Stannous chloride dihydrate → Methyl 1-(4-(3-amino-6-bromoquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate

HRID 336888Notes

Reaction equation

HRID 336888 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-])=O)=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]2)=[C:18]([C:32]([F:35])([F:34])[F:33])[CH:17]=1.O.O.[Sn](Cl)Cl.C([O-])(O)=O.[Na+]>O1CCOCC1>[NH2:12][C:6]1[CH:7]=[N:8][C:9]2[C:4]([C:5]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]3[CH2:23][CH2:24][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:26][CH2:27]3)=[C:18]([C:32]([F:33])([F:35])[F:34])[CH:17]=1)=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2

Participants

5

Reactant 3

HCID 61436Stannous chloride dihydrateHCID 516892Sodium BicarbonateHCID 67008148Methyl 1-(4-(6-bromo-3-nitroquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate

Product 1

HCID 67008348Methyl 1-(4-(3-amino-6-bromoquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylateYield 73.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of compound 8.2 methyl 1-(4-(6-bromo-3-nitroquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (0.26 g, 0.47 mmol, 1 equiv.) in dioxane (3 mL) at room temperature was added Tin(II) chloride dihydrate (0.53 g, 2.35 mmol, 5 equiv.). The resulting mixture was heated to 80° C. under argon for 5 hours. Upon cooling to room temperature, the mixture was neutralized with aqueous NaHCO3 and filtered. The flitrate was extrated with EtOAc (30 mL×2) and the combined organic layer was washed with water (50 mL) and brine (50 mL). The organic phase was dried over Na2SO4. After removal of solvent under vacuum, the resulting residue was purified via flash chromatography (hexanes:EtOAc 1:1) to afford desired product 8.3 methyl 1-(4-(3-amino-6-bromoquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (0.18 g; 73%). LC-MS (M+H): 523.10

Workup

  1. temperatureUpon cooling to room temperature
  2. filtrationfiltered
  3. washthe combined organic layer was washed with water (50 mL) and brine (50 mL)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. customAfter removal of solvent under vacuum
  6. customthe resulting residue was purified via flash chromatography (hexanes:EtOAc 1:1)

Sources & evidence

ORD record
ord-1b623228fb084badb3f91f2787b63b19
Source dataset
uspto-grants-2014_11
Patent number
US08889706B2

Reaction notes

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