Iodo benzene diacetate → 8-(Tert-butyldimethylsilyloxy)-2-(6-fluoro[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline

HRID 2035603Notes

Reaction equation

HRID 2035603 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH:19]=O)[CH:15]=[CH:14]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:21][C:22]1[CH:23]=[CH:24][C:25]([NH:28][NH2:29])=[N:26][CH:27]=1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>O.C(Cl)Cl>[Si:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([C:19]1[N:26]3[CH:27]=[C:22]([F:21])[CH:23]=[CH:24][C:25]3=[N:28][N:29]=1)[CH:15]=[CH:14]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 12217721Iodo benzene diacetate2×HCID 199167865-Fluoro-2-hydrazinylpyridineHCID 585670828-(Tert-butyldimethylsilyloxy)quinoline-2-carbaldehyde

Product 1

HCID 672311328-(Tert-butyldimethylsilyloxy)-2-(6-fluoro[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolineYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

8-(tert-butyldimethylsilyloxy)quinoline-2-carbaldehyde (1.39 g, 4.83 mmol) and 5-fluoro-2-hydrazinylpyridine (1.28 g, 6.04 mmol) were combined in DCM (12.1 mL, 4.83 mmol) at ambient temperature and stirred for 15 minutes. The mixture was cooled to 0° C. followed by addition of iodobenzene diacetate (IBD; 1.87 g, 5.80 mmol). The reaction was warmed to ambient temperature and stirred overnight. Additional IBD (0.8 equivalents, 4.64 mmol) was added and the reaction was allowed to stir at ambient temperature for 48 hours total. The mixture was transferred to a separatory funnel, diluting with water and DCM. The organic phase was washed with saturated aqueous Na2SO3, followed by back extraction of the aqueous phase 2 times with DCM. The organics were combined and washed with brine, dried over Na2SO4, filtered and concentrated to a residue under reduced pressure, followed by purification by flash column chromatography to give the product (1.08 g, 57% yield). MS APCI (+) m/z 395.3 (M+1) detected.

Workup

  1. temperatureThe reaction was warmed to ambient temperature
  2. stirringstirred overnight
  3. stirringto stir at ambient temperature for 48 hours total
  4. customThe mixture was transferred to a separatory funnel
  5. washThe organic phase was washed with saturated aqueous Na2SO3
  6. extractionfollowed by back extraction of the aqueous phase 2 times with DCM
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to a residue under reduced pressure
  11. customfollowed by purification by flash column chromatography

Sources & evidence

ORD record
ord-b4ab0c2a2bc64e42b16b0e2873245ad9
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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