Potassium Hydroxide → HCID 71558160, compound

HRID 2203430Notes

Reaction equation

HRID 2203430 reaction equation
C([NH:5][C:6]1[N:10]2[CH:11]=[C:12]([C:15]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:16]=3[O:17][C:18]3[C:23]([F:24])=[CH:22][C:21]([S:25]([NH:28][C:29]4[S:33][N:32]=[CH:31][N:30]=4)(=[O:27])=[O:26])=[C:20]([F:34])[CH:19]=3)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)(C)(C)C.[OH-].[K+]>ClCCl.FC(F)(F)C(O)=O.CO.O>[NH2:5][C:6]1[N:10]2[CH:11]=[C:12]([C:15]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:16]=3[O:17][C:18]3[C:23]([F:24])=[CH:22][C:21]([S:25]([NH:28][C:29]4[S:33][N:32]=[CH:31][N:30]=4)(=[O:26])=[O:27])=[C:20]([F:34])[CH:19]=3)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1

Participants

7

Reactant 2

HCID 14797Potassium HydroxideHCID 90389172HCID 90389172, compound

Product 1

HCID 71558160HCID 71558160, compoundYield 15%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-(2-(3-(tert-butylamino)imidazo[1,2-a]pyridin-6-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.35 g, 0.47 mmol) in dichloromethane (3 mL) and trifluoroacetic acid (3 mL) was heated at 80° C. for 16 h in a sealed tube. The mixture was allowed to cool to ambient temperature and was concentrated in vacuo. Methanol (30 mL) was added to the residue. The mixture was filtered and the filtrate concentrated in vacuo. The residue obtained was dissolved in methanol (8 mL) and water (8 mL), and potassium hydroxide (0.079 g, 1.4 mmol) was added. The mixture was heated at 60° C. for 4 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was partitioned between dichloromethane (100 mL) and water (10 mL). The aqueous phase was adjusted to pH 7 with 1 N hydrochloric acid and extracted with dichloromethane (2×30 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse-phase HPLC to afford 4-(2-(3-aminoimidazo[1,2-a]pyridin-6-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as an off-white solid in 15% yield (0.037 g): 1H NMR (300 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.13-7.95 (m, 2H), 7.87-7.72 (m, 3H), 7.67-7.52 (m, 3H), 7.29-7.15 (m, 3H), 5.85 (br s, 1H); MS (ES+) m/z 534.8 (M+1), 536.8 (M+1).

Workup

  1. concentrationwas concentrated in vacuo
  2. additionMethanol (30 mL) was added to the residue
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe residue obtained
  6. temperatureThe mixture was heated at 60° C. for 4 h
  7. temperatureto cool to ambient temperature
  8. concentrationconcentrated in vacuo
  9. customThe residue was partitioned between dichloromethane (100 mL) and water (10 mL)
  10. extractionextracted with dichloromethane (2×30 mL)
  11. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-283a9173ff1249918bbc6b324e57b4b9
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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