Methanol → 13-Cyclohexyl-n-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-6,7-dihydro-5h-indolo[2,1-a] [2]benzazepine-10-carboxamide

HRID 273357Notes

Reaction equation

HRID 273357 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32]([NH:34][S:35]([N:38]([CH3:40])[CH3:39])(=[O:37])=[O:36])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)=[CH:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CO.[H][H]>C1COCC1.[Pd]>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32]([NH:34][S:35]([N:38]([CH3:39])[CH3:40])(=[O:36])=[O:37])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][CH:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)[CH2:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 887MethanolHCID 2473840713-Cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamideHCID 178418361HCID 178418361, compound

Product 1

HCID 2473840613-Cyclohexyl-n-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-6,7-dihydro-5h-indolo[2,1-a] [2]benzazepine-10-carboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

13-Cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (45 mg, 0.08 mMol) was dissolved in 3.8 mL of THF and 0.9 mL of methanol added. 10% palladium on carbon (13 mg) was added and the reaction placed under 1 atm (balloon) of hydrogen atmosphere and stirred at room temperature for 18 hrs. The reaction was filtered through a plug of celite and the celite rinsed using dichloromethane. Removal of volatiles from the filtrate in vacuuo yield 47 mg of material which was purified by prep. HPLC under the following conditions: Shimadzu prep. HPLC using Discovery VP software; % A=10% methanol, 90% water, 0.1% TFA; % B=90% methanol, 10% water, 0.1% TFA; Initial % B=50; Final % B=100; Gradient=15 min; Runtime=20 min; Flow rate=25 ml/min; Column=Waters Sunfire 19 mm×100 mm; Peak collection=10.09 min to 10.88 min. Obtained 33.7 mg (75%) of the title compound as a colorless solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.20-1.31 (m, 1.1 H) 1.31-1.52 (m, 2.1 H) 1.66 (d, J=13.12 Hz, 1.1 H) 1.78 (d, J=9.16 Hz, 2.0 H) 1.93 (d, J=13.12 Hz, 1.1 H) 1.96-2.09 (m, 2.9 H) 2.82-2.98 (m, 2.2 H) 3.03-3.08 (m, 6.0 H) 3.11-3.19 (m, 1.0 H) 3.73-3.81 (m, 1.0 H) 3.84 (s, 1.3 H) 3.90 (s, 1.8 H) 3.97-4.02 (m, 0.9 H) 4.05 (dd, J=14.95, 5.80 Hz, 0.7 H) 4.75-4.85 (m, 0.4 H) 4.90 (d, J=14.95 Hz, 0.6 H) 6.84 (d, J=2.44 Hz, 0.4 H) 6.94 (dd, J=8.55, 2.44 Hz, 0.5 H) 6.97-7.01 (m, 1.2 H) 7.09-7.17 (m, 1.0 H) 7.32-7.49 (m, 2.0 H) 7.64 (s, 0.6 H) 7.69 (s, 0.4 H) 7.78-7.87 (m, 1.2 H) 7.90 (d, J=8.55 Hz, 0.4 H) 8.02 (s, 0.4 H) 8.42 (s, 0.5 H) 8.59 (s, 0.4H). 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=3.02 min, purity 99%; Flow injection Mass Spectrometry: MS m/z 563(MH+), m/z 561(M-H)−.

Workup

  1. filtrationThe reaction was filtered through a plug of celite
  2. washthe celite rinsed
  3. customRemoval of volatiles from the filtrate in vacuuo yield 47 mg of material which
  4. customwas purified by prep
  5. customGradient=15 min
  6. customRuntime=20 min
  7. customPeak collection=10.09 min to 10.88 min

Sources & evidence

ORD record
ord-061ee6986332444898001b378d685551
Source dataset
uspto-grants-2008_11
Patent number
US07456165B2

Reaction notes

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