Boronic Acid → 3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-isopropylbenzamide

HRID 1396548Notes

Reaction equation

[CH:1]([NH:4][C:5]([C:7]1[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][CH:12]=1)=[O:6])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:25]1[C:33]2[C:28](=[N:29][C:30]([NH2:34])=[N:31][CH:32]=2)[N:27]([CH3:35])[N:26]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.B(O)O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:34][C:30]1[N:29]=[C:28]2[N:27]([CH3:35])[N:26]=[C:25]([C:9]3[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=3)[C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:6])[C:33]2=[CH:32][N:31]=1

Participants

Conditions

Temperature: 100 °C

Procedure

3-(N-isopropylaminocarbonyl)benzene boronic acid (0.99 g, 0.48 mmol) and 1.27M aqueous potassium phosphate solution (0.591 ml, 0.75 mmol) are stirred in 1,4-dioxane (1 ml), under an inert atmosphere of argon for 15 minutes. Separately, 3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (0.1 g, 0.44 mmol), PCy3 (4 mg, 0.012 mmol) and Pd2(dba)3 (5 mg, 0.005 mmol) are stirred in 1,4-dioxane (1 ml) before being added to the boronic acid solution. The reaction mixture is heated to 100° C. for 1.5 hours and then filtered hot to remove the palladium residues. The filtrate is diluted with a little MeOH/water and the resulting precipitate is collected by filtration and dried under vacuum at 45° C. to afford the title compound.

Workup

filtrationfiltered hot
customto remove the palladium residues
additionThe filtrate is diluted with a little MeOH/water
filtrationthe resulting precipitate is collected by filtration
customdried under vacuum at 45° C.

Sources & evidence

ORD record: ord-e1eb937903a346deb74e47162674f999
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901134B2

Reaction notes

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