Formic Acid → N-(8-(1,3-dioxoisoindolin-2-yl)-2,7-naphthyridin-3-yl) formamide

HRID 874693Notes

Reaction equation

C(OC(=O)C)(=O)C.[CH:8]([OH:10])=O.[NH2:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][N:21]=1)[C:18]([N:22]1[C:30](=[O:31])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]1=[O:32])=[N:17][CH:16]=[CH:15]2>C(Cl)Cl>[O:31]=[C:30]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:32])[N:22]1[C:18]1[N:17]=[CH:16][CH:15]=[C:14]2[C:19]=1[CH:20]=[N:21][C:12]([NH:11][CH:8]=[O:10])=[CH:13]2

Participants

Conditions

Temperature: 60 °C

Procedure

Acetic anhydride (2.01 mL, 20.6 mmol) was added to formic acid (0.75 mL, 20.6 mmol) at 0° C. The mixture was heated to 60° C. for 30 minutes. After that 2-(6-amino-2,7-naphthyridin-1-yl)isoindoline-1,3-dione 4-7 (300 mg, 1.03 mmol) dissolved in CH2Cl2 (10 mL) was added at 0° C. The mixture was stirred for 1 h at room temperature. The mixture was concentrated and the residue was triturated with CH2Cl2/hexane (1:1) to give 240 mg (73%) of 4-8 as a pale yellow solid: 1H NMR (300 MHz, CDCl3)1H NMR (rotamer ratio: s-cis/s-trans=4:1) δ 9.46 (0.2H, br d, J=10.3 Hz), 9.01 (0.8H, br s), 8.75 (0.2H, br d, J=10.3 Hz), 8.68 (1H, br d, J=5.4 Hz), 8.60 (1H, br s), 8.56 (1H, br s), 8.48 (0.8H, br s), 8.03 (2H, m), 7.86 (2H, m), 7.77 (0.8H, br d, J=5.4 Hz), 7.67 (0.2H, br d, J=5.4 Hz); ESI-MS m/z 319 [C17H10N4O3+H]+.

Workup

additionwas added at 0° C
concentrationThe mixture was concentrated
customthe residue was triturated with CH2Cl2/hexane (1:1)

Sources & evidence

ORD record: ord-6d93b25035924b91abaaa28e485adf2c
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980916B2

Reaction notes

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