Hydrochloric Acid → 2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-(3,3-difluoropiperidin-4-yloxy)-6-fluoroquinoline dihydrochloride salt

HRID 876476Notes

Reaction equation

HRID 876476 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:21][CH:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][C:23]4([F:36])[F:35])[CH:14]=[C:15]([F:20])[CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[ClH:37].O1CCOCC1.CCOCC>CO>[ClH:37].[ClH:37].[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:21][CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]4([F:36])[F:35])[CH:14]=[C:15]([F:20])[CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 312751,4-DioxaneHCID 67234219Tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-yloxy)-3,3-difluoropiperidine-1-carboxylate

Product 1

HCID 672344932-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-(3,3-difluoropiperidin-4-yloxy)-6-fluoroquinoline dihydrochloride salt

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-yloxy)-3,3-difluoropiperidine-1-carboxylate (0.072 g, 0.144 mmol) was dissolved in MeOH (0.72 mL) and treated with 4.0 M HCl in dioxane (0.360 mL, 1.44 mmol), then stirred at ambient temperature for 2 hours. The reaction mixture was concentrated in vacuo. The residue was taken up in MeOH and concentrated three times. The residue was chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride. The desired product was dissolved in MeOH (2 mL), treated with 2.0 M HCl in ether (0.809 mL, 1.62 mmol) and concentrated in vacuo. The residue was again dissolve in MeOH and concentrated in vacuo several times, then placed under vacuum to give the desired product as a white solid (27.8 mg). MS APCI (+) m/z 400.3 (M+1) detected.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. concentrationconcentrated three times
  3. customThe residue was chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride
  4. dissolutionThe desired product was dissolved in MeOH (2 mL)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was again dissolve in MeOH
  7. concentrationconcentrated in vacuo several times

Sources & evidence

ORD record
ord-f386d05673094dc2a158f0c5d8682b66
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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