4-Toluenesulfonyl chloride → HCID 118079739, compound

HRID 1485677Notes

Reaction equation

HRID 1485677 reaction equation
[NH2:1][C:2]1[C:3]([NH:9][C@@H:10]([CH3:13])[CH2:11][OH:12])=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>N1C=CC=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][S:20]([C:17]2[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=2)(=[O:22])=[O:21])[C:3]([NH:9][C@@H:10]([CH3:13])[CH2:11][OH:12])=[N:4][CH:5]=1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 93632892HCID 93632892, compound

Product 1

HCID 118079739HCID 118079739, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

A solution of crude (S)-2-(3-amino-5-bromopyridin-2-ylamino)propane-1-ol (5.85 g, 23.77 mmol) dissolved in pyridine (58 mL) was cooled to 0° C. and treated with p-toluenesulfonyl chloride (4.53 g, 23.77 mmol) in one portion. The reaction mixture was stirred at 0° C. After 45 min, the solution was concentrated under reduced pressure. The residue was partitioned between water (60 mL) and ethyl acetate. The ethyl acetate layer was separated and washed with 5% aqueous sodium chloride solution (2×50 mL) and concentrated under reduced pressure. The resulting syrup was dissolved in toluene (100 mL), which was then removed under reduced pressure in an effort to remove residual pyridine. The crude product (10.4 g) was purified by column chromatography on silica gel (eluting with 3:1 dichloromethane-ethyl acetate followed by 2:1 dichloromethane-ethyl acetate and finally 3:2 dichloromethane-ethyl acetate). The product-containing fractions were combined and concentrated. The resulting syrup was dissolved in dichloromethane and the solution diluted with heptane. The mixture was concentrated under reduced pressure to yield (S)-N-(5-bromo-2-(1-hydroxypropan-2-ylamino)pyridin-3-yl)-4-methylbenzenesulfonamide (8.6 g, 21.5 mmol, 90%) as a nearly colorless foam/solid. MS (ESI, pos. ion) m/z 400, 402 [M+1]+.

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. customThe residue was partitioned between water (60 mL) and ethyl acetate
  3. customThe ethyl acetate layer was separated
  4. washwashed with 5% aqueous sodium chloride solution (2×50 mL)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting syrup was dissolved in toluene (100 mL)
  7. customwhich was then removed under reduced pressure in an effort
  8. customto remove residual pyridine
  9. customThe crude product (10.4 g) was purified by column chromatography on silica gel (
  10. washeluting with 3:1 dichloromethane-ethyl acetate
  11. concentrationconcentrated
  12. dissolutionThe resulting syrup was dissolved in dichloromethane
  13. additionthe solution diluted with heptane
  14. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6414ab6546904b97a775f6ddce6330cd
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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