These common heterocyclic compound, 6306-61-2, name is N-(2-Chloroethyl)propan-2-amine hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Formula: C5H13Cl2N
In anhydrous conditions under argon atmosphere, NaH (60% in mineral oil, 0.232 g, 5.8 mmol) was added slowly to a suspension of intermediate 9 (0.35 g, 0.97 mmol) in N,N- dimethylformamide (10 ml) at 0C and the mixture was stirred at 0C for 10 minutes. Isopropylaminoethyl chloride hydrochloride (0.459 g, 2.9 mmol) was added portionwise and the reaction mixture was stirred at room temperature for 48 h ours. The reaction mixture was quenched with a saturated solution of ammonium chloride (15 ml) and the mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic layers were washed with a saturated solution of sodium chloride (2 x 50 ml), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified bychromatography over silica gel (mobile phase, gradient from 95% DCM, 5%MeOH to 90% DCM, 10%). The fractions were collected and the solvent was evaporated yielding 0.22g of fraction 2 composed of a mixture of compound 4 and compound 6..Fraction 1 and Fraction 2 were combined and purified by achiral SFC (mobile phase, 0.3% isopropylamine, 86% C02, 14% MeOH). The desired fractions were collected and concentrated, yielding 17 mg of compound 5, 168 mg of compound 4 and 60 mg of product fraction 3 containing compound 4 and compound 6..Compound 4 was converted into the HCI salt (3eq. 1 M solution in water) in Et20 and triturated . The precipitate was filtered off, washed with Et20 and dried under vacuum, yielding 153 mg of compound 4 (mp = 175C Kofler).Product fraction 3 was purified by chiral SFC on (5muiotaeta mobile phase, 0.3%isopropylamine, 85% C02, 15% MeOH), yielding 22mg of compound 6.
The synthetic route of N-(2-Chloroethyl)propan-2-amine hydrochloride has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ASTEX THERAPEUTICS LIMITED; ANGIBAUD, Patrick Rene; OBRINGER, Michel; MARIN, Julien Jeremie Joseph; JEANTY, Matthieu; WO2013/61077; (2013); A1;,
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