1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → HCID 58451265, compound

HRID 2366789Notes

Reaction equation

HRID 2366789 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.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[O:34])=[CH:28][C:27]=1[C:35]([F:38])([F:37])[F:36]>N1C=CC=CC=1.C(OCC)(=O)C.O1CCCC1>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:1][C:2]2[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=2[F:24])[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)=[O:34])=[CH:28][C:27]=1[C:35]([F:36])([F:37])[F:38]

Participants

6

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzene2×HCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58451265HCID 58451265, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

N-[5-(3-Amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.44 mmol) produced in Example 16(vi) was dissolved in pyridine (3.0 ml), 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene (145 mg, 0.65 mmol) was added, and the mixture was stirred at 70° C. for 12 hr. 1-Chloro-4-isocyanato-2-(trifluoromethyl)benzene (70 mg, 0.32 mmol) was added to the reaction mixture, and the mixture was further stirred at 70° C. for 4 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL) and tetrahydrofuran (1 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (5 mL), and the suspension was stirred at room temperature for 10 min. The solid was collected by filtration, and washed successively with ethyl acetate and n-hexane to give the title compound (170 mg, 70%) as a colorless powder.

Workup

  1. stirringthe mixture was further stirred at 70° C. for 4 hr
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. stirringthe suspension was stirred at room temperature for 10 min
  7. filtrationThe solid was collected by filtration
  8. washwashed successively with ethyl acetate and n-hexane

Sources & evidence

ORD record
ord-1beb26b84f8e4c7fbe99da16570f63d4
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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