1-Hydroxybenzotriazole → (2S)-N-[(3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-2-phenylbutanamide

HRID 1092477

Reaktionsgleichung

Reaktionsgleichung von HRID 1092477
[C:1]1([C@H:7]([CH2:11][CH3:12])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.CC[N+](CCCN(C)C)=C=N.[CH2:34]([N:41]1[CH2:45][C@H:44]2[C@H:46]([NH2:49])[CH2:47][CH2:48][C@H:43]2[CH2:42]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[CH2:34]([N:41]1[CH2:45][C@H:44]2[C@H:46]([NH:49][C:8](=[O:10])[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11][CH3:12])[CH2:47][CH2:48][C@H:43]2[CH2:42]1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Komponenten

6

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 785329(S)-2-Phenylbutyric acidHCID 218833923-(Dimethylamino)propyl-ethyl-(iminomethylidene)azaniumHCID 25918977(3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine

Produkt 1

HCID 54673710(2S)-N-[(3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-2-phenylbutanamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

(S)-2-Phenylbutanoic acid (41.7 mg, 0.254 mmol), 1-hydroxybenzotriazole (38.9 mg, 0.254 mmol), and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (0.045 mL, 0.254 mmol) were combined in dichloromethane (1 mL). The reaction was stirred at room temperature for 10 minutes, and then (3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine (50 mg, 0.231 mmol) from Step E was added in 0.5 mL of dichloromethane. The reaction was stirred at room temperature for 20 hours, and then quenched with 0.5 mL of water. The organic layer was separated. The crude material was chromatographed using a silica gel cartridge (Analogix®, Burlington, Wis., RS-4) eluting with 1-10% methanol(ammonia)/dichloromethane to give the title compound: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.47 (d, J=7.0, 1H), 7.59 (m, 2H), 7.42 (d, J=7.1, 2H), 7.34 (dd, J=7.6, 16.5, 4H), 7.25 (dt, J=5.0, 10.1, 2H), 4.45-4.29 (m, 1H), 3.62-3.51 (m, 2H), 3.44 (d, J=13.2, 1H), 2.85 (dd, J=2.7, 9.0, 1H), 2.58-2.50 (m, 1H), 2.50-2.42 (m, 2H), 2.40-2.31 (m, 1H), 2.31-2.22 (m, 2H), 1.97 (dq, J=6.1, 12.1, 1H), 1.85 (td, J=6.9, 13.6, 1H), 1.74 (dt, J=6.4, 14.3, 1H), 1.46 (dt, J=7.1, 19.2, 1H), 1.31 (dt, J=6.2, 20.5, 1H), 0.96 (dd, J=5.5, 9.1, 3H); MS (ESI+) m/z 363 (M+H)+.

Aufarbeitung

  1. stirringThe reaction was stirred at room temperature for 20 hours
  2. customquenched with 0.5 mL of water
  3. customThe organic layer was separated
  4. customThe crude material was chromatographed
  5. washeluting with 1-10% methanol(ammonia)/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-710f827f90094aaa9df9eb66d8007e17
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129417B2

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