Diisopropylethylamine → (12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate

HRID 1425946Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1425946
[NH2:1][C@H:2]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].C(N(C(C)C)CC)(C)C.[C:33]([O:37][C:38]([NH:40][CH2:41][CH2:42][N:43]([CH2:60][CH2:61][NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[C:44](=[O:59])[CH2:45][CH2:46][C@H:47]([NH:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:48](O)=[O:49])=[O:39])([CH3:36])([CH3:35])[CH3:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[C:55]([O:54][C:52]([NH:51][C@H:47]([C:48](=[O:49])[NH:1][C@H:2]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:18][CH:19]=1)[C:3]([O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:4])[CH2:46][CH2:45][C:44](=[O:59])[N:43]([CH2:42][CH2:41][NH:40][C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[CH2:60][CH2:61][NH:62][C:63](=[O:64])[O:65][C:66]([CH3:69])([CH3:67])[CH3:68])=[O:53])([CH3:56])([CH3:57])[CH3:58]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59366705(S)-5-[Bis[2-(Boc-amino)ethyl]amino]-2-(Boc-amino)-5-oxopentanoic AcidHCID 86702807(R)-benzyl 2-amino-3-(4-(trifluoromethyl)phenyl)propanoate

Produkt 1

HCID 86702806(12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oateAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a suspension of (R)-benzyl 2-amino-3-(4-(trifluoromethyl)phenyl)propanoate (CLXV) (3 g, 8.33 mmol) in DCM (25 mL) was added diisopropylethylamine (3.57 mL, 20.83 mmol). To this solution was added (S)-5-(bis(2-(tert-butoxycarbonylamino)ethyl)amino)-2-(tert-butoxycarbonylamino)-5-oxopentanoic acid (XVI) (4.88 g, 9.16 mmol) and TBTU (2.94 g, 9.16 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was then diluted with DCM (50 mL) and washed with 2 N aqueous HCl, 1 N aqueous NaOH, brine, dried over MgSO4 and concentrated under vacuum to dryness. The residue was purified on a silica gel column using DCM:MeOH (100:1) to yield (12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate (6.1 g, 7.28 mmol, 88% yield). 1H NMR (DMSO-d6) δ ppm 1.41 (s, 27H), 1.78-1.96 (m, 2H), 2.17 (brs, 1H), 2.59 (brs, 1H), 3.09-3.15 (m, 1H), 3.16-3.27 (m, 2H), 3.28-3.39 (m, 2H), 3.42-3.52 (m, 1H), 3.62 (brs, 1H), 4.06-4.14 (m, 1H), 4.83-4.91 (m, 1H), 5.08 (d, J=12 Hz, 1H), 5.17 (d, J=12 Hz, 1H), 5.76 (brs, 1H), 7.19 (d, J=8 Hz, 1H), 7.23-7.29 (m, 3H), 7.3-7.39 (m, 3H), 7.44 (d, J=8 Hz, 2H), 7.62 (brs, 1H); 19F NMR (DMSO-d6) δ ppm −61.84 (s, 3F); ESIMS found for C41H58F3N5O10 m/z 838.9 (M+H).

Aufarbeitung

  1. washwashed with 2 N aqueous HCl, 1 N aqueous NaOH, brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under vacuum to dryness
  4. customThe residue was purified on a silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-8e116659be0e4b8ea81a8a3c5fef4963
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933018B2

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