반응 #85377

ord-3db52075048748a29fc6b7314b45c919

반응 방정식

CCBr
bromoethane
CC(=O)Nc1cn(-c2cccnc2)nc1Cl
N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide
C1CCOC1
tetrahydrofuran
CC(C)(C)[O-].[Na+]
Sodium tert-butoxide
CCN(C(C)=O)c1cn(-c2cccnc2)nc1Cl
title product
수율 74.0%
CCN(C(C)=O)c1cn(-c2cccnc2)nc1Cl
N-(3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamide
수율 74.0%

반응 조건

온도
35°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타from 22° C. to 27.9° C.
  2. 2
    농축The reaction mixture was concentrated
  3. 3
    기타to give a brown residue, which
  4. 4
    추출The aqueous layer was extracted with ethyl acetate (4×50 mL)
  5. 5
    농축the combined organics were concentrated
  6. 6
    기타to give a brown residue
  7. 7
    기타purified by flash column chromatography
  8. 8
    workup.ADDITIONThe fractions containing pure product
  9. 9
    농축concentrated

실험 절차

To a 3-neck, 100-mL round bottom flask was charged N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (5.00 g, 21.1 mmol) and tetrahydrofuran (50 mL). Sodium tert-butoxide (3.05 g, 31.7 mmol) was added (causing a temperature rise from 22° C. to 27.9° C.), followed by bromoethane (4.70 mL, 63.4 mmol). The reaction was stirred at 35° C. for 168 hours, at which point HPLC analysis indicated that only 2.9% (area under the curve, AUC) starting material remained. The reaction mixture was concentrated to give a brown residue, which was diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (4×50 mL) and the combined organics were concentrated to give a brown residue. The residue was dissolved in dichloromethane (2×10 mL) and purified by flash column chromatography using 60-100% ethyl acetate/hexanes as eluent. The fractions containing pure product were combined and concentrated to afford the title product as a yellow solid (4.20 g, 74%): 1H NMR (400 MHz, CDCl3) δ 8.98 (d, J=2.7, 0.8 Hz, 1H), 8.62 (dd, J=4.8, 1.4 Hz, 1H), 8.06 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 8.00 (s, 1H), 7.47 (dd, J=8.3, 4.7 Hz, 1H), 3.71 (q, J=7.1 Hz, 2H), 1.97 (s, 3H), 1.16 (t, J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.69, 148.56, 140.89, 139.95, 135.64, 126.22, 126.08, 124.86, 124.09, 43.77, 22.27, 13.15; mp: 87-91° C.; ESIMS m/z 265 ([M+H]+).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09434712B2uspto-grants-2016_09