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

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole	HCID 2773987	—
Reactant	1-(8-Bromo-9-methyl-9H-purin-6-yl)-4-phenylpiperidine-4-carbonitrile	HCID 68298140	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	1-[9-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]-4-phenylpiperidine-4-carbonitrile	HCID 66799804	0.5%

Reaction Conditions

Temperature	150 °C

Reaction Steps

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+).

Provenance & Evidence

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