Methyl vinyl ketone → HCID 86722469, compound

HRID 718854Notes

Reaction equation

HRID 718854 reaction equation
[Na].[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[N:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21](=O)[CH:22]([CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=5)[C:14]4=[CH:13][C:12]=3[CH:11]=[N:10]2)=[CH:5][CH:4]=1.[CH3:31][C:32](=[O:35])[CH:33]=[CH2:34]>CCO>[F:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:17]3[N:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21]5[C:22]([CH2:23][C:24]6[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=6)([CH2:34][CH2:33][C:32](=[O:35])[CH:31]=5)[C:14]4=[CH:13][C:12]=3[CH:11]=[N:10]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 5360545SodiumHCID 86722467HCID 86722467, compound

Product 1

HCID 86722469HCID 86722469, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Sodium (1.09 g, 47.4 mmol) and EtOH (355 mL) were stirred together until a solution was formed then 1-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one (115, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (16.47 g, 42.6 mmol) was added. The mixture was heated to about 60° C. then but-3-en-2-one (4.14 mL, 50.2 mmol) was added over about 50 min. The mixture was stirred at about 60° C. for about 90 min then it was cooled and concentrated under reduced pressure. The material was partitioned between EtOAc (250 mL) and water (150 mL) then the aqueous layer was extracted with EtOAc (100 mL). The combined organics were washed with brine (30 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified on silica gel (330 g) using a gradient from 0-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,5,6,7,9,12b-hexahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3(2H)-one (116, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (9.28 g, 50%); LC/MS, method 3, Rt=1.61, 2.40 min, MS m/z 439 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.83 (s, 1H), 8.43 (s, 1H), 8.36-8.28 (m, 3H), 7.61-7.57 (m, 1H), 7.44-7.36 (m, 2H), 7.18-7.11 (m, 2H), 5.97 (s, 1H), 3.88 (d, J=13.4 Hz, 1H), 3.67 (d, J=13.5 Hz, 1H), 3.27-3.15 (m, 1H), 2.98-2.93 (m, 1H), 2.87-2.74 (m, 1H), 2.48-2.40 (m, 1H), 2.39-2.27 (m, 1H), 2.23-2.09 (m, 2H), 1.94-1.75 (m, 2H), 1.56-1.49 (m, 1H).

Workup

  1. customwas formed
  2. temperatureit was cooled
  3. concentrationconcentrated under reduced pressure
  4. customThe material was partitioned between EtOAc (250 mL) and water (150 mL)
  5. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  6. washThe combined organics were washed with brine (30 mL)
  7. dry with materialthen dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe material was purified on silica gel (330 g)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1fe34d4258964aee88778dbcde796550
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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