反応 #90805

反応方程式

6-chloro-4-iodo-nicotinonitrile

2-amino-N-methoxy-benzamide

K3PO4

DPEPhos

→

title compound

2-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamide

溶媒

1,4-dioxane

反応条件

後処理

1. 1
   その他was degassed with N2 for 1 h
2. 2
   その他The resulting reaction mixture
3. 3
   その他was degassed with N2 for another 15 min after which
4. 4
   その他the resulting reaction mixture
5. 5
   その他After completion of reaction solid material
6. 6
   ろ過was collected by filtration
7. 7
   workup.DISSOLUTIONdissolved in water (500 mL)
8. 8
   抽出extracted with ethyl acetate (5×200 mL)
9. 9
   乾燥Combined organic layers were dried over sodium sulfate
10. 10
    ろ過filtered
11. 11
    濃縮concentrated under reduced pressure
12. 12
    その他to give crude material
13. 13
    その他It was purified by column chromatography over silica gel (60-120 mesh)

実験手順

A mixture of 6-chloro-4-iodo-nicotinonitrile (14 g, 53.03 mmole, 1 eq), 2-amino-N-methoxy-benzamide (7.96 g, 53.03 mmole, 1 eq) and K3PO4 (28.14 g, 132.57 mmole, 2.5 eq) in 1,4-dioxane (250 mL) was degassed with N2 for 1 h. To this mixture were added Pd(OAC)2 (0.238 g, 1.06 mmole, 0.02 eq) and DPEPhos (2.28 g, 4.24 mmole, 0.08 eq). The resulting reaction mixture was degassed with N2 for another 15 min after which the resulting reaction mixture was stirred at 110° C. overnight. After completion of reaction solid material was collected by filtration, dissolved in water (500 mL), and extracted with ethyl acetate (5×200 mL). Combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude material. It was purified by column chromatography over silica gel (60-120 mesh) using 0.2% methanolic ammonia (10% ammonia in MeOH) in dichloromethane as the eluant to give the title compound as a pale yellow solid (9 g, 59%). 1H-NMR (400 MHz, DMSO-d6): δ 2.75 (d, 3H, J=4.56 Hz), 7.09 (s, 1H), 7.25-7.35 (m, 1H), 7.53-7.60 (m, 2H), 7.72 (d, 1H, J=7.48 Hz), 8.56 (s, 1H), 8.69-8.79 (brs, 1H), 10.65 (s, 1H). LC-MS calculated for C14H11ClN4O (M+H) 287.06, found 286.9.

出典