Tributylstannane → t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoate semicarbazone

HRID 363860Notes

Reaction equation

HRID 363860 reaction equation
[O:1]=[C:2]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5](=[O:18])[N:4]2[C@H:19]([C:23]([OH:25])=O)[CH2:20][CH2:21][CH2:22][N:3]12.C(OC([NH:32][CH:33]([CH:47]=[O:48])[CH2:34][CH2:35][C:36](=[N:42][NH:43][C:44]([NH2:46])=[O:45])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=O)C=C.[SnH](CCCC)(CCCC)CCCC.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CCOC(C)=O.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>[C:10]([NH:9][CH:6]1[C:5](=[O:18])[N:4]2[CH:19]([C:23]([NH:32][CH:33]([CH:47]=[O:48])[CH2:34][CH2:35][C:36](=[N:42][NH:43][C:44]([NH2:46])=[O:45])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:25])[CH2:20][CH2:21][CH2:22][N:3]2[C:2](=[O:1])[CH2:8][CH2:7]1)(=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

9

Reactant 5

HCID 5948TributylstannaneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 183965489(S)-benzoylamino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1(S)-carboxylic acidHCID 54326573t-Butyl N-Allyloxycarbonyl-4-amino-5-oxopentanoate semicarbazone

Product 1

HCID 53703560t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoate semicarbazoneYield 49%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (1S, 9S) 6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-9-(benzoylamino)-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (212e) (345 mg, 1.0 mmol), (4S) t-butyl N-(allyloxycarbonyl)-4-amino-5-oxopentanoate semicarbazone (208a) (361 mg, 1.1 mmol, 1.1 equiv) and (Ph3P)2PdCl2 (20 mg) in CH2Cl2 (5 ml), was treated dropwise with n-Bu3SnH (0.621 ml, 2.3 mmol, 2.1 equiv). The resulting orange brown solution was stirred at 25° C. for 10 min and then 1-hydroxybenzotriazole (297 mg, 2.2 mmol, 2 equiv) was added. The mixture was cooled to 0° C. and ethyldimethylaminopropyl carbodiimide (253 mg, 1.3 mmol, 1.2 equiv) added. After stirring at 0° C. for 10 min and then at room temperature overnight, the mixture was diluted with EtOAc (50 ml) and the resulting solution washed successively with 1M HCl (3×25 ml), 10% NaHCO3 (3×25 ml) and sat. aq. NaCl, dried (MgSO4) and concentrated. Flash chromatography on silica gel (2-10% methanol in CH2Cl2) afforded compound 233e (280 mg, 49%) as a tan solid: [α]D° -95° (c 0.09, MeOH); IR (KBr) 3477, 3333, 2968, 2932, 1633, 1580, 1535, 1423, 1378, 1335, 1259, 1156, 1085, 709; 1H NMR (CDCl3) δ 9.32 (1H, s), 7.83-7.39 (6H, m), 7.11-7.09 (1H, m), 6.30-5.30 (2H, brs), 5.17-5.05 (2H, m), 4.62-4.38 (2H, m), 3.30-3.15 (1H, m), 3.13-2.65 (2H, m), 2.46-2.19 (3H, m), 2.15-1.54 (8H, m), 1.42 (9H, s).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringAfter stirring at 0° C. for 10 min
  3. washthe resulting solution washed successively with 1M HCl (3×25 ml), 10% NaHCO3 (3×25 ml) and sat. aq. NaCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-19e3c1a7c4094a6fb4140f4d12a4b8ca
Source dataset
uspto-grants-1999_02
Patent number
US05874424

Reaction notes

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