Hydrochloric Acid → 4-tert-Butyl-N-[5-chloro-2-(2-fluoro-benzoyl)-pyridin-3-yl]-benzenesulfonamide

HRID 419010Notes

Reaction equation

HRID 419010 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.[F:26][C:27]1[CH:38]=[CH:37][CH:36]=[CH:35][C:28]=1[C:29](N(OC)C)=[O:30].Cl.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](=[O:30])[C:28]3[CH:35]=[CH:36][CH:37]=[CH:38][C:27]=3[F:26])=[N:3][CH:4]=[C:5]([Cl:25])[CH:6]=2)(=[O:11])=[O:10])=[CH:13][CH:14]=1)([CH3:19])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 183575562-fluoro-N-methoxy-N-methylbenzamideHCID 57942088N-(2-bromo-5-chloro-pyridin-3-yl)-4-tert-butyl-N-methoxymethyl-benzenesulfonamide

Product 1

HCID 579424074-tert-Butyl-N-[5-chloro-2-(2-fluoro-benzoyl)-pyridin-3-yl]-benzenesulfonamideYield 0.1%

Reagents, catalysts & solvents 1

HCID 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 2-fluoro-N-methoxy-N-methyl-benzamide (140 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 sulfonamide was finally purified via preparatory TLC (20% EtOAc/hexanes) and recrystallization from MeCN/H2O to afford 98 mg of the title compound: 1H NMR (400 MHz, CDCl3) δ 10.6 (s, 1H), 8.3 (d, 1H), 8.2 (d, 1H), 7.74 (d, 2H), 7.6 (d, 1H), 7.5 (d, 1H), 7.43 (d, 2H), 7.42-7.37 (m, 2H), 1.26 (s, 9H); MS (ES) M+H expect 447.1, found 447.5.

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 sulfonamide was finally purified via preparatory TLC (20% EtOAc/hexanes) and recrystallization from MeCN/H2O

Sources & evidence

ORD record
ord-8dd29c89b20c4d05a884e18eaffc70ed
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

Loading…