تفاعل #84019

ord-8cdc94bb6ce1435fa4135eab835ea47a

معادلة التفاعل

O=C(Cl)CCCl
3-chloropropanoyl chloride
Cl.Nc1c[nH]nc1Cl
3-chloro-1H-pyrazol-4-amine•hydrochloride
C1CCOC1
tetrahydrofuran
O=C([O-])O.[Na+]
sodium bicarbonate
O=C(CCCl)Nc1c[nH]nc1Cl
desired product
O=C(CCCl)Nc1c[nH]nc1Cl
3-chloro-N-(-3-chloro-1H-pyrazol-4-yl) propanamide

المذيبات

ظروف التفاعل

درجة الحرارة
5°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىwas consumed

الإجراء التجريبي

A 250-mL 3-neck flask was charged with 3-chloro-1H-pyrazol-4-amine•hydrochloride (10.0 g, 64.9 mmol), tetrahydrofuran (50 mL), and water (50 mL). The resulting suspension was cooled to 5° C. and sodium bicarbonate (17.6 g, 210 mmol) was added, followed by dropwise addition of 3-chloropropanoyl chloride (7.33 g, 57.7 mmol) at <5° C. The reaction was stirred at <10° C. for 1 hour, at which point thin layer chromatography (TLC) [Eluent: 1:1 ethyl acetate (EtOAc)/hexane] analysis indicated the starting material was consumed and the desired product was formed. It was diluted with water (50 mL) and ethyl acetate (50 mL) and the layers separated. The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were concentrated to dryness to afford a pale brown solid, which was purified by flash column chromatography using ethyl acetate as eluent. The pure fractions were concentrated to afford a white solid (9.20 g, 77%): mp: 138-140° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 9.68 (s, 1H), 8.03 (d, J=1.7 Hz, 1H), 3.85 (t, J=6.3 Hz, 2H), 2.85 (t, J=6.3 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 167.52, 130.05, 123.59, 116.48, 40.75, 37.91; EIMS m/z 207 (m+).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09433215B2uspto-grants-2016_09