Compound 2
(R)-7-Bromo-3-((4-hydroxy-1-(3-phenylbutanoyl)piperidin-4-yl)methyl)thieno[3,2-d]pyrimidin-4(3H)-one
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.
DIPEA (0.359 mL, 2.06 mmol) was added to a suspension of 7-bromo-3-((4-hydroxypiperidin-4-yl)methyl)thieno[3,2-d]pyrimidin-4(3H)-one 11 (177 mg, 0.514 mmol), (R)-3-phenylbutanoic acid (101 mg, 0.617 mmol) and HATU (235 mg, 0.617 mmol) in DCM (10.3 mL). After 10 min, the reaction was quenched by the addition of saturated NaHCO3(aq) (30 mL) and the mixture was extracted with DCM (3 x 40 mL) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica 40 g cartridge, 0-100% EtOAc in cyclohexane then 0-30% MeOH in EtOAc) to give the title compound (134 mg, 53%) as a colourless solid. LCMS: RT = 1.28 min (purity >95% at 254 nm), m/z = 490, 492 [M+H]+. 1H NMR (500 MHz, DMSO-d6): δ 8.57 – 8.16 (m, 2H), 7.46 – 7.03 (m, 5H), 5.00 – 4.88 (m, 1H), 4.13 – 3.87 (m, 3H), 3.71 – 3.58 (m, 1H), 3.25 – 3.08 (m, 2H), 2.91 – 2.77 (m, 1H), 2.66 – 2.52 (m, 2H), 1.58 – 1.13 (m, 7H). 13C NMR (126 MHz, DMSO-d6): δ 169.08 + 169.06 (conformers), 156.67 + 156.62 (conformers), 153.38, 151.23 + 151.20 (conformers), 146.66 + 146.54 (conformers), 132.49, 128.18 + 128.15 (conformers), 126.88 + 126.85 (conformers), 125.93 + 125.89 (conformers), 121.87, 108.30, 69.20 + 69.15 (conformers), 53.61, 41.01 + 40.90 (conformers), 40.22 + 40.19 (conformers), 36.87, 36.21 + 35.99 (conformers), 34.93 + 34.80 (conformers), 34.25 + 34.12 (conformers), 22.06 + 21.86 (conformers). HRMS (TOF MS ES+): m/z [M + H]+ Calcd for C22H25N3O3SBr 490.0800, found 490.0793.
- PubChemID:
-
348266821
- MDL Molfile:
- ChemDraw:
