Bromine → N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1800472Notes

Reaction equation

HRID 1800472 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]2[CH:14]=[C:15]([NH:21][C:22](=[O:34])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])[CH:24]=3)[CH:16]=[CH:17][C:18]=2[CH2:19][CH3:20])=[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]([O:12][C:13]1[CH:14]=[C:15]([NH:21][C:22](=[O:34])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])[CH:24]=3)[CH:16]=[CH:17][C:18]=1[CH2:19][CH3:20])[N:10]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 68417667N-{3-[(5-aminopyridin-2-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 86646003N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamideYield 87.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

Potassium thiocyanate (972 mg, 10 mmol) was suspended in acetic acid (20 mL), and the mixture was stirred at room temperature for 10 min. A solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide (1.0 g, 2.50 mmol) in acetic acid (20 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 15 min. A solution of bromine (439 mg, 2.75 mmol) in acetic acid (14 mL) was slowly added dropwise to the obtained solution. After the completion of the dropwise addition, the mixture was stirred at room temperature for 12 hr. The yielded yellow insoluble material was filtered off, and washed with acetic acid. The filtrate and washing solution were combined and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (250 mL), and the suspension was washed with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (1.0 g, 87%) as a pale-yellow amorphous substance.

Workup

  1. stirringthe mixture was further stirred at room temperature for 15 min
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 12 hr
  4. filtrationThe yielded yellow insoluble material was filtered off
  5. washwashed with acetic acid
  6. washThe filtrate and washing solution
  7. concentrationconcentrated under reduced pressure
  8. washthe suspension was washed with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  13. concentrationthe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-fa4b4fcaa7874469bb8f529a4983db63
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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