Dichloromethane → 3-(2-(6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2,2-dimethylpropan-1-amine dihydrochloride

HRID 2035608Notes

Reaction equation

HRID 2035608 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[C:14]([O:21][CH2:22][C:23]([CH3:34])([CH3:33])[CH2:24][NH:25]C(=O)OC(C)(C)C)[CH:15]=[CH:16][CH:17]=4)[N:12]=3)=[N:9][N:10]=2)[CH:7]=1.C(O)(C(F)(F)F)=O.[Cl:42]CCl>>[ClH:42].[ClH:42].[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[C:14]([O:21][CH2:22][C:23]([CH3:34])([CH3:33])[CH2:24][NH2:25])[CH:15]=[CH:16][CH:17]=4)[N:12]=3)=[N:9][N:10]=2)[CH:7]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67230058Tert-butyl 3-(2-(6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2,2-dimethylpropylcarbamate

Product 1

HCID 672346403-(2-(6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2,2-dimethylpropan-1-amine dihydrochlorideYield 41%

Procedure

To a solution of tert-butyl 3-(2-(6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2,2-dimethylpropylcarbamate (0.108 g, 0.205 mmol) in 2 mL dichloromethane was added neat TFA (0.395 mL, 5.13 mmol). The reaction mixture was stirred at ambient temperature for 4 hours, after which it was concentrated. The residue was concentrated twice from dichloromethane/hexanes to give solids, which were dried in vacuo. The solids were dissolved in several drops of methanol and minimal dichloromethane, and this solution was added to a vigorously stirring solution of 20 mL ether and 1.5 mL 2M HCl/ether, causing precipitation. The solids were stirred 5 minutes, then isolated by filtration through a medium glass fitted funnel by pushing the solvent through the funnel with nitrogen pressure, rinsed twice with ether, twice with 1:1 dichloromethane:ether, twice with ether, and dried in vacuo to give the title compound (0.042 g, 0.0841 mmol, 41.0% yield) as a pale yellow powder. MS APCI (+) m/z 426/428 (M+1)(Br isotope) detected.

Workup

  1. concentrationafter which it was concentrated
  2. concentrationThe residue was concentrated twice from dichloromethane/hexanes
  3. customto give solids, which
  4. customwere dried in vacuo
  5. dissolutionThe solids were dissolved in several drops of methanol
  6. additionminimal dichloromethane, and this solution was added to a vigorously stirring solution of 20 mL ether and 1.5 mL 2M HCl/ether
  7. customprecipitation
  8. stirringThe solids were stirred 5 minutes
  9. customisolated by filtration through a medium glass
  10. customfitted funnel
  11. washrinsed twice with ether, twice with 1:1 dichloromethane
  12. dry with materialether, twice with ether, and dried in vacuo

Sources & evidence

ORD record
ord-a51529b432ca4bba9c80ab73ddcbfc8d
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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