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Diisopropylethylamine → methyl N-{(2R,3R)-3-[(2S)-1-{(3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoyl}pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninate

HRID 2282864
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2282864
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:42])[C@@H:26]([C@@H:38]([CH3:41])[CH2:39][CH3:40])[C@H:27]([O:36][CH3:37])[CH2:28][C:29](OC(C)(C)C)=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.[CH3:44][O:45][C@@H:46]([C@@H:64]1[CH2:68][CH2:67][CH2:66][NH:65]1)[C@@H:47]([CH3:63])[C:48]([NH:50][C@H:51]([C:59]([O:61][CH3:62])=[O:60])[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:49].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:42])[C@@H:26]([C@@H:38]([CH3:41])[CH2:39][CH3:40])[C@H:27]([O:36][CH3:37])[CH2:28][C:29]([N:65]3[CH2:66][CH2:67][CH2:68][C@H:64]3[C@H:46]([O:45][CH3:44])[C@@H:47]([CH3:63])[C:48]([NH:50][C@H:51]([C:59]([O:61][CH3:62])=[O:60])[CH2:52][C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)=[O:49])=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
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Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86685718(3R,4S,5S)-tert-butyl 4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoateHCID 118704819(S)-methyl 2-((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanamido)-3-phenylpropanoate hydrochloride

Produkt

1
HCID 86685782methyl N-{(2R,3R)-3-[(2S)-1-{(3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoyl}pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirring mixture of dimer acid #5 (12.1 g, 23.0 mM) and #67 (11.5 g, 23.0 mM) in 75 mL of dichloromethane under nitrogen, HATU (10.8 g, 27.6 mM) was added followed by Hunig's base (12.1 mL, 69.0 mM). The reaction was allowed to stir at room temperature for 15 hours. Reaction was concentrated to a smaller volume, taken up with ethyl acetate and washed with 1 N HCl two times. The organic layer was then washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Residue was then purified by silica gel chromatography (Gradient: 0% to 70% acetone in heptanes), producing #113 (12.3 g, 62%) as a white solid. LC-MS (Protocol Q): m/z 855.3 [M+H+], 877.2 [M+Na+], retention time=2.32 minutes; HPLC (Protocol R): /z 855.5 [M+H+], retention time=9.596 minutes (purity >97%).

Aufarbeitung

  1. customReaction
  2. concentrationwas concentrated to a smaller volume
  3. washwashed with 1 N HCl two times
  4. washThe organic layer was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customResidue was then purified by silica gel chromatography (Gradient: 0% to 70% acetone in heptanes)

Quellen und Nachweise

ORD-Eintrag
ord-ba2120faf91d4fd78afdfa28b316023e
Quelldatensatz
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09138486B2

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