Methyl Acrylate → Methyl (2E)-3-(3-fluoro-2-((((2-methoxy-5-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-2-propenoate

HRID 2410221Notes

Reaction equation

HRID 2410221 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[N:8]([C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[O:23][CH3:24])[CH:7]2[CH2:25][C:26]([O:28][CH3:29])=[O:27].FC1C=CC=CC=1NC(NC1C=C(C(F)(F)F)C=CC=1OC)=O.C(OC)(=O)C=C>>[F:1][C:2]1[C:11]([NH:10][C:9]([NH:8][C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[O:23][CH3:24])=[O:12])=[C:6](/[CH:7]=[CH:25]/[C:26]([O:28][CH3:29])=[O:27])[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 7294Methyl AcrylateHCID 120019934-QuinazolineAcetic Acid 8-Fluoro-1,2,3,4-Tetrahydro-3-[2-Methoxy-5-(TrifluoroMethyl)Phenyl]-2-Oxo-Methyl esterHCID 57857532N-(2-fluorophenyl)-N'-[2-methoxy-5-(trifluoromethyl)phenyl]urea

Product 1

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

Procedure

In addition, it has surprisingly been found that the structural unit methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate can be synthesized efficiently by means of an ortho-palladization. Here, N-(2-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea is reacted with methyl acrylate and an oxidizing agent in the presence of an acid to give methyl (2E)-3-{3-fluoro-2-[({[2-methoxy-5-(trifluoromethyl)phenyl]amino}-carbonyl)amino]phenyl}acrylate. The ring closure to the tetrahydroquinazoline then follows under basic reaction conditions.

Workup

  1. customcan be synthesized efficiently by means of an ortho-palladization

Sources & evidence

ORD record
ord-33f0587895ce4e088149d4843530cd9b
Source dataset
uspto-grants-2014_08
Patent number
US08816075B2

Reaction notes

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