Methylamine → HCID 86726285, compound

HRID 1776916Notes

Reaction equation

HRID 1776916 reaction equation
Br[C:2]1[C:3]([N:21]2[CH2:25][CH2:24][CH2:23][C:22]2=[O:26])=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:7]([C:17]([OH:19])=O)[C:6]=2[CH:20]=1.C1C=CC2N(O)N=[N:33][C:31]=2C=1.CCN=C=NCCCN(C)C.CN>CN(C=O)C.CCN(CC)CC>[F:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]2[O:9][C:5]3[CH:4]=[C:3]([N:21]4[CH2:25][CH2:24][CH2:23][C:22]4=[O:26])[CH:2]=[CH:20][C:6]=3[C:7]=2[C:17]([NH:33][CH3:31])=[O:19])=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 71295159HCID 71295159, compound

Product 1

HCID 86726285HCID 86726285, compoundYield 93.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

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.

Workup

  1. stirringto stir for about 15 hours
  2. concentrationAfter being concentrated in vacuo, water
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customthe resulting resulting residue
  10. customwas purified
  11. washcolumn chromatography (eluted with petroleum ether:EtOAc=1:1)

Sources & evidence

ORD record
ord-61ddda00f21c4d5c929c6ed8e2e70d99
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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