Potassium Iodide → HCID 89994509, compound

HRID 718791Notes

Reaction equation

HRID 718791 reaction equation
[I-].[K+].[CH2:3]([C@:5]1([OH:37])[CH2:29][C@@H:9]2[CH2:10][CH2:11][CH2:12][C:13]3[C:14](=[CH:15][C:16]4[CH:17]=[N:18][N:19]([C:22]5[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=5)[C:20]=4[CH:21]=3)[C@:8]2([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:7][CH2:6]1)[CH3:4].[O:38](C(C)(C)C)O>CC#N>[CH2:3]([C@:5]1([OH:37])[CH2:29][C@@H:9]2[CH2:10][CH2:11][C:12](=[O:38])[C:13]3[C:14](=[CH:15][C:16]4[CH:17]=[N:18][N:19]([C:22]5[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=5)[C:20]=4[CH:21]=3)[C@:8]2([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:7][CH2:6]1)[CH3:4]

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 6410tert-Butyl hydroperoxideHCID 89994508HCID 89994508, compound

Product 1

HCID 89994509HCID 89994509, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium iodide (1 M solution in water, 0.365 mL, 0.365 mmol) was added to a solution of (3R,4aS,12bS)-3-ethyl-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (13, R1=4-Fluorophenyl, R2=Pyridyin-2-ylmethyl, R3=Ethyl) (0.143 g, 0.305 mmol) and MeCN (3 mL) under air. 2-Hydroperoxy-2-methylpropane (0.717 mL, 5.18 mmol) was added dropwise over about 5 min. The reaction was mixed at rt for about 24 h. The reaction was quenched with sat. aq. sodium sulfite (5 mL) and then a 1:1 solution of sat. aq. NaHCO3/water (5 mL) was added. The solution was extracted with EtOAc (3×5 mL). The combined organics were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 50-86% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure. The residue was further purified by reverse phase HPLC (Atlantis Prep T3 OBD (Waters), 5 μm particle size 19×100 mm) using a gradient of 0-95% MeCN in aqueous NH4OAc (50 mM). The fractions containing product were combined and concentrated under reduced pressure to remove the organic volatiles. The resulting mixture was frozen then lyophilized to give (3R,4aS,12bS)-3-ethyl-9-(4-fluorophenyl)-3-hydroxy-12b-(pyridin-2-ylmethyl)-1,2,3,4,4a,5,6,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-7(9H)-one (48, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Ethyl) (0.008 g, 6% yield). LC/MS, method 2, Rt=2.32 min.; MS m/z: 484 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.38 (d, J=4.8 Hz, 1H), 8.30 (d, J=0.9 Hz, 1H), 7.88-7.78 (m, 2H), 7.69 (s, 1H), 7.54 (s, 1H), 7.48-7.41 (m, 2H), 7.35 (td, J=7.6, 1.8 Hz, 1H), 7.10-7.04 (m, 1H), 6.34-6.30 (m, 1H), 3.95 (s, 1H), 3.02-2.86 (m, 3H), 2.74-2.64 (m, 2H), 2.47-2.43 (m, 1H), 2.12-2.03 (m, 1H), 2.02-1.90 (m, 1H), 1.73-1.62 (m, 1H), 1.55-1.46 (m, 2H), 1.39-1.25 (m, 2H), 1.20 (q, J=7.8 Hz, 2H), 0.73 (t, J=7.4 Hz, 3H).

Workup

  1. additionThe reaction was mixed at rt for about 24 h
  2. customThe reaction was quenched with sat. aq. sodium sulfite (5 mL)
  3. additiona 1:1 solution of sat. aq. NaHCO3/water (5 mL) was added
  4. extractionThe solution was extracted with EtOAc (3×5 mL)
  5. dry with materialThe combined organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel (12 g)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was further purified by reverse phase HPLC (Atlantis Prep T3 OBD (Waters), 5 μm particle size 19×100 mm)
  11. additionThe fractions containing product
  12. concentrationconcentrated under reduced pressure
  13. customto remove the organic volatiles
  14. temperatureThe resulting mixture was frozen

Sources & evidence

ORD record
ord-a6b714abb7054ebda5a7e0f25fa0d49c
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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