Cyclopropanecarbonyl chloride → Methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylate

HRID 455233Notes

Reaction equation

HRID 455233 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=4)=[O:24])[CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH:36]1([C:39](Cl)=[O:40])[CH2:38][CH2:37]1>N1C=CC=CC=1>[C:34]([C:31]([C:27]1[CH:26]=[C:25]([C:23]([NH:22][C:18]2[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=2)[O:15][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:39]([CH:36]4[CH2:38][CH2:37]4)=[O:40])[S:3][C:4]=3[C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[O:24])[CH:30]=[CH:29][CH:28]=1)([CH3:32])[CH3:33])#[N:35]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 71818881Methyl 2-amino-6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylate

Product 1

HCID 59454479Methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of methyl 2-amino-6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylate (0.92 g, 1.88 mmol) in pyridine (5 mL) was added cyclopropanecarbonyl chloride (371 μL, 4.1 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (100 mL), washed successively with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was suspended in methanol (10 mL), sodium carbonate (250 mg) was added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed successively with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was successively purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0) and silica gel column chromatography (ethyl acetate/n-hexane=40/60→60/40), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (706 mg, 68%) as a pale-yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionThe obtained residue was diluted with ethyl acetate (100 mL)
  3. washwashed successively with water (100 mL) and saturated brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationInsoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. additionsodium carbonate (250 mg) was added
  8. stirringthe mixture was stirred at room temperature for 4 hr
  9. additionThe reaction mixture was diluted with ethyl acetate (100 mL)
  10. washwashed successively with water (100 mL) and saturated brine (100 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationInsoluble material was filtered off
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe obtained residue was successively purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0) and silica gel column chromatography (ethyl acetate/n-hexane=40/60→60/40)
  15. concentrationthe obtained solution was concentrated under reduced pressure
  16. customThe residue was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-fd1e523f7bfe43a798ade65939326054
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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