Acetic Acid → Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(3-{2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-ethyl}phenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 1055303Notes

Reaction equation

HRID 1055303 reaction equation
C([N:8]([CH2:51][C@@H:52]([C:61]1[CH:70]=[CH:69][C:68]([O:71]CC2C=CC=CC=2)=[C:67]2[C:62]=1[CH:63]=[CH:64][C:65](=[O:79])[NH:66]2)[O:53][Si:54]([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55])[CH2:9][CH2:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]([CH2:20][CH2:21][CH2:22][N:23]([CH3:50])[C:24]([CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([O:34][C:35](=[O:49])[NH:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:30][CH2:29]2)=[O:25])=[O:19])[CH:14]=[CH:15][CH:16]=1)C1C=CC=CC=1.C(O)(=O)C.O>CO.[OH-].[Pd+2].[OH-]>[Si:54]([O:53][C@H:52]([C:61]1[CH:70]=[CH:69][C:68]([OH:71])=[C:67]2[C:62]=1[CH:63]=[CH:64][C:65](=[O:79])[NH:66]2)[CH2:51][NH:8][CH2:9][CH2:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]([CH2:20][CH2:21][CH2:22][N:23]([CH3:50])[C:24]([CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([O:34][C:35](=[O:49])[NH:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH2:30][CH2:29]2)=[O:25])=[O:19])[CH:14]=[CH:15][CH:16]=1)([C:57]([CH3:60])([CH3:58])[CH3:59])([CH3:55])[CH3:56]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 86704960Biphenyl-2-ylcarbamic Acid 1-[2-({3-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]propyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester

Product 1

HCID 86704961Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(3-{2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-ethyl}phenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of biphenyl-2-ylcarbamic acid 1-[2-({3-[3-(2-{benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2- (tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]propyl}methylcarbamoyl)ethyl]piperidin-4-yl ester (258 mg, 0.238 mmol) in MeOH (3 mL) at room temperature was added a solution of acetic acid in water (17.4 M, 41.4 μL, 0.720 mmol). The resulting solution was purged with nitrogen (3 cycles of vacuum following by dry nitrogen) and then palladium hydroxide (47 mg, 0.34 mmol) was added. This mixture was again purged with nitrogen and then with hydrogen (5×) and then stirred at room temperature under hydrogen (balloon with submerged needle) for 6 h. LC-MS (Method 2-90) showed product was present (Rt 3.71 min; m/z 903.6 [M+H]+). The reaction mixture was filtered through a membrane filter and the filtrate was concentrated under reduced pressure to give the title compound, which was used in the next reaction without further purification.

Workup

  1. customThe resulting solution was purged with nitrogen (3 cycles of vacuum following by dry nitrogen)
  2. customThis mixture was again purged with nitrogen
  3. filtrationThe reaction mixture was filtered through a membrane
  4. filtrationfilter
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-924b8d82f89749c8a1f6d8958bfd1183
Source dataset
uspto-grants-2016_07
Patent number
US09394275B2

Reaction notes

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