1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate

HRID 2204988Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204988
[C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@@H:19]([C:38](O)=[O:39])[NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:56][C@@H:57]([CH2:68][CH3:69])[CH2:58][O:59][CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(OCC)(=O)C.C1COCC1.CN(C=O)C>[C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@H:19]([NH:20][C:21]([O:22][CH2:23][CH:24]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:30]=2[C:31]2[C:36]1=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:37])[C:38](=[O:39])[NH:56][C@@H:57]([CH2:68][CH3:69])[CH2:58][O:59][CH2:60][C:61](=[O:62])[O:63][C:64]([CH3:65])([CH3:67])[CH3:66])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67414703(5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acidHCID 87385354(S)-tert-butyl 2-(2-aminobutoxy)acetate

Produkt 1

HCID 86678282(8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 21974620tetrahydrofuran N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acid (6, 1 eq) and (S)-tert-butyl 2-(2-aminobutoxy)acetate (1.5 eq, from the previous step) in 2:1 THF/DMF (0.13 M) was added EDCI (1.3 eq), HOBT (1.3 eq), and DIEA (5 eq). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with 2:1 saturated aqueous NaHCO3/water, brine, dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-40% ethyl acetate in hexanes to give the product.

Aufarbeitung

  1. washThe organic layer was washed with 2:1 saturated aqueous NaHCO3/water, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated en vaccuo
  4. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  5. customto give the product

Quellen und Nachweise

ORD-Eintrag
ord-00381a7d7c264e32963e2e1824d16d30
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365506B2

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