3-Butyn-2-amine, 2-methyl- → (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

HRID 896091Notes

Reaction equation

HRID 896091 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:25])=[C:6]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)=[O:9])[CH:7]=1.NC(C)(C)C#C>CCN(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:25])=[C:6]([CH:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)[OH:9])[CH:7]=1

Participants

6

Reactant 2

HCID 763193-Butyn-2-amine, 2-methyl-2×HCID 22349591(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Product 1

HCID 22349578(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8471TriethylamineSolvent

Procedure

(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone (1.5 g; 3.5 mmol) is dissolved in NEt3 (110 ml), 3-amino-3-methyl-1-butyne (1.7 ml; 15.9 mmol), CuI (200 mg; 1 mmol), PdCl2(PPh3)2 (250 mg; 0.35 mmol) added and refluxed for 45 min. Since only small amount of product is formed, more PdCl2(PPh3)2 (500 mg; 0.7 mmol), CuI (500 mg; 2.5 mmol) and 3-amino-3-methyl-1-butyne (2 ml; 18.7 mmol) is added and refluxing continued for 2.5 hours. The reaction mixture is decanted, the solvent evaporated and the residue purified by chromatography (SiO2; toluene/ethanol/NH3conc 95/5/0.2) to yield the title compound as slightly colored foam (730 mg; 48%).

Workup

  1. temperaturerefluxed for 45 min
  2. customSince only small amount of product is formed
  3. temperaturerefluxing
  4. customThe reaction mixture is decanted
  5. customthe solvent evaporated
  6. customthe residue purified by chromatography (SiO2; toluene/ethanol/NH3conc 95/5/0.2)

Sources & evidence

ORD record
ord-ba33644dc0524c5699d2ada5985d8904
Source dataset
uspto-grants-2005_07
Patent number
US06919336B2

Reaction notes

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