ChemicalBook CAS DataBase List 4-BROMO-1-METHYL-1H-INDAZOLE

4-BROMO-1-METHYL-1H-INDAZOLE synthesis

5synthesis methods

Product Name:4-BROMO-1-METHYL-1H-INDAZOLE
CAS Number:365427-30-1
Molecular formula:C8H7BrN2
Molecular Weight:211.06

74-88-4

186407-74-9

365427-30-1

590417-93-9

GENERAL METHOD: 4-Bromo-1H-indazole (1 eq.) was mixed with potassium carbonate (3 eq.) in acetone (15-30 mL) and stirred at room temperature for 30 minutes. Subsequently, iodomethane (1.2-1.8 eq.) was slowly added to the reaction system and the reaction was heated under reflux conditions for 3-8 hours. After completion of the reaction, acetone was removed by evaporation under reduced pressure and the residue was dissolved in ethyl acetate (30 mL). The organic phase was washed with saturated saline (3 x 15 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel fast column chromatography (eluent: ethyl acetate/cyclohexane, 1:2 or dichloromethane) to afford the target products 4-bromo-1-methyl-1H-indazole and 4-bromo-2-methyl-2H-indazole, respectively.

74-88-4
355 suppliers
$15.00/10g

186407-74-9 Synthesis

186407-74-9
315 suppliers
$5.00/1g

365427-30-1
102 suppliers
$42.00/1g

590417-93-9 Synthesis

590417-93-9
131 suppliers
$45.00/250mg

Yield: 59.8% ， 24.3%

Reaction Conditions:

Stage #1:4-bromoindazole with potassium carbonate in N,N-dimethyl-formamide for 0.5 h;
Stage #2:methyl iodide in N,N-dimethyl-formamide at 25; for 3 h;

Steps:

5
K2CO3 (5.26 g, 38.06 mmol) was added to a mixture of 4-bromo-lHindazole(5 g, 25.38 mmol) in DMF (50 mL). 30 min later, Mel (18.2 g, 128.22 mmol, 8.0mL) was added and the mixture was stirred at 25 oc for 3h. The mixture was treated withH20 (150 mL) and EA (50 mL). The organic layer was separated and the aqueous layer wasextracted with EA (50 mL x 2). The combined organic layer was washed brine (50 mL x 2),dried over MgS04, filtered and concentrated. The residue was purified by flash columnchromatography over silica gel (PE/EA = 10/l to 5/1) to afford a pair of isomers. Isomer 1 (Compound 32A, Rf '" 0.54, PE/EA '" 5/1): 4-bromo-1-methylindazole(3.2 g, 59.8% yield) was obtained as white solid. 1H NMR (DMSO-d6, 400 MHz): ,57.98 (d, J '" 0.9 Hz, HI), 7.67- 7.65 (m, HI), 7.35- 7.27 (m, 2H), 4.04 (s, 3H). Isomer 2 (Compound 32B, Rr '" 0.24, PE/EA '" 5/1): 4-bromo-2-methylindazole(1.3 g, 24.3% yield) was obtained as colorless sticky oiL 1H NMR (DMSO-d6, 400MHz): J 8.37 (s, 1H), 7.60- 7.57 (m, 1H), 7.26- 7.21 (m, 1H), 7.13 (dd, Jooo7.3, 8.6 Hz, lH),4.16 (s, 3H).

References:

BLADE THERAPEUTICS, INC.;BUCKMAN, Brad Owen;YUAN, Shendong;EMAYAN, Kumaraswamy;ADLER, Marc;IBRAHIM, Prabha WO2019/190885, 2019, A1 Location in patent:Paragraph 0335-0337

360575-28-6 Synthesis