4-Chlorobutyryl chloride → 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide
Reaction equation
[NH2:1][C:2]1[C:21]([Br:22])=[CH:20][C:5]2[C:6]([C:16]([NH:18][CH3:19])=[O:17])=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.Cl[CH2:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>>[Br:22][C:21]1[C:2]([N:1]2[CH2:24][CH2:25][CH2:26][C:27]2=[O:28])=[CH:3][C:4]2[O:8][C:7]([C:9]3[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=3)=[C:6]([C:16]([NH:18][CH3:19])=[O:17])[C:5]=2[CH:20]=1Participants
Procedure
A solution of 5-bromo-2-(4-fluorophenyl)-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxylic acid (280 mg, 0.67 mmol), HOBT (150 mg, 1.11 mmol) and EDCI (280 mg, 1.47 mmol) in dry DMF (2 mL) was allowed to stir at room temperature for 1 hour. Then Et3N (0.2 mL) and CH3NH2 (HCl salt, 100 mg, 1.48 mmol) was added to the mixture, and the reaction was allowed to stir for about 15 hours. After being concentrated in vacuo, water was added and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried and concentrated in vacuo and the resulting resulting residue was purified using column chromatography (eluted with petroleum ether:EtOAc=1:1) to provide 5-bromo-2-(4-fluorophenyl-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide (220 mg, yield: 73%), which was also prepared from 6-amino-5-bromo-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide and 4-chlorobutanoyl chloride using the method described in step 1 above. 1H-NMR (CDCl3, 400 MHz) δ 7.94 (s, 1H), 7.82˜7.86 (m, 2H), 7.32 (s, 1H), 7.09˜7.14 (m, 2H), 6.29 (s, 1H), 3.75˜3.78 (m, 2H), 2.97 (d, J=4.8 Hz, 3H), 2.56˜2.60 (m, 2H), 2.24˜2.26 (m, 2H). MS (M+H)+: 431/433.
Sources & evidence
- ORD record
- ord-087578c95bd74581b2747661cf157b3f
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09265773B2
Reaction notes
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