Dimethyl Sulfoxide → HCID 89994502, compound

HRID 718824Notes

Reaction equation

HRID 718824 reaction equation
[H-].[Na+].CS(C)=O.[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]6C=CC=CN=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>[CH2:34]([C@:33]12[CH2:39][CH2:40][C@:36]3([CH2:35][O:38]3)[CH2:37][C@@H:32]1[CH2:31][CH2:30][CH2:29][C:26]1[C:25]2=[CH:24][C:23]2[CH:22]=[N:21][N:20]([C:17]3[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=3)[C:28]=2[CH:27]=1)[CH3:47]

Participants

6

Reactant 4

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

Product 1

HCID 89994502HCID 89994502, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of sodium hydride (60 wt % in oil, 0.038 g, 1.594 mmol) and DMSO (5 mL) was heated to about 65° C. for about 30 min then cooled to rt and diluted with THF (2.5 mL). The reaction mixture was cooled in an ice water bath and trimethyl sulfoxonium iodide (0.149 g, 0.68 mmol) was added then stirred for about 15 min. (4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (10, R1=4-Fluorophenyl, R2=Ethyl) was then added in one portion dissolved in THF (2.5 mL) and the mixture was stirred to rt for about 5 h. The solvents were removed and the residue was diluted with about 15 mL water and extracted with EtOAc (15 mL×3). The combined organics were washed with sat. aq. NaCl (15 mL). The organic layer was dried over MgSO4 filtered and concentrated to about 220 mg of a crude viscous oil. The sample was further purified on silica gel (12 g) using DCM/EtOAc with ramp conditions of 0-100% EtOAc in DCM over 20 min followed by 10 min at 100% EtOAc. The product fractions were concentrated to colorless viscous dried on a high vacuum to yield (2′R,4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (14, R1=4-Fluorophenyl, R2=Ethyl) (131 mg,50%) of a white crystalline solid. LC/MS, method 4, Rt=2.08 min, MS m/z 391 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.27 (s, 1H), 7.93 (s, 1H), 7.85-7.77 (m, 2H), 7.56 (s, 1H), 7.45-7.36 (m, 2H), 4.03 (q, J=7.1 Hz, 1H), 3.25-3.17 (m, 1H), 3.00-2.90 (m, 1H), 2.67 (d, J=4.7 Hz, 1H), 2.62 (d, J=4.7 Hz, 1H), 2.38-2.30 (m, 1H), 2.25-1.92 (m, 3H), 1.93-1.67 (m, 3H), 1.62-1.53 (m, 1H), 1.40-1.24 (m, 1H), 1.18 (t, J=7.1 Hz, 2H), 1.04-0.95 (m, 1H), 0.40 (t, J=7.3 Hz, 3H). Sign of rotation is negative.

Workup

  1. temperaturethen cooled to rt
  2. temperatureThe reaction mixture was cooled in an ice water bath
  3. additionwas then added in one portion
  4. customThe solvents were removed
  5. additionthe residue was diluted with about 15 mL water
  6. extractionextracted with EtOAc (15 mL×3)
  7. washThe combined organics were washed with sat. aq. NaCl (15 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to about 220 mg of a crude viscous oil
  11. customThe sample was further purified on silica gel (12 g)
  12. customover 20 min
  13. waitfollowed by 10 min at 100% EtOAc
  14. concentrationThe product fractions were concentrated to colorless
  15. customviscous dried on a high vacuum

Sources & evidence

ORD record
ord-cfec7290092d440f9ed6b034432d7e31
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…