Methyl 5-bromo-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate → HCID 66674175, compound

HRID 1510537Notes

Reaction equation

HRID 1510537 reaction equation
F[C:2]1[N:3](C)C(=O)C(NC2C=CC=CC=2)=C(SC)C=1C([O-])=O.Br[C:23]1[C:28](=[O:29])[N:27]([CH3:30])[C:26]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([S:38][CH3:39])=[CH:34][C:33]=2[F:40])=[C:25]([C:41]([O:43][CH3:44])=[O:42])[CH:24]=1>CCOC(C)=O.O.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].[C-]#N.[C-]#N.[Zn+2]>[C:2]([C:23]1[C:28](=[O:29])[N:27]([CH3:30])[C:26]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([S:38][CH3:39])=[CH:34][C:33]=2[F:40])=[C:25]([C:41]([O:43][CH3:44])=[O:42])[CH:24]=1)#[N:3]

Participants

7

Reactant 2

HCID 66673475Methyl 5-bromo-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 866336772-Fluoro-4-(methylthio)phenylamino-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Product 1

HCID 66674175HCID 66674175, compoundYield 29%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Methyl 5-cyano-2-(2-fluoro-4-(methylthio)phenylamino-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate: A mixture of methyl 5-bromo-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.020 g, 0.050 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.046 g, 0.050 mmol), 1,1′-bis(diphenylphosphine)-ferrocene (0.055 g, 0.100 mmol) and Zn(CN)2 (0.006 g, 0.055 mmol) was heated at 120° C. for 2 hours. The reaction mixture was diluted with EtOAc and H2O and the layers separated. The EtOAc layer was washed with saturated NH4Cl and saturated NaCl, dried (Na2SO4) and concentrated under reduced pressure to a dark yellow gum. Purification by flash column chromatography (methylene chloride/EtOAc, 10:1) gave 0.005 g (29%) pure desired product as a yellow solid. MS APCI (−) m/z 346 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.84 (s, 1H), 8.39 (s, 1H), 6.95-7.06 (m, 3H), 3.90 (s, 3H), 3.17 (s, 3H), 2.50 (s, 3H).

Workup

  1. customthe layers separated
  2. washThe EtOAc layer was washed with saturated NH4Cl and saturated NaCl
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure to a dark yellow gum
  5. customPurification by flash column chromatography (methylene chloride/EtOAc, 10:1)

Sources & evidence

ORD record
ord-c2a015b217d8449ea6833d81e0298523
Source dataset
uspto-grants-2012_07
Patent number
US08211920B2

Reaction notes

Loading…