Triphenylphosphine → N-(2-benzyloxy-5-oxotetrahydrofuran-3-yl)-6,10-dioxo-9-(isoquinolin-1-oylamino)-1,2,3,4,7,8,9,10-octahydro-6-H-pyridazino[1,2-a][1,2]diazepine-1-carboxamide

HRID 988029Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 988029
C(O[C:5]([NH:7][C@H:8]1[CH2:12][C:11](=[O:13])[O:10][CH:9]1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:6])C=C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:41]1([C:51]([NH:53][CH:54]2[C:60](=[O:61])[N:59]3[CH:62](C([O-])=O)[CH2:63][CH2:64][CH2:65][N:58]3[C:57](=[O:69])[CH2:56][CH2:55]2)=[O:52])[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[CH:43][N:42]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>ClCCl.O>[CH2:15]([O:14][CH:9]1[CH:8]([NH:7][C:5]([CH:62]2[N:59]3[C:60](=[O:61])[CH:54]([NH:53][C:51]([C:41]4[C:50]5[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=5)[CH:44]=[CH:43][N:42]=4)=[O:52])[CH2:55][CH2:56][C:57](=[O:69])[N:58]3[CH2:65][CH2:64][CH2:63]2)=[O:6])[CH2:12][C:11](=[O:13])[O:10]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Komponenten

8

Edukt 5

HCID 11776TriphenylphosphineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10989944(3S,2RS)3-allyloxycarbonylamino-2-benzyloxy-5-oxotetrahydrofuranHCID 867592179-(isoquinolin-1-oylamino)-6,10-dioxo-1,2,3,4,7,8,9, 10-octahydro-6-H-pyridazino[1,2-a][1,2]diazepine-1-carboxylateHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 72754309N-(2-benzyloxy-5-oxotetrahydrofuran-3-yl)-6,10-dioxo-9-(isoquinolin-1-oylamino)-1,2,3,4,7,8,9,10-octahydro-6-H-pyridazino[1,2-a][1,2]diazepine-1-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (3S, 2RS) 3-allyloxycarbonylamino-2-benzyloxy-5-oxotetrahydrofuran [Bioorg. & Med. Chem. Lett., 2, pp. 615-618 (1992)] (4.4 g, 15.1 mmol) in dichloromethane was added N,N-dimethylbarbituric acid (5.9 g, 3.8 mmol) then tetrakispalladium(0) triphenyl phosphine (1.7 g, 1.5 mmol) and the resulting mixture was allowed to stir at ambient temperature for 15 minutes. To the resulting mixture was added the acid, compound XIII (from step C) (5.0 g, 12.6 mmol), hydroxybenzotriazole(2.0 g, 14.8 mmol), then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.7 g, 14 mmol) and the reaction was allowed to stir for 3 hours at ambient temperature. The reaction mixture was then poured into water and extracted with ethyl acetate. The organics were washed with 0.5M sodium bisulfate, water, sodium bicarbonate, brine, dried over magnesium sulfate and concentrated in vacuo to afford 2.6 g of the crude product as a yellow foam. The crude material was purified by column chromatography (SiO2, dichloromethane:acetone 9:1-3:1) to afford 1.2 g of the compound 4-b.

Aufarbeitung

  1. stirringto stir for 3 hours at ambient temperature
  2. extractionextracted with ethyl acetate
  3. washThe organics were washed with 0.5M sodium bisulfate, water, sodium bicarbonate, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford 2.6 g of the crude product as a yellow foam
  7. customThe crude material was purified by column chromatography (SiO2, dichloromethane:acetone 9:1-3:1)

Quellen und Nachweise

ORD-Eintrag
ord-98b6db93231b4d0ead9f86a38facab65
Quelldatensatz
uspto-grants-2003_10
Patentnummer
US06632942B2

Notizen zur Reaktion

Wird geladen…