p-Toluenesulfonic acid → N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

HRID 929683Notes

Reaction equation

HRID 929683 reaction equation
FC1C=C(NC2N=C3NN=CC3=C([C:24]3[CH:25]=[C:26]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])[CH:27]=[CH:28][CH:29]=3)N=2)C=CC=1N1CCOCC1.ClC1N=C(Cl)N=C2NN=CC=12.O1C=CCCC1.CC1C=CC(S(O)(=O)=O)=CC=1.Cl[C:64]1[N:69]=[C:68]([Cl:70])[N:67]=[C:66]2[N:71]([CH:74]3[CH2:79][CH2:78][CH2:77][CH2:76][O:75]3)[N:72]=[CH:73][C:65]=12.C(NC1C=C(B(O)O)C=CC=1)(=O)C=C>C(Cl)Cl.C1COCC1>[Cl:70][C:68]1[N:67]=[C:66]2[N:71]([CH:74]3[CH2:79][CH2:78][CH2:77][CH2:76][O:75]3)[N:72]=[CH:73][C:65]2=[C:64]([C:28]2[CH:27]=[C:26]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])[CH:25]=[CH:24][CH:29]=2)[N:69]=1

Participants

9

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 103213313-Acrylamidophenylboronic acidHCID 120664494,6-Dichloro-1H-pyrazolo(3,4-d)pyrimidineHCID 576542774,6-dichloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidineHCID 68388406N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 86677518N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

As an example, N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide can be prepared according to Route II. Beginning with 4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine, protection can be accomplished by reaction with 3,4-dihydro-2H-pyran in the presence of p-TsOH in a suitable solvent such as a solution of THF and methylene chloride. The reaction is carried out for a suitable period of time, e.g. about 8-18 hr, at a suitable temperature, e.g. about 15-30° C., until the reaction is complete. The completeness of the reaction can be ascertained by several convenient methods, including monitoring the reaction by TLC. The resulting 4,6-dichloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine can then be coupled with (3-acrylamidophenyl)boronic acid under palladium catalyzed conditions to provide N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide.

Workup

  1. customThe completeness of the reaction
  2. customthe reaction by TLC

Sources & evidence

ORD record
ord-a55214ef2fbd404899144307cb0eb1cb
Source dataset
uspto-grants-2016_03
Patent number
US09296703B2

Reaction notes

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