Dichloromethane → Trifluoroacetic acid

HRID 456913Notes

Reaction equation

HRID 456913 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21](C(OC(C)(C)C)=O)[C:20]([C:32]2[C:33](=[O:42])[NH:34][C:35]4[C:40]([CH:41]=2)=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:19]3)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(Cl)Cl.[F:46][C:47]([F:52])([F:51])[C:48]([OH:50])=[O:49]>CS(C)=O.O>[N:11]1([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][C:20]([C:32]2[C:33](=[O:42])[NH:34][C:35]4[C:40]([CH:41]=2)=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:19]3)=[O:15])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1.[C:48]([OH:50])([C:47]([F:52])([F:51])[F:46])=[O:49]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 22668227HCID 22668227, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 5329377HCID 5329377, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideCatalystHCID 962WaterSolvent

Procedure

A solution of tert-butyl 5-{[4-(tert-butoxycarbonyl)-1-piperazinyl]carbonyl}-2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-indole-1-carboxylate (6-2, 213 mg, 0.373 mmol, 1 equiv) in a 1:1 mixture of CH2Cl2 and trifluoroacetic acid (40 mL) was treated with 3 drops of DMSO and H2O, and the resulting mixture was heated at reflux for 45 minutes. The solution was concentrated, and the residue was dried by azeotropic removal of water using a 90:10 mixture of toluene and methanol (100 mL). It was then purified by reverse phase chromatography (H2O/CH3CN gradient with 0.1% TFA present) to provide 3-[5-(1-piperazinylcarbonyl)-1H-indol-2-yl]-2(1H)-quinolinone (6-3) as a TFA salt (brown solid). 1H NMR (500 MHz, DMSO) δ 12.21 (s, 1H), 11.83 (s, 1H), 8.59 (s, 1H), 7.75 (d, 1H, J=7.9 Hz), 7.74 (s, 1H), 7.59 (d, 1H, J=8.3 Hz), 7.54 (t, 1H, J=7.6 Hz), 7.42 (s, 1H), 7.39 (d, 1H, J=8.3 Hz), 7.25 (m, 2H), 3.86–3.15 (br m, 8H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 45 minutes
  3. concentrationThe solution was concentrated
  4. dry with materialthe residue was dried by azeotropic removal of water using
  5. additiona 90:10 mixture of toluene and methanol (100 mL)
  6. customIt was then purified by reverse phase chromatography (H2O/CH3CN gradient with 0.1% TFA present)

Sources & evidence

ORD record
ord-678fd22041bd4fc1a40884956ae22dc8
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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