3-amino-3-methylbutan-1-ol

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 150-mL round-bottomed flask was added 3-amino-3-methyl-butan-1-ol (2.18 mL, 19.39 mmol, Tyger Sci. Inc) and Na2CO3 (3.08 g, 29.1 mmol) (1 M in water) and the solution was cooled to 0° C. Benzyl chloroformate (3.03 mL, 21.33 mmol, Sigma-Aldrich) was added dropwise and the mixture was stirred at 0° C. for 2 h. The mixture was extracted with EtOAc (100 mL×3) and the combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified with silica gel chromatography (eluted with 10-50% EtOAc in Hex) to give benzyl(4-hydroxy-2-methylbutan-2-yl)carbamate (3.33 g, 14.03 mmol, 72% yield) as a clear oil. MS (ESI, pos. ion) m/z: 238.1 (M+1). The mixture was extracted with EtOAc (100 mL×3) the combined organic layers were dried (MgSO4) filtered concentrated The residue was purified with silica gel chromatography (eluted with 10-50% EtOAc in Hex)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 150-mL round-bottomed flask was added 3-amino-3-methyl-butan-1-ol (2.18 mL, 19.39 mmol, Tyger Sci. Inc) and Na2CO3 (3.08 g, 29.1 mmol) (1 M in water) and the solution was cooled to 0° C. Benzyl chloroformate (3.03 mL, 21.33 mmol, Sigma-Aldrich) was added dropwise and the mixture was stirred at 0° C. for 2 h. The mixture was extracted with EtOAc (100 mL×3) and the combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified with silica gel chromatography (eluted with 10-50% EtOAc in Hex) to give benzyl(4-hydroxy-2-methylbutan-2-yl)carbamate (3.33 g, 14.03 mmol, 72% yield) as a clear oil. MS (ESI, pos. ion) m/z: 238.1 (M+1). The mixture was extracted with EtOAc (100 mL×3) the combined organic layers were dried (MgSO4) filtered concentrated The residue was purified with silica gel chromatography (eluted with 10-50% EtOAc in Hex)

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and 3-amino-3-methyl-butan-1-ol (CAN 42514-50-1) as starting materials, LC-MS (UV peak area/ESI) 100%, 319.1 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and 3-amino-3-methyl-butan-1-ol (CAN 42514-50-1) as starting materials, LC-MS (UV peak area/ESI) 100%, 319.1 (M+H)+.

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

Procedure: A mixture of 0.62 g of 60% sodium hydride, 1.91 g of 3,6-dichloropyridazine and 10 ml of benzene was stirred while being cooled with ice, and a solution consisting of 1.32 g of 3-amino-3-methylbutanol, 3 ml of t-butanol and 5 ml of benzene was added dropwise. After stirring at room temperature for 30 minutes, ether was added to the reaction mixture, and the solid was removed by filtration with Hyflo Super-Cel. The filtrate was concentrated under reduced pressure. n-Hexane was added to the resulting oily product, and the mixture was allowed to stand to give 2.34 g of 3-(3-amino-3-methylbutoxy)-6-chloropyridazine as colorless crystals having a melting point of 63.5° to 65.0° C. while being cooled with ice was added dropwise After stirring at room temperature for 30 minutes the solid was removed by filtration with Hyflo Super-Cel The filtrate was concentrated under reduced pressure n-Hexane was added to the resulting oily product

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

Procedure: To a solution of 3-amino-3-methyl-butan-1-ol (941 mg, 9.12 mmol) in 10 mL THF was added 4-(trifluoromethylthio)phenylisocyanate (2.0 g, 9.12 mmol). The reaction was stirred at ambient temperature for 16 h. The solution was concentrated and subjected to a hot filtration with CH2Cl2 to give solid 1-(4-hydroxy-2-methylbutan-2-yl)-3-{4-[(trifluoromethyl)sulfanyl]phenyl}urea (95%). LCMS [M+H]+=323.1. The solution was concentrated subjected to a hot filtration with CH2Cl2

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

Procedure: 3-Amino-3-methyl-1-butanol (20.60 g, 0.20 mol) was added to ethyl formate (29.60 g, 0.40 mol), and the resulting clear solution was heated to reflux under nitrogen for 2 hours, and then allowed to cool to room temperature. The ethyl formate and ethanol by-product were removed by rotary evaporation (35° C., 25 Torr). The resulting oil was dried under vacuum (25° C., 0.1 Torr) to yield 25.86 g (99%). the resulting clear solution was heated to reflux under nitrogen for 2 hours The ethyl formate and ethanol by-product were removed by rotary evaporation (35° C., 25 Torr) The resulting oil was dried under vacuum (25° C., 0.1 Torr) to yield 25.86 g (99%)

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

Procedure: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and 3-amino-3-methyl-butan-1-ol (CAN 42514-50-1) as starting materials, LC-MS (UV peak area/ESI) 100%, 319.1 (M+H)+.

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

Procedure: A stirred solution of ethyl (2,3,4,5-tetrafluorobenzoyl)acetate (3.73 g, 14.1 mmol), Ac2O (8.50 mL, 85.7 mmol) and triethyl orthoformate (4.70 mL, 28.2 mmol) was heated at 120° C. for 3 h. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (50 mL) was added 3-amino-3-methyl-1-butanol (1.45 g, 14.1 mmol) in anhydrous toluene (20 mL) very slowly at 0° C. and stirred at room temperature for 2 h. The solvent was removed by evaporation. Flash chromatography (EtOAc:Hexane=1:1) of the residue gave ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-[(1-hydroxy-3-methylbutane-3-yl)amino]acrylate as a colorless solid (3.91 g, 73%). The mixture was concentrated in vacuo dried under high vacuum To the mixture of the residue in anhydrous toluene (50 mL) The solvent was removed by evaporation

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

Procedure: A stirred solution of ethyl (2,3,4,5-tetrafluorobenzoyl)acetate (3.73 g, 14.1 mmol), Ac2O (8.50 mL, 85.7 mmol) and triethyl orthoformate (4.70 mL, 28.2 mmol) was heated at 120° C. for 3 h. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (50 mL) was added 3-amino-3-methyl-1-butanol (1.45 g, 14.1 mmol) in anhydrous toluene (20 mL) very slowly at 0° C. and stirred at room temperature for 2 h. The solvent was removed by evaporation. Flash chromatography (EtOAc:Hexane=1:1) of the residue gave ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-3-[(1-hydroxy-3-methylbutane-3-yl)amino]acrylate as a colorless solid (3.91 g, 73%). The mixture was concentrated in vacuo dried under high vacuum To the mixture of the residue in anhydrous toluene (50 mL) The solvent was removed by evaporation

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