4-(Methylsulfonyl)aniline hydrochloride → 2-methyl-N-[4-(methylsulfonyl)phenyl]-3-pyridinecarboximidamide

HRID 1166383Notes

Reaction equation

HRID 1166383 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].C([Al](CC)CC)C.[C:20]([C:22]1[C:23]([CH3:28])=[N:24][CH:25]=[CH:26][CH:27]=1)#[N:21]>ClC(Cl)C>[CH3:28][C:23]1[C:22]([C:20](=[NH:21])[NH:10][C:9]2[CH:11]=[CH:12][C:6]([S:3]([CH3:2])(=[O:4])=[O:5])=[CH:7][CH:8]=2)=[CH:27][CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 27351804-(Methylsulfonyl)aniline hydrochlorideHCID 47383082-Methylpyridine-3-carbonitrileHCID 16682930Triethylaluminum

Product 1

HCID 1784326842-methyl-N-[4-(methylsulfonyl)phenyl]-3-pyridinecarboximidamideYield 60%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

To a suspension of 4-(methylsulfonyl)aniline hydrochloride (6.85 g, 0.040 mol) in dichloroethane (400 mL) was added triethylaluminum (1.9M solution in toluene, 32.0 mL, 60 mmol) over 15 minutes at 0° C. The reaction mixture was warmed to room temperature and stirred for 2 hours. A solution of 3-cyano-2-methylpyridine, from step 2, in 70 mL of dichloroethane was added over 10 minutes and the mixture was stirred at 75° C. for 16 hours. The reaction mixture was cooled to room temperature and treated with 50 g of silica gel. The mixture was stirred for 30 minutes and filtered. The filtrate and washings were concentrated under reduced pressure and the residue was washed with ether to give 7.3 g of crude 2-methyl-N-[4-(methylsulfonyl)phenyl]-3-pyridinecarboximidamide (60%). To a mixture of the above crude amidine (7.0 g, 0.024 mol) and sodium bicarbonate (4.0 g, 0.048 mol) in isopropanol (350 mL) was added 3-bromo-1,1,1-trifluoroacetone (6.9 g, 0.036 mol) rapidly at room temperature. After heating the reaction mixture at 75-80° C. for 16 hours, the solvent was removed and the residue was partitioned between water and methylene chloride. The organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (ethyl acetate/acetone, 98:2) to give 4.02 g of pure 2-methyl-3-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine as a yellow solid (25%): mp (DSC) 237-239° C. Anal. Calc'd. for C17H16F3N3O3S: C, 51.12, H, 4.04, N, 10.52, S, 8.03. Found: C, 50.92, H, 4.12, N, 10.04, S, 7.83.

Workup

  1. stirringthe mixture was stirred at 75° C. for 16 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiontreated with 50 g of silica gel
  4. stirringThe mixture was stirred for 30 minutes
  5. filtrationfiltered
  6. concentrationThe filtrate and washings were concentrated under reduced pressure
  7. washthe residue was washed with ether

Sources & evidence

ORD record
ord-b2d2b2f524ca4bcda73d1a51a07367ee
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

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