(R)-6-((3-((2-(4-(2-((2-(8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl)-2-((tert-butyldimethylsilyl)oxy)ethyl)amino)ethyl)phenoxy)ethyl)(methyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide → (R)-6-((3-((2-(4-(2-((2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)ethyl)phenoxy)ethyl)(methyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide

HRID 1944954Notes

Reaction equation

HRID 1944954 reaction equation
C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:70][Si:71]([C:74]([CH3:77])([CH3:76])[CH3:75])([CH3:73])[CH3:72])[CH2:21][NH:22][CH2:23][CH2:24][C:25]2[CH:69]=[CH:68][C:28]([O:29][CH2:30][CH2:31][N:32]([CH3:67])[C:33]([C:35]3[CH:36]=[C:37]([S:41]([C:44]4[CH:45]=[C:46]5[C:51](=[C:52]([CH3:54])[CH:53]=4)[N:50]=[CH:49][C:48]([C:55]([NH2:57])=[O:56])=[C:47]5[NH:58][C:59]4[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH3:66])[CH:60]=4)(=[O:43])=[O:42])[CH:38]=[CH:39][CH:40]=3)=[O:34])=[CH:27][CH:26]=2)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)C1C=CC=CC=1>CO>[Si:71]([O:70][C@H:20]([C:12]1[CH:11]=[CH:10][C:9]([OH:8])=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16](=[O:19])[NH:17]2)[CH2:21][NH:22][CH2:23][CH2:24][C:25]1[CH:69]=[CH:68][C:28]([O:29][CH2:30][CH2:31][N:32]([CH3:67])[C:33]([C:35]2[CH:36]=[C:37]([S:41]([C:44]3[CH:45]=[C:46]4[C:51](=[C:52]([CH3:54])[CH:53]=3)[N:50]=[CH:49][C:48]([C:55]([NH2:57])=[O:56])=[C:47]4[NH:58][C:59]3[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH3:66])[CH:60]=3)(=[O:43])=[O:42])[CH:38]=[CH:39][CH:40]=2)=[O:34])=[CH:27][CH:26]=1)([C:74]([CH3:77])([CH3:75])[CH3:76])([CH3:72])[CH3:73]

Participants

3

Reactant 1

HCID 86675627(R)-6-((3-((2-(4-(2-((2-(8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl)-2-((tert-butyldimethylsilyl)oxy)ethyl)amino)ethyl)phenoxy)ethyl)(methyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide

Product 1

HCID 86675628(R)-6-((3-((2-(4-(2-((2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)ethyl)phenoxy)ethyl)(methyl)carbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamideYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Intermediate 141 (0.3769 g, 0.3505 mmol) in MeOH (7 mL) was degassed by bubbling N2 through the solution for approximately 10 minutes. The solution was cooled to 0° C. and Pd/C (0.3850 g of 10 wt %) was added slowly. The reaction flask was purged and filled with H2 3× before stirring under H2 (1 atm, balloon). The reaction mixture was warmed to room temperature and reaction progress was monitored by LC-MS. After 72 h, the reaction mixture was filtered through a pad of Celite. The filter cake was washed with 1:1 DCM/MeOH. The filtrate was concentrated and the residue was dissolved in 3:1 MeOH/EtOAc. The solution was degassed and cooled as described above; Pd/C (0.311 g of 10 wt %) was added and the mixture was placed under H2 atmosphere as described above. Reaction progress was monitored by LC-MS. After 24 h, the reaction mixture was filtered through a pad of Celite and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (gradient elution 1:19 to 1:3 MeOH/DCM) to yield the title compound (0.155 g, 45%) as a yellow solid. ES/MS calcd for C53H61N6O9SSi+ 985.4. Found m/z=985.5 (M+H)+.

Workup

  1. customby bubbling N2 through the solution for approximately 10 minutes
  2. additionPd/C (0.3850 g of 10 wt %) was added slowly
  3. customThe reaction flask was purged
  4. additionfilled with H2 3×
  5. temperatureThe reaction mixture was warmed to room temperature
  6. customreaction progress
  7. filtrationthe reaction mixture was filtered through a pad of Celite
  8. washThe filter cake was washed with 1:1 DCM/MeOH
  9. concentrationThe filtrate was concentrated
  10. dissolutionthe residue was dissolved in 3:1 MeOH/EtOAc
  11. customThe solution was degassed
  12. temperaturecooled
  13. additionPd/C (0.311 g of 10 wt %) was added
  14. customReaction progress
  15. waitAfter 24 h
  16. filtrationthe reaction mixture was filtered through a pad of Celite
  17. concentrationthe filtrate was concentrated under reduced pressure
  18. customThe residue was purified by column chromatography on silica gel (gradient elution 1:19 to 1:3 MeOH/DCM)

Sources & evidence

ORD record
ord-07c4b3f675e24c1697e3438d0540bbc3
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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