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Stage #1: With Dess-Martin periodane In tetrahydrofuran at 20℃; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water; ethyl acetate
Synthesis of lH-IndazoIe-4-carbaIdehyde (12i): The alcohol obtained above (54 mg, 0.36 mmol) was dissolved in 3 mL of THF, and then Dess-Martin periodinine (247 mg, 0.58 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with Na2S2O3 (2.0 M) solution. The mixture was extracted with ethyl acetate, and the combined organic layers were combined and washed with saturated NaHCO3 solution, brine, and dried over MgSO4. Solvent was then removed and the residue was purified by column chromatography (75percent ethyl acetate/hexanes). The product (37 mg, 70percent) was obtained as a white solid. MS (ES) M+H expected = 147.1, found = 147.2
Stage #1: With diisobutylaluminium hydride In tetrahydrofuran at 0℃; Stage #2: With water; Rochelle's salt In tetrahydrofuran at 20℃;
Synthesis of (lH-Indazol-4-yl)-methanol (18b): The ester obtained above (40 mg, 0.23 mmol) was dissolved in 1 mL of THF and cooled to 00C. A solution of DEAL in THF (1.0 M, 2.3 mL, 2.3 mmol) was added dropwise. More DIBAL was added until the starting material disappeared. The reaction was then quenched with saturated potassium sodium tartrate solution and warmed up to room temperature. The reaction mixture was extracted with ethyl acetate. The organic layers were combined and dried over MgSO4. Solvent was then removed and the residue was purified by column chromatography (75percent ethyl acetate/hexanes). The product (20 mg, 60percent) was obtained as a white solid. MS (ES) M+H expected = 149.1, found = 149.1.
Synthesis of (lH-Indazol-4-yl)-methanol (18b): The ester obtained above (40 mg, 0.23 mmol) was dissolved in 1 mL of THF and cooled to 00C. A solution of DEAL in THF (1.0 M, 2.3 mL, 2.3 mmol) was added dropwise. More DIBAL was added until the starting material disappeared. The reaction was then quenched with saturated potassium sodium tartrate solution and warmed up to room temperature. The reaction mixture was extracted with ethyl acetate. The organic layers were combined and dried over MgSO4. Solvent was then removed and the residue was purified by column chromatography (75% ethyl acetate/hexanes). The product (20 mg, 60%) was obtained as a white solid. MS (ES) M+H expected = 149.1, found = 149.1.
Synthesis of lH-IndazoIe-4-carbaIdehyde (12i): The alcohol obtained above (54 mg, 0.36 mmol) was dissolved in 3 mL of THF, and then Dess-Martin periodinine (247 mg, 0.58 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with Na2S2O3 (2.0 M) solution. The mixture was extracted with ethyl acetate, and the combined organic layers were combined and washed with saturated NaHCO3 solution, brine, and dried over MgSO4. Solvent was then removed and the residue was purified by column chromatography (75% ethyl acetate/hexanes). The product (37 mg, 70%) was obtained as a white solid. MS (ES) M+H expected = 147.1, found = 147.2
6-(4-(hydroxymethyl)-1H-indazol-1-yl)pyrimidine-4-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 0.416667h;
A solution of <strong>[709608-85-5]4-(hydroxymethyl)-1H-indazole</strong> 1 (233 mg, 1.57 mmol), 6-chloropyrimidine-4-carbonitrile (200 mg, 1.43 mmol), and DMF (4 mL) was added dropwise at RT to NaH (57 mg of a 60% dispersion in mineral oil, 1.43 mmol). The mixture was stirred at RT for 25 mm. The mixture was partitioned between aq HC1, brine, and EtOAc. The organic layer was separated, dried (Na2504), filtered, and concentrated under reduced pressure. The residue was purified (silica gel; eluting 0 to 100% EtOAc in hexanes), to afford compound 2 (162 mg, 45%) as a yellow solid. LCMS Mass: 252.0 (M+1).
4-(bromomethyl)-1H-indazole hydrobromide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48.2%
With hydrogen bromide; In water; at 80℃; for 2.0h;
1H-Indazol-4-yl)methanol (202 mg, 1.363 mmol, commercially available from, for example, Apollo Scientific) and HBr (3.3 mL, 48% in water, 27.4 mmol) were heated at 80 C for 2 h. The resulting suspension was allowed to cool to rt, filtered under vacuum, washed with cold water anddried in a vacuum oven to give 4-(bromomethyl)-1H-indazole, hydrobromide (213 mg, 0.657 mmol,48.2 % yield) as an off white solid.LCMS (2 mm Formic): Rt=0.85 mi [MH] = 211, 213.
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