1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(2-aminopyridin-3-yl)-N-(2-fluoro-5-methylphenyl)-1-benzothiophene-5-carboxamide

HRID 2205563Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]([OH:19])=O)=[CH:13][C:11]=3[CH:12]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[F:20][C:21]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:22]=1[NH2:23].CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.ClCCCl.CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]([NH:23][C:22]4[CH:24]=[C:25]([CH3:28])[CH:26]=[CH:27][C:21]=4[F:20])=[O:19])=[CH:13][C:11]=3[CH:12]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

The reaction mixture of 2-(2-aminopyridin-3-yl)-1-benzothiophene-5-carboxylic acid (54 mg, 0.2 mmol, 1 eq), 2-fluoro-5-methylaniline (0.048 mL, 2.1 eq), DMAP (5 mg, 0.2 eq), and EDCI (46.1 mg, 1.2 eq) in anhydrous 1,2-dichloroethane (2 mL) and anhydrous DMF (0.5 mL) was stirred and heated at 60° C. for 1 hour. It was then diluted with ethyl acetate, washed sequentially with aqueous NH4Cl, saturated aqueous NaHCO3, and brine, and finally dried with anhydrous sodium sulfate. The upper, clear solution-layer was decanted, concentrated, and the solid residue was subject to a gradient column chromatography (EtOAc-Hex 1:4 to 1:1) to yield 2-(2-aminopyridin-3-yl)-N-(2-fluoro-5-methylphenyl)-1-benzothiophene-5-carboxamide as a white solid in amount of 39.8 mg.

Workup

washwashed sequentially with aqueous NH4Cl, saturated aqueous NaHCO3, and brine
dry with materialfinally dried with anhydrous sodium sulfate
customThe upper, clear solution-layer was decanted
concentrationconcentrated

Sources & evidence

ORD record: ord-41019ef9e05743c0a1854c39a6240a27
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371314B2

Reaction notes

Loading…