2,4-Dimethylnicotinaldehyde → 4-chloro-N-{5-chloro-2-[(2,4-dimethyl-pyridin-3-yl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 418999Notes

Reaction equation

HRID 418999 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]Br)(C)C.[CH3:32][C:33]1[C:38]([CH:39]=[O:40])=[C:37]([CH3:41])[CH:36]=[CH:35][N:34]=1>C1COCC1.[Cl-].[NH4+]>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([N:8]([C:7]2[C:2]([CH:39]([C:38]3[C:33]([CH3:32])=[N:34][CH:35]=[CH:36][C:37]=3[CH3:41])[OH:40])=[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

6

Reactant 3

HCID 104417552,4-DimethylnicotinaldehydeHCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418365HCID 178418365, compound

Product 1

HCID 579424994-chloro-N-{5-chloro-2-[(2,4-dimethyl-pyridin-3-yl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-20 °C

Procedure

N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (0.494 g, 1 mmol) placed in a 10 mL round bottom flask under nitrogen atmosphere was dissolved in anhydrous THF (5 mL). The solution was cooled to −20° C. The magnetically stirring solution was treated with solution of 2.0 M isopropylmagnesium bromide in THF (1.05 mL, 2.1 mmol) drop wise and after the addition was complete the reaction mixture was allowed to warm to 0° C. and maintained at this temperature for 1 h. The resulting deep purple solution was cooled to −20° C. and treated with a solution of 2,4-dimethyl-pyridine-3-carbaldehyde (0.28 g, 2.1 mmol) in THF (2 mL). The mixture was allowed to warm to room temperature and stirred at room temperature over night. After diluting with saturated ammonium chloride solution (10 mL) the product was extracted with ethyl acetate (3×25 mL). The combined organic extract was concentrated and product purified by flash chromatography on silica gel column (10-30% ethyl acetate in hexanes). Product containing fractions were combined and the solvent evaporated to afford 0.33 g of 4-chloro-N-{5-chloro-2-[(2,4-dimethyl-pyridin-3-yl)-hydroxy-methyl]-pyridin-3-yl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide as an off white solid. MS: (M+H)/z=550.

Workup

  1. additionafter the addition
  2. temperatureto warm to 0° C.
  3. temperaturemaintained at this temperature for 1 h
  4. temperatureThe resulting deep purple solution was cooled to −20° C.
  5. temperatureto warm to room temperature
  6. extractionwas extracted with ethyl acetate (3×25 mL)
  7. extractionThe combined organic extract
  8. concentrationwas concentrated
  9. customproduct purified by flash chromatography on silica gel column (10-30% ethyl acetate in hexanes)
  10. additionProduct containing fractions
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-5d4c4d1aaf1b4ef98b9b995c33786219
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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