Water → HCID 178510250, compound

HRID 1875208Notes

Reaction equation

HRID 1875208 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[N:8]([C:11]1[NH:12][C:13]([C:17]([NH:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][C:29]3[CH:34]=[C:33]([CH:35]([F:37])[F:36])[CH:32]=[C:31]([C:38]#[N:39])[CH:30]=3)[C:22]=2[F:40])=[O:18])=[C:14]([Cl:16])[N:15]=1)=[N+]=[N-].O.CP(C)C>C1COCC1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH2:8][C:11]1[NH:12][C:13]([C:17]([NH:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][C:29]3[CH:34]=[C:33]([CH:35]([F:36])[F:37])[CH:32]=[C:31]([C:38]#[N:39])[CH:30]=3)[C:22]=2[F:40])=[O:18])=[C:14]([Cl:16])[N:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 68983TrimethylphosphineHCID 178510253HCID 178510253, compound

Product 1

HCID 178510250HCID 178510250, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-azido-4-chloro-N-[(4-chloro-3-{[3-cyano-5-(difluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide trifluoroacetate (39.0 mg, 0.079 mmol) in THF (6 ml) was added water (2.83 μl, 0.157 mmol) followed by trimethyl phosphine (2.0 M solution in THF) (0.039 ml, 0.079 mmol) and the reaction mixture was stirred at RT for 15 minutes. The solvent was removed and the crude material was purified via reverse phase HPLC to give 2-amino-4-chloro-N-[(4-chloro-3-{[3-cyano-5-(difluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide trifluoroacetate (28 mg, 0.048 mmol, 61.0% yield). 1H NMR (DMSO-d6) δ ppm 7.76-7.88 (m, 2H) 7.68 (s, 1H) 7.39-7.54 (m, 2H) 7.31 (t, 1H) 6.84-7.20 (m, 1H) 5.97 (br.s., 2H) 4.45 (d, 2H). LC-MS (ES+) m/z 470.05 [M+H].

Workup

  1. customThe solvent was removed
  2. customthe crude material was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-bf9eeddf62e6492abad08118c54d539b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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