Trifluoroacetic acid → 2-(6-Amino-2,7-naphthyridin-1-yl)isoindoline-1,3-dione

HRID 874692Notes

Reaction equation

COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][N:18]=2)[C:15]([N:19]2[C:27](=[O:28])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]2=[O:29])=[N:14][CH:13]=[CH:12]3)=CC=1.FC(F)(F)C(O)=O>ClCCl>[NH2:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][N:18]=1)[C:15]([N:19]1[C:27](=[O:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]1=[O:29])=[N:14][CH:13]=[CH:12]2

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 4-6 (3.94 g, 7.43 mmol), trifluoroacetic acid (30.0 mL, 392 mmol), and dichloromethane (30.0 mL) was stirred at 40° C. for 19 hours under an atmosphere of nitrogen gas and concentrated under reduced pressure. To the resulting residue was added saturated aqueous NaHCO3 (300 mL) and hexane/dichloromethane (5:1) (150 mL) at ambient temperature. The resulting mixture was stirred vigorously at ambient temperature for 30 minutes. The precipitated solid was filtered, washed with water (60 mL) and hexane/dichloromethane (5:1) (60 mL), and dried under high vacuum to give 2.08 g (96%) of 4-7 as a pale yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 9.04 (1H, br s), 8.28 (1H, d, J=6.0 Hz), 8.05 (2H, m), 7.97 (2H, m), 7.55 (1H, br d, J=6.0 Hz), 6.78 (2H, br s), 6.63 (1H, br s); ESI-MS m/z 291 [C16H10N4O2+H]+.

Workup

concentrationconcentrated under reduced pressure
additionTo the resulting residue was added saturated aqueous NaHCO3 (300 mL) and hexane/dichloromethane (5:1) (150 mL) at ambient temperature
stirringThe resulting mixture was stirred vigorously at ambient temperature for 30 minutes
filtrationThe precipitated solid was filtered
washwashed with water (60 mL) and hexane/dichloromethane (5:1) (60 mL)
customdried under high vacuum

Sources & evidence

ORD record: ord-86b1275df0e14f56abe471bbf749f622
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980916B2

Reaction notes

Loading…