Trifluoroacetic acid → HCID 178509937, compound

HRID 1875079Notes

Reaction equation

HRID 1875079 reaction equation
FC(F)(F)C(O)=O.CC(OC([N:15]([C:23]1[NH:24][CH:25]=[C:26]([C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([O:39][C:40]3[CH:45]=[C:44]([C:46]#[N:47])[CH:43]=[C:42]([Cl:48])[CH:41]=3)[C:33]=2[F:49])=[O:29])[N:27]=1)C(OC(C)(C)C)=O)=O)(C)C>ClCCl>[NH2:15][C:23]1[NH:24][CH:25]=[C:26]([C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([O:39][C:40]3[CH:45]=[C:44]([C:46]#[N:47])[CH:43]=[C:42]([Cl:48])[CH:41]=3)[C:33]=2[F:49])=[O:29])[N:27]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178454350bis(1,1-dimethylethyl) (4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate

Product 1

HCID 178509937HCID 178509937, compoundYield 38.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

EDC (0.035 g, 0.183 mmol) and HOBT (0.025 g, 0.183 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.048 g, 0.153 mmol) and 2-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-imidazole-4-carboxylic acid (0.050 g, 0.153 mmol) in DMF (2 mL). The mixture was stirred at RT overnight. Saturated aqueous sodium bicarbonate was added and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to give crude bis(1,1-dimethylethyl)(4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate as an oil. Trifluoroacetic acid (0.3 mL, 3.89 mmol) was added to a solution of bis(1,1-dimethylethyl)(4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate (0.066 g, 0.106 mmol) in dichloromethane (2 mL). The mixture was stirred at RT overnight, concentrated and purified by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) to give the title compound (0.017 g, 27%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09-8.18 (m, 2H), 7.81 (s, 1H), 7.51 (s, 1H), 7.44-7.50 (m, 2H), 7.30 (t, 1H), 7.10 (s, 1H), 5.45 (br. s., 2H), 4.44 (d, 2H). MS m/z 420 (M+1).

Workup

  1. concentrationconcentrated
  2. custompurified by reverse phase HPLC (acetonitrile:water with 0.1% formic acid)

Sources & evidence

ORD record
ord-f111eb15d7c545e6aff601d978263b16
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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