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Diisopropylethylamine → (S)-benzyl 4-(tert-butoxycarbonylamino)-5-((R)-1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-4-(4-(trifluoromethyl)phenyl)butan-2-ylamino)-5-oxopentanoate

HRID 1425950
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1425950
[NH2:1][C@H:2]([CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)[C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([CH3:15])([CH3:14])[O:12][B:11]([OH:16])[C:10]=2[CH:17]=1)=[O:4].[NH:30]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C@H:31]([C:44](O)=[O:45])[CH2:32][CH2:33][C:34](=[O:43])[O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:50]([O:49][C:47]([NH:30][C@H:31]([C:44]([NH:1][C@H:2]([CH2:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:25]=1)[C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([CH3:15])([CH3:14])[O:12][B:11]([OH:16])[C:10]=2[CH:17]=1)=[O:4])=[O:45])[CH2:32][CH2:33][C:34]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:43])=[O:48])([CH3:53])([CH3:52])[CH3:51]
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Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 83589L-Glutamic acid, N-((1,1-dimethylethoxy)carbonyl)-, 5-(phenylmethyl) esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68281487HCID 68281487, Verbindung

Produkt 1

HCID 86702808
(S)-benzyl 4-(tert-butoxycarbonylamino)-5-((R)-1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-4-(4-(trifluoromethyl)phenyl)butan-2-ylamino)-5-oxopentanoate
Ausbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of (R)-2-amino-N-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-4-(4-(trifluoromethyl)phenyl)butanamide (CLXIX) (1.2 g, 2.71 mmol) and Boc-Glu(OBzl)-OH (CLXX) (0.915 g, 2.71 mmol) in DCM (10 mL) was added DIPEA (1.39 mL, 8.13 mmol). To this solution was added HATU (1.03 g, 2.71 mmol) and the mixture was stirred at room temperature overnight. The mixture was washed with 2 N aqueous HCl, 1 M aqueous K2CO3, brine and dried over MgSO4. The solution was evaporated to dryness under vacuum to give (S)-benzyl 4-(tert-butoxycarbonylamino)-5-((R)-1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-4-(4-(trifluoromethyl)phenyl)butan-2-ylamino)-5-oxopentanoate as an orange foam (1.83 g, 2.52 mmol, 93% yield). 1H NMR (DMSO-d6) δ ppm 1.33 (s, 9H), 1.4 (s, 6H), 1.8-1.88 (m, 1H), 1.9-1.96 (m, 2H), 2.08 (brs, 1H), 2.42 (brs, 2H), 2.6-2.66 (m, 1H), 2.7-2.76 (m, 1H), 3.98-4.05 (m, 1H), 4.4 (brs, 1H), 5.07 (s, 2H), 7.1 (brs, 1H), 7.28-7.34 (m, 6H), 7.37-7.44 (m, 2H), 7.55-7.63 (m, 3H), 7.89 (s, 1H), 8.34 (brs, 1H), 9.0 (s, 1H), 9.86 (s, 1H); 19F NMR (DMSO-d6) δ ppm −60.11 (s, 3F); ESIMS found for C37H43BF3N3O8 m/z 726.7 (M+H).

Aufarbeitung

  1. washThe mixture was washed with 2 N aqueous HCl, 1 M aqueous K2CO3, brine
  2. dry with materialdried over MgSO4
  3. customThe solution was evaporated to dryness under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-c66dbe05337d4ee985a9b44b45c042e1
Quelldatensatz
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08933018B2

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