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

HRID 661323Notes

Reaction equation

HRID 661323 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[NH:8][C:7](=[O:16])[N:6]1[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1[O:27][CH3:28].FC1C=CC=CC=1NC(NC1C=C(C(F)(F)F)C=CC=1OC)=O.C(OC)(=O)C=C>>[F:15][C:10]1[C:9]([NH:8][C:7]([NH:6][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=2[O:27][CH3:28])=[O:16])=[C:14](/[CH:5]=[CH:4]/[C:3]([O:2][CH3:1])=[O:29])[CH:13]=[CH:12][CH:11]=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-d874331fe0394bbdae56e4259065c74e
Source dataset
uspto-grants-2011_12
Patent number
US08084604B2

Reaction notes

Loading…