3-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid → 3-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-propionic acid

HRID 1877431Notes

Reaction equation

HRID 1877431 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([C:15]([N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH:27]4[CH2:29][CH2:28]4)[CH2:19][CH2:18]3)=[O:16])=[CH:13][CH:12]=[CH:11][N:10]=2)[C:5]([Cl:30])=[CH:4][C:3]=1[CH:31]=[CH:32][C:33]([OH:35])=[O:34]>C(O)C.[Pd]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([C:15]([N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH:27]4[CH2:28][CH2:29]4)[CH2:19][CH2:18]3)=[O:16])=[CH:13][CH:12]=[CH:11][N:10]=2)[C:5]([Cl:30])=[CH:4][C:3]=1[CH2:31][CH2:32][C:33]([OH:35])=[O:34]

Participants

4

Reactant 1

HCID 673687943-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid

Product 1

HCID 592944963-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-propionic acidYield 33.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a suspension of 3-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid (36 mg, 0.07 mmol, 1.0 equiv; Example 172) in ethanol (1.5 mL) was added palladium on carbon (1.5 mg, 0.001 mmol, 0.02 equiv; 10% Pd/C; [CAS RN 7440-05-3]) and the reaction mixture stirred under an atmosphere of hydrogen (3 bar) at rt over night. Removal of the solvent mixture under reduced pressure, filtration over Celite® and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 auto sampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 12 mg (33%) of the title compound as a slightly yellow viscous oil. MS (ISP): 513.8 [M+H]+.

Workup

  1. customRemoval of the solvent mixture
  2. filtrationunder reduced pressure, filtration
  3. customover Celite® and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  4. customequipped with a Gilson Liquid Handler 215 auto sampler, two Rainin Dynamax® SD-300 pumps
  5. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-8f4dc67e06a844baa394def9cecfa523
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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