Cesium carbonate → N-(2-bromo-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-4-yl)acetamide

HRID 2402376Notes

Reaction equation

HRID 2402376 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:5]=[C:4]([Br:12])[N:3]=1.[NH2:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:12][C:4]1[CH:5]=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:7]=[C:2]([NH:13][C:14]2[CH:19]=[C:18]([C:20]([F:22])([F:21])[F:23])[CH:17]=[CH:16][N:15]=2)[N:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27783152-Amino-4-(trifluoromethyl)pyridineHCID 86680798HCID 86680798, compound

Product 1

HCID 86680799N-(2-bromo-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-4-yl)acetamideYield 50%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

A microwave tube was charged with a stir bar, N-(2,6-dibromopyridin-4-yl)acetamide (0.95 g, 3.23 mmol), 2-Amino-4-(trifluoromethyl)pyridine (0.576 g, 3.56 mmol), Pd(OAc)2 (0.073 g, 0.323 mmol), Xantphos (0.281 g, 0.485 mmol), and Cs2CO3 (2.106 g, 6.46 mmol). The mixture was vacuum-purged with argon 3 times, then degassed dioxane (6.46 mL) was added. The reaction was sealed and heated to 100° C. for 3 hours, after which time the reaction was cooled to rt, diluted with MeOH (10 mL) and concentrated under reduced pressure. The product was purified by silica gel chromatography using a gradient solvent system of 0-100% EtOAc/Hexanes. The product containing fractions were collected and concentrated to give N-(2-bromo-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-4-yl)acetamide (605 mg, 50%) as a white solid. MS ESI calcd for C13H10BrF3N4O [M+H]+ 375, found 375.

Workup

  1. additionA microwave tube was charged with a stir bar
  2. customThe mixture was vacuum-purged with argon 3 times
  3. additiondegassed dioxane (6.46 mL) was added
  4. customThe reaction was sealed
  5. temperatureafter which time the reaction was cooled to rt
  6. additiondiluted with MeOH (10 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by silica gel chromatography
  9. additionThe product containing fractions
  10. customwere collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-5de074f60a0b4ca2aa82541a1e1f7a66
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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