Methanol → N-[6-(5-amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

HRID 1097478Notes

Reaction equation

HRID 1097478 reaction equation
[BH4-].[Na+].CO.[Cl:5][C:6]1[CH:29]=[C:28]([F:30])[C:27]([NH:31]C(=O)C(F)(F)F)=[CH:26][C:7]=1[O:8][C:9]1[CH:23]=[CH:22][C:12]2[N:13]=[C:14]([NH:16][C:17]([CH:19]3[CH2:21][CH2:20]3)=[O:18])[S:15][C:11]=2[C:10]=1[C:24]#[N:25]>C(O)C>[NH2:31][C:27]1[C:28]([F:30])=[CH:29][C:6]([Cl:5])=[C:7]([CH:26]=1)[O:8][C:9]1[CH:23]=[CH:22][C:12]2[N:13]=[C:14]([NH:16][C:17]([CH:19]3[CH2:21][CH2:20]3)=[O:18])[S:15][C:11]=2[C:10]=1[C:24]#[N:25]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 86644691HCID 86644691, compound

Product 1

HCID 86644692N-[6-(5-amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of sodium borohydride (266 mg, 7.02 mmol) in ethanol (10 mL) was added dropwise methanol (1 mL), and N-(6-{2-chloro-4-fluoro-5-[(trifluoroacetyl)amino]phenoxy}-7-cyano-1,3-benzothiazol-2-yl)cyclopropanecarboxamide (350 mg, 0.70 mmol) was added to the suspension. The reaction mixture was stirred at 60° C. for 1 hr, and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (100 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 preparative thin layer chromatography (ethyl acetate/n-hexane=50/50), and the band containing the object product was scraped off, and eluted with 10% tetrahydrofuran/ethyl acetate. The obtained solution was purified by basic silica gel column chromatography (eluate: ethyl acetate). The obtained solution was concentrated under reduced pressure to give the title compound (180 mg, 64%) as a white powder.

Workup

  1. additionwas added to the suspension
  2. concentrationconcentrated under reduced pressure
  3. additionThe obtained residue was diluted with ethyl acetate (100 mL)
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (50 ml) and saturated brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationInsoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by preparative thin layer chromatography (ethyl acetate/n-hexane=50/50)
  9. additionthe band containing the object product
  10. washeluted with 10% tetrahydrofuran/ethyl acetate
  11. customThe obtained solution was purified by basic silica gel column chromatography (eluate: ethyl acetate)
  12. concentrationThe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-72a7c6d7736f4a3da378946d0c74995b
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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