Hydrogen Bromide → 4-Methoxybenzyl-[4-[2-piperidin-4-yl-5-(3-trifluoromethylphenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]amine

HRID 342692Notes

Reaction equation

HRID 342692 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][C:19]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38][CH2:39][C:40]4[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=4)[N:33]=3)=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.Br>C(Cl)Cl.C(O)(=O)C.C(OCC)C>[CH3:47][O:46][C:43]1[CH:42]=[CH:41][C:40]([CH2:39][NH:38][C:34]2[N:33]=[C:32]([C:19]3[NH:18][C:17]([CH:14]4[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]4)=[N:21][C:20]=3[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:29])[F:31])[CH:23]=3)[CH:37]=[CH:36][N:35]=2)=[CH:45][CH:44]=1

Participants

6

Reactant 2

HCID 260Hydrogen BromideHCID 158406444-[5-(2-(4-Methoxybenzylamino)-pyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 105296364-Methoxybenzyl-[4-[2-piperidin-4-yl-5-(3-trifluoromethylphenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]amineYield 22.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a stirred solution of 4-[5-[2-(4-methoxybenzylamino)-pyrimidin-4-yl]-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester (1.0 g, 0.00156 mole) in methylene chloride (16 mL) under argon was slowly added 30% hydrogen bromide in acetic acid (16 mL). The mixture was stirred at 20° C. for 30 minutes and then diluted with diethyl ether (160 mL). The resulting mixture was stirred for I hour, filtered and solid washed with ether (10 mL). The resulting solid was dissolved in 10% aqueous sodium bicarbonate (40 mL) and methylene chloride (50 mL). The methylene chloride was separated and the aqueous layer washed with methylene chloride (25 mL). The organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated to a foam (0.80 g). The solid was chromatographed on silica using methylene chloride/methanol/aqueous ammonium hydroxide (90:10:2) to give upon concentration of product containing fractions 180 mg of the title compound.

Workup

  1. stirringThe resulting mixture was stirred for I hour
  2. filtrationfiltered
  3. washsolid washed with ether (10 mL)
  4. dissolutionThe resulting solid was dissolved in 10% aqueous sodium bicarbonate (40 mL)
  5. customThe methylene chloride was separated
  6. washthe aqueous layer washed with methylene chloride (25 mL)
  7. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a foam (0.80 g)
  10. customThe solid was chromatographed on silica
  11. customto give upon concentration of product

Sources & evidence

ORD record
ord-14c76240bb114c5a9bc163e7e1635e99
Source dataset
uspto-grants-1999_01
Patent number
US05859041

Reaction notes

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