Trifluoroacetic acid → HCID 178509548, compound

HRID 1874927Notes

Reaction equation

HRID 1874927 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5](COCC[Si](C)(C)C)[C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH:22]=[C:21]([C:29]#[N:30])[CH:20]=2)[C:12]=1[F:31])=[O:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][CH:26]3[CH2:27][CH2:28]3)[CH:22]=[C:21]([C:29]#[N:30])[CH:20]=2)[C:12]=1[F:31])=[O:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 684866314-chloro-N-[(4-chloro-3-{[3-cyano-5-(cyclopropylmethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Product 1

HCID 178509548HCID 178509548, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-chloro-N-[(4-chloro-3-{[3-cyano-5-(cyclopropylmethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (0.027 g, 0.046 mmol) dissolved in DCM (3 mL) was treated with TFA (3 mL) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness and the residue purified by mass-directed HPLC on a SunFire prep C-18 column eluted with 30 to 85% CH3CN/H2O (0.1% formic acid buffer). Appropriate fractions were combined, concentrated to dryness, chased twice with ethanol and twice with toluene to remove residual water to give 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(cyclopropylmethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (0.016 g, 0.035 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.31 (br. s., 1H), 7.61 (s, 1H), 7.20-7.36 (m, 4H), 7.14 (s, 1H), 6.87 (s, 1H), 4.72 (d, J=5.91 Hz, 2H), 2.56 (d, J=6.96 Hz, 2H), 0.84-1.03 (m, 1H), 0.53-0.63 (m, 2H), 0.14-0.27 (m, 2H). LC-MS (ES−) m/z 457.14, 459.12 [M−1]. LC-MS (ES+) m/z 459.09, 461.07 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue purified by mass-directed HPLC on a SunFire prep C-18 column
  3. washeluted with 30 to 85% CH3CN/H2O (0.1% formic acid buffer)
  4. concentrationconcentrated to dryness
  5. customto remove residual water

Sources & evidence

ORD record
ord-bd6d616984334d6c8aebf341c2e6c33b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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