O-Phenylenediamine → N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-1H-benzo[d]imidazol-2-amine

HRID 1993607Notes

Reaction equation

HRID 1993607 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:19]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([F:29])[CH:20]=2)([N:16]=[C:17]=S)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[C:30]1([NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[NH2:36].CCN=C=NCCCN(C)C>ClC(Cl)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:16][C:17]2[NH:37][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[N:36]=2)([C:19]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([F:29])[CH:20]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 7243O-PhenylenediamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 866129665-Chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine

Product 1

HCID 16743759N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-1H-benzo[d]imidazol-2-amineYield 47.2%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine (0.036 g, 0.083 mmol) in dichloroethane (1 mL) in a two drum vial was added phenylenediamine (12 mg, 0.108 mmol) and TEA (13 mL, 0.091 mmol). The reaction was heated at 80° C. for 2 hours. EDCI (24 mg, 0.124 mmol) was added and the reaction was continued to be heated at 80° C. overnight. The reaction was concentrated and the crude mixture was purified by ISCO chromatography (12 g column) using hexanes/EtOAc (0-40% over 25 min) to give N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-1H-benzo[d]imidazol-2-amine as a white solid (20 mg, 47% yield). LCMS: 3.2 min [M+1] 511.22 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CD3OD) d ppm 4.01-4.10 (m, 1H), 4.51 (d, J=13.21 Hz, 1H), 6.48 (d, J=7.34 Hz, 2H), 6.93-7.04 (m, 5H), 7.22 (dd, J=5.50, 3.06 Hz, 2H), 7.34 (d, J=8.31 Hz, 1H), 7.51-7.58 (m, 1H), 7.71-7.77 (m, 2H), 7.82 (dd, J=8.56, 2.45 Hz, 1H), 8.41 (d, J=2.45 Hz, 1H).

Workup

  1. temperatureto be heated at 80° C. overnight
  2. concentrationThe reaction was concentrated
  3. customthe crude mixture was purified by ISCO chromatography (12 g column)
  4. customhexanes/EtOAc (0-40% over 25 min)

Sources & evidence

ORD record
ord-4227f6bae80d45f292aa3bd2f0222a2a
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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