Pyridine → HCID 86657961, compound

HRID 2366759Notes

Reaction equation

HRID 2366759 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:25])[C:10]2[N:15]=[C:14]3[S:16][C:17]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[N:26]([C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=1)=[C:27]=[O:28].N1C=CC=CC=1>CN(C)C=O.C(OCC)(=O)C>[F:8][C:7]1[CH:6]=[CH:5][C:4]([N:9]([CH3:25])[C:10]2[N:15]=[C:14]3[S:16][C:17]([NH:19][C:20]([CH:22]4[CH2:23][CH2:24]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)=[CH:3][C:2]=1[NH:1][C:27](=[O:28])[NH:26][C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]([F:37])([F:39])[F:38])=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 92298p-(Trifluoromethoxy)phenyl isocyanate2×HCID 86646059N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

Product 1

HCID 86657961HCID 86657961, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-{5-[(3-Amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (120 mg, 0.34 mmol) produced in Example 1(x) was dissolved in N,N-dimethylformamide (1.5 mL), 1-isocyanato-4-(trifluoromethoxy)benzene (70 μl, 0.46 mmol) was added, and the mixture was stirred at room temperature for 12 hr. 1-Isocyanato-4-(trifluoromethoxy)benzene (70 μL, 0.46 mmol) was further added to the reaction mixture, and the mixture was further stirred at 70° C. for 3 hr. Pyridine (1.5 mL) was added to the reaction mixture, and the mixture was further stirred at 70° C. for 2 hr. The reaction mixture was diluted with ethyl acetate (20 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (69 mg, 37%) as a colorless powder.

Workup

  1. stirringthe mixture was further stirred at 70° C. for 3 hr
  2. stirringthe mixture was further stirred at 70° C. for 2 hr
  3. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-b2a5215860a7440a9534f4d25279452b
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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