1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → N-(5-{[3-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-4-fluorophenyl]amino}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide

HRID 2366775Notes

Reaction equation

HRID 2366775 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][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].[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>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:1][C:2]2[CH:3]=[C:4]([NH:9][C:10]3[N:15]=[C:14]4[S:16][C:17]([NH:19][C:20]([CH:22]5[CH2:23][CH2:24]5)=[O:21])=[N:18][C:13]4=[CH:12][CH:11]=3)[CH:5]=[CH:6][C:7]=2[F:8])=[O:34])=[CH:28][C:27]=1[C:35]([F:36])([F:37])[F:38]

Participants

5

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 86646062N-{5-[(3-amino-4-fluorophenyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 58451256N-(5-{[3-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-4-fluorophenyl]amino}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamideYield 39.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

N-{5-[(3-Amino-4-fluorophenyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (200 mg, 0.58 mmol) produced in Example 12(v) was dissolved in pyridine (3.0 mL), 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene (190 mg, 0.88 mmol) was added, and the mixture was stirred at 70° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), and washed successively with water (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 purified by basic silica gel column chromatography (ethyl acetate/hexane=10/90→80/20), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (130 mg, 39%) as a colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed successively with water (10 mL) and saturated brine (10 ml)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=10/90→80/20)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-b85cd19af3f94fa7b6ef057ebd505582
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

Loading…