di-tert-butyl 1-(5-pyrimidinyl)-1,2-hydrazinedicarboxylate synthesis

Yield:-

Reaction Conditions:

with copper diacetate in methanol at 60; for 1 h;

Steps:

2 Step 2: 5-Hydrazinylpyrimidine hydrochloride (A2)

In a pressure vessel pyrimidine-5-boronic acid (10 g, 80.7 mmol, 1eq.), di-tert-butyl- azodicarboxylate (18.6 g, 80.7 mmol, 1 eq.), anhydrous copper(ll)acetate (0.5 g, 2.7 mmol, 0.033 eq) in dry methanol (320ml_) were heated at 60° C for 1h. The mixture was concentrated in vacuum. The residue was solved in diethyl ether and washed with sat. aq. NaHCO₃-so|. and brine. The organic layer was dried over Na₂SO₄ and concentrated under reduced pressure to yield the intermediate di-tert-butyl 1- (pyrimidin-5-yl)hydrazine-1 ,2-dicarboxylate. The intermediate was solved in dioxane (130 ml_) and 4M HCI in dioxane (150 mL, 592 mmol, 10.5 eq.) was slowly added. After 30 h at RT, the solid was filtered off and washed twice with diethyl ether. The solid was dried in vacuum yielding A2 (9.3 g, 79%). ¹H NMR (300 MHz, DMSO, 300 K) δ [ppm] 10.43 (br.s, 1 H), 9.05 (br.s, 3H), 8.78 (s, 1 H), 8.58 (s, 2H). MS (ES) C₄H₆N₄ requires: 110, found: 111 (M+H)⁺.

References:

WO2014/194975,2014,A1 Location in patent:Page/Page column 31