2011-48-5

(4-Methoxybenzyl)hydrazine Hydrochloride is used in preparation of Heterocyclic derivatives useful as SHP2 inhibitors.

Step 1: Synthesis of (4-methoxybenzyl)hydrazine hydrochloride Hydrazine hydrate (40 g, 0.80 mol) and anhydrous ethanol (280 mL) were added to a 500 mL three-necked round bottom flask. A solution of anhydrous ethanol (30 mL) of 4-methoxybenzyl chloride (12.5 g, 0.080 mol) was slowly added dropwise to the above mixture at room temperature. The reaction mixture was heated to 90 °C and stirred for 2 hours. Upon completion of the reaction, the mixture was concentrated under reduced pressure to remove the solvent and the residue was subsequently redissolved in anhydrous ethanol (150 mL). The solution was cooled to 0 °C and acidified by slowly adding 5 M hydrochloric acid (120 mL). The precipitated white solid precipitate was collected by filtration and dried to give 8.72 g of the target product (4-methoxybenzyl)hydrazine hydrochloride in 72% yield. Mass spectrometry analysis showed m/z: 153(M+H)+.

[1] Patent: US2010/120741, 2010, A1. Location in patent: Page/Page column 87
[2] Patent: WO2011/112731, 2011, A2. Location in patent: Page/Page column 189-190
[3] Patent: WO2014/139150, 2014, A1. Location in patent: Page/Page column 84; 85
[4] Patent: WO2014/150114, 2014, A1. Location in patent: Page/Page column 84; 85
[5] Patent: US2017/145026, 2017, A1. Location in patent: Paragraph 1027; 1028