Diethyl Ether → HCID 86751468, compound

HRID 1490284Notes

Reaction equation

HRID 1490284 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:16]2[N:15]([CH3:19])[C:14]3[C:6]([N:7]=[C:8]4[C:13]=3[CH:12]=[CH:11][CH:10]=[CH:9]4)=[C:5]([Cl:20])[C:4]=2[CH:3]=1.[C:21]1([Mg]Br)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOCC>O1CCOCC1>[ClH:20].[F:1][C:2]1[CH:18]=[CH:17][C:16]2[NH+:15]([CH3:19])[C:14]3[C:6]([N:7]=[C:8]4[C:13]=3[CH:12]=[CH:11][CH:10]=[CH:9]4)=[C:5]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 67598476HCID 67598476, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 86751468HCID 86751468, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of 2-fluoro-5-methyl-11-chloroquindoline from Example 24 (300 mg, 0.35 mmol) in dry dioxane (30 mL) was added to a 1.0M solution of C6H5MgBr in ether (6 mL, 6.0 mmol, obtained from Aldrich Chemical Co.) at room temperature. The reaction mixture was stirred for 1 hour at room temperature, then heated for 1 hour at 50° C. The reaction mixture was cooled, poured into ice-water (300 mL), allowed to stand overnight to effect hydrolysis (pH ~7), and then extracted with EtOAc (4×50 mL) and chloroform (4×50 mL). The combined chloroform and ethyl acetate extracts were washed with water, dried, concentrated, and then purified by chromatography on a basic alumina column, eluting 0.5-1.5% MeOH in CHCl3. The product containing fractions were combined, acidified with 1.0M HCl solution in ether and concentrated to afford 175 mg (45.8%) of the title compound as a yellow solid, mp 251.4°-251.8° C.; 1H NMR (DMSO-d6) δ 12.44 (s, NH), 9.00 (dd, J=4.4, J=9.2, 1H), 8.85 (d, J=8.4, 1M), 8.17 (t, J=7.6, 1H), 7.93 (t, J=7.8, 1H), 7.81-7.79 (m, 4H), 7.74-7.70 (m, 2H), 7.62 (d, J=9.2, 1H), 7.54 (t, J=7.2, 1H), 5.12 (s, 3H); 13C NMR (DMSO-d6) δ 159.66 (J=249.1), 146.35, 138.27, 136.45, 134.13, 132.80 (J=4.2), 131.15, 130.34, 129.94, 129.60, 129.39, 126.20 (J=9.9), 121.88 (J=9.1), 121.72, 121.66, 121.46, 114.01, 113.49, 109.94 (J=24.1), 49.94; (LSIMS, m/z) 327 (MH+).

Workup

  1. temperatureheated for 1 hour at 50° C
  2. temperatureThe reaction mixture was cooled
  3. customto stand overnight to effect hydrolysis (pH ~7)
  4. extractionextracted with EtOAc (4×50 mL) and chloroform (4×50 mL)
  5. washThe combined chloroform and ethyl acetate extracts were washed with water
  6. customdried
  7. concentrationconcentrated
  8. custompurified by chromatography on a basic alumina column
  9. washeluting 0.5-1.5% MeOH in CHCl3
  10. additionThe product containing fractions
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-dc1b79f088034b47b3c608f06d671f12
Source dataset
uspto-grants-1997_10
Patent number
US05681958

Reaction notes

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