Hydrogen Bromide → HCID 447721, compound

HRID 342695Notes

Reaction equation

HRID 342695 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[N:18]([CH3:47])[C:19]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38][C@H:39]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH3:40])[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>ClCCl.C(O)(=O)C.C(OCC)C>[C:41]1([C@@H:39]([NH:38][C:34]2[N:33]=[C:32]([C:19]3[N:18]([CH3:47])[C:17]([CH:14]4[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]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)[CH3:40])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 2

HCID 260Hydrogen BromideHCID 10532174HCID 10532174, compound

Product 1

HCID 447721HCID 447721, compoundYield 95.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester(12.5 gm, 0.0195 mole) in dichloromethane (170 mL) at 0° C., under argon, was slowly added 30% hydrogen bromide in acetic acid (170 mL). The solution was allowed to stir for 1.5 h at 0° C. and then diluted with diethyl ether (2.0 L). The resulting solid was filtered under argon, washed with diethyl ether (500 ml) and sucked dry under argon. The solid was then dissolved in dichloromethane (500 mL) and 10% aqueous sodium bicarbonate (500 mL) and mixed well. The dicholormethane solution was removed and the aqueous layer washed with dichloromethane (200 mL). The dichloromethane extracts were dried over anhydrous sodium sulfate, concentrated and the resulting foam (9.6 gm) chromatographed on silica using (dichloromethane/methanol/acetic acid/water--90/10/1/1). The resulting product containing fractions were washed with 10% aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated to give (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine (9.4 gm). The solid was dissolved in ethyl acetate (400 ml) filtered and then treated with a solution of hydrochloric acid/ethyl acetate (84 mL, 0.033 gm HCl/mL, 4 eq.). The resulting solid was filtered, dissolved in water (100 ml) and lyophilized to give (S)-4-[5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine trihydrochloride (12.0 gm).

Workup

  1. customat 0° C.
  2. filtrationThe resulting solid was filtered under argon
  3. washwashed with diethyl ether (500 ml)
  4. customsucked dry under argon
  5. dissolutionThe solid was then dissolved in dichloromethane (500 mL)
  6. addition10% aqueous sodium bicarbonate (500 mL) and mixed well
  7. customThe dicholormethane solution was removed
  8. washthe aqueous layer washed with dichloromethane (200 mL)
  9. dry with materialThe dichloromethane extracts were dried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customthe resulting foam (9.6 gm) chromatographed on silica using (dichloromethane/methanol/acetic acid/water--90/10/1/1)
  12. additionThe resulting product containing fractions
  13. washwere washed with 10% aqueous sodium bicarbonate
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-1a5ae10d98a4466db08514e644811c51
Source dataset
uspto-grants-1999_01
Patent number
US05859041

Reaction notes

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