Water → 3-(1-cyanocyclopropyl)-N-(3-{[2-(glycoloylamino)-1,3-benzothiazol-6-yl]oxy}-4-methoxyphenyl)benzamide

HRID 2190407Notes

Reaction equation

HRID 2190407 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:20][C:21](=[O:33])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]5([C:31]#[N:32])[CH2:30][CH2:29]5)[CH:23]=4)[CH:15]=[CH:16][C:17]=3[O:18][CH3:19])[CH:8]=[CH:7][C:5]=2[N:6]=1.C([O:37][CH2:38][C:39](Cl)=[O:40])(=O)C.O>CN(C)C=O>[C:31]([C:28]1([C:24]2[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=2)[C:21]([NH:20][C:14]2[CH:15]=[CH:16][C:17]([O:18][CH3:19])=[C:12]([O:11][C:9]3[CH:8]=[CH:7][C:5]4[N:6]=[C:2]([NH:1][C:38](=[O:37])[CH2:39][OH:40])[S:3][C:4]=4[CH:10]=3)[CH:13]=2)=[O:33])[CH2:30][CH2:29]1)#[N:32]

Participants

5

Reactant 3

HCID 962WaterHCID 26297Acetoxyacetyl chlorideHCID 86655365N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 866553673-(1-cyanocyclopropyl)-N-(3-{[2-(glycoloylamino)-1,3-benzothiazol-6-yl]oxy}-4-methoxyphenyl)benzamideYield 21.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide (91 mg, 0.20 mmol) produced in Example A18(iv) and 2-chloro-2-oxoethyl acetate (137 mg, 1.00 mmol) in N,N-dimethylformamide (2 mL) was stirred at room temperature for 18 hr. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 30 min. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=1:1), and triturated with acetone to give the title compound (22 mg, 21%) as a pale-yellow solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL)
  5. additionwas added under ice-
  6. temperaturecooling
  7. stirringthe mixture was stirred at room temperature for 30 min
  8. additionThe reaction mixture was poured into water
  9. extractionthe mixture was extracted with ethyl acetate
  10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=1:1)
  13. customtriturated with acetone

Sources & evidence

ORD record
ord-b9b675e2ab8f4aed98cb72d4fb750631
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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