Hydrochloric Acid → N-[5-chloro-2-(2-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-4-isopropoxy-benzenesulfonamide

HRID 1898025Notes

Reaction equation

HRID 1898025 reaction equation
Br[C:2]1[C:7]([N:8](COC)[S:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:25])=[CH:4][N:3]=1.CON(C)[C:29](=[O:37])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][C:31]=1[CH3:36].Cl.O1CCOCC1>O>[Cl:25][C:5]1[CH:6]=[C:7]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH:19]([CH3:20])[CH3:21])=[CH:16][CH:17]=2)(=[O:10])=[O:11])[C:2]([C:29]([C:30]2[C:31]([CH3:36])=[N:32][CH:33]=[CH:34][CH:35]=2)=[O:37])=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 18720602HCID 18720602, compoundHCID 57942115N-(2-bromo-5-chloro-pyridin-3-yl)-4-isopropoxy-N-methoxymethyl-benzenesulfonamide

Product 1

HCID 57942218N-[5-chloro-2-(2-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-4-isopropoxy-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N-(2-bromo-5-chloro-pyridin-3-yl)-4-isopropoxy-N-methoxymethyl-benzenesulfonamide (592 mg, 1.32 mmol) was placed in a dry 25 mL round-bottom flask. The flask was evacuated and purged with nitrogen, followed by the addition of THF (5 mL). The homogeneous mixture was lowered to −5° C. and iPrMgCl (1.72 mL, 2.0 M) was added dropwise. Upon completion of the addition, the reaction was stirred 60 minutes, followed by the addition of N-methoxy-2,N-dimethyl-nicotinamide (379 mg, 2.11 mmol). The reaction was stirred overnight, during which the ice-bath warmed to room temperature. The following day, the reaction was quenched with a small quantity of MeOH and the solvents evaporated in vacuo. The residue was subsequently treated with 4.0 M HCl in dioxane (6 mL, 24.0 mmol) and H2O (6.0 mL), and then stirred at 80° C. for two hours. The resultant solution was concentrated in vacuo and saturated sodium bicarbonate was added to adjust to neutral pH. The solution was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude sulfonamide was finally purified via automated flash chromatography to afford the title compound: 1H NMR (400 MHz, CDCl3) δ 10.90 (s, 1H), 8.58 (d, 1H), 8.17 (m, 2H), 7.80 (d, 2H), 7.49 (d, 1H), 7.16 (m, 1H), 6.89 (d, 2H), 4.57 (sep, 1H), 2.34 (s, 3H), 1.33 (d, 6H); MS (ES) M+H expect 445.9. found 446.1.

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen
  3. additionfollowed by the addition of THF (5 mL)
  4. customwas lowered to −5° C.
  5. additioniPrMgCl (1.72 mL, 2.0 M) was added dropwise
  6. additionUpon completion of the addition
  7. customThe following day, the reaction was quenched with a small quantity of MeOH
  8. customthe solvents evaporated in vacuo
  9. stirringstirred at 80° C. for two hours
  10. concentrationThe resultant solution was concentrated in vacuo and saturated sodium bicarbonate
  11. additionwas added
  12. extractionThe solution was extracted with ethyl acetate
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe crude sulfonamide was finally purified via automated flash chromatography

Sources & evidence

ORD record
ord-030f347256d9430ea9186baa023e2e5c
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

Loading…