1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[[(3S)-3-[[2-[(3-thienyl)sulfonyl]-2-cyano-1-[(2-methyl-5-benzofuranyl)amino]-1-ethenyl]amino]hexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine

HRID 1264640Notes

Reaction equation

HRID 1264640 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([S:6]([CH2:9][C:10]#[N:11])(=[O:8])=[O:7])=[CH:2]1.[H-].[Na+].[N:14]([C:17]1[CH:18]=[CH:19][C:20]2[O:24][C:23]([CH3:25])=[CH:22][C:21]=2[CH:26]=1)=[C:15]=S.[NH2:27][C@H:28]1[CH2:34][CH2:33][CH2:32][CH2:31][N:30]([CH2:35][C:36]([N:38]2[CH2:42][CH2:41][CH2:40][CH2:39]2)=[O:37])[C:29]1=[O:43].CCN=C=NCCCN(C)C>CN(C=O)C.CN(C)C1C=CN=CC=1.O>[S:1]1[CH:5]=[CH:4][C:3]([S:6]([C:9]([C:10]#[N:11])=[C:15]([NH:27][C@H:28]2[CH2:34][CH2:33][CH2:32][CH2:31][N:30]([CH2:35][C:36]([N:38]3[CH2:39][CH2:40][CH2:41][CH2:42]3)=[O:37])[C:29]2=[O:43])[NH:14][C:17]2[CH:18]=[CH:19][C:20]3[O:24][C:23]([CH3:25])=[CH:22][C:21]=3[CH:26]=2)(=[O:8])=[O:7])=[CH:2]1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24758Sodium hydrideHCID 27975192-(3-Thienylsulfonyl)acetonitrileHCID 120478195-Isothiocyanato-2-methylbenzofuranHCID 12047820(S)-1-[(3-amino-hexahydro-2-oxo-1H-azepin-1-yl)acetyl]pyrrolidine

Product 1

HCID 699844791-[[(3S)-3-[[2-[(3-thienyl)sulfonyl]-2-cyano-1-[(2-methyl-5-benzofuranyl)amino]-1-ethenyl]amino]hexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidineYield 41%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-thienylsulphonyl)acetonitrile (59.4 mg, 0.318 mmol) in DMF (1 mL) was added NaH (95%, 8.08 mg, 0.344 mmol). After stirring 5 min at room temperature, 5-isothiocyanato-2-methylbenzofuran (50 mg, 0.265 mmol) was added in one portion. The reaction was heated at 50° C. for 30 min. To the mixture was added 1-[[(3S)-3-aminohexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (76.0 mg, 0.318 =mol), WSC (101.7 mg, 0.53 mmol) and N,N-dimethyl 4-pyridinamine (cat.) in that order. The reaction mixture was stirred at room temperature overnight. Water was added to the reaction and the mixture was extracted with ethyl acetate three times. The combined organic fractions were washed once with brine, dried over magnesium sulfate and evaporated. The residue was chromatographed (silica, 5% methanol/ethyl acetate) to provide 1-[[(3S)-3-[[2-[(3-thienyl)sulfonyl]-2-cyano-1-[(2-methyl-5-benzofuranyl)amino]-1-ethenyl]amino]hexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (63.0 mg, 41%): HPLC (method A) tR 3.65 min; LRMS (ESI, pos. ion spectrum) m/z 582 (M+H).

Workup

  1. temperatureThe reaction was heated at 50° C. for 30 min
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. extractionthe mixture was extracted with ethyl acetate three times
  4. washThe combined organic fractions were washed once with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customThe residue was chromatographed (silica, 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-6b94f901fb3046edb2fc1bbd2d45e38b
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

Loading…