反応 #168434

反応方程式

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid

HATU

DIPEA

methylamine

MeOH

→

4-(5-chloropyridin-3-yl)-N-methyl-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxamide

溶媒

H2O

DMF

反応条件

後処理

1. 1
   抽出the aqueous layer was extracted with EtOAc
2. 2
   洗浄the organic layer was washed with water and brine
3. 3
   乾燥dried over anhydrous Na2SO4
4. 4
   ろ過filtered
5. 5
   濃縮concentrated in vacuo
6. 6
   その他Purification of the residue on a silica gel column (0 to 10% MeOH/CH2Cl2)

実験手順

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (Example 3.22, prepared from Example 2.1, Step 4 using a procedure similar to that described for Example 1.1, Step 5; 50 mg, 0.09 mmol) in DMF (2.0 mL) were added HATU (15 mg, 0.11 mmol), DIPEA (0.03 mL, 0.18 mmol), and 2.0 M methylamine in MeOH (0.09 mL, 0.18 mmol) at room temperature. After being stirred for 2 hours, the reaction mixture was diluted with H2O (10 mL), the aqueous layer was extracted with EtOAc and then the organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification of the residue on a silica gel column (0 to 10% MeOH/CH2Cl2) afforded 4-(5-chloropyridin-3-yl)-N-methyl-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxamide. 1H NMR (300 MHz, CD3OD) δ 8.71 (d, J=2.1 Hz, 1H), 8.66 (s, 1H), 8.17-8.19 (m, 2H) 7.40-7.42 (m, 2H), 7.24-7.26 (m, 3H), 4.66-4.69 (m, 1H), 3.98-4.06 (m, 4H), 3.66-3.75 (m, 2H), 3.41-3.50 (m, 2H), 3.48 (s, 3H), 1.28-1.43 (m, 2H), 1.10-1.19 (m, 1H), 0.82-0.99 (m, 2H), 0.74 (d, J=6.3 Hz, 3H) 0.61-0.65 (m, 3H), 0.41-0.45 (m, 2H). MS APCl calc'd. for C31H35ClN6O2 [M+H]+ 559. found 559.

出典