Dimethyl Sulfoxide → HCID 90201130, compound

HRID 718758Notes

Reaction equation

HRID 718758 reaction equation
CS(C)=O.[H-].[Na+].[I-].C[S+](C)(C)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][C:25]4[C@@:33]5([CH2:39][C:40]6[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=6)[CH2:34][CH2:35][C:36](=[O:38])[CH2:37][C@H:32]5[CH2:31][CH2:30][CH2:29][C:26]=4[CH:27]=3)[CH:22]=[N:21]2)=[CH:16][CH:15]=1.F[C:47]1C=CC(N2C3C(=CC4[C@]5(CC6C=CC=CN=6)CCC(=O)C[C@@H]5CCCC=4C=3)C=N2)=CC=1>C1COCC1.CCOC(C)=O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[CH:27]=[C:26]4[CH2:29][CH2:30][CH2:31][CH:32]5[CH2:37][C:36]6([CH2:47][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

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 131734185HCID 131734185, compound

Product 1

HCID 90201130HCID 90201130, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A flask with stir bar and nitrogen line was charged with DMSO (2 mL) and sodium hydride (60 wt % in oil, 0.021 g, 0.523 mmol). The mixture was warmed in an oil bath heated to about 65° C. for about 30 min then cooled to rt. THF (1 mL) was added and the mixture was cooled to about 0° C. Trimethylsulfoxonium iodide (0.115 g, 0.523 mmol) was added and the mixture was stirred for about 15 min. (4aS,12bS)-9-(4-Fluorophenyl)-12b-pyridin-2-ylmethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one; compound with (4aR,12bR)-9-(4-fluoro-phenyl)-12b-pyridin-2-ylmethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (10, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.115 g, 0.262 mmol) in THF (3 mL) was added and the mixture was allowed to warm to rt for about 18 h. The mixture was diluted with EtOAc (25 mL) and washed with water (25 mL). The aqueous layer was extracted with EtOAc (25 mL) then the combined organic layers were washed with water (2×25 mL) and brine (25 mL), dried over MgSO4, filtered 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[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.115 g, 97%); LC/MS, method 3, Rt=2.63 min, MS m/z 454 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.37-8.35 (m, 1H), 8.14 (d, J=0.7 Hz, 1H), 7.85-7.77 (m, 2H), 7.65 (s, 1H), 7.44-7.32 (m, 4H), 7.08-7.04 (m, 1H), 6.48 (d, J=7.8 Hz, 1H), 3.61 (d, J=12.7 Hz, 1H), 3.34-3.26 (m, 1H), 3.13-3.06 (m, 1H), 3.01 (d, J=12.8 Hz, 1H), 2.60-2.43 (m, 1H), 2.39-2.25 (m, 2H), 2.21-2.12 (m, 1H), 1.87-1.78 (m, 2H), 1.75-1.56 (m, 3H), 1.54-1.50 (m, 1H), 1.28-1.19 (m, 1H), 1.17-1.09 (m, 1H), 0.88-0.74 (m, 1H).

Workup

  1. temperatureThe mixture was warmed in an oil bath
  2. temperaturethen cooled to rt
  3. temperaturethe mixture was cooled to about 0° C
  4. additionwas added
  5. temperatureto warm to rt for about 18 h
  6. washwashed with water (25 mL)
  7. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  8. washthe combined organic layers were washed with water (2×25 mL) and brine (25 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eab387a6c8b0450bad3696e62c0b91c7
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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