Triethylamine → 3-(2-Amino-pyridin-5-yl)-but-2-enoic Acid Methyl Ester

HRID 1394646Notes

Reaction equation

HRID 1394646 reaction equation
[C:1]([O:6][CH3:7])(=[O:5])/[CH:2]=[CH:3]/[CH3:4].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[NH2:37][C:38]1[CH:43]=[CH:42][C:41](Br)=[CH:40][N:39]=1>CN(C=O)C.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:7][O:6][C:1](=[O:5])[CH:2]=[C:3]([C:41]1[CH:40]=[N:39][C:38]([NH2:37])=[CH:43][CH:42]=1)[CH3:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 706222-Amino-5-bromopyridineHCID 80271Tri-o-tolylphosphineHCID 638132Methyl Crotonate

Product 1

HCID 692203773-(2-Amino-pyridin-5-yl)-but-2-enoic Acid Methyl EsterYield 41%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Methyl crotonate (1.35 ml, 12.8 mmol), tris(dibenzylideneacetone)-dipalladium(0) (106 mg, 0.12 mmol), tri-o-tolylphosphine (1.41 g, 4.6 mmol), and triethylamine (3.22 ml, 23.1 mmol) were added to a solution of 2-amino-5-bromo pyridine (2 g, 11.6 mmol) in DMF (25 mL). The reaction mixture was heated to 120° C. in a nitrogen atmosphere overnight, then cooled to ambient temperature and diluted with ethyl acetate (50 mL). The reaction was filtered, then washed with saturated ammonium chloride solution (2×25 mL), and the organic layer dried over MgSO4 and concentrated in vacuo. The residue was then purified by flash column (2% methanol in dichloromethane) to give 3-(6-amino-pyridin-3-yl)-but-2-enoic acid methyl ester as a yellow solid (904.7 mg, 41%). 1H NMR (250 MHz, DMSO): δ 8.22 (d, 1H, J=3.1), 7.68 (dd, 1H, J=7.5, J=3.1), 6.46 (d, 1H, J=7.5), 6.40 (bs, 2H), 6.11 (d, 1H, J=0.62), 3.65 (s, 3H), 2.48 (d, 3H, J=0.62). MS [EI+] 193 (M+H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationThe reaction was filtered
  3. washwashed with saturated ammonium chloride solution (2×25 mL)
  4. dry with materialthe organic layer dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was then purified by flash column (2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a411e60d68e14eeaaa4464aac1cb80df
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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