2-(Trifluoromethyl)phenyl isocyanate → HCID 58451276, compound

HRID 2366797Notes

Reaction equation

HRID 2366797 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F:24])[O:5][C:6]1[N:11]=[C:10]2[S:12][C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])=[N:14][C:9]2=[CH:8][CH:7]=1.[N:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([F:37])([F:36])[F:35])=[C:26]=[O:27]>N1C=CC=CC=1.C(OCC)(=O)C.O1CCCC1>[F:24][C:23]1[CH:22]=[CH:21][C:4]([O:5][C:6]2[N:11]=[C:10]3[S:12][C:13]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])=[N:14][C:9]3=[CH:8][CH:7]=2)=[CH:3][C:2]=1[NH:1][C:26](=[O:27])[NH:25][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([F:35])([F:37])[F:36]

Participants

6

Reactant 2

HCID 167942-(Trifluoromethyl)phenyl isocyanateHCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58451276HCID 58451276, compoundYield 61.6%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.290 mmol) produced in Example 16(vi) in pyridine (3 mL) was added 1-isocyanato-2-(trifluoromethyl)benzene (53 μL, 0.348 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (15 mL)/tetrahydrofuran (5 mL), and washed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 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→90/10), and the obtained solution was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate (10 mL) to give the title compound (95 mg, 61%) as a white solid.

Workup

  1. washwashed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→90/10)
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. washThe obtained residue was washed with ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-2fa995e11d0e4322a5e3a57dfa2347d0
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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