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

HRID 2402453Notes

Reaction equation

HRID 2402453 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-f810104311f54c17a179436370f31d45
Source dataset
uspto-grants-2014_08
Patent number
US08796314B2

Reaction notes

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