p-Toluenesulfonic acid → HCID 67053536, compound

HRID 535773Notes

Reaction equation

HRID 535773 reaction equation
[NH2:1][C:2]1[C:3]([Cl:40])=[C:4]([C:9]2[N:10]=[C:11]([CH:37]3[CH2:39][CH2:38]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][C@@H:22]([NH:24][C:25](=[O:28])[O:26][CH3:27])[CH3:23])[N:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[NH2:1][C:2]1[C:3]([Cl:40])=[C:4]([C:9]2[N:10]=[C:11]([CH:37]3[CH2:38][CH2:39]3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][C@@H:22]([NH:24][C:25](=[O:28])[O:26][CH3:27])[CH3:23])[N:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 67053590HCID 67053590, compound

Product 1

HCID 67053536HCID 67053536, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of the crude (S)-methyl 1-(4-(4-(3-amino-2-chloro-5-fluorophenyl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (15.349 g), p-toluenesulfonic acid (3.64 g, 21.132 mmol) and methanol (70 mL) in a 100 mL, 3-necked round bottomed flask was heated at reflux for 1 hour. HPLC indicted completion of reaction. The reaction mixture was evaporated under vacuum and the residue was stirred with 2 N HCl (50 mL) and ethyl acetate (75 mL). The aqueous layer was separated and the organic layer was extracted once with 2 N HCl (40 mL). The combined aqueous layers were extracted once with ethyl acetate (50 mL) and then neutralized with aq NaOH (4 N). The product was extracted with 2×50 mL of ethyl acetate. The organic layer was washed once with water (40 mL), dried over MgSO4 and evaporated under vacuum to give 5.136 g (11.190 mmol) of crude (S)-methyl 1-(4-(4-(3-amino-2-chloro-5-fluorophenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate as a brown oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. customcompletion of reaction
  4. customThe reaction mixture was evaporated under vacuum
  5. customThe aqueous layer was separated
  6. extractionthe organic layer was extracted once with 2 N HCl (40 mL)
  7. extractionThe combined aqueous layers were extracted once with ethyl acetate (50 mL)
  8. extractionThe product was extracted with 2×50 mL of ethyl acetate
  9. washThe organic layer was washed once with water (40 mL)
  10. dry with materialdried over MgSO4
  11. customevaporated under vacuum

Sources & evidence

ORD record
ord-3377a8e71b43409b80c39be208cf07ab
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

Loading…