Cesium carbonate → 3-((4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-phenyl-1H-isochromen-1-one

HRID 634457Notes

Reaction equation

HRID 634457 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[O:14][C:15](=[O:29])[C:16]4[C:21]([C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[N:9]=[C:10](I)[C:3]=12.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[C:35]([OH:37])[CH:36]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[O:14][C:15](=[O:29])[C:16]4[C:21]([C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[N:9]=[C:10]([C:33]3[CH:34]=[C:35]([OH:37])[CH:36]=[C:31]([F:30])[CH:32]=3)[C:3]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 1181310463-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-phenyl-1H-isochromen-1-one2×

Product 1

HCID 1181313963-((4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-phenyl-1H-isochromen-1-oneYield 12.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-phenyl-1H-isochromen-1-one (intermediate D1, 50 mg, 0.101 mmol), 3-fluoro-5-hydroxyphenylboronic acid (32 mg, 0.201 mmol), Cs2CO3 (69 mg, 0.202 mmol), Pd(PPh3)4 (9.3 mg, 8.0 umol), were reacted in DMF (0.5 mL) at 110° C. under mw irradiation. The resulting crude was straightforward purified via reverse phase chromatography using a Biotage C18 30 g SNAP with a gradient of water and acetonitrile to give the title compound (6 mg, 12%).

Workup

  1. customThe resulting crude was straightforward purified via reverse phase chromatography

Sources & evidence

ORD record
ord-122be676c26448168f1356c55c199605
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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