反応 #43694

反応方程式

methyl iodide

HCl

title compound

4-(7-Benzyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile

4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile

LHMDS

→

4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride

溶媒

diethyl ether

acetone

THF

反応条件

後処理

1. 1
   workup.STIRRINGthe solution is stirred for 15 min
2. 2
   その他The reaction mixture is quenched by addition of NH4Cl
3. 3
   抽出extracted with EtOAc
4. 4
   洗浄The organic solution is washed with brine
5. 5
   乾燥dried (anhydrous sodium sulfate)
6. 6
   その他evaporated to an oil
7. 7
   その他Purification by flash chromatography (silica gel)
8. 8
   洗浄eluting with EtOAc:MeOH:NH4OH (95:5:0.5)
9. 9
   その他gives the free base which

実験手順

To a solution of the title compound of Example 3, 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile (0.24 g, 0.63 mmol) in 5 mL of THF at −78° C. is added LHMDS (0.70 mL, 0.70 mmol) and the resulting solution is stirred for 15 min. To this solution is added methyl iodide (0.040 mL, 0.67 mmol) and the solution is stirred for 15 min, then warmed gradually to RT. The reaction mixture is quenched by addition of NH4Cl and extracted with EtOAc. The organic solution is washed with brine, dried (anhydrous sodium sulfate) and evaporated to an oil. Purification by flash chromatography (silica gel) eluting with EtOAc:MeOH:NH4OH (95:5:0.5) gives the free base which is dissolved in acetone and HCl (g) in diethyl ether is added to afford 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride: m.p. 230-232° C.; 1H-NMR (DMSO-d6) δ 9.54 (1H, s), 7.90 (2H, d, J=8.7), 7.74 (1H, s), 7.32 (3H, m), 7.22 (2H, d, J=8.7), 7.15 (2H, m), 4.73 (1H, d, J=16.9), 4.71 (1H, d, J=14.6), 4.66 (1H, d, J=14.6), 4.12 (1H, d, J=16.9), 2.25 (3H, s); 13C-NMR (DMSO-d6) δ 163.1, 141.1, 133.8, 132.3, 131.3, 126.8, 125.8, 125.7, 124.0, 123.7, 116.2, 114.2, 110.0, 64.6, 48.4, 38.5, 22.6; e/z (ES) 343 (M+1, 100%); calculated for C21H18N4O HCl, C, 66.58; H, 5.05; N, 14.79. found C, 66.41; H, 5.01; N, 14.80.

出典