| 1382979-44-3 Basic information More.. |
Product Name: | GDC-0084 | Synonyms: | GDC-0084;5-[8,9-Dihydro-6,6-dimethyl-4-(4-morpholinyl)-6H-[1,4]oxazino[4,3-e]purin-2-yl]-2-pyrimidinamine;5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine;2-Pyrimidinamine, 5-[8,9-dihydro-6,6-dimethyl-4-(4-morpholinyl)-6H-[1,4]oxazino[4,3-e]purin-2-yl]-;5-[6,6-Dimethyl-4-(4-morpholinyl)-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl]-2-pyrimidinamine;GDC-0084(RG7666);CS-2290;GDC-0084 (GDC0084 | CAS: | 1382979-44-3 | MF: | C18H22N8O2 | MW: | 382.42 | EINECS: | | Mol File: | 1382979-44-3.mol | |
Use
Stumpf et al. at Genentech Inc. (Roche group) developed an efficient multikilogram process to synthesize the brain penetrant PI3K inhibitor, GDC‐0084, a potential drug candidate for the treatment of several brain cancers. An efficient Suzuki coupling reaction between a chloropyrimidine and an arylboronic ester using a palladium catalyst at low loading was reported. The optimized conditions were demonstrated on 6.75 kg of a chloropyrimidine intermediate, providing 7.49 kg of crude GDC‐0084 (94% yield, 99.4% HPLC purity). Using the commercially available XPhos Pd G2 catalyst, instead of the usual PdCl2(dppf)CH2Cl2 catalyst, it was possible to reduce the catalyst loading from 2 to 0.5 mol%. A final scavenging/recrystallization combination from Si‐Thiol (a solid‐supported resin) and acetic acid/water provided the crude GDC‐0084 with the required purity and polymorphic form (off‐white solid, 6.41 kg, 83% yield, 99.7% HPLC purity).
Genentechs route to GDC‐0084 employing a pivotal Suzuki reaction.
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1382979-44-3
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