1,2-Dichloroethane → 2-(4-bromo-2-fluorophenyl)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)acetamide

HRID 1050099Notes

Reaction equation

HRID 1050099 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][C:11]=2[C:17]([F:20])([F:19])[F:18])[CH2:5][CH2:4]1)[CH3:2].[Br:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29](O)=[O:30])=[C:24]([F:32])[CH:23]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C(Cl)Cl>[Br:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29]([NH:14][C:13]2[CH:15]=[CH:16][C:10]([CH2:9][N:6]3[CH2:7][CH2:8][N:3]([CH2:1][CH3:2])[CH2:4][CH2:5]3)=[C:11]([C:17]([F:20])([F:18])[F:19])[CH:12]=2)=[O:30])=[C:24]([F:32])[CH:23]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 591345644-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

Product 1

HCID 904158182-(4-bromo-2-fluorophenyl)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)acetamideYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
26 °C

Procedure

A suspension of 4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (247 mg, 0.858 mmol) in DCM (35 mL) was added to a solution of 2-(4-bromo-2-fluorophenyl)acetic acid (200 mg, 0.858 mmol) in DCM (35 mL). HOBt (197 mg, 1.287 mmol), EDC (247 mg, 1.287 mmol) and Et3N (0.359 mL, 2.57 mmol) was added and the mixture was stirred at 26° C. for 3 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=10/1). All fractions found to contain product by TLC (PE/EA=5/1, Rf=0.6) were combined and concentrated to yield a light yellow solid of 2-(4-bromo-2-fluorophenyl)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)acetamide (413 mg, 0.822 mmol, 96.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.98-7.91 (m, 1H), 7.79-7.67 (m, 2H), 7.40-7.27 (m, 3H), 3.74 (s, 2H), 3.61 (s, 2H), 2.58-2.39 (m, 11H), 1.09 (s, 4H); ES-LCMS m/z 502.0 (M+H).

Workup

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica column chromatography (PE/EA=10/1)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-45291ada5e744f508ce1960e795ff11e
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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