Ethyl Acetate → N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide

HRID 632986Notes

Reaction equation

HRID 632986 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[N:8]=[C:7]([CH3:9])[C:6]([C:10](Cl)=[O:11])=[CH:5][CH:4]=1.[Cl:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.CCOC(C)=O>C1COCC1>[Cl:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:10]([C:6]2[C:7]([CH3:9])=[N:8][C:3]([C:2]([F:14])([F:13])[F:1])=[CH:4][CH:5]=2)=[O:11])=[CH:18][C:17]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 27756752-Methyl-6-(trifluoromethyl)nicotinoyl chlorideHCID 401519254-Chloro-3-(pyridin-2-yl)aniline

Product 1

HCID 44626323N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamideYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

6-(trifluoromethyl)-2-methylpyridine-3-carbonyl chloride (1.68 g, 7.51 mmol) in 3 mL THF was added dropwise to a solution of 4-chloro-3-(pyridine-2-yl)aniline (1.21 g, 5.93 mmol) in THF (15 mL) at 0° C. The solution was stirred for 10 min., poured into EtOAc and washed with saturated aq. NaHCO3 (2×), and brine. The organics were dried (Na2SO4) and concentrated. The crude product was suspended in iPrOAc/Et2O (10 mL, 1:1), stirred at 0° C. for ½ hr, and collected by suction filtration to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide (2.04 g, 5.21 mmol, 88% yield) as a white solid: TLC Rf=0.28 (35% EtOAc/Hex); 1H NMR (CDCl3, 400 MHz) δ 8.88 (bs, 1H), 8.41 (d, 1H), 7.96 (dd, 1H), 7.74 (m, 4H), 7.52 (d, 1H), 7.22 (m, 1H), 2.75 (s, 3H); MS (Q1) 392 (M)+.

Workup

  1. washwashed with saturated aq. NaHCO3 (2×), and brine
  2. dry with materialThe organics were dried (Na2SO4)
  3. concentrationconcentrated
  4. stirringstirred at 0° C. for ½ hr
  5. filtrationcollected by suction filtration

Sources & evidence

ORD record
ord-4d8269e1002644f0a3839c7139316511
Source dataset
uspto-grants-2016_04
Patent number
US09321761B2

Reaction notes

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