Water → Tert-butyl [4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]carbamate

HRID 2095898Notes

Reaction equation

HRID 2095898 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:14][C:13]=1[F:26])[N:5]=2.[CH:27]1([C:30](Cl)=[O:31])[CH2:29][CH2:28]1.C(N(CC)CC)C.O>CN(C)C(=O)C>[CH:27]1([C:30]([NH:1][C:2]2[S:3][C:4]3[C:9]([N:10]=2)=[CH:8][CH:7]=[C:6]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[CH:14][C:13]=2[F:26])[N:5]=3)=[O:31])[CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 58158490Tert-butyl {4-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-3-fluorophenyl}carbamate

Product 1

HCID 58158551Tert-butyl [4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]carbamateYield 56%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of tert-butyl {4-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-3-fluorophenyl}carbamate (2.02 g, 5.37 mmol) in N,N-dimethylacetamide (20.2 mL) were added cyclopropanecarbonyl chloride (0.97 mL, 10.7 mmol) and triethylamine (2.24 mL, 16.1 mmol), and the mixture was stirred at room temperature for 24 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, methanol (20 mL) and 5% aqueous sodium carbonate solution (10 mL) were added to the residue, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was extracted with ethyl acetate/tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with hexane/ethyl acetate (=1/1) and collected by filtration to give the title compound (1.33 g, 56%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated under reduced pressure, methanol (20 mL) and 5% aqueous sodium carbonate solution (10 mL)
  6. additionwere added to the residue
  7. stirringthe mixture was stirred at room temperature for 3 hr
  8. extractionThe reaction mixture was extracted with ethyl acetate/tetrahydrofuran
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customThe solvent was evaporated under reduced pressure
  13. washthe residue was washed with hexane/ethyl acetate (=1/1)
  14. filtrationcollected by filtration

Sources & evidence

ORD record
ord-1f2234855b0841089b02b8af046f7937
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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