Lithium Chloride → 3-(pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1775020Notes

Reaction equation

I[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][N:3]=1.C([Sn](CCCCC)(CCCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)CCC.[Li+].[Cl-]>[Cu]I.O1CCOCC1>[N:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][N:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a microwave tube was added 3-iodo-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine from Example 4 (120 mg, 0.37 mmol), 2-(butyldipentylstannyl)pyridine (168 mg, 0.45 mmol), Pd(PPh)3 (12 mg, 0.015 mmol), LiCl (48 mg, 1.14 mmol), CuI (12 mg, 0.06 mmol) and 1,4-dioxane (0.3 mL). The tube was flushed with nitrogen for 2 minutes and heated in a Biotage microwave at 140° C. for 15 minutes. The solvent was distilled off and the crude product was purified via reverse phase combiflash eluting with 10% to 80% CH3CN in aqueous 0.5% NH4OH solution to afford 204 as a pale red solid (11 mg, 11%). 1H NMR (400 MHz, DMSO) 1H NMR (500 MHz, DMSO) δ 14.0 (s, 1H), 9.30 (s, 1H), 9.25 (s, 1H), 8.97 (s, 1H), 8.81 (d, J=4.0 Hz, 1H), 8.62-8.61 (m, 1H), 8.45 (d, J=8.5 Hz, 1H), 8.22 (d, J=7.5 Hz, 1H), 7.97-7.94 (m, 1H), 7.55-7.53 (m, 1H), 7.45-7.43 (m, 1H). ESI MS m/z=274 (M+1)

Workup

customThe tube was flushed with nitrogen for 2 minutes
distillationThe solvent was distilled off
customthe crude product was purified via reverse phase combiflash
washeluting with 10% to 80% CH3CN in aqueous 0.5% NH4OH solution

Sources & evidence

ORD record: ord-403b82a52d434fa6be3affd8d73253a8
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260425B2

Reaction notes

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