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 2257409노트

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HRID 2257409 반응식
[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

참가 물질

10

반응물 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

생성물 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-carboxamide수율 81%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-63e1ecc205d04f77bd5cead47e6e3d54
출처 데이터셋
uspto-grants-1997_08
특허 번호
US05656627

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