Triethylamine → 6-Amino-5-bromo-N-methyl-3-benzofurancarboxamide

HRID 595637Notes

Reaction equation

HRID 595637 reaction equation
[NH2:1][C:2]1[C:13]([Br:14])=[CH:12][C:5]2[C:6]([C:9](O)=[O:10])=[CH:7][O:8][C:4]=2[CH:3]=1.C[CH2:16][N:17]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.CN.Cl>CN(C=O)C>[NH2:1][C:2]1[C:13]([Br:14])=[CH:12][C:5]2[C:6]([C:9]([NH:17][CH3:16])=[O:10])=[CH:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6364545Methylamine hydrochlorideHCID 903324196-Amino-5-bromobenzofuran-3-carboxylic acid

Product 1

HCID 903323986-Amino-5-bromo-N-methyl-3-benzofurancarboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-amino-5-bromobenzofuran-3-carboxylic acid (51 g, 199 mmol) in dry DMF (500 mL) was added EDCI (53.1 g, 298.77 mmol) and HOBT (40.4 g, 299 mmol). The reaction mixture was stirred at room temperature for 2 h, and then Et3N (60.5 g, 598 mmol) and MeNH2.HCl (40.3 g, 598 mmol) were added to the reaction mixture. After stirring for another 2 hours, the reaction mixture was concentrated in vacuum and then 300 mL Na2CO3 (sat., a.q.) was added to the mixture. The resulting solid was filtered to give the crude product, which was purified by column chromatography (DCM:MeOH=30:1) to give the product 6-amino-5-bromo-N-methylbenzofuran-3-carboxamide (38 g, yield: 71%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.19˜8.21 (m, 2H), 7.98 (s, 1H), 6.97 (s, 1H), 5.46 (br s, 2H), 2.75 (d, J=4.4 Hz, 3H). MS (M+H)+: 269/271.

Workup

  1. stirringAfter stirring for another 2 hours
  2. concentrationthe reaction mixture was concentrated in vacuum
  3. addition300 mL Na2CO3 (sat., a.q.) was added to the mixture
  4. filtrationThe resulting solid was filtered
  5. customto give the crude product, which
  6. customwas purified by column chromatography (DCM:MeOH=30:1)

Sources & evidence

ORD record
ord-e9375ffff1744f6f8149ec63a2cc04fe
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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