Hydrochloric Acid → 4-Tert-butyl-n-[5-chloro-2-(2-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-benzenesulfonamide

HRID 419014Notes

Reaction equation

HRID 419014 reaction equation
Br[C:2]1[C:7]([N:8](COC)[S:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[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.CCOC(C)=O>[C:18]([C:15]1[CH:16]=[CH:17][C:12]([S:9]([NH:8][C:7]2[C:2]([C:29]([C:30]3[C:31]([CH3:36])=[N:32][CH:33]=[CH:34][CH:35]=3)=[O:37])=[N:3][CH:4]=[C:5]([Cl:25])[CH:6]=2)(=[O:10])=[O:11])=[CH:13][CH:14]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 18720602HCID 18720602, compoundHCID 57942088N-(2-bromo-5-chloro-pyridin-3-yl)-4-tert-butyl-N-methoxymethyl-benzenesulfonamide

Product 1

HCID 579421134-Tert-butyl-n-[5-chloro-2-(2-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(2-Bromo-5-chloro-pyridin-3-yl)-4-tert-butyl-N-methoxymethyl-benzenesulfonamide (140 mg, 300 mmol) was placed in a dry 2-neck 10 mL round-bottom flask. The flask was evacuated and purged with nitrogen, followed by the addition of THF (1 mL). The homogeneous mixture was lowered to −5° C. and iPrMgCl (0.33 mL, 2.0 M) was added dropwise. Upon completion of the addition, the reaction was stirred 90 minutes, followed by the slow addition of N-methoxy-2,N-dimethyl-nicotinamide (135 mg, 750 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 (1 mL, 4.0 mmol) and H2O (0.33 mL), and then stirred at 80° C. for two hours. The resultant solution was diluted with EtOAc, washed with water, saturated sodium bicarbonate, and brine; dried with MgSO4, and evaporated employing reduced pressure. The crude residue was subsequently purified via automated flash chromatography to afford the desired sulfonamide: 1H NMR (400 MHz, CDCl3) δ 10.9 (s, 1H), 8.58 (d, 1H), 8.22 (d, 2H), 7.81 (d, 2H), 7.53-7.46 (m, 3H), 7.20-7.14 (m, 1H), 2.30 (s, 3H), 1.31 (s, 9H); MS (ES) M+H expect 444.1, found 444.5.

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen
  3. additionfollowed by the addition of THF (1 mL)
  4. customwas lowered to −5° C.
  5. additioniPrMgCl (0.33 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. washwashed with water, saturated sodium bicarbonate, and brine
  11. dry with materialdried with MgSO4
  12. customevaporated
  13. customThe crude residue was subsequently purified via automated flash chromatography

Sources & evidence

ORD record
ord-afc35a39baca4c5097b45470ed516c18
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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