Hydrochloric Acid → HCID 86682363, compound

HRID 2283612Notes

Reaction equation

HRID 2283612 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][C:9]=2[O:10][C:11]2[C:16]([Cl:17])=[CH:15][C:14]([S:18]([N:21](CC3C=CC(OC)=CC=3OC)[C:22]3[N:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=3)(=[O:20])=[O:19])=[C:13]([F:40])[CH:12]=2)[CH:5]=[CH:4][N:3]=1.Cl.[CH3:50][C:51]1[CH:56]=[CH:55][C:54]([S:57]([OH:60])(=[O:59])=[O:58])=[CH:53][CH:52]=1>O1CCOCC1.CO>[CH3:50][C:51]1[CH:52]=[CH:53][C:54]([S:57]([OH:60])(=[O:59])=[O:58])=[CH:55][CH:56]=1.[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:44]=[C:43]([C:45]([F:47])([F:48])[F:46])[CH:42]=[CH:41][C:9]=2[O:10][C:11]2[C:16]([Cl:17])=[CH:15][C:14]([S:18]([NH:21][C:22]3[N:23]=[CH:24][C:25]([F:28])=[CH:26][N:27]=3)(=[O:20])=[O:19])=[C:13]([F:40])[CH:12]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 86682364HCID 86682364, compound

Product 1

HCID 86682363HCID 86682363, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

4-[2-(2-Aminopyridin-4-yl)-4-(trifluoromethyl)phenoxy]-5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide (Preparation 20, 2.24 g, 3.16 mmol) was dissolved in 1,4-dioxane (6.0 mL) and a 4.0 M solution of hydrogen chloride in 1,4-dioxane (4.0 mL, 16 mmol) was added. The reaction mixture was stirred for 18 hours then concentrated in vacuo. The residue was partitioned between water and dichloromethane. A large amount of undissolved solid was present. The aqueous phase was adjusted to pH10 with 1N aqueous sodium hydroxide solution, then back to pH3 with citric acid. The mixture was filtered and the solid was set aside. The organic phase was collected and combined with the solid and the solvent removed in vacuo. The residue was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane gradient elution). The resulting residue was then slurried in methanol before 1 equivalent of 4-methylbenzenesulfonic acid was added and the mixture concentrated in vacuo. The residue was dissolved in a minimum amount of hot methanol and filtered while hot. The filtrate was diluted with tert-butyl methyl ether. Crystals formed on standing which were collected by filtration and washed with tert-butyl methyl ether to afford the title compound as a white solid (1.48 g containing 0.5 mol % tert-butyl methyl ether). The solid was dissolved in a minimum amount of boiling methanol, then water was added slowly. Fine crystals formed which were collected by filtration and rinsed with water to afford the title compound as a white powder (1.45 g).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between water and dichloromethane
  3. filtrationThe mixture was filtered
  4. customThe organic phase was collected
  5. customthe solvent removed in vacuo
  6. customThe residue was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane gradient elution)
  7. additionwas added
  8. concentrationthe mixture concentrated in vacuo
  9. dissolutionThe residue was dissolved in a minimum amount of hot methanol
  10. filtrationfiltered while hot
  11. additionThe filtrate was diluted with tert-butyl methyl ether
  12. customCrystals formed on standing which
  13. filtrationwere collected by filtration
  14. washwashed with tert-butyl methyl ether

Sources & evidence

ORD record
ord-26f6b57c03c24e359ba62461a5aadad8
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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