Compound 10
tert-Butyl 4-((7-bromo-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)methyl)-4-hydroxypiperidine-1-carboxylate
From: Discovery and characterization of highly potent and selective allosteric USP7 inhibitors
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
A mixture of tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (640 mg, 3.00 mmol), 7-bromothieno[3,2-d]pyrimidin-4(3H)-one1 (578 mg, 2.50 mmol) and Cs2CO3 (978 mg, 3.00 mmol) in DMF (8.3 mL) was heated at 80 °C for 16 h. Upon cooling to RT, the mixture was diluted with saturated NH4Cl(aq) (40 mL) and extracted with DCM (3 x 30 mL) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica 80 g cartridge, 0-100% EtOAc in cyclohexane) to give the title compound (867 mg, 78%) as a pale yellow solid. LCMS: RT = 1.31 min, m/z = 466, 468 [M+Na]+. 1H NMR (300 MHz, DMSO-d6): δ 8.40 (s, 2H), 4.95 (s, 1H), 4.11 – 3.95 (m, 2H), 3.76 – 3.54 (m, 2H), 3.14 – 2.91 (m, 2H), 1.57 – 1.27 (m, 4H), 1.39 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 157.99, 154.72, 154.01, 149.91, 131.82, 122.92, 109.26, 79.80, 70.44, 55.50, 39.46, 34.98, 28.48.
- PubChemID:
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348266812
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