Methyl (2E)-3-(3-fluoro-2-((((2-methoxy-5-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-2-propenoate → 4-QuinazolineAcetic Acid 8-Fluoro-1,2,3,4-Tetrahydro-3-[2-Methoxy-5-(TrifluoroMethyl)Phenyl]-2-Oxo-Methyl ester

HRID 2410236Notes

Reaction equation

HRID 2410236 reaction equation
[F:1][C:2]1[C:3]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=2[O:28][CH3:29])=[O:16])=[C:4](/[CH:8]=[CH:9]/[C:10]([O:12][CH3:13])=[O:11])[CH:5]=[CH:6][CH:7]=1>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[NH:14][C:15](=[O:16])[N:17]([C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[O:28][CH3:29])[CH:8]2[CH2:9][C:10]([O:12][CH3:13])=[O:11]

Participants

3

Reactant 1

HCID 57857531Methyl (2E)-3-(3-fluoro-2-((((2-methoxy-5-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-2-propenoate

Product 1

HCID 120019934-QuinazolineAcetic Acid 8-Fluoro-1,2,3,4-Tetrahydro-3-[2-Methoxy-5-(TrifluoroMethyl)Phenyl]-2-Oxo-Methyl esterYield 89%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
56 °C

Procedure

Methyl (2E)-3-{3-fluoro-2-[({[2-methoxy-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]-phenyl}acrylate (50 g) is suspended in acetone (1.2 l) and treated with 1,8-diazobicyclo[5.4.0]undec-7-ene (3.7 g). The suspension is warmed to reflux (ca. 56° C.) and stirred for 4 h. The resulting clear solution is filtered warm through kieselguhr (5 g). The kieselguhr is rinsed with warm acetone (100 ml). Subsequently, acetone (550 g) is distilled off. The resulting suspension is cooled to 0° C. in the course of 3 h and stirred. The product is filtered off with suction, washed twice with cold acetone (50 ml) and dried at 45° C. overnight in the vacuum drying oven using entraining nitrogen. A total of 44.5 g of methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate are obtained as a solid, corresponding to 89% of theory.

Workup

  1. temperatureThe suspension is warmed
  2. filtrationThe resulting clear solution is filtered
  3. temperaturewarm through kieselguhr (5 g)
  4. washThe kieselguhr is rinsed with warm acetone (100 ml)
  5. distillationSubsequently, acetone (550 g) is distilled off
  6. temperatureThe resulting suspension is cooled to 0° C. in the course of 3 h
  7. stirringstirred
  8. filtrationThe product is filtered off with suction
  9. washwashed twice with cold acetone (50 ml)
  10. customdried at 45° C. overnight in the vacuum
  11. customdrying oven

Sources & evidence

ORD record
ord-9d1ac1e28308439685628de07dda9ac7
Source dataset
uspto-grants-2014_08
Patent number
US08816075B2

Reaction notes

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