Hydrochloric Acid → 2-((S)-1-Amino-propyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carbonitrile

HRID 243049Notes

Reaction equation

HRID 243049 reaction equation
Cl.C(OC(=O)[NH:8][C@H:9]([C:12](=O)[NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]#[N:22])[C:15]=1[NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:10][CH3:11])(C)(C)C>O1CCOCC1>[NH2:8][C@H:9]([C:12]1[N:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:15]2[C:16]([C:21]#[N:22])=[C:17]([F:20])[CH:18]=[CH:19][C:14]=2[N:13]=1)[CH2:10][CH3:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68157031[(S)-1-(3-Cyano-4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester

Product 1

HCID 681574452-((S)-1-Amino-propyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carbonitrileYield 69.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

HCl in dioxane (4M, 10 mL, 0.04 mol) was added to a solution of [(S)-1-(3-cyano-4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester (0.54 g, 1.32 mmol) in dioxane (5 mL) at 20° C., and the resultant mixture stirred at 80° C. for 17 h. After cooling, the reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (3×20 mL). The combined EtOAc extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by chromatography (SiO2 0-20% methanol in EtOAc) to give the title compound as an oil (0.27 g, 69%) LCMS (method H): RT 2.03 min, [M+H]+ 295.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (3×20 mL)
  3. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by chromatography (SiO2 0-20% methanol in EtOAc)

Sources & evidence

ORD record
ord-c697babf7dde4b28942bed0327461342
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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