Water → 3-Methoxypropyl indazole amide

HRID 23002Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([NH2:12])=[O:11])=[N:2]1.Br[CH2:14][CH2:15][CH2:16][O:17][CH3:18].[H-].[Na+].O>CN(C=O)C>[CH3:18][O:17][CH2:16][CH2:15][CH2:14][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[C:3]([C:10]([NH2:12])=[O:11])=[N:2][NH:1]2

Participants

Conditions

Temperature: 60 °C

Procedure

Following the procedure for converting Compound 1e to Compound 1f, the indazole amide Compound 1e (0.31 g, 17.8 mmol) was treated with 1-bromo-3-methoxypropane (0.3 g, 19.6 mmol) in the presence of 95% NaH (0.05 g, 19.6 mmol) in DMF (50 mL) at 0° C. for 20 min and then warmed to 60° C. for 2 h. The mixture was cooled down to rt. Water was added and the aqueous solution was extracted with EtOAc several times. The organic layers were combined and washed with brine, then dried (Na2SO4) and evaporated in vacuo to an oil. The oil was purified by flash column chromatography (96:4:0.4; DCM:MeOH:NH4OH) to afford a 3-methoxypropyl indazole amide analog of Compound 1f (0.32 g, 73%). 1H NMR (CDCl3) δ 7.69 (d, J=8.13 Hz, 1H), 7.4 (m, 2H), 7.17 (m, 1H), 6.57 (bd s, 1H), 5.39 (bd s, 1H), 4.47 (t, J=6.65 Hz, 2H), 3.96 (s, 2H), 3.30 (t, J=5.78 Hz, 2H), 3.28 (s, 3H), 2.16 (m, 2H). ES-MS m/z 248 (MH+).

Workup

temperatureThe mixture was cooled down to rt
extractionthe aqueous solution was extracted with EtOAc several times
washwashed with brine
dry with materialdried (Na2SO4)
customevaporated in vacuo to an oil
customThe oil was purified by flash column chromatography (96:4:0.4; DCM:MeOH:NH4OH)

Sources & evidence

ORD record: ord-13736acf64db4915ace7a9a9b5695486
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06849643B2

Reaction notes

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