Bromine → N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)(methyl)amino]-2-fluorophenyl)-2,2,2-trifluoroacetamide

HRID 2366751Notes

Reaction equation

HRID 2366751 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([N:12]([CH3:27])[C:13]2[CH:14]=[CH:15][C:16]([F:26])=[C:17]([NH:19][C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH:18]=2)=[N:10][CH:11]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:11]2[C:6]([N:5]=1)=[CH:7][CH:8]=[C:9]([N:12]([CH3:27])[C:13]1[CH:14]=[CH:15][C:16]([F:26])=[C:17]([NH:19][C:20](=[O:25])[C:21]([F:24])([F:22])[F:23])[CH:18]=1)[N:10]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 86646056N-{5-[(5-aminopyridin-2-yl)(methyl)amino]-2-fluorophenyl}-2,2,2-trifluoroacetamide

Product 1

HCID 86646057N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)(methyl)amino]-2-fluorophenyl)-2,2,2-trifluoroacetamideYield 43%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

Potassium thiocyanate (2.96 g, 30.5 mmol) was suspended in acetic acid (20 mL), and the suspension was stirred at room temperature for 10 min. To the obtained solution was added N-{5-[(5-aminopyridin-2-yl)(methyl)amino]-2-fluorophenyl}-2,2,2-trifluoroacetamide (2.0 g, 6.96 mmol), and the mixture was further stirred at room temperature for 10 min. The obtained solution was slowly added dropwise to a solution of bromine (1.17 g, 7.30 mmol) in acetic acid (10 mL). After the completion of the dropwise addition, the mixture was stirred at room temperature for 20 hr. The resultant black insoluble material was filtered off, and washed with acetic acid. The combined filtrate and washing were concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (100 mL), washed with saturated aqueous sodium hydrogen carbonate solution (70 mL) and saturated brine (100 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (1.00 g, 43%) as a colorless powder.

Workup

  1. stirringthe mixture was further stirred at room temperature for 10 min
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 20 hr
  4. filtrationThe resultant black insoluble material was filtered off
  5. washwashed with acetic acid
  6. washThe combined filtrate and washing
  7. concentrationwere concentrated under reduced pressure
  8. washwashed with saturated aqueous sodium hydrogen carbonate solution (70 mL) and saturated brine (100 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→0/100)
  13. concentrationthe obtained solution was concentrated under reduced pressure
  14. customThe residue was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-96539dd7002044d28613d1e0780e5c80
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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