(2,2-difluorocyclopropyl)methanamine hydrochloride synthesis

Yield:-

Reaction Conditions:

Stage #1:2-(2,2-difluorocyclopropylmethyl)isoindole-1,3-dione with hydrazine hydrate in ethanol at 90; for 1 h;
Stage #2: with hydrogenchloride in water

Steps:

58 Preparation of compound 4
To a mixture of compound 3 (100 mg, 421.58 umol, 1 eq) in EtOH (2 mL) was added NH₂NH₂•H₂O (29.79 mg, 505.90 umol, 28.93 uL, 85% purity, 1.2 eq), the mixture was stirred at 90°C for 1 hr .TLC showed part of compound 3 was remained, and a new spot was observed. The mixture was cooled to room temperature, filtered to remove the white solid. The filtrate was diluted with HCl (1 mL, 1 N) and concentrated to give compound 3 (45 mg, crude, HCl) as white solid. 1H NMR (400 MHz, MeOD) d = 3.22 (td, J = 1.7, 3.3 Hz, 1H), 3.11 - 2.90 (m, 2H), 1.97 - 1.86 (m, 1H), 1.62 (ddt, J = 5.1, 8.1, 11.6 Hz, 1H), 1.38 - 1.28 (m, 1H)

References:

INSILICO MEDICINE IP LIMITED;ZAVORONKOVS, Aleksandrs;IVANENKOV, Yan;ALIPER, Aleksandr;VANTSKUL, Anton, S. WO2020/198583, 2020, A1 Location in patent:Paragraph 000357; 000358