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

HRID 1775002Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][NH:8][C:5]2=[CH:6][N:7]=1.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14](B(O)O)[CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+].CO[CH2:29][CH2:30]OC>CC#N.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(O)C>[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:10]2[C:4]3[C:5](=[CH:6][N:7]=[C:2]([C:3]4[CH:2]=[N:7][CH:6]=[CH:29][CH:30]=4)[CH:3]=3)[NH:8][N:9]=2)[CH:13]=1

Participants

Conditions

Temperature: 160 °C

Procedure

To a microwave tube was added 5-bromo-3-iodo-1H-pyrazolo[3,4-c]pyridine (100 mg, 0.31 mmol), pyridin-3-ylboronic acid (343 mg, 2.79 mmol), Pd(dppf)Cl2 (24 mg, 0.03 mmol), sodium carbonate (131 mg, 1.24 mmol), 1,2-dimethoxyethane (2 mL), ethanol (0.5 mL) and water (0.5 mL). The tube was flushed with nitrogen for 2 minutes and heated in a Biotage microwave at 160° C. for 1 hour. The solvent was distilled off and the crude product was purified via reverse phase HPLC eluting with 15% CH3CN in aqueous 10 mmol NH4HCO3 to afford 176 as a pale yellow solid (30 mg, 28%). 1H NMR (500 MHz, DMSO) 1H NMR (500 MHz, DMSO) δ 14.1 (s, 1H), 9.44 (s, 1H), 9.37 (s, 3H), 9.26 (s, 1H), 8.71 (s, 1H), 8.67-8.66 (m, 1H), 8.60-8.59 (m, 2H), 8.56-8.54 (m, 1H), 7.60-7.58 (m, 1H), 7.52-7.51 (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 HPLC

Sources & evidence

ORD record: ord-7658a1a6ad0b4cb68b63eff18ba59ffa
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260425B2

Reaction notes

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