反応 #159988

反応方程式

2-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-4 trifluoromethanesulfonyloxy-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepine-7-carboxylic acid tert-butyl ester

(4-methylphenyl)-boronic acid

K2CO3

→

title compound

収率 64.0%

2-(1,1-Dioxo-1λ6-thiomorpholin-4-yl)-4-p-tolyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine

収率 64.0%

溶媒

2-propanone toluene water

反応条件

後処理

1. 1
   ろ過The separated organic layer was filtered over silica gel
2. 2
   濃縮the filtrate was concentrated
3. 3
   その他The residue was purified by FCC (petroleum ether/Et2O)
4. 4
   その他The product fractions were collected
5. 5
   その他the solvent was evaporated
6. 6
   workup.DISSOLUTIONThis residue was dissolved in TFA/DCM/water (5:12:1, 12 mL)
7. 7
   workup.STIRRINGstirred at rt for 90 min
8. 8
   濃縮The mixture was concentrated
9. 9
   workup.ADDITIONresidue was diluted with 1 M NaOH
10. 10
    抽出extracted with DCM (2×)
11. 11
    洗浄The combined organic layers were washed with satd
12. 12
    乾燥NaCl, dried
13. 13
    濃縮concentrated
14. 14
    その他The residue was recrystallized from 2-propanol

実験手順

A mixture of 2-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-4 trifluoromethanesulfonyloxy-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepine-7-carboxylic acid tert-butyl ester (0.0008 mol), (4-methylphenyl)-boronic acid (0.0008 mol), Pd(dppf)Cl2 (0.00008 mol) and K2CO3 (0.0016 mol) in 2-propanone/toluene/water (4:4:1, 8 mL) was stirred in a microwave for 30 min at 130° C. The separated organic layer was filtered over silica gel and the filtrate was concentrated. The residue was purified by FCC (petroleum ether/Et2O). The product fractions were collected and the solvent was evaporated. This residue was dissolved in TFA/DCM/water (5:12:1, 12 mL) and stirred at rt for 90 min. The mixture was concentrated and residue was diluted with 1 M NaOH and extracted with DCM (2×). The combined organic layers were washed with satd. NaCl, dried, and concentrated. The residue was recrystallized from 2-propanol to give 0.190 g (64%) of the title compound.

出典