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

HRID 1496783Notes

Reaction equation

HRID 1496783 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: tR 14.38 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-bd22986eb47d4670ae49ea020fa7354e
Source dataset
uspto-grants-2015_12
Patent number
US09198978B2

Reaction notes

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