Diisopropylethylamine → N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl ester

HRID 2370897Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2370897
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:18])[CH3:17])[NH2:15].[C:24]([O:28][C:29]([NH:31][C@H:32]([C:42](O)=[O:43])[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:17])[CH3:18])[NH:15][C:42](=[O:43])[C@H:32]([CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[NH:31][C:29]([O:28][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:30]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86671346L-valyl L-valine methyl ester trifluoroacetate

Produkt 1

HCID 86671351N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl esterAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Versuchsvorschrift

L-valyl L-valine methyl ester trifluoroacetate 6 (11.62 g, 33.75 mmol) was dissolved in 60 mL DMF. N-tert-butoxycarbonyl O-benzyl L-serine 14 (9.97 g, 33.8 mmol) was added together with 10 mL DMF. The solution was cooled to 0° C. (icebath) before N,N-diisopropylethyl amine (4.36 g, 33.7 mmol), HOBt hydrate (5.17 g, 33.8 mmol) and EDC hydrochloride (7.12 g, 37.1 mmol) were added together with an additional 30 mL DMF. The reaction mixture was stirred overnight and the solvent evaporated. The residue was taken up in 200 mL EtOAc and washed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a white solid (16.22 g, 95%); δH (300 MHz; d6-DMSO) 8.20 (1H, d, J 8, NH(Valx)), 7.65 (1H, d, J 9, NH(Valy)), 7.35-7.23 (5H, m, Ph), 7.08 (1H, d, J 8, NH(Ser(Bn)), 4.46 (2H, s, CH2Ph), 4.35 (1H, dd, J 7 and 9, CαH(Valy)), 4.25 (1H, m, CαH(Ser(Bn))), 4.12 (1H, dd, J 6 and 8, CαH(Valx)), 3.63-3.54 (2H, m, CH2), 3.60 (3H, s, OCH3), 2.07-1.89 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.88-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.6, 171.0, 169.4, 155.1, 138.0, 128.0, 127.3, 127.3, 78.2, 71.9, 69.8, 57.4, 56.8, 54.5, 51.4, 31.1, 29.5, 28.0, 18.9, 18.7, 18.2, 17.7; m/z (ESI) 530.2824 ([M+Na]+; C26H41N3O7Na requires 530.2842)

Aufarbeitung

  1. customthe solvent evaporated
  2. washwashed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL)
  3. dry with materialThe solution was dried with anhydrous MgSO4
  4. customthe solvent evaporated

Quellen und Nachweise

ORD-Eintrag
ord-c8543a77007647dc9aec47fa7aa0063e
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08710008B2

Notizen zur Reaktion

Wird geladen…