Hydrochloric Acid → HCID 58164447, compound

HRID 535769Notes

Reaction equation

HRID 535769 reaction equation
[CH:1]1([C:4]2[N:5](COCC[Si](C)(C)C)[C:6]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH3:28])[N:22]=3)=[C:7]([C:9]3[C:10]([F:20])=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=3)[N:8]=2)[CH2:3][CH2:2]1.Cl>CCO>[CH:1]1([C:4]2[NH:5][C:6]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH3:28])[N:22]=3)=[C:7]([C:9]3[C:10]([F:20])=[C:11]([NH:15][S:16]([CH3:19])(=[O:17])=[O:18])[CH:12]=[CH:13][CH:14]=3)[N:8]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 69812049HCID 69812049, compound

Product 1

HCID 58164447HCID 58164447, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-(3-(2-cyclopropyl-5-(2-(methylamino)pyrimidin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-2-fluorophenyl)methanesulfonamide (78 mg, 0.14 mmol) in EtOH (2 mL) was treated with aqueous 6.0 N HCl solution and the resulting reaction was heated at 60° C. for 1 hour. LCMS indicated complete reaction, and the reaction was allowed to cool to room temperature. The volatiles were removed in vacuo, and the resulting residue was dissolved in DMSO and purified by reverse phase HPLC. Product fractions were combined, neutralized with saturated aqueous NaHCO3 solution (pH=6), and extracted with DCM (2×). The combined organic portions were dried (Na2SO4), and concentrated. The resulting free base (3A-1) was dissolved in ACN, treated with aqueous 1.0 N HCl solution, frozen, and lyophilized to provide N-(3-(2-cyclopropyl-5-(2-(methylamino)pyrimidin-4-yl)-1H-imidazol-4-yl)-2-fluorophenyl)methanesulfonamide (23 mg) as the HCl salt (3A-2): LCMS (m/z) 402.9, (MH+), tR=0.44 minute; 1H NMR (300 MHz, CD3CO2D) δ 1.26-1.38 (m, 2H) 1.37-1.52 (m, 2H) 2.41-2.60 (m, 1H) 2.84 (br s, 3H) 3.12 (s, 3H) 7.03 (d, J=6.5 Hz, 1H) 7.29-7.41 (m, 1H) 7.44-7.59 (m, 1H) 7.69-7.84 (m, 1H) 8.29 (d, J=6.5 Hz, 1H).

Workup

  1. customthe resulting reaction
  2. customreaction
  3. temperatureto cool to room temperature
  4. customThe volatiles were removed in vacuo
  5. dissolutionthe resulting residue was dissolved in DMSO
  6. custompurified by reverse phase HPLC
  7. extractionextracted with DCM (2×)
  8. dry with materialThe combined organic portions were dried (Na2SO4)
  9. concentrationconcentrated
  10. dissolutionThe resulting free base (3A-1) was dissolved in ACN
  11. additiontreated with aqueous 1.0 N HCl solution
  12. temperaturefrozen

Sources & evidence

ORD record
ord-f243995f8899471eab887a7f4d8f6252
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

Loading…