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

HRID 1800424Notes

Reaction equation

HRID 1800424 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]4([C:32]#[N:33])[CH2:31][CH2:30]4)[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]4([C:32]#[N:33])[CH2:31][CH2:30]4)[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 68418573N-{3-[(5-aminopyridin-2-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 86645989N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamideYield 59%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

Potassium thiocyanate (4.44 g, 45.7 mmol) was suspended in acetic acid (100 mL), and the mixture was stirred at room temperature for 30 min. A solution of N-{3-[(5-aminopyridin-2-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide (4.1 g) in acetic acid (100 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 30 min. A solution of bromine (2.65 g, 16.6 mmol) in acetic acid (100 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 16 hr. The yielded yellow solid was filtered off, and washed with acetic acid, and the filtrate and the washing solution were combined and concentrated under reduced pressure. The residue was suspended in ethyl acetate (300 mL), and the suspension was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL×2) 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 to give the title compound (2.68 g, total of 2 steps 59%) as a yellow amorphous substance.

Workup

  1. stirringthe mixture was further stirred at room temperature for 30 min
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 16 hr
  4. filtrationThe yielded yellow solid 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 (100 mL×2) and saturated brine (100 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-0346bb9f003144f2a17ee5abbc07a3b6
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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