1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-methyl 4-(tert-butoxycarbonylamino)-5-((S)-1-(4-iodobenzylamino)-5-methoxy-1,5-dioxopentan-2-ylamino)-5-oxopentanoate

HRID 333131Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 333131
[NH2:1][C@H:2]([C:9]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([I:19])=[CH:15][CH:14]=1)=[O:10])[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[CH3:20][C:21]([O:24][C:25]([NH:27][C@H:28]([C:35](O)=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])([CH3:23])[CH3:22].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:21]([O:24][C:25]([NH:27][C@H:28]([C:35]([NH:1][C@@H:2]([CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6])[C:9]([NH:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([I:19])=[CH:17][CH:18]=1)=[O:10])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])([CH3:22])([CH3:20])[CH3:23]

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7018756(S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acidHCID 68858394(S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate

Produkt 1

HCID 68630252(S)-methyl 4-(tert-butoxycarbonylamino)-5-((S)-1-(4-iodobenzylamino)-5-methoxy-1,5-dioxopentan-2-ylamino)-5-oxopentanoateAusbeute 77,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of (S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate (2.129 g, 4.47 mmol) in DCM (15 mL) and TFA (10 mL) was stirred at room temperature for 4 h. After the solvent was evaporated, the reaction mixture was diluted with DCM, washed with sat. K2CO3 aqueous solution and concentrated in vacuo to afford (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g). A solution of (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g), Boc-Glu(OMe)—OH.DCHA (1.97 g, 4.44 mmol), EDCI (1.02 g, 5.33 mmol), HOBt (0.599 g, 4.44 mmol) in DCM (100 mL) containing DIPEA (2.26 mL) was stirred at room temperature under nitrogen for 20 h. The reaction mixture was diluted with DCM, washed with 1N HCl aqueous solution, sat. NaHCO3 aqueous solution and brine. The organic phase was separated and evaporated under reduced pressure to give a crude product, which was purified by flash chromatography with hexane/ethyl acetate as eluent to give (S)-methyl 4-(tert-butoxycarbonylamino)-5-((S)-1-(4-iodobenzylamino)-5-methoxy-1,5-dioxopentan-2-ylamino)-5-oxopentanoate (2.137 g, 77% over 2 steps) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=8.4 Hz, 2H), 7.20 (s, 1H), 7.00 (d, J=8.4 Hz, 2H), 5.44 (brs, 1H), 4.48-4.30 (m, 3H), 4.06-4.02 (m, 1H), 3.69 (s, 6H), 2.54-2.37 (m, 4H), 2.20-1.93 (m, 3H), 1.37 (s, 9H); MS (ESI), 620 (M+H)+.

Aufarbeitung

  1. washwashed with 1N HCl aqueous solution, sat. NaHCO3 aqueous solution and brine
  2. customThe organic phase was separated
  3. customevaporated under reduced pressure
  4. customto give a crude product, which
  5. customwas purified by flash chromatography with hexane/ethyl acetate as eluent

Quellen und Nachweise

ORD-Eintrag
ord-970b81d105ff4a37b01c46b14452d065
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877970B2

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