Carbamic acid, pyrazinyl-, 1,1-dimethylethyl ester (9CI) synthesis

Yield:264600-78-4 84%

Reaction Conditions:

Stage #1: 2-Aminopyrazine;di-tert-butyl dicarbonatewith dmap in tetrahydrofuran; for 2 h;Inert atmosphere;
Stage #2: with triethylamine in tetrahydrofuran; for 2 h;Inert atmosphere;
Stage #3: with sodium hydroxide in methanol at 20; for 2 h;

Steps:

GO (1544) 3-[(Pyrazin-2-yl)({5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]thiophen-2- yl}methyl)amino]pyrazine-2-carboxamide

To a stirred solution of pyrazin-2-amine (1 .902 g, 20 mmol) in THF (10 ml_) at rt under an argon atmosphere, was added DMAP (catalytic amount) followed by (B0C)₂0 (1 M solution in THF, 22 ml_, 22 mmol) dropwise. The reaction mixture was stirred for 2 h and then Et₃N (2.024 g, 20 mmol) was added. After 1 h (BOC)₂0 (1 M solution in THF, 5 ml_, 5 mmol) was added dropwise and the reaction mixture stirred for a further 1 h. The reaction mixture was poured into 10% HCI solution (30 ml_) and extracted with CH₂CI₂ (30 ml_) twice. The combined organic fractions were dried over MgS0₄, filtered and the solvent removed by evaporation in vacuo. The crude product was dissolved in MeOH (30 ml_) and 1 M NaOH solution (20 ml_, 20 mmol) added. The reaction mixture was stirred for 2 h at rt and then neutralised using solid C0₂. Water (50 ml_) was added and the product extracted with CH₂CI₂ (50 ml_) twice. The combined organic fractions were dried over MgS0₄, filtered and the solvent removed by evaporation in vacuo. The product was dissolved in hexane/CH₂CI₂ treated with activated charcoal, filtered and the solvent removed by evaporation in vacuo to yield intermediate 1 as a white solid (3.18 g, 84%). (1547) ¹H NMR (300 MHz, DMSO-cf6) d: 10.20 (br s, 1 H), 9.10 (d, J=1.5 Hz, 1 H), 8.36 (dd, J=2.5, 1.6 Hz, 1 H), 8.32 (d, J=2.6 Hz, 1 H), 1.54 (s, 9H).

References:

WO2019/166824,2019,A1 Location in patent:Page/Page column 191; 192