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Hydrochloric Acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 879246
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 879246
F[C:2](F)(F)C([O-])=O.[Na+].[CH3:9][NH:10][C@H:11]([C:15]([NH:17][C@H:18]([C:22]([N:24]([C@@H:26]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:27]([O:66][CH3:67])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:64][CH3:65])[C@@H:37]([CH3:63])[C:38]([NH:40][C@@H:41]([CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:42]([O:44][CH2:45][C:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[CH:48][CH:47]=1)=[O:43])=[O:39])=[O:30])[CH3:25])=[O:23])[CH:19]([CH3:21])[CH3:20])=[O:16])[CH:12]([CH3:14])[CH3:13].C([BH3-])#N.[Na+].Cl.C([O:81][C:82](=[O:111])[CH2:83][C@@H:84](OC)[C@@H](N(C(=O)[C@H](C(C)C)NC(OCC1C=CC=CC=1)=O)C)[C@@H](C)CC)(C)(C)C>>[C:82]([CH2:83][CH2:84][CH2:9][N:10]([CH3:2])[C@H:11]([C:15]([NH:17][C@H:18]([C:22]([N:24]([C@@H:26]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:27]([O:66][CH3:67])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:64][CH3:65])[C@@H:37]([CH3:63])[C:38]([NH:40][C@@H:41]([CH2:56][C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)[C:42]([O:44][CH2:45][C:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[CH:48][CH:47]=1)=[O:43])=[O:39])=[O:30])[CH3:25])=[O:23])[CH:19]([CH3:20])[CH3:21])=[O:16])[CH:12]([CH3:14])[CH3:13])([OH:111])=[O:81]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 4

HCID 313Hydrochloric Acid2×HCID 5003444Sodium cyanoborohydride2×HCID 10529182(3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoateHCID 86698261N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide sodium trifluoroacetate
2×

Produkt 1

HCID 56953551N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

24 mg (24 μmol) of N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide sodium trifluoroacetate (intermediate 21) and 31.5 μl of 15% aqueous amber aldehyde acid solution (49 μmol) were dissolved in 900 μl of a 1:1-dioxane/water composition and heated for 1 hour at a temperature of 100° C. After a short cooling period 1.7 mg (27 μmol) of sodium cyanoborohydride were added. The reaction composition was formulated with 0.1 of N hydrochloric acid to pH 3 and heated for 2 hours at a temperature of 100° C. It was reheated again for 2 hours at 100° C. after the same amounts of amber aldehyde acid solution, sodium cyanoborohydride, and hydrochloric acid had been added once again. Afterwards, the reaction composition had been separated directly by means of preparative HPLC. The yield was 20.1 mg (86% o. th.) of the title compound.

Aufarbeitung

  1. additionwere added
  2. customAfterwards, the reaction composition had been separated directly by means of preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-76236c85a8064b6fadcc444c5bf4e16d
Quelldatensatz
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08987209B2

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