Phosphorus oxychloride → HCID 24740038, compound

HRID 273352Notes

Reaction equation

HRID 273352 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([O:41][CH3:42])=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([NH:23][CH2:24][C:25](=[O:32])[CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=O)=[CH:18][C:17]4[CH:33]=[C:34]([O:37][CH3:38])[CH:35]=[CH:36][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([O:41][CH3:42])=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:32][C:25]([CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:24][N:23]=4)=[CH:18][C:17]4[CH:33]=[C:34]([O:37][CH3:38])[CH:35]=[CH:36][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 59837545HCID 59837545, compound

Product 1

HCID 24740038HCID 24740038, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Methyl 13-cyclohexyl-3-(methyloxy)-6-(((5-(methyloxy)-2,5-dioxopentyl)amino)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate (1.60 g, 2.79 mMol) was suspended in 38 ml of toluene along with phosphorus oxychloride (0.58 mL, 6.34 mMol). The mixture was heated to reflux under nitrogen for 3 hrs, cooled and poured into a sepratory funnel containing ice and saturated aqueous sodium bicarbonate solution. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed sequentially with aqueous saturated bicarbonate, brine and dried over magnesium sulfate. Removal of volatiles and drying in vacuuo produced the title product in quantitative yield (1.55 g). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.27 (1 H, br. s.), 1.36-1.45 (2 H, m), 1.59 (2 H, br. s.), 1.78 (2 H, d, J=9.77 Hz), 1.96 (1 H, br. s.), 2.06 (2 H, br. s.), 2.71 (2 H, t, J=7.48 Hz), 2.81-2.90 (1 H, m), 3.04 (2 H, t, J=7.32 Hz), 3.70 (3 H, s), 3.95 (3 H, s), 3.98 (3 H, s), 4.37 (1 H, d, J=11.60 Hz), 5.93 (1 H, d, J=12.51 Hz), 6.91 (1 H, s), 7.02 (1 H, d, J=2.75 Hz), 7.07 (1 H, dd, J=8.70, 2.59 Hz), 7.53 (2 H, s), 7.74 (1 H, d, J=8.55 Hz), 7.85 (1 H, d, J=8.55 Hz), 8.38 (1 H, s). HPLC analysis: Shimadzu Analytical HPLC using Discovery VP software: % A=10% methanol, 90% water, 0.1% trifluoroacetic acid; % B=90% methanol, 10% water, 0.1% trifluoroacetic acid; Initial % B=50; Final % B=100; Gradient=5 min; Runtime=6 min; Flow rate=5 ml/min; Wavelength=220 nm; Column=Phenomenex Luna 3.0 mm×50 mm S10; Retention Time=4.48 min, purity 96%. Flow injection Mass Spectrometry: MS m/z 555(MH+).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux under nitrogen for 3 hrs
  3. temperaturecooled
  4. additionpoured into a sepratory funnel
  5. extractionThe aqueous mixture was extracted with ethyl acetate
  6. washThe organic layer was washed sequentially with aqueous saturated bicarbonate, brine
  7. dry with materialdried over magnesium sulfate
  8. customRemoval of volatiles
  9. customdrying in vacuuo

Sources & evidence

ORD record
ord-4a37609f3c4f4779888df3abde4d7709
Source dataset
uspto-grants-2008_11
Patent number
US07456165B2

Reaction notes

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