Iodine → HCID 49779307, compound

HRID 1400502Notes

Reaction equation

HRID 1400502 reaction equation
[Mg].II.[CH:4]1(Br)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.[CH3:11][N:12]1[CH2:35][CH2:34][C:15]2[N:16]([CH2:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[O:26])[C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][C:22]=3[C:14]=2[CH2:13]1.C1([Mg]Br)CCCCC1>C1COCC1>[CH:4]1([C:25]([C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)([OH:26])[CH2:24][N:16]2[C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][C:22]=3[C:14]3[CH2:13][N:12]([CH3:11])[CH2:35][CH2:34][C:15]2=3)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1

Participants

7

Reactant 5

HCID 807IodineHCID 7960Cyclohexyl bromideHCID 5462224MagnesiumHCID 49779911HCID 49779911, compoundHCID 178419651HCID 178419651, compound

Product 1

HCID 49779307HCID 49779307, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Activated magnesium turnings (480 mg, 20 g/atom) and 2-3 crystals of iodine were stirred under anhydrous conditions. The excess of iodine was removed by heating with a heat gun. The magnesium turnings were now yellow in color. To this was added diethyl ether (15 mL) at 0° C. and stirred for 15 min. (until the color of the magnesium becomes white). To this was added cyclohexyl bromide (2.5 mL, 20 mmol) dropwise with constant stirring. The reaction mixture was stirred until a dark grey-colored solution was obtained. Into a separate flask was placed 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(4-fluorophenyl)ethanone (168 mg, 5 mmol) in THF under anhydrous conditions. The solution of the prepared cyclohexylmagnesium bromide (5 mL) was added dropwise. After addition, the mixture was allowed to come to RT and stirred at RT for 2 h. The reaction was monitored by TLC and NMR. The reaction was quenched with ice water and the product extracted into EtOAc. The organic extracts were concentrated and the residue purified by silica gel column chromatography (#100-200 mesh) using 0-3% MeOH:DCM as eluent. The compound was further purified by HPLC. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.25 (m, 2H), 7.10 (d, 1H), 6.92 (m, 1H), 6.80 (m, 3H), 4.60 (m, 1H), 4.65 (m, 1H), 4.22 (m, 2H), 3.70 (m, 1H), 3.40 (m, 1H), 3.20 (m, 2H), 3.0 (s, 3H), 2.70 (m, 1H), 2.38 (s, 3H), 2.20 (m, 2H), 1.80 (m, 2H), 1.70 (m, 3H), 1.50-1.20 (m, 4H).

Workup

  1. customThe excess of iodine was removed
  2. temperatureby heating with a heat gun
  3. additionTo this was added diethyl ether (15 mL) at 0° C.
  4. stirringThe reaction mixture was stirred until a dark grey-colored solution
  5. customwas obtained
  6. customInto a separate flask was placed
  7. additionAfter addition
  8. customto come to RT
  9. stirringstirred at RT for 2 h
  10. customThe reaction was quenched with ice water
  11. extractionthe product extracted into EtOAc
  12. concentrationThe organic extracts were concentrated
  13. customthe residue purified by silica gel column chromatography (#100-200 mesh)
  14. customThe compound was further purified by HPLC

Sources & evidence

ORD record
ord-fc87e7ad566a409889288a1fe1aa02ea
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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