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Diisopropylethylamine → (S)-7-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1-methyl-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

HRID 391861
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 391861
[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22]([OH:24])=O)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:26]4[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]5[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=5)=[CH:28][CH:27]=4)[CH2:15][N:16]3[CH3:25])=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:75][O:76][C:77](=[O:95])[C@@H:78]([NH2:94])[CH2:79][C:80]1[CH:85]=[CH:84][C:83]([C:86]2[CH:91]=[CH:90][C:89]([C:92]#[N:93])=[CH:88][CH:87]=2)=[CH:82][CH:81]=1>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22](=[O:24])[NH:94][C@H:78]([C:77]([O:76][CH3:75])=[O:95])[CH2:79][C:80]2[CH:81]=[CH:82][C:83]([C:86]3[CH:91]=[CH:90][C:89]([C:92]#[N:93])=[CH:88][CH:87]=3)=[CH:84][CH:85]=2)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:26]4[CH:27]=[CH:28][C:29]([O:32][CH2:33][C:34]5[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=5)=[CH:30][CH:31]=4)[CH2:15][N:16]3[CH3:25])=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59337513Methyl (s)-2-amino-3-(4'-cyano-[1,1'-biphenyl]-4-yl)propanoateHCID 66719462(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1-methyl-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester

Produkt 1

HCID 66719482
(S)-7-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1-methyl-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirring solution of (S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1-methyl-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester, HBTU (95 mg) and DIEA in DMF (5 mL) was added (S)-2-amino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (79 mg). After 4 hours a sufficient amount of water was added and the mixture was extracted with ethyl acetate. The organic was washed with 1 N HCl, saturated NaHCO3 and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to provide the crude amide. The residue was purified by column chromatography on silica gel (hexanes/ethyl acetate from 80:20 to 60:40) to afford the product (180 mg).

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic was washed with 1 N HCl, saturated NaHCO3 and brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customto provide the crude amide
  6. customThe residue was purified by column chromatography on silica gel (hexanes/ethyl acetate from 80:20 to 60:40)

Quellen und Nachweise

ORD-Eintrag
ord-d1189dcb586e48c4b7551ee72aa3c3f7
Quelldatensatz
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08383644B2

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