Dichloromethane → Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 2366338Notes

Reaction equation

HRID 2366338 reaction equation
F.F.[OH:3][C@H:4]([C:49]1[CH:58]=[CH:57][C:56]([OH:59])=[C:55]2[C:50]=1[CH:51]=[CH:52][C:53](=[O:60])[NH:54]2)[CH2:5][NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH3:48])[C:22]([CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([O:32][C:33](=[O:47])[NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:28][CH2:27]2)=[O:23])=[O:16])=[CH:10][CH:9]=1.C(Cl)Cl.[OH-].[NH4+]>CO>[OH:3][C@H:4]([C:49]1[CH:58]=[CH:57][C:56]([OH:59])=[C:55]2[C:50]=1[CH:51]=[CH:52][C:53](=[O:60])[NH:54]2)[CH2:5][NH:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15]([CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH3:48])[C:22]([CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([O:32][C:33](=[O:47])[NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:28][CH2:27]2)=[O:23])=[O:16])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 6344Dichloromethane2×HCID 14923Ammonium Hydroxide2×HCID 66831448Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester Dihydrofluoric Acid Salt

Product 1

HCID 56953428Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl EsterYield 103.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl ester dihydrofluoric acid salt (15.2 g, 16.7 mmol) in a DCM solution containing 10% 0.5 M ammonium hydroxide in MeOH (150 mL total solution) was loaded onto silica gel (80 g) in a coarse fritted glass funnel which had been previously wetted with a DCM solution containing 10% 0.5 M ammonium hydroxide in MeOH (200 mL). The silica gel was rinsed with a DCM solution containing 20% 0.5 M ammonium hydroxide in MeOH (1×1000 mL); and then with a DCM solution containing 25% 0.5 M ammonium hydroxide in MeOH (1×1000 mL). The filtrate was concentrated under reduced pressure to give a yellow glassy solid (13.6 g). This material was dissolved in DCM (600 mL) and the resulting solution was filtered through a fritted glass filter and the filter was washed with DCM (3×150 mL). The filtrate was concentrated under reduced pressure and the residue was warmed to 50° C. using an oil bath and held under high vacuum overnight to provide the title compound (12.7 g) (contained about 6 wt. % of DCM).

Workup

  1. washThe silica gel was rinsed with a DCM solution
  2. additioncontaining 20% 0.5 M ammonium hydroxide in MeOH (1×1000 mL)
  3. additionand then with a DCM solution containing 25% 0.5 M ammonium hydroxide in MeOH (1×1000 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-74edd48fb05a47c09086599d9b26e9b9
Source dataset
uspto-grants-2014_04
Patent number
US08697724B2

Reaction notes

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