Diisopropylethylamine → Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

HRID 1865715Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1865715
[C:1]12([CH:11]([NH:15][CH3:16])[C:12]([OH:14])=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:50]/[C:51](=[CH:57]\[C@@H:58]([N:62]([CH3:71])[C:63](=[O:70])[C@H:64]([C:66]([CH3:69])([CH3:68])[CH3:67])[NH2:65])[CH:59]([CH3:61])[CH3:60])/[C:52]([O:54][CH2:55][CH3:56])=[O:53].C(N(C(C)C)CC)(C)C>ClCCl>[C:1]12([C@@H:11]([NH:15][CH3:16])[C:12]([NH:65][C@H:64]([C:63]([N:62]([CH3:71])[C@@H:58]([CH:59]([CH3:61])[CH3:60])/[CH:57]=[C:51](\[CH3:50])/[C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:70])[C:66]([CH3:69])([CH3:68])[CH3:67])=[O:14])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 11229817Adamantan-1-yl-methylamino-acetic acid

Produkt 1

HCID 86596600Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To adamantan-1-yl-methylamino-acetic acid (0.447 g, 2.0 mmol, from Reference Example 6) in dichloromethane (17 mL) is added PyBOP (1.04 g, 2.0 mmol). After 15 min ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.625 g, 2.0 mmol, WO 99/32509) in dichlormethane (5 mL) is added, followed by diisopropylethylamine (0.75 mL, 4.3 mmol). This is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo and the residue treated with ethyl acetate and water. The ethyl acetate layer is dried over sodium sulfate and purified by hplc. The two diastereomers are partially separated. The first isomer is assigned the SSS configuration and contained 33.4% of the RSS isomer. MS: m/z 518.3 (M+1). The second isomer is assigned the RSS configuration and contained 8.9% of the SSS isomer. MS: m/z 518.3 (M+1).

Aufarbeitung

  1. customThe reaction mixture is evaporated in vacuo
  2. additionthe residue treated with ethyl acetate and water
  3. dry with materialThe ethyl acetate layer is dried over sodium sulfate
  4. custompurified by hplc
  5. customThe two diastereomers are partially separated

Quellen und Nachweise

ORD-Eintrag
ord-4578af892eb84d9fa455a9a03fd04b52
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07626023B2

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