Hydrochloric Acid → N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-methanesulfonamide

HRID 472478Notes

Reaction equation

HRID 472478 reaction equation
[Cl:1][C:2]1[N:19]=[C:5]2[C:6]([C:10]#[C:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH2:18])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.C(N(CC)C(C)C)(C)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31].Cl.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>ClCCCl>[Cl:1][C:2]1[N:19]=[C:5]2[C:6]([C:10]#[C:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:18][S:30]([CH3:29])(=[O:32])=[O:31])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 8028TetrahydrofuranHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 674790482-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine

Product 1

HCID 67478887N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
5 °C

Procedure

189 b) To a cooled solution of 2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine (840.0 mg, 3.126 mmol) and N,N-diisopropylethylamine (2.8 mL, 16 mmol) in 1,2-dichloroethane (10 mL) in a ice/water bath at 5° C. was added dropwise methanesulfonyl chloride (0.64 mL, 8.2 mmol). The mixture was stirred 1 hour at 5° C. then at room temperature overnight. 0.1N hydrochloric acid (50 mL) was added to reaction mixture, stirred for 20 minutes then extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water (50 mL) and saturated aqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered and evaporated to a tan solid (1.34 g). To a suspension of the tan solid (1.34 g) from in tetrahydrofuran (10 mL) was added 1.0 M of tetra-n-butylammonium fluoride in tetrahydrofuran (12.50 mL, 12.50 mmol). The mixture was stirred at room temperature for 18 hours. The volatiles were evaporated to yield a viscous oil. Hydrochloric acid (2N, 30 mL) was added to viscous oil and stirred then was extracted with ethyl acetate (3×50 mL). The combined organic layer were dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography (silica gel column 40 g 20%→100% ethyl acetate:hexane). N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-methanesulfonamide was isolated as a tan solid (0.90 g, 83%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.50 (d, J=6.7 Hz, 1H), 7.93 (br s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.71 (d, J=7.3 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.44 (t, J=7.9 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H), 7.11 (t, J=7.1 Hz, 1H), 3.17 (s, 3H). MS=347, 349 (MH)+.

Workup

  1. customat room temperature
  2. customovernight
  3. stirringstirred for 20 minutes
  4. extractionthen extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with water (50 mL) and saturated aqueous sodium chloride (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to a tan solid (1.34 g)
  9. additionTo a suspension of the tan solid (1.34 g) from in tetrahydrofuran (10 mL)
  10. stirringThe mixture was stirred at room temperature for 18 hours
  11. customThe volatiles were evaporated
  12. customto yield a viscous oil
  13. stirringstirred
  14. extractionthen was extracted with ethyl acetate (3×50 mL)
  15. dry with materialThe combined organic layer were dried over magnesium sulfate
  16. filtrationfiltered
  17. customevaporated
  18. customThe residue was purified via chromatography (silica gel column 40 g 20%→100% ethyl acetate:hexane)

Sources & evidence

ORD record
ord-9bc6ec04331140219b1bd47a7dbbdf11
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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