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 988029Notes

Reaction equation

HRID 988029 reaction equation
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

Participants

8

Reactant 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, compound

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-98b6db93231b4d0ead9f86a38facab65
Source dataset
uspto-grants-2003_10
Patent number
US06632942B2

Reaction notes

Loading…