Ammonium formate → 5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]-8-hydroxyquinolin-2(1H)-one

HRID 1433267Notes

Reaction equation

HRID 1433267 reaction equation
C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:59][Si:60]([C:63]([CH3:66])([CH3:65])[CH3:64])([CH3:62])[CH3:61])[CH2:21][NH:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([OH:42])=[C:38]([C@@H:43]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[CH2:44][CH2:45][N:46]([CH:50]([CH3:52])[CH3:51])[CH:47]([CH3:49])[CH3:48])[CH:37]=3)=[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.C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[Si:60]([O:59][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:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([OH:42])=[C:38]([C@@H:43]([C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)[CH2:44][CH2:45][N:46]([CH:47]([CH3:49])[CH3:48])[CH:50]([CH3:52])[CH3:51])[CH:37]=2)=[CH:27][CH:26]=1)([C:63]([CH3:66])([CH3:64])[CH3:65])([CH3:62])[CH3:61]

Participants

5

Reactant 2

HCID 2723923Ammonium formate3×HCID 579331708-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]quinolin-2(1H)-one

Product 1

HCID 579331955-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]-8-hydroxyquinolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst3×HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}amino)ethyl]quinolin-2(1H)-one (Preparation 31, 406 mg, 0.45 mmol), ammonium formate (560 mg, 9.0 mmol) and 20% palladium hydroxide on carbon (60 mg) were mixed in methanol (8 ml) and stirred at 70° C. for 1 hour under nitrogen. Further ammonium formate (300 mg, 4.8 mmol) and 20% palladium hydroxide on carbon (30 mg) were then added and heating continued at 70° C. for further 1 hour. Reaction mixture was then cooled and filtered, the filtrate was collected and the solvent removed in vacuo. The residue was dissolved in methanol (8 ml) and ammonium formate (560 mg, 8.9 mmol) and 20% palladium hydroxide on carbon (60 mg) were added and stirred at 70° C. for 1 hour under nitrogen. Reaction mixture was then cooled and filtered, the filtrate was collected and the solvent removed in vacuo. Residue was dissolved in ethyl acetate (25 ml) and saturated aqueous sodium hydrogen carbonate (25 ml). Organics were separated and washed with brine (15 ml), dried (magnesium sulphate) and solvent was removed in vacuo to furnish the title compound as a yellow solid, 305 mg.

Workup

  1. temperatureheating
  2. waitcontinued at 70° C. for further 1 hour
  3. customReaction mixture
  4. temperaturewas then cooled
  5. filtrationfiltered
  6. customthe filtrate was collected
  7. customthe solvent removed in vacuo
  8. dissolutionThe residue was dissolved in methanol (8 ml)
  9. stirringstirred at 70° C. for 1 hour under nitrogen
  10. customReaction mixture
  11. temperaturewas then cooled
  12. filtrationfiltered
  13. customthe filtrate was collected
  14. customthe solvent removed in vacuo
  15. dissolutionResidue was dissolved in ethyl acetate (25 ml)
  16. customOrganics were separated
  17. washwashed with brine (15 ml)
  18. dry with materialdried (magnesium sulphate) and solvent
  19. customwas removed in vacuo

Sources & evidence

ORD record
ord-bd5befebec734a529625a759ab53be74
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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