2-Amino-3-bromo-5-methylpyridine → HCID 58880142, compound

HRID 2060919Notes

Reaction equation

HRID 2060919 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4](I)[CH:3]=1.[Br:11][C:12]1[C:13]([NH2:19])=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=1>CCOCC.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:11][C:12]1[C:13]([NH:19][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=2[O:8][CH3:9])=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=1

Participants

6

Reactant 2

HCID 5193802-Amino-3-bromo-5-methylpyridineHCID 28009784-Chloro-2-iodoanisole

Product 1

HCID 58880142HCID 58880142, compoundYield 84.3%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolvent

Procedure

In a oven dried 50 mL round bottom flask were sequentially added 4-chloro-2-iodo-1-methoxybenzene (1.13 g, 4.2 mmol), 3-bromo-5-methylpyridin-2-amine (945 mg, 5.05 mmol), Pd2(dba)3 (192 mg, 0.21 mmol), xantphos (146 mg, 0.25 mmol) and NatBuO (605 mg, 6.3 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 (10 mL). The heterogeneous mixture was stirred at room temperature for 15 min. and then at 100° C. for 1 h. Finally upon completion of the reaction, it was diluted with ether 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 title compound (1.16 g, 84%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.26 (s, 3H) 3.94 (s, 3H) 6.81 (d, J=8.59 Hz, 1H) 6.93 (dd, J=8.72, 2.65 Hz, 1H) 7.65 (d, J=2.02 Hz, 1H) 7.77 (br. s, 1H) 8.07 (d, J=1.26 Hz, 1H) 8.58 (d, J=2.27 Hz, 1H). [M+H] calc'd for C13H13ClN2O, 326.98; found 327.2.

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 (10 mL)
  7. waitat 100° C. for 1 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-1259ea2423194d44ba8b3fae1ad96369
Source dataset
uspto-grants-2012_10
Patent number
US08278450B2

Reaction notes

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