Water → TAK-632

HRID 1097532Notes

Reaction equation

HRID 1097532 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:10]([C:11]#[N:12])=[C:9]([O:13][C:14]3[CH:15]=[CH:16][C:17]([F:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[CH:19]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.N1C=CC=CC=1.[CH:41]1([C:44](Cl)=[O:45])[CH2:43][CH2:42]1.O>CN(C)C(=O)C>[C:11]([C:10]1[C:4]2[S:3][C:2]([NH:1][C:44]([CH:41]3[CH2:43][CH2:42]3)=[O:45])=[N:6][C:5]=2[CH:7]=[CH:8][C:9]=1[O:13][C:14]1[CH:15]=[CH:16][C:17]([F:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=2)[CH:19]=1)#[N:12]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 77637Cyclopropanecarbonyl chloride2×HCID 86644708HCID 86644708, compound

Product 1

HCID 46209401TAK-632Yield 95.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{5-[(2-amino-7-cyano-1,3-benzothiazol-6-yl)oxy]-2-fluorophenyl}-2-[3-(trifluoromethyl)phenyl]acetamide (980 mg, 2.01 mmol) in N,N-dimethylacetamide (8 mL) were added pyridine (242 μL, 3.02 mmol) and cyclopropanecarbonyl chloride (255 μL, 2.81 mmol), and the mixture was stirred at room temperature for 2 hr. Cyclopropanecarbonyl chloride (255 μL, 2.81 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 2 hr. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL), and dried over anhydrous magnesium sulfate. Insoluble material was filtered off, the filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate), and the obtained solution was concentrated under reduced pressure. A pale-brown oil residue was crystallized from ethanol/water (1/1) to give the title compound (1.06 g, 95%) as a white powder.

Workup

  1. stirringthe mixture was further stirred at room temperature for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate (20 mL)
  3. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationInsoluble material was filtered off
  6. customthe filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customA pale-brown oil residue was crystallized from ethanol/water (1/1)

Sources & evidence

ORD record
ord-0ce7d8867e8f46fa80ab9b512dd434d0
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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