VS-5584 synthesis

Yield: 47%

Reaction Conditions:

(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride in 1,4-dioxane;n-heptane at 65;Sealed tube;

Steps:

1
Synthesis of 55--((99--j/-s soopprropyl-8-methyl-2-morpholin-4-yl-9H-purin-6-yl)-pyrimidin-2- ylamine; To a solution of 5-(8-bromo-9-/sopropyl-2-morpholin-4-yl-9H-puhn-6-yl)-pyrimidin-2- ylamine, (30 mg, 0.072 mmol) and Pd(dppf)CI₂, (3 mg, 5% mmol) in 3 ml of anhydrous dioxane, was added slowly dimethyl zinc (210 μl, 1.0 M in heptane solution) in a sealed tube. The mixture was heated to about 65"C. MeOH was adde d drop wise and the solvents removed in vacuo. EtOAc was added to the residue and the resulting solution washed with 1 M HCI, water, brine and then dried over Na₂SO₄. The solvent was removed and the crude mixture was subjected to flash chromatography on silica gel to obtain 5-(9-/sopropyl-8-methyl- 2-morpholin-4-yl-9H-purin-6-yl)-pyrimidin-2-ylamine 8 mg in a yield of 47%. ¹H NMR, MeOD: 9.40 (s, 2H), 4.81 (m, 1 H), 3.89 (m, 4H), 3.82 (s, 4H), 3.71 (s, 3H), 1.73 (d, 6H). m/z: 355.16 [MH]⁺.

References:

S*BIO PTE LTD;CHEN, DiZhong;WILLIAMS, Meredith WO2010/114484, 2010, A1 Location in patent:Page/Page column 21