(R)-N-((S)-1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide → (S)-1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)-2,2,2-trifluoroethanamine

HRID 40285Notes

Reaction equation

HRID 40285 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([CH2:17][O:18][C:19]4[C:28]5[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=5)[N:22]=[CH:21][CH:20]=4)=[N:15][N:16]=3)[N:13]=2)[CH:5]=[CH:4][C:3]=1[C@H:31]([NH:36][S@@](C(C)(C)C)=O)[C:32]([F:35])([F:34])[F:33]>CO.Cl>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([CH2:17][O:18][C:19]4[C:28]5[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=5)[N:22]=[CH:21][CH:20]=4)=[N:15][N:16]=3)[N:13]=2)[CH:5]=[CH:4][C:3]=1[C@H:31]([NH2:36])[C:32]([F:33])([F:35])[F:34]

Participants

4

Reactant 1

HCID 67503342(R)-N-((S)-1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 57691263(S)-1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)-2,2,2-trifluoroethanamine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of (R)—N—((S)-1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide (135 mg, 218 μmol) in MeOH (2 mL) and 4M HCl (2 mL) was stirred for 30 min at 35° C. LCMS suggests full conversion. Solvents removed under reduced pressure with azeotroping from toluene. Residue dissolved in MeOH (10 mL) and Si-Carbonate (2 g; 1.4 mmol) added. Suspension stirred for 30 min, then filtrated collected by filtration. Solvents removed under reduced pressure and residue purified on silica (12 g) eluting product with 0>5% MeOH/DCM. MS (ESI pos. ion) m/z: 515 (MH+). Calc'd exact mass for C24H18ClF3N6O2: 514.

Workup

  1. customSolvents removed under reduced pressure
  2. customwith azeotroping from toluene
  3. dissolutionResidue dissolved in MeOH (10 mL)
  4. filtrationfiltrated
  5. filtrationcollected by filtration
  6. customSolvents removed under reduced pressure and residue
  7. custompurified on silica (12 g)
  8. washeluting product with 0>5% MeOH/DCM

Sources & evidence

ORD record
ord-e7fef49e8a26430392cd9de6ef22bf65
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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