Water → 3-(1-cyanocyclopropyl)-N-{4-methoxy-3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide

HRID 2190408Notes

Reaction equation

HRID 2190408 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.Cl[CH2:35][C:36](Cl)=[O:37].O.[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>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:36](=[O:37])[CH2:35][N:44]5[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]5)[S:3][C:4]=4[CH:10]=3)[CH:13]=2)=[O:33])[CH2:30][CH2:29]1)#[N:32]

Participants

6

Reactant 4

HCID 962Water2×HCID 6577Chloroacetyl chlorideHCID 531671-MethylpiperazineHCID 86655365N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 866553683-(1-cyanocyclopropyl)-N-{4-methoxy-3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamideYield 39.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

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 chloroacetyl chloride (113 mg, 1.00 mmol) in N,N-dimethylformamide (5 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, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=1:1) to give a colorless oil. This was dissolved in N,N-dimethylformamide (2 mL), 1-methylpiperazine (100 mg, 1.00 mmol) was added, and the mixture was stirred at room temperature for 2 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 purified by basic silica gel chromatography (eluent:ethyl acetate/methanol=10:1), and triturated with diethyl ether to give the title compound (47 mg, 39%) as a white 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. customthe residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=1:1)
  5. customto give a colorless oil
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by basic silica gel chromatography (eluent:ethyl acetate/methanol=10:1)
  11. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-3d50c0a6908f4f3abbc6f0e86ea8e275
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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