Hydrochloric Acid → HCID 67053543, compound

HRID 535768Notes

Reaction equation

HRID 535768 reaction equation
[NH2:1][C:2]1[C:3]([F:36])=[C:4]([C:9]2[N:10]=[C:11]([CH:33]3[CH2:35][CH2:34]3)[N:12](COCC[Si](C)(C)C)[C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]#[N:24])[N:15]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl>CCO>[NH2:1][C:2]1[C:3]([F:36])=[C:4]([C:9]2[N:10]=[C:11]([CH:33]3[CH2:35][CH2:34]3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]#[N:24])[N:15]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67053539HCID 67053539, compound

Product 1

HCID 67053543HCID 67053543, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-(4-(4-(3-amino-5-chloro-2-fluorophenyl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (0.58 g, 1.1 mmol) in EtOH (10 mL) was added concentrated HCl (1 mL). The resulting reaction was maintained at room temperature for 9 hours after which the reaction mixture was concentrated and partitioned between water (60 mL) and EtOAc (250 mL). The layers were separated and the aqueous portion was neutralized with solid NaHCO3, and then extracted with EtOAc (200, 100 mL). The combined organic portions were then extracted with 0.1 M aqueous HCl solution (2×100 mL). The combined acidic aqueous extracts were neutralized with solid NaHCO3 and extracted with EtOAc (2×100 mL). The combined organic phases were washed with brine, dried (Na2SO4), and then concentrated to furnish 3-(4-(4-(3-amino-5-chloro-2-fluorophenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (328 mg) as an amber residue which was carried forward without further purification: LCMS (m/z) 398.1 (MH+), tR=0.55 minute.

Workup

  1. customThe resulting reaction
  2. concentrationwas concentrated
  3. custompartitioned between water (60 mL) and EtOAc (250 mL)
  4. customThe layers were separated
  5. extractionextracted with EtOAc (200, 100 mL)
  6. extractionThe combined organic portions were then extracted with 0.1 M aqueous HCl solution (2×100 mL)
  7. extractionextracted with EtOAc (2×100 mL)
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-5e50d8785acf40d183274b113228e0da
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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