p-Xylyl bromide → 2-[(4-Methylbenzyl)amino]-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one

HRID 2215035Notes

Reaction equation

[NH2:1][C:2]1[N:3]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:4]2[C:9]([C:10](=[O:12])[CH:11]=1)=[CH:8][CH:7]=[CH:6][N:5]=2.[CH3:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1>C1COCC1>[CH3:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:1][C:2]2[N:3]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=3)[C:4]3[C:9]([C:10](=[O:12])[CH:11]=2)=[CH:8][CH:7]=[CH:6][N:5]=3)=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one (50 mg, 0.16 mmol), CsCO3 (160 mg, 0.49 mmol) and 4-methylbenzyl bromide (35 mg, 0.25 mmol) in THF (3 mL) was heated to 80° C. in a sealed tube for 16 h. The reaction was cooled to room temperature and quenched with water (3 mL). The mixture was extracted with CH2Cl2 (3×), and the combined organic extracts were dried with Na2SO4 and concentrated in vacuo. The residue was purified by prep-HPLC (YMC-Pack Pro C 18 Column, 150×20 mm I.D.; first run: 20–80% CH3CN in water, 11 min.; second run: 50–90% MeOH in water, 20 min.) to afford 2-[(4-Methylbenzyl)amino]-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one (2.2 mg, 3%): LCMS RT: 2.75 min, MH+: 410.2.

Workup

temperatureThe reaction was cooled to room temperature
customquenched with water (3 mL)
extractionThe mixture was extracted with CH2Cl2 (3×)
dry with materialthe combined organic extracts were dried with Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by prep-HPLC (YMC-Pack Pro C 18 Column, 150×20 mm I.D.; first run: 20–80% CH3CN in water, 11 min.; second run: 50–90% MeOH in water, 20 min.)

Sources & evidence

ORD record: ord-d36174782ea240b28fc39911fde318a9
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07109196B2

Reaction notes

Loading…