Sodium Carbonate → HCID 59506950, compound

HRID 1800526Notes

Reaction equation

HRID 1800526 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[C:13]([Cl:33])=[CH:14][C:15]([F:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=3)[CH:17]=1)[N:5]=2.C([O:37][CH2:38][C:39](Cl)=[O:40])(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:33][C:13]1[C:12]([O:11][C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:38](=[O:37])[CH2:39][OH:40])=[N:10][C:9]3=[CH:8][CH:7]=2)=[CH:17][C:16]([NH:18][C:19](=[O:31])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=2)=[C:15]([F:32])[CH:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 26297Acetoxyacetyl chlorideHCID 86646015N-(5-[(2-Amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59506950HCID 59506950, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide (100 mg, 0.207 mmol) produced in Example C52(v) in pyridine (2.0 mL) was added acetoxyacetyl chloride (48.9 μL, 0.455 mmol), and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate (10 mL), washed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in methanol (2.0 mL), sodium carbonate (100 mg, 0.943 mmol) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in ethyl acetate (10 mL). The obtained suspension was washed with 5% aqueous ammonium chloride solution (10 mL), 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give the title compound (63.0 mg, 56%) as a colorless powder.

Workup

  1. washwashed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationThe insoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionThe obtained residue was dissolved in methanol (2.0 mL)
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. washThe obtained suspension was washed with 5% aqueous ammonium chloride solution (10 mL), 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15)
  13. concentrationthe obtained solution was concentrated under reduced pressure
  14. customThe residue was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-6386d727dbed47f88c163cbbfd8fe8b1
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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