p-Toluenesulfonic acid → 1-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one

HRID 718822Notes

Reaction equation

HRID 718822 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]4[CH2:25][C:20]5(OCC[O:21]5)[CH2:19][CH2:18][CH2:17][C:14]=4[CH:15]=3)[CH:10]=[N:9]2)[CH:5]=[CH:4][N:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CC(C)=O.O>[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]4[CH2:25][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][C:14]=4[CH:15]=3)[CH:10]=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 867224311-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydro-1H-spiro[cyclohepta[f]indazole-6,2'-[1,3]dioxolane]

Product 1

HCID 867224321-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-oneYield 99%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A 200 mL round-bottom flask equipped with air cooled reflux condenser outfitted with a nitrogen inlet adapter was charged with 1-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydro-1H-spiro[cyclohepta[f]indazole-6,2′-[1,3]dioxolane] (82, R1=2-methylpyridin-4-yl) (3.26 g, 9.72 mmol) and PTSA (2.31 g, 12.2 mmol) in acetone (49 mL). The mixture was heated to reflux. After 24 h, the reaction was diluted with additional acetone (50 mL) and water (2.5 mL) was added. After 1 h the reaction was cooled before adding sat. aq. NaHCO3 (30 mL). The mixture was then concentrated under reduced pressure. EtOAc (70 mL) was added, and after separating the layers, the aqueous phase was extracted with EtOAc (2×25 mL). The combined organic phases were washed with brine (75 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 1-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (6, R1=2-methylpyridin-4-yl) (2.8 g, 99%); LC/MS, method 3, Rt=1.71 min, MS m/z 292 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.65-8.60 (m, 1H), 8.20-8.16 (m, 1H), 7.71 (s, 1H), 7.69-7.65 (m, 1H), 7.63-7.59 (m, 2H), 3.85 (s, 2H), 3.21-3.11 (m, 2H), 2.71 (s, 3H), 2.62-2.54 (m, 2H), 2.14-1.94 (m, 2H).

Workup

  1. customA 200 mL round-bottom flask equipped with air
  2. temperaturecooled
  3. temperaturereflux condenser
  4. customoutfitted with a nitrogen inlet adapter
  5. temperatureThe mixture was heated to reflux
  6. additionwas added
  7. temperatureAfter 1 h the reaction was cooled
  8. concentrationThe mixture was then concentrated under reduced pressure
  9. additionEtOAc (70 mL) was added
  10. customafter separating the layers
  11. extractionthe aqueous phase was extracted with EtOAc (2×25 mL)
  12. washThe combined organic phases were washed with brine (75 mL)
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1cf928d68bf446cbb2d59fa14ce22202
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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