Diisopropylethylamine → N-tert-butoxycarbonyl O-allyl L-seryl alpha,alpha-dimethylglycyl L-valyl O-allyl L-seryl glycine methyl ester

HRID 2370904Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2370904
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:22])[CH2:11][NH:12][C:13](=[O:21])[C@H:14]([CH2:16][O:17][CH2:18][CH:19]=[CH2:20])[NH2:15].[C:23]([O:27][C:28]([NH:30][C@H:31]([C:37]([NH:39][C:40]([CH3:52])([CH3:51])[C:41]([NH:43][C@H:44]([C:48](O)=[O:49])[CH:45]([CH3:47])[CH3:46])=[O:42])=[O:38])[CH2:32][O:33][CH2:34][CH:35]=[CH2:36])=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:22])[CH2:11][NH:12][C:13](=[O:21])[C@H:14]([CH2:16][O:17][CH2:18][CH:19]=[CH2:20])[NH:15][C:48](=[O:49])[C@H:44]([CH:45]([CH3:46])[CH3:47])[NH:43][C:41](=[O:42])[C:40]([CH3:52])([CH3:51])[NH:39][C:37](=[O:38])[C@H:31]([CH2:32][O:33][CH2:34][CH:35]=[CH2:36])[NH:30][C:28]([O:27][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:29]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86671353N-tert-butoxycarbonyl O-allyl L-seryl alpha,alpha-dimethylglycyl L-valineHCID 86671357O-allyl L-seryl glycine methyl ester trifluoroacetate

Produkt 1

HCID 86762377N-tert-butoxycarbonyl O-allyl L-seryl alpha,alpha-dimethylglycyl L-valyl O-allyl L-seryl glycine methyl esterAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

O-allyl L-seryl glycine methyl ester trifluoroacetate 20 (4.42 g, 13.4 mmol) was dissolved in CH2Cl2 (40 mL) and N-tert-butoxycarbonyl O-allyl L-seryl α,α-dimethylglycyl L-valine 16 (5.75 g, 13.4 mmol) added. N,N-diisopropylethyl amine (1.73 g, 13.4 mmol) and HOBt hydrate (2.05 g, 13.4 mmol) were added and the solution cooled to 0° C. EDC hydrochloride (2.82 g, 14.7 mmol) was added in small portions together with 10 mL CH2Cl2. The reaction mixture was stirred for 1 h 30 min at 0° C. after which the icebath was removed and the mixture stirred for an additional 26 hours. The solution was diluted by addition of CH2Cl2 (60 mL) and washed with 2 M aqueous H2SO4 (3×90 mL), 7.5% (w/w) aqueous K2CO3 (3×90 mL) and saturated brine (90 mL). The volume was increased by addition of CH2Cl2, the solution dried with anhydrous MgSO4 and the solvent evaporated affording a slightly orange solid (6.14 g, 73%); δH (300 MHz; d6-DMSO) 8.25 (1H, t, J 6, NH(Gly)), 8.14 (1H, s, NH(Aib)), 7.88 (1H, d, J 8, NH(Ser(All))), 7.14 (1H, d, J 8, NH(Val)), 6.84 (1H, d, J 7, NH (Ser(All)1)), 5.92-5.74 (2H, m, CH═CH2), 5.28-5.11 (4H, m, CH═CH2), 4.50 (1H, m, CαH(Ser(All)2)), 4.17-4.09 (2H, m, CαH(Ser(All)1)/CαH(Val)), 3.95 (4H, m, CH2CH═CH2), 3.85 (2H, d, J 6, CαH2(Gly)), 3.61 (3H, s, OCH3), 3.58-3.46 (4H, m, CH2), 2.06-1.95 (1H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 1.35 (3H, s, CH3(Aib)), 1.34 (3H, s, CH3(Aib)), 0.83 (3H, d, J 7, CH3(Val)), 0.78 (3H, d, J 7, CH3(Val)); δC (75 MHz; d6-DMSO) 173.9, 170.7, 169.9, 169.8, 169.7, 155.3, 134.8, 116.4, 116.3, 78.4, 71.0, 69.4, 58.2, 56.2, 54.8, 54.5, 52.5, 51.6, 40.6, 30.0, 28.0, 24.9, 24.7, 19.0, 17.8; m/z 650.3366 ([M+Na]+; C29H49N5O10Na requires 650.3377)

Aufarbeitung

  1. customwas removed
  2. stirringthe mixture stirred for an additional 26 hours
  3. additionThe solution was diluted by addition of CH2Cl2 (60 mL)
  4. washwashed with 2 M aqueous H2SO4 (3×90 mL), 7.5% (w/w) aqueous K2CO3 (3×90 mL) and saturated brine (90 mL)
  5. temperatureThe volume was increased by addition of CH2Cl2
  6. dry with materialthe solution dried with anhydrous MgSO4
  7. customthe solvent evaporated

Quellen und Nachweise

ORD-Eintrag
ord-7de31ebd30464dcbba82c554062bf832
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08710008B2

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