1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate

HRID 1092565

Reaktionsgleichung

Reaktionsgleichung von HRID 1092565
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1([CH:23]([CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[C:24]([NH:26][C@H:27]2[C@H:34]3[C@H:30]([CH2:31][NH:32][CH2:33]3)[CH2:29][CH2:28]2)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.OC1C2N=NNC=2C=CC=1.CN(C)CCCN=C=NCC>ClCCl>[CH:35]1([CH:23]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:24]([NH:26][C@H:27]2[C@H:34]3[C@H:30]([CH2:31][N:32]([C:14](=[O:16])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH:11]([CH3:12])[CH3:13])[CH2:33]3)[CH2:29][CH2:28]2)=[O:25])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]1

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 637604tert-Butoxycarbonyl-D-leucineHCID 546741702,2-dicyclohexyl-N-[(3aS,4R,6aR)-octahydrocyclopenta[c]pyrrol-4-yl]acetamideHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 131729483tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

N-(tert-Butoxycarbonyl)-D-leucine (72.7 mg, 0.314 mmol), 2,2-dicyclohexyl-N-[(3aS,4R,6aR)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide (95 mg, 0.286 mmol) from Example 74, and hydroxybenzotriazole (48.1 mg, 0.314 mmol) were combined in dichloromethane (10 mL). After 20 minutes, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (0.056 mL, 0.314 mmol) was added, and the reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with water. The separated organic layer was reduced in volume, and the crude material was applied to a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) and eluted first with 10% to 100% ethyl acetate/hexanes and then with 1-10% methanol (2 N ammonia)/dichloromethane to give tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.26 (dd, J=7.2, 24.0, 1H), 7.91 (d, J=8.6, 1H), 4.48-4.36 (m, 1H), 4.12-3.96 (m, 1H), 3.87 (dd, J=7.4, 10.3, 1H), 3.70 (ddd, J=8.0, 14.4, 23.7, 1H), 3.40 (dd, J=5.7, 12.3, 1H), 2.77 (s, 1H), 2.58 (d, J=6.1, 1H), 2.08 (s, 1H), 2.01 (dd, J=5.6, 10.4, 2H), 1.96-1.55 (m, 17H), 1.54-1.50 (m, 9H), 1.49-1.37 (m, 2H), 1.19 (qdd, J=12.3, 22.3, 24.7, 11H), 1.00 (t, J=6.6, 3H), 0.88 (d, J=6.6, 1H).

Aufarbeitung

  1. customThe reaction was quenched with water
  2. washeluted first with 10% to 100% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-320bc4fc329e4f45a24332e01f4b3703
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129417B2

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