18-Crown-6 → 3-Fluoro-8-methylbenzo[f][1,7]naphthyridin-5-amine

HRID 340316Notes

Reaction equation

Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([NH2:17])[N:6]=[C:7]3[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:8]3=2)[N:3]=1.[F-:18].[K+].C1OCCOCCOCCOCCOCCOC1>CN1C(=O)CCC1>[F:18][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([NH2:17])[N:6]=[C:7]3[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:8]3=2)[N:3]=1

Participants

Conditions

Temperature: 210 °C

Procedure

A mixture of 3-chloro-8-methylbenzo[f][1,7]naphthyridin-5-amine (from the previous step) (1.0 eq.) potassium fluoride (4.0 eq.), and 18-crown-6 (0.4 eq.) in NMP (0.1M) was heated in microwave reactor at 210° C. for 2 hours. After cooling to ambient temperature, the reaction residue was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-30% EtOAc/Hexanes to give 3-fluoro-8-methylbenzo[f][1,7]naphthyridin-5-amine as a white solid. 1H NMR (acetone-d6): δ 9.20 (dd, 1H), 8.32 (d, 1H), 7.58 (dd, 1H), 7.46 (d, 1H), 7.21 (dd, 1H), 6.51 (br s, 2H), 2.47 (s, 3H). LRMS [M+H]=228.1.

Workup

temperatureAfter cooling to ambient temperature
customthe reaction residue was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record: ord-f8edbbc41a00486a8d0b86279641cade
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895577B2

Reaction notes

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