(2R)-2-aminohexan-1-ol

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process is performed as in Example 2, starting with 1.14 g of (2R)-2-amino-2-butyl-1-ethanol and 1.36 cm3 of tert-butyl isothiocyanate in 15 cm3 of ethanol, with stirring for 18 hours at a temperature in the region of 20° C. and then for 3 hours in the region of 60° C. After concentration of the reaction medium under reduced pressure (5 kPa) at a temperature in the region of 40° C. 2.38 g of N-(tert-butyl)-N′-[(1R)-1-butyl-2-hydroxyethyl]thiourea are obtained in the form of a yellow oil. Infrared spectrum (CH2Cl2):3620; 4430; 4410; 2960; 1560; 1500; 1395; 1375 and 1205 cm−1. for 3 hours in the region of 60° C in the region of 40° C

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

Procedure: Using amino alcohol alkylation method A, but adding 1.1 equivalents of 4-methanesulfonyloxymethyl-piperidine-1-carboxylic acid tert-butyl ester instead of 1 equivalent, (R)-norleucinol (400 mg, 3.4 mmol) afforded, after purification (SiO2: 7:3:1 hexane:EtOAc:isopropyl amine), 195 mg (18%) of the title compound. afforded after purification (SiO2: 7:3:1 hexane:EtOAc:isopropyl amine), 195 mg (18%) of the title compound

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process is performed as in Example 2, starting with 1.14 g of (2R)-2-amino-2-butyl-1-ethanol and 1.36 cm3 of tert-butyl isothiocyanate in 15 cm3 of ethanol, with stirring for 18 hours at a temperature in the region of 20° C. and then for 3 hours in the region of 60° C. After concentration of the reaction medium under reduced pressure (5 kPa) at a temperature in the region of 40° C. 2.38 g of N-(tert-butyl)-N′-[(1R)-1-butyl-2-hydroxyethyl]thiourea are obtained in the form of a yellow oil. Infrared spectrum (CH2Cl2):3620; 4430; 4410; 2960; 1560; 1500; 1395; 1375 and 1205 cm−1. for 3 hours in the region of 60° C in the region of 40° C

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

Procedure: Using amino alcohol alkylation method A, but adding 1.1 equivalents of 4-methanesulfonyloxymethyl-piperidine-1-carboxylic acid tert-butyl ester instead of 1 equivalent, (R)-norleucinol (400 mg, 3.4 mmol) afforded, after purification (SiO2: 7:3:1 hexane:EtOAc:isopropyl amine), 195 mg (18%) of the title compound. afforded after purification (SiO2: 7:3:1 hexane:EtOAc:isopropyl amine), 195 mg (18%) of the title compound

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

Procedure: 2 g of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid (Example 3A, 6.28 mmol, 1 equivalent), 2.2 g of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU; 6.9 mmol, 1.1 equivalents) and 3.45 ml of 4-methylmorpholine (31.4 mmol, 5 equivalents) were initially charged in 15 ml of dichloromethane and 10 ml of DMF. 810 mg of (R)-(−)-2-amino-1-hexanol (6.9 mmol, 1.1 equivalents) were added at RT, and the mixture was stirred for 3 h. The mixture was then diluted with dichloromethane and adjusted to pH4 with water and 1 N aqueous hydrochloric acid. The organic phase was separated off and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed twice with water, dried over sodium sulphate, filtered and concentrated. The crude mixture was purified by preparative HPLC (Method 9). This gave 1066 mg (41% of theory) of the title compound. The organic phase was separated off the aqueous phase was extracted twice with dichloromethane The combined organic phases were washed twice with water dried over sodium sulphate filtered concentrated The crude mixture was purified by preparative HPLC (Method 9)

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

Procedure: 2 g of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid (Example 3A, 6.28 mmol, 1 equivalent), 2.2 g of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU; 6.9 mmol, 1.1 equivalents) and 3.45 ml of 4-methylmorpholine (31.4 mmol, 5 equivalents) were initially charged in 15 ml of dichloromethane and 10 ml of DMF. 810 mg of (R)-(−)-2-amino-1-hexanol (6.9 mmol, 1.1 equivalents) were added at RT, and the mixture was stirred for 3 h. The mixture was then diluted with dichloromethane and adjusted to pH4 with water and 1 N aqueous hydrochloric acid. The organic phase was separated off and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed twice with water, dried over sodium sulphate, filtered and concentrated. The crude mixture was purified by preparative HPLC (Method 9). This gave 1066 mg (41% of theory) of the title compound. The organic phase was separated off the aqueous phase was extracted twice with dichloromethane The combined organic phases were washed twice with water dried over sodium sulphate filtered concentrated The crude mixture was purified by preparative HPLC (Method 9)

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

Procedure: The title compound was synthesized in analogy to the procedure described for the preparation of Example 6, using 5-bromo-1,6-dihydro-6-oxo-3-pyridinecarboxylic acid methyl ester, 2-methoxy-ethanol (commercially available), 4-chlorophenyl-boronic acid (commercially available) and (R)-(−)-2-amino-1-hexanol (commercially available) as starting materials. MS (ISP): 407.4 (M+H+). described for the preparation of Example 6

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

Procedure: 14 mg (0.04 mmol) of 8-[(2,6-difluorobenzyl)oxy]-7-fluoro-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 112A, 20 mg (0.06 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 17 mg (0.17 mmol) of 4-methylmorpholine were initially charged in 0.28 ml of DMF. 7.5 mg (0.06 mmol) of (2R)-2-aminohexan-1-ol were then added, and the mixture was stirred at RT overnight. Another 2.6 mg of TBTU, 4 mg of 4-methylmorpholine and 1 mg of (2R)-2-aminohexan-1-ol were added, and the mixture was stirred at RT for 2 h. The reaction mixture was concentrated and purified by thick-layer chromatography (mobile phase: dichloromethane/methanol=10/1). This gave 12 mg (66% of theory; purity 99%) of the title compound. the mixture was stirred at RT for 2 h The reaction mixture was concentrated purified by thick-layer chromatography (mobile phase: dichloromethane/methanol=10/1)

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

Procedure: 150 mg (0.39 mmol) of 2,6-dimethyl-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo[1,2-a]-pyridine-3-carboxylic acid Example 91A and 163 mg (0.43 mmol) of HATU were initially charged in 2.5 ml of DMF. 0.2 ml (1.17 mmol) of N,N-diisopropylethylamine and 50.3 mg (0.43 mmol) of (R)-(−)-2-amino-1-hexanol were then added, and the mixture was stirred at RT overnight. 10 ml of water were added, the reaction solution was extracted twice with 20 ml of ethyl acetate and the combined organic phases were washed with 20 ml of water and with 20 ml of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid), the product fractions were combined and concentrated to dryness and the residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water and lyophilized overnight. This gave 42 mg of the target compound (95% pure, 21% of theory). the reaction solution was extracted twice with 20 ml of ethyl acetate the combined organic phases were washed with 20 ml of water and with 20 ml of saturated aqueous sodium chloride solution dried over magnesium sulphate filtered concentrated The residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid) concentrated to dryness the residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water lyophilized overnight

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

Procedure: 75 mg (0.27 mmol) of 2,6-dimethyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxylic acid Example 89A, 96 mg (0.30 mmol) of TBTU and 110 mg (1.09 mmol) of 4-methylmorpholine were initially charged in 1.73 ml of DMF. 35 mg (0.30 mmol) of (R)-(−)-2-aminohexanol were then added, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with water/TFA and purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The concentrated fractions were taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted two more times with dichloromethane, the combined organic phases were dried over sodium sulphate and filtered and the filtrate was concentrated and lyophilized. This gave 91 mg of the target compound (87.5% of theory, purity 98%). purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA) washed twice with saturated aqueous sodium bicarbonate solution The aqueous phase was extracted two more times with dichloromethane the combined organic phases were dried over sodium sulphate filtered the filtrate was concentrated

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

Procedure: Under argon, 50 mg (0.15 mmol) of 8-[(2,6-difluorobenzyl)oxy]-6-ethynyl-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid were dissolved in 0.5 ml of dry dimethylformamide, 20.54 mg (0.18 mmol, 1.2 equivalents) of (R)-(−)-2-aminohexanol, 72 μl of diisopropylethylamine (0.44 mmol, 3 equivalents) and 72 mg of HATU (0.19 mmol, 1.3 equivalents) were added and the mixture was stirred at room temperature overnight. A little water was then added, and the mixture was purified directly by preparative HPLC (Method 8). This gave 37.5 mg of the target compound (58% of theory). the mixture was purified directly by preparative HPLC (Method 8)

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

Procedure: Under argon, 4 g (14.17 mmol) of 8-(benzyloxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 1.83 g (15.59 mmol) of (R)-(−)-2-aminohexanol and 7.166 g (70.85 mmol) of 4-methylmorpholine were suspended in 28 ml of dichloromethane. 5 g (15.59 mmol) of TBTU were then added, and the mixture was stirred at room temperature overnight. After 16 h, the mixture was diluted with 200 ml of dichloromethane and washed with 10% strength aqueous citric acid solution, with water and with saturated aqueous sodium chloride solution. The organic phase was concentrated and the residue obtained was purified on a silica gel cartridge (mobile phase dichloromethane:methanol=100:3). Concentration of the product fractions thus gave 3.83 g (71% of theory) of 8-(benzyloxy)-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide. After 16 h washed with 10% strength aqueous citric acid solution, with water and with saturated aqueous sodium chloride solution The organic phase was concentrated the residue obtained was purified on a silica gel cartridge (mobile phase dichloromethane:methanol=100:3)