Benzylamine → N-benzyl-5-bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxamide

HRID 2282126Notes

Reaction equation

HRID 2282126 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])[C:3]=1[C:18]#[N:19].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[CH2:52]([NH2:59])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C(Cl)Cl>[CH2:52]([NH:59][C:7]([C:5]1[S:6][C:2]([Br:1])=[C:3]([C:18]#[N:19])[C:4]=1[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=1[Cl:17])=[O:9])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

7

Reactant 5

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 668554875-Bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxylic acid

Product 1

HCID 66854726N-benzyl-5-bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxamideYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxylic acid (0.623 g, 1.65 mmol), 1-Hydroxybenzotriazole hydrate (0.253 g, 1.65 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.570 g, 2.97 mmol) were taken up in DCM (30 mL) and the mixture was stirred for 5 minutes at room temperature. N,N-Diisopropylethylamine (0.460 mL, 2.64 mmol) was added followed by benzylamine (0.216 mL, 1.98 mmol) and the solution was stirred at room temperature overnight. The mixture was quenched with water, extracted with DCM (3×50 mL), washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified using ISCO chromatography on silica gel, elution with 10-25% EA in hexanes to give the product (0.574 g, 74%). LCMS: (FA) ES+, 465, 467, 469. 1H NMR (400 MHz, d1-chloroform) δ: 7.46 (d, J=2.00 Hz, 1H), 7.32-7.27 (m, 4H), 7.26-7.23 (d, J=7.78 Hz, 1H), 6.99-6.96 (m, 2H), 5.38 (bs, 1H), 4.36 (d, J=5.52 Hz, 2H).

Workup

  1. stirringthe solution was stirred at room temperature overnight
  2. customThe mixture was quenched with water
  3. extractionextracted with DCM (3×50 mL)
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified
  9. washon silica gel, elution with 10-25% EA in hexanes

Sources & evidence

ORD record
ord-0c04d31f1b0a44cf9c6250a343d78318
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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