Water → 1-[9-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]-4-phenylpiperidine-4-carbonitrile

HRID 528042Notes

Reaction equation

Br[C:2]1[N:3]([CH3:25])[C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][C:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([C:17]#[N:18])[CH2:13][CH2:12]1)[N:7]=[CH:6][N:5]=2.[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.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]>[CH3:25][N:3]1[C:2]([C:30]2[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=2)=[N:10][C:9]2[C:4]1=[N:5][CH:6]=[N:7][C:8]=2[N:11]1[CH2:16][CH2:15][C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([C:17]#[N:18])[CH2:13][CH2:12]1

Participants

Conditions

Temperature: 150 °C

Procedure

1-(8-bromo-9-methyl-9H-purin-6-yl)-4-phenylpiperidine-4-carbonitrile (400 mg, 1.0 mmol), 1-Methylpyrazole-4-boronic acid pinacol ester (419 mg, 2.0 mmol), and potassium phosphate (427 mg, 2.0 mmol) were suspended in dioxane (5 mL). To that mixture was added Pd(dppf)Cl2 (82 mg, 0.10 mmol) and water. This suspension was heated to 150° C. in the microwave for 30 minutes. Upon cooling, the resulting mixture was filtered through Celite and a PL-thiol SPE cartridge. The filtrate was then purified by prep HPLC to afford 2 mg of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 8.42 (s, 1H), 8.26 (s, 1H), 8.03 (s, 1H), 7.59-7.51 (m, 2H), 7.42 (m, 2H), 7.35 (m, 1H), 5.62 (s, 2H), 3.93 (s, 3H), 3.84 (s, 3H), 3.34 (m, 4H), 2.27 (m, 2H), 2.08 (m, 2H). EI (MS) for C22H22N8: 399.29 (MH+).

Workup

temperatureUpon cooling
filtrationthe resulting mixture was filtered through Celite
customThe filtrate was then purified by prep HPLC

Sources & evidence

ORD record: ord-6ad598d415d24e35b1a3f97b8cb98f0e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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