Triethylamine → Tricyclo [3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-thienyl)ethyl]amino]ethyl]carbamate

HRID 1080548

Reaktionsgleichung

Reaktionsgleichung von HRID 1080548
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[O:11][C:12]([NH:14][C:15]([CH3:29])([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=1)=[O:13])[CH2:8]2.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[S:59]1[CH:63]=[CH:62][CH:61]=[C:60]1[CH2:64][CH2:65][NH2:66]>C(OCC)(=O)C.CN(C)C=O>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([CH2:16][C:15]([NH:14][C:12](=[O:13])[O:11][CH:2]2[CH:1]3[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][CH:3]2[CH2:4]4)[CH2:8]3)([CH3:29])[C:26](=[O:27])[NH:66][CH2:65][CH2:64][C:60]2[S:59][CH:63]=[CH:62][CH:61]=2)=[CH:18]1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 4585722-Thiopheneethylamine, hydrochlorideHCID 148025032-adamantyloxycarbonyl-alpha-methyl-DL-tryptophan

Produkt 1

HCID 86747496Tricyclo [3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-thienyl)ethyl]amino]ethyl]carbamateAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

To a solution of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan (0.401 g, 1.01 mmol) in dry ethyl acetate (6 mL) and N,N-dimethylformamide (4 mL) under nitrogen atmosphere was added 1-hydroxybenzotriazole (0.138 g, 1.02 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.199 g, 1.04 mmol). This mixture was stirred 2 hours, then triethylamine (0.18 mL, 1.3 mmol) and 2-thiopheneethaneamine hydrochloride (0.214 g, 1.30 mmol) were added. After stirring the resulting mixture an additional 18 hours, the mixture was diluted with ethyl acetate (20 mL), and washed with aqueous 1N citric acid, saturated aqueous sodium bicarbonate, and brine solutions. The organic phase was dried over MgSO4, concentrated, purified by flash chromatography (SiO2, 4×20 cm, 230-400 mesh, 67% ethyl acetate/hexane eluant), and dried for 48 hours under vacuum at 60° C. to provide 0.310 g (61%) of product; 1H NMR (CDCl3) δ1.49-1.60 (2H, m), 1.55 (3H, s), 1.65-2.00 (12H, m), 2.88 (2H, t, J 6 Hz), 3.26 (1H, d, J 14 Hz), 3.40-3.60 (3H, m), 4.82 (1H, br s), 5.17 (1H, br s), 6.36 (1H, br s), 6.69 (1H, d, J 2 Hz), 6.85-6.90 (1H, m), 6.95 (1H, d, J 2 Hz), 7.00-7.22 (3H, m), 7.36 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.29 (1H, br s).

Aufarbeitung

  1. stirringAfter stirring the resulting mixture an additional 18 hours
  2. washwashed with aqueous 1N citric acid, saturated aqueous sodium bicarbonate, and brine solutions
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated
  5. custompurified by flash chromatography (SiO2, 4×20 cm, 230-400 mesh, 67% ethyl acetate/hexane eluant)
  6. customdried for 48 hours under vacuum at 60° C.

Quellen und Nachweise

ORD-Eintrag
ord-bd1556ed3eef4a74a1f21fa314359eeb
Quelldatensatz
uspto-grants-1996_12
Patentnummer
US05580896

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