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 387194Notes

Reaction equation

HRID 387194 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-b14d74cef7454a4b96062127d5300eb6
Source dataset
uspto-grants-2013_02
Patent number
US08372972B2

Reaction notes

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