Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-[(4-{[2-(3-{(R)-2-{(R)-2-(8-Benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)-ethylamino]propyl}phenyl)ethylcarbamoyl]methyl}phenyl)-methylcarbamoyl]ethyl}piperidin-4-yl Ester

HRID 2412301Notes

Reaction equation

HRID 2412301 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][C@H:11]([NH:13][CH2:14][C@@H:15]([C:24]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[C:30]3[C:25]=2[CH:26]=[CH:27][C:28](=[O:42])[NH:29]3)[O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH3:12])[CH:7]=[CH:8][CH:9]=1.[C:43]1([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH:49][C:50]([O:52][CH:53]1[CH2:58][CH2:57][N:56]([CH2:59][CH2:60][C:61](CNC2C=CC(CC(O)=O)=CC=2)=[O:62])[CH2:55][CH2:54]1)=[O:51].[O-]S(C(F)(F)F)(=O)=O.C([N:92]([CH2:96]C)[CH:93]([CH3:95])[CH3:94])(C)C>C(Cl)Cl>[CH2:35]([O:34][C:31]1[CH:32]=[CH:33][C:24]([C@@H:15]([O:16][Si:17]([C:20]([CH3:21])([CH3:23])[CH3:22])([CH3:19])[CH3:18])[CH2:14][NH:13][C@H:11]([CH3:12])[CH2:10][C:6]2[CH:5]=[C:4]([CH2:3][CH2:2][NH:1][C:15]([CH2:24][C:25]3[CH:30]=[CH:94][C:93]([N:92]([CH3:96])[C:61]([CH2:60][CH2:59][N:56]4[CH2:57][CH2:58][CH:53]([O:52][C:50](=[O:51])[NH:49][C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=5[C:75]5[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=5)[CH2:54][CH2:55]4)=[O:62])=[CH:95][CH:26]=3)=[O:16])[CH:9]=[CH:8][CH:7]=2)=[C:25]2[C:30]=1[NH:29][C:28](=[O:42])[CH:27]=[CH:26]2)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2758875TrifluoromethanesulfonateHCID 667815115-[(R)-2-{(R)-2-[3-(2-Aminoethyl)phenyl]-1-methylethylamino}-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneHCID 66781677[4-({3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}methylamino)-phenyl]acetic acid

Product 1

HCID 86704962Biphenyl-2-ylcarbamic Acid 1-[2-[(4-{[2-(3-{(R)-2-{(R)-2-(8-Benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)-ethylamino]propyl}phenyl)ethylcarbamoyl]methyl}phenyl)-methylcarbamoyl]ethyl}piperidin-4-yl EsterYield 76.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-[(R)-2-{(R)-2-[3-(2-aminoethyl)phenyl]-1-methylethylamino}-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (0.586 g, 1.00 mmol); [4-({3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}methylamino)-phenyl]acetic acid (0.516 g, 1.00 mmol); 2-chloropyridium triflate on Wang resin (polymer-supported Mukaiyama reagent) (1.19 mmol/g loading; 1.68 g, 2.00 mmol); and N,N-diisopropylethylamine (522 μL, 3.00 mmol) in DCM (5.00 mL) was stirred at room temperature overnight. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-5% MeOH in DCM) to give the title compound (412 mg, 38% yield) as an off-white oil.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography (0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-43a08373c6964da7862d54b5bfd69807
Source dataset
uspto-grants-2014_08
Patent number
US08816088B2

Reaction notes

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