Ethanol → 6-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)pyridin-3-amine

HRID 2241208Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][N:19]=4)=[C:11]3[C:10]([CH3:27])=[N:9]2)=[CH:5][CH:4]=1.CCO>C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[N:19]=[CH:20][C:21]([NH2:24])=[CH:22][CH:23]=4)=[C:11]3[C:10]([CH3:27])=[N:9]2)=[CH:28][CH:29]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A 25 mL round-bottomed flask was charged with 1-(4-methoxybenzyl)-3-methyl-4-(5-nitropyridin-2-yloxy)-1H-pyrazolo[3,4-b]pyridine (1.25 g, 3.19 mmol) and EtOH (10 mL). SnCl2 dihydrate (3.60 g, 16.0 mmol) was added under nitrogen and the reaction mixture was heated to 80° C. for 4 hours. The reaction mixture was cooled to room temperature, diluted with Na2CO3 (100 mL, 2N) and extracted with chloroform (2×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to a dark oil. The crude material was purified on a Biotage 40S column, eluting with EtOAc, to provide the product (800 mg, 65%) as a green oil. 1H NMR (CDCl3, 400 MHz) δ 8.31 (d, J=5.1 Hz, 1H), 7.82 (m, 1H), 7.29 (m, 2H), 7.18 (m, 1H), 6.93 (d, J=8.6 Hz, 1H), 6.82 (m, 2H), 6.40 (d, J=5.5 Hz, 1H), 5.56 (s, 2H), 3.76 (m, 5H), 2.63 (s, 3H). LRMS (APCI pos) m/e 362 (M+1).

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with chloroform (2×100 mL)
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated to a dark oil
customThe crude material was purified on a Biotage 40S column
washeluting with EtOAc

Sources & evidence

ORD record: ord-d8229792fc9e485f8752c373ff1d0c59
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723330B2

Reaction notes

Loading…