1,1-Bis(methylthio)-2-nitroethylene → 1-[[(3S)-Hexahydro-3-[[1-[(2-methyl-6-benzofuranyl)amino]-2-nitroethenyl]amino]-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine

HRID 1264637Notes

Reaction equation

HRID 1264637 reaction equation
[CH3:1][C:2]1[O:3][C:4]2[CH:10]=[C:9]([NH2:11])[CH:8]=[CH:7][C:5]=2[CH:6]=1.CS[C:14](SC)=[CH:15][N+:16]([O-:18])=[O:17].[NH2:21][C@H:22]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]([CH2:29][C:30]([N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[O:31])[C:23]1=[O:37]>C(OCC)(=O)C>[CH3:1][C:2]1[O:3][C:4]2[CH:10]=[C:9]([NH:11][C:14]([NH:21][C@H:22]3[CH2:28][CH2:27][CH2:26][CH2:25][N:24]([CH2:29][C:30]([N:32]4[CH2:33][CH2:34][CH2:35][CH2:36]4)=[O:31])[C:23]3=[O:37])=[CH:15][N+:16]([O-:18])=[O:17])[CH:8]=[CH:7][C:5]=2[CH:6]=1

Participants

5

Reactant 3

HCID 836231,1-Bis(methylthio)-2-nitroethyleneHCID 12047820(S)-1-[(3-amino-hexahydro-2-oxo-1H-azepin-1-yl)acetyl]pyrrolidineHCID 186125392-Methyl-1-benzofuran-6-amine

Product 1

HCID 700300201-[[(3S)-Hexahydro-3-[[1-[(2-methyl-6-benzofuranyl)amino]-2-nitroethenyl]amino]-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidineYield 12.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Preparation of title compound. To 2-methyl-6-benzofuranamine (30 mg, 0.16 mmol) in ethyl acetate (1 ML) was added 1,1-bis(methylthio)-2-nitroethylene (26 mg, 0.16 mmol) and the mixture heated at reflux for 30 minutes. After cooling to room temperature, 1-[[(3S)-3-aminohexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (38 mg, 0.16 mmol) was added and the resultant mixture heated for an additional 2 h. The reaction mixture was placed directly on a silica column and the product was eluted with 2% methanol/chloroform. Product-containing fractions were concentrated in vacuo and the residue was then further purified by elution through a reverse-phase cartride (Varian C-18 Mega Bond Elut) with a gradient of 100% water to 100% methanol. Concentration of product-containing fractions in vacuo provided the title compound (9 mg, 12%): MS (ESI, pos. ion spectrum) m/z 456 (M+H); HPLC (method C) tR 3.5 min.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 30 minutes
  3. washthe product was eluted with 2% methanol/chloroform
  4. concentrationProduct-containing fractions were concentrated in vacuo
  5. customthe residue was then further purified by elution through a reverse-phase cartride (Varian C-18 Mega Bond Elut) with a gradient of 100% water to 100% methanol

Sources & evidence

ORD record
ord-5072c89815024dfa908b7d98e0fbcbdd
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

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