Bromine → HCID 86646006, compound

HRID 1800484Notes

Reaction equation

HRID 1800484 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[O: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[O:19][CH3:20])[N:10]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 68416806HCID 68416806, compound

Product 1

HCID 86646006HCID 86646006, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

Potassium thiocyanate (1.26 g, 13.0 mmol) was suspended in acetic acid (15 mL), and the mixture was stirred at room temperature for 15 min. To the obtained solution was added a solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-methoxyphenyl}-3-(1-cyano-1-methylethyl)benzamide obtained above in acetic acid (25 mL), and the mixture was further stirred at room temperature for 15 min. A solution of bromine (690 mg, 4.32 mmol) in acetic acid (30 mL) was added dropwise to the obtained solution for 30 min or more. After the completion of the dropwise addition, the mixture was stirred at room temperature for 10 hr. The yielded yellow insoluble material was filtered off, and washed with acetic acid. The filtrate and the washing fluid were combined, and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (100 mL)/tetrahydrofuran (10 mL), and the suspension was washed with saturated aqueous sodium hydrogen carbonate solution (50 mL) and aqueous ammonium chloride solution (50 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 silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (1.00 g, 65%, 3 step yield) as a colorless 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 10 hr
  4. filtrationThe yielded yellow insoluble material was filtered off
  5. washwashed with acetic acid
  6. concentrationconcentrated under reduced pressure
  7. washthe suspension was washed with saturated aqueous sodium hydrogen carbonate solution (50 mL) and aqueous ammonium chloride solution (50 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80→0/100)
  12. concentrationthe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b9f78b1bb54e4c7c8972da6c1449cfbe
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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