Methyl triflate → HCID 86751475, compound

HRID 1490317Notes

Reaction equation

HRID 1490317 reaction equation
[Cl:1][C:2]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:12][C:11]2[C:3]=1[N:4]=[C:5]1[C:10]=2[CH:9]=[CH:8][C:7]([F:19])=[CH:6]1.O(C)S([C:24](F)(F)F)(=O)=O>C1(C)C=CC=CC=1.C(OCC)C>[ClH:1].[Cl:1][C:2]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH+:12]([CH3:24])[C:11]2[C:3]=1[N:4]=[C:5]1[C:10]=2[CH:9]=[CH:8][C:7]([F:19])=[CH:6]1

Participants

5

Reactant 2

HCID 9526Methyl triflateHCID 178505417HCID 178505417, compound

Product 1

HCID 86751475HCID 86751475, compoundYield 159.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 11-chloro-8-fluoroquindoline from Example 89 (1.00 g, 3.69 mmol) in toluene (25 ml, freshly distilled) stirring under nitrogen was added methyl triflate (1.05 mL, 9.24 mmol). The mixture stirred for 24 h at room temperature and was diluted with diethyl ether (60 mL) and filtered. The orange filter cake was placed under high vacuum for 24 h. The orange residue was suspended in chloroform and adsorbed onto neutral alumina and chromatographed over basic alumina (eluting with chloroform-ethyl acetate gradient from 1:0 to 1:1 until the eluent was free of impurities by TLC then eluting with 3% methanol in chloroform). The violet fractions were collected and concentrated to a small volume (50 mL). The violet solution was acidified with ethereal 1M HCl to a bright yellow endpoint. The mixture was cooled below room temperature and filtered. The filter cake rinsed with diethyl ether (10 mL) and dried under high vacuum at 45° C. for several days to yield 0.949 g (90%) of the title compound as a bright orange solid. A portion of this material was further purified by HPLC. The title compound is poorly soluble in all common NMR solvents; 1H NMR (DMSO-d6) δ 13.55 (s, 1H), 8.93 (dd, J=9.0, J=5.2, 1H), 8.87 (d, J=8.8, 1H), 8.68 (d, J=8.0, 1H), 8.27 (t, J=8.0, 1H), 8.11 (t, J=7.6, 1H), 7.64 (dd, J=9.0, J=2.2, 1H), 7.47 (J=9.2, J =2.2, 1H), 5.00 (s, 3H); MS (FAB, m/z) 285 (M+).

Workup

  1. stirringThe mixture stirred for 24 h at room temperature
  2. filtrationfiltered
  3. customchromatographed over basic alumina (
  4. washeluting with chloroform-ethyl acetate gradient from 1:0 to 1:1 until the eluent
  5. washthen eluting with 3% methanol in chloroform)
  6. customThe violet fractions were collected
  7. concentrationconcentrated to a small volume (50 mL)
  8. temperatureThe mixture was cooled below room temperature
  9. filtrationfiltered
  10. washThe filter cake rinsed with diethyl ether (10 mL)
  11. customdried under high vacuum at 45° C. for several days

Sources & evidence

ORD record
ord-88bedfba78a244c4acb51a5df560feef
Source dataset
uspto-grants-1997_10
Patent number
US05681958

Reaction notes

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