Pyridine → HCID 57942254, compound

HRID 419018Notes

Reaction equation

HRID 419018 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[O:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:18]([O:21][C:22]1N=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1)([CH3:20])[CH3:19].N1C=CC=C[CH:33]=1>ClCCl>[Cl:8][C:6]1[CH:7]=[C:2]([NH:1][S:28]([C:25]2[CH:26]=[CH:33][C:22]([O:21][CH:18]([CH3:20])[CH3:19])=[CH:23][CH:24]=2)(=[O:30])=[O:29])[C:3]([C:9](=[O:10])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 55279353899424-91-0HCID 57942160HCID 57942160, compound

Product 1

HCID 57942254HCID 57942254, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 25 mL round-bottom flask was charged with (3-amino-5-chloropyridin-2-yl)(3-fluorophenyl)methanone (130 mg, 0.52 mmol), 6-isopropoxypyridine-3-sulfonyl chloride (130 mg, 0.55 mmol), pyridine (2 mL) and dichloromethane (2 mL). The resultant solution was heated to 70° C. and stirred for 15 h. The pyridine was removed in vacuo and THF (5 mL) and 4.0 N NaOH (2 mL) were added. The mixture was stirred at 60° C. for 24 h. The solvent was subsequently removed in vacuo and the residue was diluted with water (5 mL) and the pH was adjusted to 6-7 with 10% HCl. The resultant aqueous solution was extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified through automated normal-phase chromatography to afford N-(5-chloro-2-(3-fluorobenzoyl)pyridin-3-yl)-4-isopropoxybenzenesulfonamide (60 mg, 26%): 1H NMR (400 MHz, CDCl3) δ 10.62 (s, 1H), 8.58 (d, 1H), 8.32 (d, 1H), 8.18 (d, 1H), 7.86 (dd, 1H), 7.60 (dd, 1H), 7.52 (dt, 1H), 7.40 (m, 1H), 7.30 (dd, 1H), 6.60 (d, 1H), 5.30 (sep, 1H), 1.30 (d, 1H); MS (ES) (M++2H) expect 250.0, found 250.1.

Workup

  1. customThe pyridine was removed in vacuo and THF (5 mL) and 4.0 N NaOH (2 mL)
  2. additionwere added
  3. stirringThe mixture was stirred at 60° C. for 24 h
  4. customThe solvent was subsequently removed in vacuo
  5. additionthe residue was diluted with water (5 mL)
  6. extractionThe resultant aqueous solution was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified

Sources & evidence

ORD record
ord-431a5b18b160426394539e291839361f
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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