Dimethylformamide → 7-(Difluoromethoxy)-4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinoline

HRID 1513786Notes

Reaction equation

HRID 1513786 reaction equation
Cl[C:2]([F:7])([F:6])C([O-])=O.[Na+].Br.[CH3:10][C:11]1[CH:15]=[C:14]([C:16]2[CH:17]=[CH:18][C:19]3[N:20]([C:22]([CH2:25][O:26][C:27]4[C:36]5[C:31](=[CH:32][C:33]([OH:37])=[CH:34][CH:35]=5)[N:30]=[CH:29][CH:28]=4)=[N:23][N:24]=3)[CH:21]=2)[O:13][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>C(O)=O>[F:7][CH:2]([F:6])[O:37][C:33]1[CH:32]=[C:31]2[C:36]([C:27]([O:26][CH2:25][C:22]3[N:20]4[CH:21]=[C:16]([C:14]5[O:13][N:12]=[C:11]([CH3:10])[CH:15]=5)[CH:17]=[CH:18][C:19]4=[N:24][N:23]=3)=[CH:28][CH:29]=[N:30]2)=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 2734985Sodium chlorodifluoroacetateHCID 1363872144-((6-(3-Methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol hydrobromide

Product 1

HCID 576909917-(Difluoromethoxy)-4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolineYield 13.4%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A 48 mL tube was charged with sodium 2-chloro-2,2-difluoroacetate (0.15 g, 1.0 mmol), 4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol hydrobromide (0.200 g, 0.44 mmol), cesium carbonate (0.43 g, 1.3 mmol), and DMF (1.7 ml, 22 mmol), flushed with argon, sealed, then placed in a 100° C. oil bath for 5 hours. The reaction mixture was concentrated, then diluted with DCM and chloroform. This was washed with water, sat. NaHCO3, and brine, then dried with MgSO4, filtered, and concentrated to give a brown oil. This was purified by HPLC to give 7-(difluoromethoxy)-4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinoline (0.025 g, 13% yield) as the formic acid salt. MS (ESI pos. ion) m/z: 424 (MH+). Calc'd exact mass for C21H15F2N5O3: 423.

Workup

  1. customflushed with argon
  2. customsealed
  3. customplaced in a 100° C.
  4. customfor 5 hours
  5. concentrationThe reaction mixture was concentrated
  6. additiondiluted with DCM and chloroform
  7. washThis was washed with water, sat. NaHCO3, and brine
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a brown oil
  12. customThis was purified by HPLC

Sources & evidence

ORD record
ord-ba351fdf370f4c7dafdc65c8d2166e4f
Source dataset
uspto-grants-2012_07
Patent number
US08217177B2

Reaction notes

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