1-(4-methoxybenzyl)-7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2(1H)-one → 7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2(1H)-one
Reaction equation
COC1C=CC(C[N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([N:18]4[CH2:21][CH:20]([N:22]5[CH2:27][CH2:26][N:25]([CH:28]([CH3:30])[CH3:29])[CH2:24][CH2:23]5)[CH2:19]4)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:31])=CC=1>C(O)(C(F)(F)F)=O>[CH:28]([N:25]1[CH2:26][CH2:27][N:22]([CH:20]2[CH2:19][N:18]([C:15]3[CH:16]=[C:17]4[C:12]([CH:11]=[CH:10][C:9](=[O:31])[NH:8]4)=[N:13][CH:14]=3)[CH2:21]2)[CH2:23][CH2:24]1)([CH3:30])[CH3:29]Participants
Procedure
1-(4-methoxybenzyl)-7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-8) (5.6 g, 12.5 mmol, 1.0 eq) was dissolved in TFA (100 mL) and the resulting mixture was stirred at reflux for 16 h. The reaction was complete based on TLC analysis. The mixture was cooled to RT and concentrated in vacuo to remove TFA. The resulting suspension was diluted with water (200 mL) and neutralized with sodium carbonate to adjust the pH value to 8-9 while keeping the temperature below 0° C. The resulting mixture was stirred at RT for 30 min. The solid was collected by filtration, rinsed with water (2×50 mL) and dried in vacuo to afford the desired product 7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-9) (3.91 g, 95.7% yield) as a white solid. ESI-MS m/z: 328.2 [M+H]+.
Workup
- temperatureat reflux for 16 h
- concentrationconcentrated in vacuo
- customto remove TFA
- additionThe resulting suspension was diluted with water (200 mL)
- customthe temperature below 0° C
- stirringThe resulting mixture was stirred at RT for 30 min
- filtrationThe solid was collected by filtration
- washrinsed with water (2×50 mL)
- customdried in vacuo
Sources & evidence
- ORD record
- ord-593aaf6220284984a0c582f342a42b29
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096590B2
Reaction notes
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