2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → Fmoc-Lys(MMT) valinol

HRID 400324Notes

Reaction equation

HRID 400324 reaction equation
[NH2:1][C@H:2]([CH2:6][OH:7])[CH:3]([CH3:5])[CH3:4].[NH:8]([C:39]([O:41][CH2:42][CH:43]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49]2[C:44]1=[CH:45][CH:46]=[CH:47][CH:48]=2)=[O:40])[C@H:9]([C:36]([OH:38])=[O:37])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:16]1[CH:23]=[CH:22][C:19]([O:20][CH3:21])=[CH:18][CH:17]=1.CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1>ClCCl>[NH:8]([C:39]([O:41][CH2:42][CH:43]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49]2[C:44]1=[CH:45][CH:46]=[CH:47][CH:48]=2)=[O:40])[C@H:9]([C:36]([OH:38])=[O:37])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:16]1[CH:17]=[CH:18][C:19]([O:20][CH3:21])=[CH:22][CH:23]=1.[NH2:1][C@H:2]([CH2:6][OH:7])[CH:3]([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 640993L-ValinolHCID 11422318(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-6-(((4-Methoxyphenyl)diphenylmethyl)amino)hexanoic acid

Product 1

HCID 131729109Fmoc-Lys(MMT) valinolYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The synthesis is schematically shown in Scheme-2. L-Valinol (40 mg) was reacted with commercially available Fmoc-Lys(MMT)-OH (253 mg) and EEDQ (107 mg) in 10 mL of anhydrous dichloromethane at ambient temperature, under argon, for 3 h. Extractive work up followed by flash chromatography furnished the product Fmoc-Lys(MMT)-valinol as a pale yellow liquid (200 mg; ˜70% yield). HPLC: tR14.38 min; electrospray mass spectrum: M+H: m/z 727. This intermediate (200 mg) was deprotected with diethylamine (10 mL), and the product (135 mg) was obtained in ˜90% purity after flash chromatography. HPLC: tR 10.91 min; electrospray mass spectrum: M+Na at m/z 527. This product (135 mg) was coupled with the commercially available O-(2-azidoethyl)-O′—(N-diglycolyl-2-aminoethyl)heptaethyleneglycol (‘PEG-N3’; 150 mg, 1.1 equiv.) in presence of EEDQ (72 mg, 1.1 equiv.) in 10 mL of dichloromethane, and stirred overnight at ambient temperature. The crude material was purified by flash chromatography to obtain 240 mg of the purified product as a light yellow oil (˜87% yield). HPLC: tR 11.55 min; electrospray mass spectrum: M+H and M+Na at m/z 1041 and 1063, respectively.

Sources & evidence

ORD record
ord-f0bb4d895b9c47f7b97a70d4b4242447
Source dataset
uspto-grants-2014_06
Patent number
US08741300B2

Reaction notes

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