N,2-Dimethoxy-N-methylnicotinamide → 4-chloro-N-[5-chloro-2-(2-methoxy-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 419147Notes

Reaction equation

HRID 419147 reaction equation
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[CH3:32][O:33][C:34]1[N:45]=[CH:44][CH:43]=[CH:42][C:35]=1[C:36](N(OC)C)=[O:37]>C1COCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([N:8]([C:7]2[C:2]([C:36]([C:35]3[C:34]([O:33][CH3:32])=[N:45][CH:44]=[CH:43][CH:42]=3)=[O:37])=[N:3][CH:4]=[C:5]([Cl:26])[CH:6]=2)[CH2:23][O:24][CH3:25])(=[O:11])=[O:10])=[CH:13][C:14]=1[C:19]([F:22])([F:21])[F:20]

Participants

5

Reactant 3

HCID 45871212N,2-Dimethoxy-N-methylnicotinamideHCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, compound

Product 1

HCID 579425224-chloro-N-[5-chloro-2-(2-methoxy-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (612 mg, 1.24 mmol) in THF (5 mL) under nitrogen atmosphere at 0° C. was added dropwise isopropylmagnesium chloride (2 M solution in THF, 1.55 mL, 3.1 mmol). The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of 2,N-dimethoxy-N-methyl-nicotinamide (487 mg, 2.48 mmol) in THF (2 mL) at 0° C. The mixture was stirred at room temperature for 6 hours, quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. The obtained residue was purified via column chromatography (SiO2, 50% EtOAc-hexanes) to obtain 4-chloro-N-[5-chloro-2-(2-methoxy-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (200 mg) in 29.2% yield. ESMS m/z (relative intensity): 550 (M+H)+ (100), 571.9 (M+Na)+ (80).

Workup

  1. stirringThe mixture was stirred at room temperature for 6 hours
  2. customquenched with saturated aqueous NH4Cl solution (5 mL)
  3. extractionextracted with EtOAc (2×25 mL)
  4. washThe combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL)
  5. dry with materialdried (anhydrous Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified via column chromatography (SiO2, 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-6aa23778bbd24832a2bb9163a6c9d8ec
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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