Sodium hydride → 4-[2-Cyano-3-[[(3S)-hexahydro-2-oxo-1-[2-oxo-2-(1-pyrrolidinyl)ethyl]-1H-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]-1-oxo-2-propenyl]benzoic acid methyl ester

HRID 1264627Notes

Reaction equation

HRID 1264627 reaction equation
[C:1]([CH2:3][C:4]([C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=1)=[O:5])#[N:2].[H-].[Na+].[N:18]([C:21]1[CH:22]=[CH:23][C:24]2[O:28][C:27]([CH3:29])=[CH:26][C:25]=2[CH:30]=1)=[C:19]=S.[NH2:31][C@H:32]1[CH2:38][CH2:37][CH2:36][CH2:35][N:34]([CH2:39][C:40]([N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)=[O:41])[C:33]1=[O:47]>CN(C=O)C.C(OCC)(=O)C.[Hg](Cl)Cl>[CH3:13][O:12][C:10](=[O:11])[C:9]1[CH:14]=[CH:15][C:6]([C:4](=[O:5])[C:3]([C:1]#[N:2])=[C:19]([NH:31][C@H:32]2[CH2:38][CH2:37][CH2:36][CH2:35][N:34]([CH2:39][C:40](=[O:41])[N:42]3[CH2:43][CH2:44][CH2:45][CH2:46]3)[C:33]2=[O:47])[NH:18][C:21]2[CH:22]=[CH:23][C:24]3[O:28][C:27]([CH3:29])=[CH:26][C:25]=3[CH:30]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 736021Methyl 4-(cyanoacetyl)benzoateHCID 120478195-Isothiocyanato-2-methylbenzofuranHCID 12047820(S)-1-[(3-amino-hexahydro-2-oxo-1H-azepin-1-yl)acetyl]pyrrolidine

Product 1

HCID 700328734-[2-Cyano-3-[[(3S)-hexahydro-2-oxo-1-[2-oxo-2-(1-pyrrolidinyl)ethyl]-1H-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]-1-oxo-2-propenyl]benzoic acid methyl esterYield 49.3%

Reagents, catalysts & solvents 3

HCID 24085Mercuric ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 4-(cyanoacetyl)benzoate (0.304 g, 1.50 mmol) in DMF (2 mL) was added sodium hydride (68.0 mg, 2.25 mmol). The reaction mixture was stirred at room temperature for 30 min. To the solution was then added 5-isothiocyanato-2-methylbenzofuran (0.284 g, 1.50 mmol). The reaction mixture was stirred at room temperature for 3 h at which time 1-[[(3S)-3-aminohexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (0.358, 1.50 mmol) and mercury (II) chloride (0.407 g, 1.50 mmol) were added. The reaction mixture was stirred for another 30 min. The reaction mixture was passed through CELITE and diluted with 50 mL of ethyl acetate. The organic solution was washed 2×25 mL with brine and was concentrated in vacuo. The residue was purified by flash chromatography (silica, 4% methanol/ethyl acetate) to give the title compound as yellow solid (0.442 g, 49% yield): HPLC (method A) tR 4.1 min; MS (ESI, pos. ion spectrum) m/z 598 (M+H).

Workup

  1. additionwere added
  2. stirringThe reaction mixture was stirred for another 30 min
  3. washThe organic solution was washed 2×25 mL with brine
  4. concentrationwas concentrated in vacuo
  5. customThe residue was purified by flash chromatography (silica, 4% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-208b33a662b7400cbe1e6fdbf618205c
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

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