7-bromo-2-methyl-1H-indole

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.7 g of 7-bromo-2-methyl-1H-indole are placed in 100 ml of THF and the mixture is cooled to −10° C. 22 ml of 3M methylmagnesium bromide in ether are added at this temperature. The mixture is allowed to return to AT and is then cooled to −5° C. and 13.5 g of 2,3-dichlorobenzoyl chloride, dissolved in 80 ml of THF, are added dropwise. The medium is allowed to return to AT and is then poured onto a saturated NH4Cl solution. Extraction is carried out with ether and then the organic phase is washed with a 10% NaOH solution, water and a saturated NaCl solution. It is dried and evaporated and the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (10/90, v/v) mixture. The product obtained crystallizes from ether and 5 g of the expected compound are obtained. is then cooled to −5° C. are added dropwise Extraction the organic phase is washed with a 10% NaOH solution, water It is dried evaporated the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (10/90 The product obtained crystallizes from ether and 5 g of the expected compound are obtained

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27.0 g of 2-bromonitrobenzene are placed in 400 ml of THF. The medium is placed under nitrogen and is cooled to −55° C. and then 800 ml of 0.5M isopropenylmagnesium bromide in THF are added dropwise. The medium is left stirring for 1 hour and then it is poured into a saturated NH4Cl solution. Extraction is carried out with ether, the extract is evaporated and then the residue is taken up in DCM. Washing is carried out with a saturated NaCl solution. The organic layer is dried and evaporated and then the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture. 10.7 g of the expected compound are obtained. The medium is left Extraction the extract is evaporated Washing The organic layer is dried evaporated the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27.0 g of 2-bromonitrobenzene are placed in 400 ml of THF. The medium is placed under nitrogen and is cooled to −55° C. and then 800 ml of 0.5M isopropenylmagnesium bromide in THF are added dropwise. The medium is left stirring for 1 hour and then it is poured into a saturated NH4Cl solution. Extraction is carried out with ether, the extract is evaporated and then the residue is taken up in DCM. Washing is carried out with a saturated NaCl solution. The organic layer is dried and evaporated and then the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture. 10.7 g of the expected compound are obtained. The medium is left Extraction the extract is evaporated Washing The organic layer is dried evaporated the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1000 mg of 7-bromo-2-methyl-indole (4.8 mmol) were dissolved in 15 ml THF and 8.9 ml of a 1.6 molar solution of n-BuLi in hexane were added at −78° C. The reaction mixture was then allowed to warm to 0-5° C. and was stirred at this temperature for 30 min. Then it was cooled again to −78° C., dry ice was added and the mixture was allowed to warm to rt. After 15 min at rt it was poured into water and extracted twice with ether. The aqueous phase was then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were then dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with pentane. Final filtration yielded 157 mg (31%) of 2-methyl-1H-indole-7-carboxylic acid as an off-white solid. MS (ISP) 174.3 (M−H)−. Then it was cooled again to −78° C. to warm to rt extracted twice with ether extracted several times with DCM The combined DCM extracts were then dried with magnesium sulfate filtered the solvent was evaporated The remaining residue was triturated with pentane Final filtration

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1000 mg of 7-bromo-2-methyl-indole (4.8 mmol) were dissolved in 15 ml THF and 8.9 ml of a 1.6 molar solution of n-BuLi in hexane were added at −78° C. The reaction mixture was then allowed to warm to 0-5° C. and was stirred at this temperature for 30 min. Then it was cooled again to −78° C., dry ice was added and the mixture was allowed to warm to rt. After 15 min at rt it was poured into water and extracted twice with ether. The aqueous phase was then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were then dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with pentane. Final filtration yielded 157 mg (31%) of 2-methyl-1H-indole-7-carboxylic acid as an off-white solid. MS (ISP) 174.3 (M−H)−. Then it was cooled again to −78° C. to warm to rt extracted twice with ether extracted several times with DCM The combined DCM extracts were then dried with magnesium sulfate filtered the solvent was evaporated The remaining residue was triturated with pentane Final filtration

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27.0 g of 2-bromonitrobenzene are placed in 400 ml of THF. The mixture is placed under nitrogen and cooled to −55° C. and then 800 ml of isopropenylmagnesium bromide at 0.5 M in THF are added dropwise. The mixture is left with stirring for 1 hour and then poured into saturated NH4Cl solution. It is extracted with ether, the extract is evaporated and then the residue is taken up in DCM. It is washed with saturated NaCl solution. It is dried and evaporated and then the residue is chromatographed on silica, eluting with an AcOEt/cyclohexane (1/9; v/v) mixture. This gives 10.7 g of the expected compound. The mixture is left It is extracted with ether the extract is evaporated It is washed with saturated NaCl solution It is dried evaporated the residue is chromatographed on silica eluting with an AcOEt/cyclohexane (1/9; v/v) mixture

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl magnesium bromide (3.0M diethyl ether solution, 72 mL) was slowly added dropwise under an argon atmosphere and ice-cooling to a solution of [1-(bromomethyl)cyclopropyl]acetonitrile (15 g) and 7-bromo-2-methyl-1H-indole (45 g) in toluene (250 mL), followed by stirring at 100° C. for 80 minutes. The reaction mixture was cooled to room temperature; quenched with a saturated aqueous ammonium chloride solution, diluted with water; and extracted with ethyl acetate. The organic layer was washed sequentially with water and brine. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by a purification system CombiFlash CompanionXL (manufactured by Isco, Co., Ltd., column: RediSep 350 g; hexane:ethyl acetate=95:5->70:30) to obtain title compound (14 g) having the following physical properties. The reaction mixture was cooled to room temperature quenched with a saturated aqueous ammonium chloride solution diluted with water and extracted with ethyl acetate The organic layer was washed sequentially with water and brine The organic layer was dried over sodium sulfate concentrated under reduced pressure The resulting residue was purified by a purification system CombiFlash CompanionXL (manufactured by Isco, Co., Ltd., column: RediSep 350 g; hexane:ethyl acetate=95:5->70:30)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.7 g of 7-bromo-2-methyl-1H-indole are placed in 100 ml of THF and the mixture is cooled to −10° C. 22 ml of 3M methylmagnesium bromide in ether are added at this temperature. The mixture is allowed to return to AT and is then cooled to −5° C. and 13.5 g of 2,3-dichlorobenzoyl chloride, dissolved in 80 ml of THF, are added dropwise. The medium is allowed to return to AT and is then poured onto a saturated NH4Cl solution. Extraction is carried out with ether and then the organic phase is washed with a 10% NaOH solution, water and a saturated NaCl solution. It is dried and evaporated and the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (10/90, v/v) mixture. The product obtained crystallizes from ether and 5 g of the expected compound are obtained. is then cooled to −5° C. are added dropwise Extraction the organic phase is washed with a 10% NaOH solution, water It is dried evaporated the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (10/90 The product obtained crystallizes from ether and 5 g of the expected compound are obtained

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27.0 g of 2-bromonitrobenzene are placed in 400 ml of THF. The medium is placed under nitrogen and is cooled to −55° C. and then 800 ml of 0.5M isopropenylmagnesium bromide in THF are added dropwise. The medium is left stirring for 1 hour and then it is poured into a saturated NH4Cl solution. Extraction is carried out with ether, the extract is evaporated and then the residue is taken up in DCM. Washing is carried out with a saturated NaCl solution. The organic layer is dried and evaporated and then the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture. 10.7 g of the expected compound are obtained. The medium is left Extraction the extract is evaporated Washing The organic layer is dried evaporated the residue is chromatographed on silica while eluting with an AcOEt/cyclohexane (1/9, v/v) mixture

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1000 mg of 7-bromo-2-methyl-indole (4.8 mmol) were dissolved in 15 ml THF and 8.9 ml of a 1.6 molar solution of n-BuLi in hexane were added at −78° C. The reaction mixture was then allowed to warm to 0-5° C. and was stirred at this temperature for 30 min. Then it was cooled again to −78° C., dry ice was added and the mixture was allowed to warm to rt. After 15 min at rt it was poured into water and extracted twice with ether. The aqueous phase was then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were then dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with pentane. Final filtration yielded 157 mg (31%) of 2-methyl-1H-indole-7-carboxylic acid as an off-white solid. MS (ISP) 174.3 (M−H)−. Then it was cooled again to −78° C. to warm to rt extracted twice with ether extracted several times with DCM The combined DCM extracts were then dried with magnesium sulfate filtered the solvent was evaporated The remaining residue was triturated with pentane Final filtration

Conditions: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27.0 g of 2-bromonitrobenzene are placed in 400 ml of THF. The mixture is placed under nitrogen and cooled to −55° C. and then 800 ml of isopropenylmagnesium bromide at 0.5 M in THF are added dropwise. The mixture is left with stirring for 1 hour and then poured into saturated NH4Cl solution. It is extracted with ether, the extract is evaporated and then the residue is taken up in DCM. It is washed with saturated NaCl solution. It is dried and evaporated and then the residue is chromatographed on silica, eluting with an AcOEt/cyclohexane (1/9; v/v) mixture. This gives 10.7 g of the expected compound. The mixture is left It is extracted with ether the extract is evaporated It is washed with saturated NaCl solution It is dried evaporated the residue is chromatographed on silica eluting with an AcOEt/cyclohexane (1/9; v/v) mixture