Potassium Carbonate → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one

HRID 634414Notes

Reaction equation

HRID 634414 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:39])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]5[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]5)[CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[F:40][C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[C:45]([OH:47])[CH:46]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:39])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]5[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]5)[CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10]([C:43]3[CH:44]=[C:45]([OH:47])[CH:46]=[C:41]([F:40])[CH:42]=3)[C:3]=12

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 1181314233-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one2×

Product 1

HCID 1181311683-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-oneYield 73.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one (Intermediate D8, 1.14 g, 1.788 mmol), (3-fluoro-5-hydroxyphenyl)boronic acid (0.558 g, 3.58 mmol), K2CO3 (0.494 g, 3.58 mmol) and PdCl2(dppf) (0.196 g, 0.268 mmol) were reacted in dioxane (30 ml) overnight at 120° C. The reaction was diluted with DCM (100 ml), filtered to remove solids, and the filtrate evaporated under reduced pressure. The crude was purified via flash chromatography on silica gel using a Biotage 100G SNAP with a gradient of DCM and MeOH to give the title compound (819 mg, 73.7%) as brown pale solid.

Workup

  1. filtrationfiltered
  2. customto remove solids
  3. customthe filtrate evaporated under reduced pressure
  4. customThe crude was purified via flash chromatography on silica gel using a Biotage 100G SNAP with a gradient of DCM and MeOH

Sources & evidence

ORD record
ord-f1c3c692e24349eb9f5eef13c9fe9e47
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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