Trifluoroacetic acid → [4,4,4-Trifluoro-1-(2-{5-[4'-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-butyl]-carbamic acid methyl ester

HRID 72019Notes

Reaction equation

HRID 72019 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4[NH:31][C:32]([CH:35]5[CH2:39][CH2:38][CH2:37][N:36]5[C:40](=[O:53])[CH:41]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH2:42][CH2:43][C:44]([F:47])([F:46])[F:45])=[N:33][CH:34]=4)=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:52][O:51][C:49](=[O:50])[NH:48][CH:41]([C:40]([N:36]1[CH2:37][CH2:38][CH2:39][CH:35]1[C:32]1[NH:31][C:30]([C:27]2[CH:26]=[CH:25][C:24]([C:21]3[CH:22]=[CH:23][C:18]([C:15]4[NH:14][C:13]([CH:9]5[CH2:10][CH2:11][CH2:12][NH:8]5)=[N:17][CH:16]=4)=[CH:19][CH:20]=3)=[CH:29][CH:28]=2)=[CH:34][N:33]=1)=[O:53])[CH2:42][CH2:43][C:44]([F:46])([F:45])[F:47]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 666209712-[5-(4'-{2-[1-(5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl]-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66621118[4,4,4-Trifluoro-1-(2-{5-[4'-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-butyl]-carbamic acid methyl esterYield 92.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[5-(4′-{2-[1-(5,5,5-trifluoro-2-methoxycarbonylamino-pentanoyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (340 mg, 0.46 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1 mL). The reaction was stirred at room temperature for 3 hours and then thoroughly concentrated. The resulting residue was dissolved in dichloromethane and washed three times with saturated aqueous NaHCO3 solution. The organic layer was dried (MgSO4), and concentrated to give the crude free pyrrolidine (270 mg, 92%), which was clean enough to use without further purification. LCMS-ESI+: calculated for C33H36F3N7O3: 635.28; observed [M+1]+: 636.17.

Workup

  1. concentrationthoroughly concentrated
  2. dissolutionThe resulting residue was dissolved in dichloromethane
  3. washwashed three times with saturated aqueous NaHCO3 solution
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a4598f6311584dafb3ebe855290ca108
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

Loading…