2-Amino-3-bromo-5-methylpyridine → 3-bromo-N-(5-chloro-2-((1-methylpiperidin-4-yl)methoxy)phenyl)-5-methylpyridin-2-amine

HRID 1882251Notes

Reaction equation

HRID 1882251 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[C:4](I)[CH:3]=1.[Br:18][C:19]1[C:20]([NH2:26])=[N:21][CH:22]=[C:23]([CH3:25])[CH:24]=1>CCOC(C)=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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:18][C:19]1[C:20]([NH:26][C:4]2[CH:3]=[C:2]([Cl:1])[CH:16]=[CH:15][C:5]=2[O:6][CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:21][CH:22]=[C:23]([CH3:25])[CH:24]=1

Participants

6

Reactant 2

HCID 5193802-Amino-3-bromo-5-methylpyridineHCID 588801664-((4-Chloro-2-iodophenoxy)methyl)-1-methylpiperidine

Product 1

HCID 588801523-bromo-N-(5-chloro-2-((1-methylpiperidin-4-yl)methoxy)phenyl)-5-methylpyridin-2-amineYield 80%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

In a oven dried 50 mL round bottom flask were sequentially added Compound 173 (620 mg, 1.69 mmol), 3-bromo-5-methylpyridin-2-amine (381 mg, 2.03 mmol), Pd2(dba)3 (77 mg, 0.08 mmol), xantphos (59 mg, 0.10 mmol) and NatBuO (244 mg, 2.53 mmol) at room temperature. The solid materials were kept under vacuum for 5 min. and then refilled with nitrogen. This process was repeated thrice before adding dry, degassed dioxane (8 mL). The heterogeneous mixture was stirred at room temperature for 15 min. and then at 100° C. for 2 h. Finally upon completion of the reaction, it was diluted with EtOAc and filtered through a small pad of silica gel with several washings. All the washings and filtrate concentrated in vacuum and the crude residue was further purified by flash chromatography to provide pure Compound 174 (574 mg, 80%).

Workup

  1. customIn a oven dried 50 mL round bottom flask
  2. customat room temperature
  3. additionrefilled with nitrogen
  4. additionbefore adding
  5. customdry
  6. customdegassed dioxane (8 mL)
  7. waitat 100° C. for 2 h
  8. customFinally upon completion of the reaction, it
  9. filtrationfiltered through a small pad of silica gel with several washings
  10. concentrationAll the washings and filtrate concentrated in vacuum
  11. customthe crude residue was further purified by flash chromatography

Sources & evidence

ORD record
ord-872b6855c77b4d1ab8c445bb2cb64329
Source dataset
uspto-grants-2012_11
Patent number
US08318939B2

Reaction notes

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