Diisopropylethylamine → N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert-butoxy-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 2282868Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2282868
[CH3:1][O:2][C@@H:3]([C@@H:24]1[CH2:28][CH2:27][CH2:26][NH:25]1)[C@@H:4]([CH3:23])[C:5]([NH:7][C@H:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6].[CH:29]1[C:41]2[CH:40]([CH2:42][O:43][C:44]([NH:46][C:47]([CH3:72])([C:49]([NH:51][C@H:52]([C:56]([N:58]([C@@H:60]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:61]([O:66][CH3:67])[CH2:62][C:63](O)=[O:64])[CH3:59])=[O:57])[CH:53]([CH3:55])[CH3:54])=[O:50])[CH3:48])=[O:45])[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]=2[CH:32]=[CH:31][CH:30]=1.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.CN(C=O)C.C(OCC)(=O)C>[CH:29]1[C:41]2[CH:40]([CH2:42][O:43][C:44]([NH:46][C:47]([CH3:72])([C:49]([NH:51][C@H:52]([C:56]([N:58]([C@@H:60]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:61]([O:66][CH3:67])[CH2:62][C:63]([N:25]3[CH2:26][CH2:27][CH2:28][C@H:24]3[C@H:3]([O:2][CH3:1])[C@@H:4]([CH3:23])[C:5]([NH:7][C@@H:8]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:6])=[O:64])[CH3:59])=[O:57])[CH:53]([CH3:55])[CH3:54])=[O:50])[CH3:48])=[O:45])[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]=2[CH:32]=[CH:31][CH:30]=1

Komponenten

8

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 86685741L-Valinamide, N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(1S,2S)-1-[(1R)-2-carboxy-1-methoxyethyl]-2-methylbutyl]-N-methyl-HCID 86685746tert-butyl N-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoyl}-L-phenylalaninate

Produkt 1

HCID 86685745N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert-butoxy-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamideAusbeute 63,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirring solution of #121 (0.55 g, 1.0 mmol, 1.0 eq.) in 10 mL of dichloromethane and 1 mL of DMF, #32 (0.62 g, 1.0 mmol, 1.0 eq.) was added followed by HATU (0.42 g, 1.1 mmol, 1.1 eq.) and Hunig's base (0.72 mL, 4.1 mmol, 4.0 eq.). The reaction was allowed to stir at room temperature for approximately 21 hours. Reaction was reduced down, diluted with ethyl acetate, and then washed with 0.5 N HCl and brine. Organic layer was dried over sodium sulfate, filtered, and concentrated to a smaller volume before being concentrated down onto silica. Silica chromatography was then performed (Gradient: 0%-40% acetone in heptane) producing #122 (0.62 g, 62%) as a white solid. LC-MS (Protocol Q): m/z 982.3 [M+H+] retention time=2.44 minutes.

Aufarbeitung

  1. customReaction
  2. washwashed with 0.5 N HCl and brine
  3. dry with materialOrganic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a smaller volume
  6. concentrationbefore being concentrated down onto silica

Quellen und Nachweise

ORD-Eintrag
ord-ede1a782b4264492a8b9c48998e2dc45
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09138486B2

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