Toluene → N-(5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotin-amide

HRID 1958140Notes

Reaction equation

HRID 1958140 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]2[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=2)[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].C1(C)C=CC=CC=1.[Cl:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][C:32]=1[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=3)[CH:5]=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:33][C:32]=1[CH3:40]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 67280716N-(5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide

Product 1

HCID 56961331N-(5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotin-amideYield 98.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

In a 25 ml sealed tube N-(5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide (520 mg, 1.38 mmol) was combined with toluene (20 mL). Under argon atmosphere, were added 4-chloro-3-methylphenylboronic acid (471 mg, 2.77 mmol), an aqueous solution of sodium carbonate (2M, 1.38 mL) and Pd(dppf)2Cl2 (30 mg, 0.041 mmol). After two hours at 90° C., the dark re suspension was cooled to room temperature, diluted with ethyl acetate (10 mL), and washed with water (10 mL) and brine (10 mL). The aqueous layer was back-extracted with ethyl acetate (15 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material (760 mg) was purified by flash chromatography (silica gel, 20 g, 20% to 100% ethyl acetate in heptane) to give the title compound as a light brown solid (575 mg, 98%); MS (EI): 422.8 (M+H).

Workup

  1. washwashed with water (10 mL) and brine (10 mL)
  2. extractionThe aqueous layer was back-extracted with ethyl acetate (15 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material (760 mg) was purified by flash chromatography (silica gel, 20 g, 20% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-016c46c745ce43baa0d985a8d7a3a35d
Source dataset
uspto-grants-2013_04
Patent number
US08410107B2

Reaction notes

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