Pyridine → HCID 86644710, compound

HRID 455246Notes

Reaction equation

HRID 455246 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][C:19]([F:22])=[C:18]([NH:23][C:24](=[O:36])[CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=4)[CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.N1C=CC=CC=1.[CH:43]1([C:46](Cl)=[O:47])[CH2:45][CH2:44]1>O1CCCC1.C(OCC)(=O)C>[CH:43]1([C:46]([NH:1][C:2]2[S:3][C:4]3[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([O:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[C:18]([NH:23][C:24](=[O:36])[CH2:25][C:26]5[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:34])([F:35])[F:33])[CH:27]=5)[CH:17]=4)[CH:8]=[CH:7][C:5]=3[N:6]=2)=[O:47])[CH2:45][CH2:44]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 77637Cyclopropanecarbonyl chlorideHCID 86644709HCID 86644709, compound

Product 1

HCID 86644710HCID 86644710, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 2-amino-6-[4-fluoro-3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylate (2.50 mg, 4.81 mmol) in tetrahydrofuran (20 mL) were added pyridine (770 μL, 9.62 mmol) and cyclopropanecarbonyl chloride (790 μL, 8.66 mmol), and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (80 mL), washed successively with saturated aqueous sodium hydrogen carbonate solution (50 ml) and saturated brine (50 mL), and the organic layer was dried over anhydrous magnesium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=40/60→80/20), and a fraction containing the object product was concentrated under reduced pressure. The obtained pale-yellow residue was recrystallized from ethyl acetate/n-hexane (3/2) to give the title compound (2.25 g, 80%) as a white powder.

Workup

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (50 ml) and saturated brine (50 mL)
  2. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationInsoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=40/60→80/20)
  6. additiona fraction containing the object product
  7. concentrationwas concentrated under reduced pressure
  8. customThe obtained pale-yellow residue was recrystallized from ethyl acetate/n-hexane (3/2)

Sources & evidence

ORD record
ord-6db517c7415f4e7f91b8c2cb255f353d
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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