3-Acrylamidophenylboronic acid → N-(3-(2-chloro-5-((3-fluorophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide

HRID 929682Notes

Reaction equation

HRID 929682 reaction equation
FC1N(C)C(O)CN(C2C=CC(N[C:17]3[N:22]=[C:21]([C:23]4[CH:24]=[C:25]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])[CH:26]=[CH:27][CH:28]=4)[C:20]([NH:34][C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=4)=[CH:19][N:18]=3)=CC=2)C1.[Cl:42]C1N=C(Cl)C(NC2C=CC=C(F)C=2)=CN=1.C(NC1C=C(B(O)O)C=CC=1)(=O)C=C>[Pd]>[Cl:42][C:17]1[N:22]=[C:21]([C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])[CH:26]=[CH:27][CH:28]=2)[C:20]([NH:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)=[CH:19][N:18]=1

Participants

5

Reactant 3

HCID 103213313-Acrylamidophenylboronic acidHCID 866775172,4-dichloro-N-(3-fluorophenyl)pyrimidin-5-amineHCID 118591002N-(3-(2-((4-(3-fluoro-5-hydroxy-4-methylpiperazin-1-yl)phenyl)amino)-5-((3-fluorophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 71469247N-(3-(2-chloro-5-((3-fluorophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

As an example, N-(3-(2-((4-(3-fluoro-5-hydroxy-4-methylpiperazin-1-yl)phenyl)amino)-5-((3-fluorophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide can be prepared according to Route I. Beginning with 2,4-dichloro-N-(3-fluorophenyl)pyrimidin-5-amine, a palladium catalyzed coupling reaction with (3-acrylamidophenyl)boronic acid provides N-(3-(2-chloro-5-((3-fluorophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide under mild conditions. Reaction of this product with 4-(4-aminophenyl)-6-fluoro-1-methylpiperazin-2-ol under palladium catalyzed aminolysis conditions can yield the desired product.

Sources & evidence

ORD record
ord-2d8d4790749e42ee892afd5e3b97c983
Source dataset
uspto-grants-2016_03
Patent number
US09296703B2

Reaction notes

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