Cyclopropanecarbonyl chloride → 3-(1-cyano-1-methylethyl)-N-[5-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-methylphenyl]benzamide

HRID 2190381Notes

Reaction equation

HRID 2190381 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[CH:14][C:15]([CH3:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>N1C=CC=CC=1>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:16]1[CH:17]=[C:12]([O:11][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:36]([CH:33]4[CH2:35][CH2:34]4)=[O:37])[S:3][C:4]=3[CH:10]=2)[CH:13]=[CH:14][C:15]=1[CH3:32])=[O:31])([CH3:27])[CH3:28])#[N:30]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 86646002N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 866553573-(1-cyano-1-methylethyl)-N-[5-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-methylphenyl]benzamideYield 56%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.452 mmol) in pyridine (4.0 mL) was added cyclopropanecarbonyl chloride (90 μL, 0.994 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methanol (2.0 mL)/tetrahydrofuran (2.0 mL)/water (2.0 mL). 1N Aqueous sodium hydroxide solution (2.0 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was neutralized with 1N hydrochloric acid, diluted with ethyl acetate (100 mL), washed with water (50 mL) and saturated brine (50 mL), successively, 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=70/30→0/100), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether to give the title compound (129 mg, 56%) as a colorless amorphous substance.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in methanol (2.0 mL)/tetrahydrofuran (2.0 mL)/water (2.0 mL)
  3. addition1N Aqueous sodium hydroxide solution (2.0 mL) was added
  4. stirringthe mixture was stirred at room temperature for 1 hr
  5. additiondiluted with ethyl acetate (100 mL)
  6. washwashed with water (50 mL) and saturated brine (50 mL)
  7. dry with materialsuccessively, and dried over anhydrous sodium sulfate
  8. filtrationThe insoluble material was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30→0/100)
  11. concentrationthe obtained solution was concentrated under reduced pressure
  12. customThe residue was triturated with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-ed43bf728c774e9eb46a5ee8e524d4d5
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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