Ethanol → 2-Cyano-3-[[(3S)-hexahydro-2-oxo-1-(2-oxo-1-phenylethyl)-1H-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]propenoic acid methyl ester

HRID 1264635Notes

Reaction equation

HRID 1264635 reaction equation
[CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][C:5]=2[CH:6]=1.Cl.[C:13]([C:15](=[C:21](SC)SC)[C:16]([O:18][CH2:19]C)=[O:17])#[N:14].[NH2:26][CH:27]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH2:34][C:35](=O)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38]C=2)[C:28]1=[O:43].[CH2:44]([OH:46])C>>[CH3:19][O:18][C:16](=[O:17])[C:15]([C:13]#[N:14])=[C:21]([NH:26][C@H:27]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([CH:34]([C:35]2[CH:36]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:44]=[O:46])[C:28]1=[O:43])[NH:11][C:8]1[CH:9]=[CH:10][C:4]2[O:3][C:2]([CH3:1])=[CH:6][C:5]=2[CH:7]=1

Participants

5

Reactant 4

HCID 702EthanolHCID 2747745Ethyl 3,3-Bis(methylthio)-2-cyanoacrylateHCID 186125753-aminohexahydro-1-(2-oxo-2-phenylethyl)-2H-azepin-2-oneHCID 216968662-Methyl-1-benzofuran-5-amine--hydrogen chloride (1/1)

Product 1

HCID 865844972-Cyano-3-[[(3S)-hexahydro-2-oxo-1-(2-oxo-1-phenylethyl)-1H-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]propenoic acid methyl esterYield 7%

Conditions

Temperature
80 °C

Procedure

A solution of 2-methyl-5-benzofuranamine·HCl (35 mg, 0.24 mmol), ethyl 2-cyano-3,3-bis(methylthio)-2-propenoate (47 mg, 0.23 mmol), and ethanol (0.4 mL) was heated at 70° C. for 12 h. To the mixture was added 3-aminohexahydro-1-(2-oxo-2-phenylethyl)-2H-azepin-2-one (56 mg, 0.23 mmol). The resulting mixture was heated at 80° C. for 2 days, and then concentrated in vacuo. The residue was purified by preparative HPLC (column-YMC-PACK ODSA S5, 30×250 mm); flow rate 25 mL/min; gradient time 55 min) to give the title compound as a pale yellow solid (8 mg, 7%): MS (ESI, pos. ion spectrum) m/z 501; HPLC (method A) tR 4.26 min.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC (column-YMC-PACK ODSA S5, 30×250 mm)

Sources & evidence

ORD record
ord-e46d842158154f2b8212e8d6a28168b9
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

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