Pyridine → N-{7-cyano-6-[3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamide

HRID 455237Notes

Reaction equation

HRID 455237 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[O:5][C:6]1[CH:20]=[CH:19][C:9]2[N:10]=[C:11]([NH:13][C:14]([CH:16]3[CH2:18][CH2:17]3)=[O:15])[S:12][C:8]=2[C:7]=1[C:21]#[N:22].[F:26][C:27]([F:39])([F:38])[C:28]1[CH:29]=[C:30]([CH2:34][C:35](O)=[O:36])[CH:31]=[CH:32][CH:33]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.N1C=CC=CC=1>C(OCC)(=O)C>[C:21]([C:7]1[C:8]2[S:12][C:11]([NH:13][C:14]([CH:16]3[CH2:18][CH2:17]3)=[O:15])=[N:10][C:9]=2[CH:19]=[CH:20][C:6]=1[O:5][C:4]1[CH:23]=[CH:24][CH:25]=[C:2]([NH:1][C:35](=[O:36])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([C:27]([F:38])([F:26])[F:39])[CH:29]=2)[CH:3]=1)#[N:22]

Participants

6

Reactant 4

HCID 1049PyridineHCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86644685N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 46222581N-{7-cyano-6-[3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (100 mg, 0.285 mmol) produced in Example 3(vi), [3-(trifluoromethyl)phenyl]acetic acid (138 mg, 0.684 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (260 mg, 0.684 mmol) and pyridine (2 mL) was stirred at 85° C. for 4 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (5 mL), washed successively with saturated aqueous ammonium chloride solution (5 mL), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-heptane (1/2) to give the title compound (87 mg, 57%) as a white powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed successively with saturated aqueous ammonium chloride solution (5 mL), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 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 residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→100/0)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate/n-heptane (1/2)

Sources & evidence

ORD record
ord-937889637cc54c91b42fa2a4b159229e
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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