反応 #1356036

反応方程式

4-(4-bromo-thiophen-2-ylmethyl)-morpholine

4-(4-Bromo-thiophen-2-ylmethyl)-morpholine

bis(pinacolato)diboron

KOAc

4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide

Na2CO3

→

66

収率 83.3%

4-Amino-2-morpholin-4-ylmethyl-thieno[3,2-c]pyridine-7-carboxylic acid amide

収率 83.3%

溶媒

DMF

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   その他degassed DMF (5 mL)
3. 3
   温度cooled down to room temperature
4. 4
   温度The resulting mixture was heated at 90° C. for 1.5 h
5. 5
   その他The solvent was then removed via vacuum
6. 6
   workup.DISSOLUTIONthe residue was dissolved in DMSO (4.0 mL)
7. 7
   その他the mixture purified by reverse phase preparative HPLC

実験手順

To a mixture of 4-(4-bromo-thiophen-2-ylmethyl)-morpholine 64 (173 mg, 0.66 mmol), bis(pinacolato)diboron (352 mg, 1.39 mmol.), Pd(PPh3)4 (76 mg, 0.07 mmol) and KOAc (194 mg, 2.0 mmol) was added degassed DMF (5 mL). The reaction mixture was heated at 120° C. under N2 for 2 h and then cooled down to room temperature. A solution of 4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide 17 (150 mg, 0.55 mmol), Pd(PPh3)4 (69 mg, 0.06 mmol) and Na2CO3 (1.0 mL of a 2M aqueous solution, 3.3 mmol) in DMF (2.0 mL) was added. The resulting mixture was heated at 90° C. for 1.5 h. The solvent was then removed via vacuum, the residue was dissolved in DMSO (4.0 mL) and the mixture purified by reverse phase preparative HPLC to give 66 (134 mg). 1H NMR (400 MHz, CDCl3) δ, 3.12 (m, 2H), 3.32 (m, 2H), 3.82 (m, 2H), 3.95 (m, 2H), 4.62 (s, 2H), 7.75 (s, 1H), 7.81 (br, 1H), 8.09 (s, 1H), 8.34 (s, 1H), 8.38 (br, 1H), 8.56 (s, 1H), 9.19 (br, 1H), 11.73 (br, 1H). MS (EI) m/z (M+H+) 375.

出典