반응 #90782

반응 방정식

2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

1,3-dimethyl-1H-pyrazol-4-amine

cesium carbonate

BINAP

→

desired product

수율 18.0%

2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

수율 18.0%

용매

dioxane THF

반응 조건

후처리

1. 1
   기타The reaction mixture was degassed under nitrogen for 10 min
2. 2
   기타It was evaporated
3. 3
   workup.DISSOLUTIONthe residue dissolved in MeOH
4. 4
   여과was filtered thru celite
5. 5
   기타purified further
6. 6
   기타evaporated
7. 7
   workup.ADDITIONEther was added to the residue
8. 8
   여과It was filtered off
9. 9
   기타dried under vacuum at 40° C. for 2 days

실험 절차

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.8 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (187 mg, 1.68 mmol), cesium carbonate (783 mg, 2.4 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (9 mg, 0.04 mmol) and BINAP (50 mg, 0.08 mmol) were added. The mixture was stirred in a microwave at 140° C. for 40 min. It was evaporated and the residue dissolved in MeOH was filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. Ether was added to the residue and a tan precipitate crashed out. It was filtered off and dried under vacuum at 40° C. for 2 days to afford the desired product (55 mg, 18%) as a tan solid. LC-MS (ES) m/z=387.1, [M+H]+=389.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.51 (br. s., 1 H) 8.03 (s, 1 H) 7.96 (s, 1 H) 7.82 (s, 1 H) 7.51-7.61 (m, 3 H) 7.07-7.15 (m, 1 H) 6.68 (s, 1 H) 3.70 (d, J=4.29 Hz, 6 H) 2.07 (s, 3 H).

출처