Tributylstannane → N-(2-Benzyloxy-5-oxotetrahydrofuran-3-yl)-6,10-dioxo-octahydro-9-(3-phenylpropionylamino)-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxamide

HRID 2257409Notes

Reaction equation

HRID 2257409 reaction equation
[O:1]=[C:2]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:19])[CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5](=[O:20])[N:4]2[C@H:21]([C:25](O)=[O:26])[CH2:22][CH2:23][CH2:24][N:3]12.C(OC([NH:34][C@H:35]1[CH2:39][C:38](=[O:40])[O:37][CH:36]1[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=O)C=C.C([SnH](CCCC)CCCC)CCC.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:42]([O:41][CH:36]1[CH:35]([NH:34][C:25]([CH:21]2[N:4]3[C:5](=[O:20])[CH:6]([NH:9][C:10](=[O:19])[CH2:11][CH2:12][C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:7][CH2:8][C:2](=[O:1])[N:3]3[CH2:24][CH2:23][CH2:22]2)=[O:26])[CH2:39][C:38](=[O:40])[O:37]1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

10

Reactant 5

HCID 5948TributylstannaneHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10989944(3S,2RS)3-allyloxycarbonylamino-2-benzyloxy-5-oxotetrahydrofuranHCID 22881931(1S, 9S) 6,10-Dioxo-octahydro-9-(3-phenylpropionylamino)-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid

Product 1

HCID 18465764N-(2-Benzyloxy-5-oxotetrahydrofuran-3-yl)-6,10-dioxo-octahydro-9-(3-phenylpropionylamino)-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxamideYield 81%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1S, 9S) 6,10-dioxo-octahydro-9-(3-phenyl-propionylamino)-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (45a) (662 mg; 1.773 mmol) in dry dichloromethane (9 ml) and dry dimethyl formamide (3 ml) at room temperature was added bis(triphenylphosphine)palladium chloride (30 mg) and (3S, 2RS)-3-allyloxycarbonylamino-2-benzyloxy-5-oxotetrahydrofuran (Chapman, Biorg. Med. Chem. Lett., 2, pp. 613-18 (1992)) (568 mg; 1.95 mmol) followed by dropwise addition of tri-n-butyltin hydride (1.19 g; 4.09 mmol). 1-Hydroxy-benzotriazole (479 mg; 3.546 mmol) was added to the mixture and the mixture was cooled to 0° C. before addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (408 mg; 2.128 mmol). The mixture was stirred at room temperature for 3.25 h then diluted with ethyl acetate (50 ml), washed twice with dilute hydrochloric acid (20 ml), twice with saturated sodium bicarbonate (20 ml), once with brine then dried (MgSO4) and concentrated. The resulting oil was purified by flash chromatography (0-100% ethyl acetate/chloroform) to afford 810 mg (81%) of 46a as a mixture of anomers: mp. 92°-94° C.; IR (KBr) 3311, 1791, 1659, 1651, 1536; 1H NMR (CDCl3) δ 7.49, 6.56 (1H, 2d, J=6.7, 7.8), 7.29 (10H, m), 6.37, 6.18 (1H, 2d, J=7.7, 7.6), 5.56, 5.34 (1H, d, s, J=5.2), 5.08-4.47 (6H), 3.18-2.80 (5H), 2.62-2.28 (5H), 2.04-1.53 (5H). MS (FAB, m/z), 563 (M+ +1), 328, 149, 91.

Workup

  1. washwashed twice with dilute hydrochloric acid (20 ml), twice with saturated sodium bicarbonate (20 ml), once with brine
  2. dry with materialthen dried (MgSO4)
  3. concentrationconcentrated
  4. customThe resulting oil was purified by flash chromatography (0-100% ethyl acetate/chloroform)

Sources & evidence

ORD record
ord-63e1ecc205d04f77bd5cead47e6e3d54
Source dataset
uspto-grants-1997_08
Patent number
US05656627

Reaction notes

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