Trifluoroacetic acid → 13-Cyclohexyl-3-methoxy-6-(4-(4-morpholinylcarbonyl)-1,3-oxazol-5-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 1097797Notes

Reaction equation

HRID 1097797 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:40]([O:42]C(C)(C)C)=[O:41])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:25][CH:24]=[N:23][C:22]=4[C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])=[CH:18][C:17]4[CH:34]=[C:35]([O:38][CH3:39])[CH:36]=[CH:37][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>ClCCCl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:40]([OH:42])=[O:41])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:25][CH:24]=[N:23][C:22]=4[C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])=[CH:18][C:17]4[CH:34]=[C:35]([O:38][CH3:39])[CH:36]=[CH:37][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59133924HCID 59133924, compound

Product 1

HCID 2521132913-Cyclohexyl-3-methoxy-6-(4-(4-morpholinylcarbonyl)-1,3-oxazol-5-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acidYield 97%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve tert-Butyl 13-cyclohexyl-3-methoxy-6-(4-(4-morpholinylcarbonyl)-1,3-oxazol-5-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate (203 mg, 0.325 mmol) in 1,2-dichloroethane (3 ml) add TFA (3 ml, 38.9 mmol). The reaction was capped under a nitrogen atmosphere at 25° C. for 2 hrs. Reaction volatiles were removed in vacuo and the residue dissolved in 80 mL of ethyl acetate with heating. The solution was washed with 1N aqueous hydrochloric acid (2×40 mL), brine and dried over magnesium sulfate. The product solution was filtered, volatiles removed and the sample dried in vacuo at room temperature overnight to give 179 mg (97%) of a yellow solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 0.74-1.03 (m, 4H) 1.06-1.31 (m, 6H) 1.32-1.50 (m, 3H) 1.56 (d, J=9.16 Hz, 2H) 1.77 (d, J=8.85 Hz, 2H) 1.86-2.18 (m, 5H) 2.83-2.91 (m, 1H) 3.60 (s, 3H) 3.64-3.89 (m, 4H) 3.88-3.93 (m, 4H) 3.95-4.08 (m, 1H) 4.43 (d, J=15.56 Hz, 1H) 5.64 (d, J=14.95 Hz, 1H) 6.99 (d, J=2.75 Hz, 1H) 7.07 (dd, J=8.70, 2.59 Hz, 1H) 7.48-7.56 (m, 2H) 7.85-7.94 (m, 2H) 8.15 (s, 1H). LC-MS retention time 1.65 min; 568 m/z (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Xterra MS 7u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customThe reaction was capped under a nitrogen atmosphere at 25° C. for 2 hrs
  2. customReaction volatiles
  3. customwere removed in vacuo
  4. dissolutionthe residue dissolved in 80 mL of ethyl acetate
  5. temperaturewith heating
  6. washThe solution was washed with 1N aqueous hydrochloric acid (2×40 mL), brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe product solution was filtered
  9. customvolatiles removed
  10. customthe sample dried in vacuo at room temperature overnight

Sources & evidence

ORD record
ord-f0ca2353cbf448ecb60b7c54e35442be
Source dataset
uspto-grants-2012_03
Patent number
US08143243B2

Reaction notes

Loading…