Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-({3-[4-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]phenyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 1097064Notes

Reaction equation

HRID 1097064 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:11][C@@H:12]([C:21]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[C:27]3[C:22]=2[CH:23]=[CH:24][C:25](=[O:39])[NH:26]3)[O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[C:47]1([C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=1[NH:53][C:54]([O:56][CH:57]1[CH2:62][CH2:61][N:60]([CH2:63][CH2:64][C:65](CNC2C=C(C=CC=2)C(O)=O)=[O:66])[CH2:59][CH2:58]1)=[O:55].ON1[C:89]2[N:90]=[CH:91][CH:92]=[CH:93][C:88]=2N=N1.C(N([CH2:101][CH3:102])C(C)C)(C)C.CCN=C=NCCCN(C)C.Cl.[C:115](=O)(O)[O-:116].[Na+]>C(Cl)Cl>[CH2:40]([N:10]([CH2:11][C@@H:12]([C:21]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:27]2[C:22]=1[CH:23]=[CH:24][C:25](=[O:39])[NH:26]2)[O:13][Si:14]([C:17]([CH3:20])([CH3:18])[CH3:19])([CH3:16])[CH3:15])[CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:115]([C:92]2[CH:93]=[C:88]([CH2:89][NH:90][C:65]([CH2:64][CH2:63][N:60]3[CH2:59][CH2:58][CH:57]([O:56][C:54](=[O:55])[NH:53][C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=4[C:78]4[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=4)[CH2:62][CH2:61]3)=[O:66])[CH:101]=[CH:102][CH:91]=2)=[O:116])=[CH:7][CH:6]=1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667720895-[(R)-2-{[2-(4-Aminophenyl)ethyl]benzylamino}-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneHCID 667823883-({3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}methylamino)benzoic Acid

Product 1

HCID 86646971Biphenyl-2-ylcarbamic Acid 1-[2-({3-[4-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]phenyl}methylcarbamoyl)ethyl]piperidin-4-yl EsterYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-[(R)-2-{[2-(4-aminophenyl)ethyl]benzylamino}-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (1.27 g, 2.00 mmol); 3-({3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}methylamino)benzoic acid (1.00 g, 2.00 mmol); 1-hydroxy-7-azabenzotriazole (0.286 g, 2.10 mmol) and N,N-diisopropylethylamine (0.697 mL, 4.00 mmol) in DCM (5.00 mL) was stirred for 30 min at room temperature. N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.575 g, 3.00 mmol) was added and the resulting mixture was stirred for 3 h. Saturated aqueous sodium bicarbonate solution (5 mL) was added and this mixture was extracted with DCM (2×5 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-10% MeOH in DCM) to give the title compound (1.74 g, 77% yield) as a yellow solid.

Workup

  1. extractionthis mixture was extracted with DCM (2×5 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-f036a69e82e947b59f0efa41939de516
Source dataset
uspto-grants-2012_03
Patent number
US08138345B2

Reaction notes

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