1-Hydroxybenzotriazole → HCID 178509951, compound

HRID 1875066Notes

Reaction equation

HRID 1875066 reaction equation
[N:1]([C:4]1[NH:5][C:6]([C:10]([OH:12])=O)=[C:7]([Cl:9])[N:8]=1)=[N+:2]=[N-:3].[NH2:13][CH2:14][C:15]1[C:16]([F:32])=[C:17]([O:22][C:23]2[CH:24]=[C:25]([CH:28]=[C:29]([Cl:31])[CH:30]=2)[C:26]#[N:27])[C:18]([Cl:21])=[CH:19][CH:20]=1.ON1C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>>[N:1]([C:4]1[NH:5][C:6]([C:10]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([O:22][C:23]3[CH:24]=[C:25]([C:26]#[N:27])[CH:28]=[C:29]([Cl:31])[CH:30]=3)[C:16]=2[F:32])=[O:12])=[C:7]([Cl:9])[N:8]=1)=[N+:2]=[N-:3]

Participants

5

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 1785145302-azido-4-chloro-1H-imidazole-5-carboxylic acid

Product 1

HCID 178509951HCID 178509951, compound

Procedure

A solution of 2-azido-4-chloro-1H-imidazole-5-carboxylic acid (0.26 g, 1.4 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.44 g, 1.40 mmol), 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.32 g, 1.68 mmol) and N-hydroxybenzotriazole (0.28 g, 1.82 mmol) was stirred at RT overnight. NaHCO3 was added and the solution was extracted with 9:1 CH2Cl2:MeOH. The combined organic phase was dried (Na2SO4), filtered, and concentrated to give 2-azido-4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide which was used without further purification after extraction. A solution of the above crude azide and catalytic Pd/CaCO3 (poisoned with lead) in EtOAc (20 mL) was then stirred under 50 psi hydrogen gas for 2 h. The solution was filtered through celite, evaporated and purified by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.95 (s, 1H), 7.82 (s, 1H), 7.77 (t, J=5.86 Hz, 1H), 7.48-7.54 (m, 2H), 7.46 (t, J=2.01 Hz, 1H), 7.34 (t, J=7.97 Hz, 1H), 5.82 (s, 2H), 4.49 (d, J=5.77 Hz, 2H). ES-LCMS: m/z 454.0, 456.0, 458.0 (M+1).

Workup

  1. extractionthe solution was extracted with 9:1 CH2Cl2
  2. dry with materialThe combined organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-839689f9eb684867a63efc9e5bd4a29f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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