Benzenamine, 3,5-bis(trifluoromethyl)- → N-(3,5-bis(trifluoromethyl)phenyl)-2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxamide

HRID 2068268Notes

Reaction equation

HRID 2068268 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[CH2:13][C:12]2([C:17]([OH:19])=O)[CH2:14][CH2:15][CH2:16][CH:11]2[C:10]1=[O:20].C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[F:35][C:36]([F:49])([F:48])[C:37]1[CH:38]=[C:39]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[NH2:40]>C1COCC1>[F:35][C:36]([F:48])([F:49])[C:37]1[CH:38]=[C:39]([NH:40][C:17]([C:12]23[CH2:14][CH2:15][CH2:16][CH:11]2[C:10](=[O:20])[N:9]([C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][C:4]=2[CH3:8])[CH2:13]3)=[O:19])[CH:41]=[C:42]([C:44]([F:45])([F:47])[F:46])[CH:43]=1

Participants

6

Reactant 4

HCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 582187902-(2,6-Dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxylic acid

Product 1

HCID 58218864N-(3,5-bis(trifluoromethyl)phenyl)-2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxamideYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxylic acid (86 mg, 0.3 mmol) and diisopropylethyl amine (104 μL, 0.6 mmol) in THF, methanesulfonyl chloride (32 μL, 0.4 mmol) was added. The mixture was treated with 3,5-bis(trifluoromethyl)aniline (137 mg, 0.6 mmol) and heated at 75° C. for 3 h. After evaporating the solvent, the crude product was applied on C18 preparative HPLC column and eluted with acetonitrile/water solvent system (5-80% acetonitrile gradient with 0.1% TFA). After neutralization and solvent evaporation of the combined product containing fractions, 80 mg of N-(3,5-bis(trifluoromethyl)phenyl)-2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxamide was obtained (53% yield). 1H NMR (400 MHz, CDCl3) 1.72-1.84 (m, 1H), 1.94-2.04 (m, 1H), 2.09 (s, 3H), 2.18 (s, 3H), 2.24-2.40 (m, 4H), 3.43 (d, 1H, J=11 Hz), 3.52-3.58 (m, 1H, 4.06 (d, 1H, J=11 Hz), 7.00-7.17 (m, 3H), 7.61 (s, 1H) 8.13 (s, 2H), 8.61 (s, 1H). LC-MS: Rt (retention time)=2.99 min, MS: (ES) m/z 485 (M+H+).

Workup

  1. customAfter evaporating the solvent
  2. washeluted with acetonitrile/water solvent system (5-80% acetonitrile gradient with 0.1% TFA)
  3. customAfter neutralization and solvent evaporation of the combined product
  4. additioncontaining fractions

Sources & evidence

ORD record
ord-0939717a33b245d1a5052d2b949a777a
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

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