Trifluoroacetic acid → (R)-6-((3-((4-(2-(4-((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)butyl)-1,3-dithiolan-2-yl)phenyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide

HRID 1944979Notes

Reaction equation

HRID 1944979 reaction equation
[Si]([O:8][C@H:9]([C:69]1[CH:78]=[CH:77][C:76]([OH:79])=[C:75]2[C:70]=1[CH:71]=[CH:72][C:73](=[O:80])[NH:74]2)[CH2:10][N:11]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]1([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35](=[O:68])[C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([S:42]([C:45]4[CH:46]=[C:47]5[C:52](=[C:53]([CH3:55])[CH:54]=4)[N:51]=[CH:50][C:49]([C:56](=[O:58])[NH2:57])=[C:48]5[NH:59][C:60]4[CH:65]=[CH:64][CH:63]=[C:62]([O:66][CH3:67])[CH:61]=4)(=[O:44])=[O:43])[CH:37]=3)=[CH:30][CH:29]=2)[S:27][CH2:26][CH2:25][S:24]1)C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>ClCCl>[OH:8][C@H:9]([C:69]1[CH:78]=[CH:77][C:76]([OH:79])=[C:75]2[C:70]=1[CH:71]=[CH:72][C:73](=[O:80])[NH:74]2)[CH2:10][NH:11][CH2:19][CH2:20][CH2:21][CH2:22][C:23]1([C:28]2[CH:29]=[CH:30][C:31]([NH:34][C:35]([C:36]3[CH:37]=[C:38]([S:42]([C:45]4[CH:46]=[C:47]5[C:52](=[C:53]([CH3:55])[CH:54]=4)[N:51]=[CH:50][C:49]([C:56]([NH2:57])=[O:58])=[C:48]5[NH:59][C:60]4[CH:65]=[CH:64][CH:63]=[C:62]([O:66][CH3:67])[CH:61]=4)(=[O:44])=[O:43])[CH:39]=[CH:40][CH:41]=3)=[O:68])=[CH:32][CH:33]=2)[S:24][CH2:25][CH2:26][S:27]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86659121(R)-tert-butyl (2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)(4-(2-(4-(3-((3-carbamoyl-4-((3-methoxyphenyl)amino)-8-methylquinolin-6-yl)sulfonyl)benzamido)phenyl)-1,3-dithiolan-2-yl)butyl)carbamate

Product 1

HCID 54588735(R)-6-((3-((4-(2-(4-((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)butyl)-1,3-dithiolan-2-yl)phenyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Intermediate 158 (90 mg, 0.08 mmol) was taken up in dichloromethane and treated with trifluoroacetic acid (0.50 mL). After 30 minutes of stirring, the mixture was concentrated to a residue under reduced pressure, taken up in tetrahydrofuran (1 mL) and treated successively with TBAF solution (1.0 M in THF, 1 mL) and glacial acetic acid (0.50 mL). The mixture was left overnight at room temperature and then concentrated under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA) to provide, after concentration, the trifluoroacetic acid salt of the title compound as a bright yellow foam (22 mg).

Workup

  1. concentrationthe mixture was concentrated to a residue under reduced pressure
  2. additiontreated successively with TBAF solution (1.0 M in THF, 1 mL) and glacial acetic acid (0.50 mL)
  3. waitThe mixture was left overnight at room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA)
  6. customto provide
  7. concentrationafter concentration

Sources & evidence

ORD record
ord-e66bd8f1fb8e416f9238c82da1b6f57a
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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