Benzenamine, 3,5-bis(trifluoromethyl)- → HCID 51034680, compound

HRID 1020973Notes

Reaction equation

HRID 1020973 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][C:7]1([C:21]([O:23]C(C)(C)C)=O)[CH2:11][C:10](=[O:12])[N:9]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[CH2:8]1.C(C1NC=CN=1)(C1NC=CN=1)=O.C(N(C(C)C)CC)(C)C.[F:49][C:50]([F:63])([F:62])[C:51]1[CH:52]=[C:53]([CH:55]=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:57]=1)[NH2:54]>Cl.O1CCOCC1.C(OCC)(=O)C>[NH:3]1[CH:4]=[CH:5][N:1]=[C:2]1[CH2:6][C:7]1([C:21]([NH:54][C:53]2[CH:55]=[C:56]([C:58]([F:59])([F:60])[F:61])[CH:57]=[C:51]([C:50]([F:49])([F:62])[F:63])[CH:52]=2)=[O:23])[CH2:11][C:10](=[O:12])[N:9]([C:13]2[C:14]([CH3:20])=[CH:15][CH:16]=[CH:17][C:18]=2[CH3:19])[CH2:8]1

Participants

8

Reactant 4

HCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 81531DiisopropylethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 67092433HCID 67092433, compound

Product 1

HCID 51034680HCID 51034680, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 3-((1H-imidazol-2-yl)methyl)-1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylate prepared in Step b above (460 mg, 1.2 mmol) was dissolved in 4 mL of 4 M HCl in dioxane and heated at 60° C. for 2 h. The solvent was evaporated to dryness and the residue suspended in THF (5 mL) was treated with carbonyl diimidazole (201 mg, 1.2 mmol) and diisopropylethyl amine (626 μL, 3.6 mmol) and heated at 40° C. for 1 h. The warm reaction mixture was treated with 3,5-bis(trifluoromethyl)aniline (550 mg, 2.4 mmol) and heating was continued for another 2 h. After cooling to room temperature the reaction mixture was diluted with 25 mL ethyl acetate and washed with water. The organic phase was dried, solvent evaporated and the residue was purified by flash chromatography (SiO2, 0-15% MeOH/DCM) to afford 260 mg of 3-((1H-imidazol-2-yl)methyl)-N-(3,5-bis(trifluoromethyl)phenyl)-1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxamide (42% yield). 1H NMR (400 MHz, CDCl3) δ 2.14 (s, 3H), 2.19 (s, 3H), 2.52 (d, 1H, J=17 Hz), 3.28 (d, 1H, J=17 Hz), 3.38-3.42 (m, 3H), 3.59 (d, 1H, J=10.6 Hz), 4.20 (d, 1H, J=10.6 Hz), 1.60 (bs, 2H), 7.00-7.20 (m, 3H), 7.57 (s, 1H), 8.18 (s, 2H). LC-MS: Rt (retention time)=2.57 min, MS: (ES) m/z 525 (M+H+).

Workup

  1. customThe solvent was evaporated to dryness
  2. temperatureheated at 40° C. for 1 h
  3. customThe warm reaction mixture
  4. temperatureheating
  5. temperatureAfter cooling to room temperature the reaction mixture
  6. washwashed with water
  7. customThe organic phase was dried
  8. customsolvent evaporated
  9. customthe residue was purified by flash chromatography (SiO2, 0-15% MeOH/DCM)

Sources & evidence

ORD record
ord-5c1526d6e9e64a9db5d6c430c858b460
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

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