Methyl vinyl ketone → HCID 86722327, compound

HRID 718751Notes

Reaction equation

HRID 718751 reaction equation
[Na].[CH2:2]([CH:4]1[C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][C:9]=2[CH2:8][CH2:7][CH2:6][C:5]1=O)[N:15]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[N:14]=[CH:13]3)[CH3:3].[CH:26]([C:28]([CH3:30])=[O:29])=[CH2:27]>CCO>[CH2:2]([C:4]12[CH2:27][CH2:26][C:28](=[O:29])[CH:30]=[C:5]1[CH2:6][CH2:7][CH2:8][C:9]1[CH:17]=[C:16]3[C:12](=[CH:11][C:10]=12)[CH:13]=[N:14][N:15]3[C:18]1[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=1)[CH3:3]

Participants

5

Reactant 3

HCID 6570Methyl vinyl ketone3×HCID 5360545SodiumHCID 86722326HCID 86722326, compound

Product 1

HCID 86722327HCID 86722327, compoundYield 80.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
35 °C

Procedure

A three necked round bottom flask with septum, nitrogen line, thermometer and stir bar was charged with EtOH (50 mL) and sodium (0.348 g, 15.1 mmol). The mixture was stirred until the reaction was complete, then 5-ethyl-1-(4-fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (7, R1=4-Fluorophenyl, R2=Ethyl) (3.25 g, 10.1 mmol) suspended in EtOH (50 mL) was added. The mixture was heated to about 35° C. for about 10 min then methyl vinyl ketone (0.777 g, 11.09 mmol) was added. The mixture was stirred for about 45 min at about 35° C. then heated to about 60° C. for about 1 h. Methyl vinyl ketone (0.27 g, 3.85 mmol) was added and stirring was continued for about 30 min. Methyl vinyl ketone (0.22 g, 3.14 mmol) was added then heating was continued for about 45 min. The mixture was cooled to rt then concentrated under reduced pressure. Water (100 mL) and EtOAc (100 mL) were added then the mixture was acidified to about pH 1 with 6 N aq. HCl. The layers were separated then the aqueous layer was extracted with EtOAc (20 mL). The combined organic solutions were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (120 g) using a gradient of 10-50% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield 12b-Ethyl-9-(4-fluorophenyl)-1,2,6,7,9,12b-hexahydro-5H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (8, R1=4-Fluorophenyl, R2=Ethyl) (3.03 g, 80%); LC/MS, method 3, Rt=2.73 min, MS m/z 375 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.32 (s, 1H), 7.89 (s, 1H), 7.85-7.78 (m, 2H), 7.63 (s, 1H), 7.47-7.38 (m, 2H), 5.89 (s, 1H), 3.03-2.95 (m, 1H), 2.88-2.63 (m, 2H), 2.58-2.27 (m, 4H), 2.21-2.00 (m, 2H), 1.93-1.73 (m, 3H), 0.92-0.84 (t, J=7.2 Hz, 3H).

Workup

  1. stirringThe mixture was stirred until the reaction
  2. additionwas added
  3. stirringThe mixture was stirred for about 45 min at about 35° C.
  4. temperaturethen heated to about 60° C. for about 1 h
  5. stirringstirring
  6. temperaturethen heating
  7. waitwas continued for about 45 min
  8. temperatureThe mixture was cooled to rt
  9. concentrationthen concentrated under reduced pressure
  10. additionWater (100 mL) and EtOAc (100 mL) were added
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with EtOAc (20 mL)
  13. dry with materialThe combined organic solutions were dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified on silica gel (120 g)
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dddd7f8b36d943cf89dbb28c215c7b06
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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