2])/[C:4]([NH:6][CH:7]([C:11]2[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:15][CH:16]=2)[CH2:8][CH2:9][CH3:10])=[O:5])[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 239Beta-AlanineHCID 962WaterHCID 27570096-Bromopyridine-2-carbaldehydeHCID 668220192-Cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acetamide

Product 1

HCID 56947930(E)-3-(6-Bromopyridin-2-yl)-2-cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acrylamideYield 80.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 2-cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acetamide (29; 116 mg, 0.35 mmol) in ethanol (2 mL) was added β-alanine (499 mg, 5.6 mmol) and water (2 mL). 6-Bromopicolinaldehyde (260 mg, 1.4 mmol) was added, and the resulting mixture was then stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with sat. aqueous NaHCO3 (2×) and sat. brine, dried over sodium sulfate, and concentrated to a crude solid. Purification by flash silica gel column chromatography, eluting with 5:95 methanol/dichloromethane, afforded 33 (140 mg, 80%) as a thick yellow oil: MS (ES+) m/z=499.1 (M+H)+.

Workup

  1. washwashed with sat. aqueous NaHCO3 (2×) and sat. brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated to a crude solid
  4. customPurification by flash silica gel column chromatography
  5. washeluting with 5:95 methanol/dichloromethane

Sources & evidence

ORD record
ord-81ba66e22f584c509a1c77c924ba0410
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

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