Hydrochloric Acid → HCID 68483615, compound

HRID 1875190Notes

Reaction equation

HRID 1875190 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][C:11]2[C:12]([F:36])=[C:13]([CH2:18][NH:19][C:20]([C:22]3[N:26]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:25]=[N:24][C:23]=3[Cl:35])=[O:21])[CH:14]=[CH:15][C:16]=2[Cl:17])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C([Sn](CCCC)(CCCC)[C:42]([O:44]CC)=[CH2:43])CCC.Cl>[Cl-].C([N+](CC)(CC)CC)C.CCOC(C)=O>[C:42]([C:2]1[CH:3]=[C:4]([O:10][C:11]2[C:12]([F:36])=[C:13]([CH2:18][NH:19][C:20]([C:22]3[N:26]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])[CH:25]=[N:24][C:23]=3[Cl:35])=[O:21])[CH:14]=[CH:15][C:16]=2[Cl:17])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1)(=[O:44])[CH3:43]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 68487527HCID 68487527, compound

Product 1

HCID 68483615HCID 68483615, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 5946Tetraethylammonium ChlorideCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of N-({3-[(3-bromo-5-cyanophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (500 mg, 0.814 mmol), tetraethylammoniumchloride (409 mg, 2.442 mmol) and dichlorobistriphenyl phosphinepalladium(II) (57.1 mg, 0.081 mmol) was added tributyl[1-(ethyloxy)ethenyl]stannane (0.302 mL, 0.894 mmol) and the reaction mixture was stirred at 80° C. overnight. The reaction mixture was cooled to RT, diluted with EtOAc and washed with water. The solvent was evaporated and the residue was dissolved in THF (7.00 mL) and HCl (1.0 M solution) (4 mL, 4.00 mmol) was added. The resulting mixture was stirred for 4 hours at RT. EtOAc was added and the organics were separated. The solvent was removed and the crude material was purifed via silica gel chromatography to give N-({3-[(3-acetyl-5-cyanophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (384 mg, 0.665 mmol, 82% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.08 (s, 1H), 7.90 (s, 1H), 7.70 (s, 1H), 7.33-7.49 (m, 3H), 5.59 (s, 2H), 4.61 (s, 2H), 3.49 (t, 2H), 2.60 (s, 3 H), 0.83 (t, 2H), −0.12-0.01 (m, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with water
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in THF (7.00 mL)
  5. stirringThe resulting mixture was stirred for 4 hours at RT
  6. customthe organics were separated
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-9fc828084c1f466e92a45d445956f003
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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