Hydrochloric Acid → HCID 66617023, compound

HRID 1892973Notes

Reaction equation

HRID 1892973 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10](S(C2SC(Cl)=CC=2)(=O)=O)[C:11]2[C:19]3[C:14](=[CH:15][C:16]([F:22])=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]#N)[CH:25]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.S1C=CC=C1S(N)(=O)=O.[OH-:50].[Na+].Cl.C[OH:54]>>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([F:22])=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:23][C:24]3[CH:25]=[C:26]([CH:27]=[CH:28][CH:29]=3)[C:30]([OH:54])=[O:50])[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium Hydroxide2×HCID 728812-ThiophenesulfonamideHCID 66663920HCID 66663920, compound

Product 1

HCID 66617023HCID 66617023, compoundYield 65%

Conditions

Temperature
60 °C

Procedure

A solution of 5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(3-cyanophenyl)methyl]-6-fluoro-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 53) (53 mg, 0.08 mmol) in methanol (10 mL) was treated with 2M NaOH solution (1 mL) was heated to 60° C. under nitrogen overnight. More 2M NaOH solution (0.5 mL) was added and the mixture was heated to 71° C. over the weekend. The mixture was allowed to cool to RT and then treated with 2M HCl solution to pH 0. The mixture was extracted with ethyl acetate and the organic solution was washed with 2M HCl, brine, dried (MgSO4) and evaporated to a gum 54 mg. The residue was dissolved in 1:1 MeOH-DMSO 1 mL and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier (Method A) collecting fractions with RT=7.77 min 19% and 8.73 min, 81%). The solvent was evaporated in vacuo from the major fraction (RT=8.73 min) to give 3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-6-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzoic acid (26 mg, 65%), as a white solid: LCMS (System A) RT=1.04 min, ES+ve m/z 496/498 (M+H)+ for carboxylic acid product. The minor component (RT=7.77 min) was evaporated under reduced pressure to give the title compound (6.2 mg, 15%) as a white solid: LCMS (System A) RT=0.97 min, ES+ve m/z 495/497 (M+H)+.

Workup

  1. temperaturethe mixture was heated to 71° C. over the weekend
  2. temperatureto cool to RT
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic solution was washed with 2M HCl, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to a gum 54 mg
  7. dissolutionThe residue was dissolved in 1:1 MeOH-DMSO 1 mL
  8. custompurified by Mass Directed AutoPrep on Sunfire C18 column
  9. customcollecting fractions with RT=7.77 min 19% and 8.73 min, 81%)
  10. customThe solvent was evaporated in vacuo from the major fraction (RT=8.73 min)

Sources & evidence

ORD record
ord-8fed2a7a3fed47e4b81110e34d68896d
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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