Pyridine → HCID 86644707, compound

HRID 455228Notes

Reaction equation

HRID 455228 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:10]([N+:11]([O-:13])=[O:12])=[C:9]([O:14][C:15]3[CH:16]=[CH:17][C:18]([F:36])=[C:19]([NH:21][C:22](=[O:35])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])[C:24]=4[Cl:34])[CH:20]=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>[Cl:34][C:24]1[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])=[CH:26][CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:19]1[CH:20]=[C:15]([O:14][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:46]([CH:43]4[CH2:45][CH2:44]4)=[O:47])[S:3][C:4]=3[C:10]=2[N+:11]([O-:13])=[O:12])[CH:16]=[CH:17][C:18]=1[F:36])=[O:35]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 77637Cyclopropanecarbonyl chloride2×HCID 86644705HCID 86644705, compound

Product 1

HCID 86644707HCID 86644707, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{5-[(2-amino-7-nitro-1,3-benzothiazol-6-yl)oxy]-2-fluorophenyl}-2-chloro-3-(1-cyano-1-methylethyl)benzamide (150 mg, 0.285 mmol) produced in Example 41(iii) in tetrahydrofuran (8 mL) were added pyridine (160 μL, 2.0 mmol) and cyclopropanecarbonyl chloride (39 μL, 0.428 mmol), and the mixture was stirred at room temperature for 1 hr. Pyridine (160 μL, 2.0 mmol) and cyclopropanecarbonyl chloride (10 μL, 0.11 mmol) were added, and the mixture was stirred at room temperature for 6 hr. The reaction mixture was diluted with ethyl acetate (50 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=60/40→100/0), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/diethyl ether to give the title compound (54 mg, 32%) as a yellow powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 6 hr
  2. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationInsoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=60/40→100/0)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was crystallized from ethyl acetate/diethyl ether

Sources & evidence

ORD record
ord-db071b2f56094bb6b5b33488b5442aa1
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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