Phthalic Anhydride → 2-(4-Chloropyrimidin-5-yl)isoindoline-1,3-dione

HRID 525366Notes

Reaction equation

[Cl:1][C:2]1[C:7]([NH2:8])=[CH:6][N:5]=[CH:4][N:3]=1.C1COCC1.[C:14]1(=O)[O:19][C:17](=[O:18])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:15](=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]2=[O:19])=[CH:6][N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a vial charged with 4-chloropyrimidin-5-amine (commercially available from Frontier Scientific, Inc., Logan Utah) (0.500 g, 3.86 mmol) were added THF (6.43 mL), toluene (6.43 mL), TEA (1.345 mL, 9.65 mmol) and phthalic anhydride (1.310 mL, 13.51 mmol). The mixture was heated to 100° C. for 72 hours. The mixture was then dried under reduced pressure and purified with a 50 g SNAP column (Biotage) ramping EtOAc in heptane from 0-45%, then isocratic at 45% to elute 2-(4-chloropyrimidin-5-yl)isoindoline-1,3-dione (0.773 g, 2.98 mmol, 77% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=9.23 (d, J=0.4 Hz, 1H), 9.09 (d, J=0.4 Hz, 1H), 8.12-8.05 (m, 2H), 8.04-7.96 (m, 2H). m/z (ESI) 260.1 (M+H)+.

Workup

customThe mixture was then dried under reduced pressure
custompurified with a 50 g SNAP column (Biotage)

Sources & evidence

ORD record: ord-cb44d5dff2ca49b99ad121897d0d31e0
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340549B2

Reaction notes

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