Dimethyl Sulfoxide → HCID 86722471, compound

HRID 718856Notes

Reaction equation

HRID 718856 reaction equation
[H-].[Na+].CS(C)=O.[I-].[CH3:8][S+](C)(C)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[N:27]=[C:26]4[CH2:29][CH2:30][CH2:31][CH:32]5[CH2:37][C:36](=[O:38])[CH2:35][CH2:34][C:33]5([CH2:39][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=5)[C:25]4=[CH:24][C:23]=3[CH:22]=[N:21]2)=[CH:16][CH:15]=1>C1COCC1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[N:27]=[C:26]4[CH2:29][CH2:30][CH2:31][CH:32]5[CH2:37][C:36]6([CH2:8][O:38]6)[CH2:35][CH2:34][C:33]5([CH2:39][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=5)[C:25]4=[CH:24][C:23]=3[CH:22]=[N:21]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 86722468HCID 86722468, compound

Product 1

HCID 86722471HCID 86722471, compoundYield 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60 wt % in oil, 0.454 g, 11.35 mmol) and DMSO (25 mL) were heated to about 65° C. for about 30 min then cooled to rt. THF (50 mL) was added then the mixture was cooled to about 0° C. Trimethylsulfoxonium iodide (2.56 g, 11.63 mmol) was added then after about 30 min rac-(4aR,12bR)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3 (2H)-one (118, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (2.5 g, 5.68 mmol) was added. The mixture was allowed to warm to rt and stir for about 12 h. The mixture was concentrated under reduced pressure then the material was partitioned between water (100 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (25 mL) then the organic solutions were combined and washed with water (75 mL) then brine (30 mL), dried over MgSO4 then filtered. The filtrate was concentrated under reduced pressure and the material was purified on silica gel (120 g) using a gradient from 0-10% MeOH in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-(2′R,4aS,12bS)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridine-3,2′-oxirane] (119, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (1.865 g, 72.3%); LC/MS, method 3, Rt=2.65 min, MS m/z 455 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.42-8.34 (m, 2H), 8.32-8.28 (m, 1H), 8.20 (s, 1H), 7.75-7.72 (m, 1H), 7.49-7.37 (m, 3H), 7.06 (ddd, J=5.2, 4.5, 0.9 Hz, 1H), 6.72-6.67 (m, 1H), 3.73 (d, J=12.8 Hz, 1H), 3.59-3.47 (m, 1H), 3.42-3.33 (m, 1H), 3.02 (d, J=12.9 Hz, 1H), 2.70-2.56 (m, 1H), 2.44-2.34 (m, 2H), 2.13-2.00 (m, 1H), 1.96-1.81 (m, 2H), 1.79-1.58 (m, 3H), 1.35-1.21 (m, 3H), 1.21-1.10 (m, 1H).

Workup

  1. temperaturethe mixture was cooled to about 0° C
  2. temperatureto warm to rt
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customthe material was partitioned between water (100 mL) and EtOAc (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  6. washwashed with water (75 mL)
  7. dry with materialbrine (30 mL), dried over MgSO4
  8. filtrationthen filtered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe material was purified on silica gel (120 g)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb514bab11574916b82163defd6f0b23
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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