N-(2,2-dimethoxyethyl)butan-1-amine

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

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

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

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

Procedure: HATU (0.337 g) was added to a stirred solution of N-(2,2-dimethoxyethyl)butan-1-amine (0.105 g), 3-(2-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-acid (0.390 g) (example 178 step d) and Hunig's Base (0.516 mL) in N,N-dimethylformamide (3 mL). After 1 h, the solution was partitioned between ethyl acetate and brine. The ethyl acetate layer was washed with brine (×3) and evaporated in vacuo. Purification was silica gel chromatography eluting with 10% triethylamine in ethyl acetate. Yield 0.4 g. the solution was partitioned between ethyl acetate and brine The ethyl acetate layer was washed with brine (×3) evaporated in vacuo Purification eluting with 10% triethylamine in ethyl acetate

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

Procedure: To a solution of butan-1-amine (limiting reagent) in EtOH (5 volumes) was added 2,2-dimethoxyacetaldehyde (60%) in water (1 molar equivalent) and the mixture was stirred at room temp for 4 clays. A slurry of 5% palladium on carbon (0.01 molar equivalent) in EtOH (1 volume) was added and the mixture was hydrogenated at 3 bar pressure for 20 hours. The mixture was filtered through a glass fibre filter paper, washed with EtOH (2×3 volumes) and the mother liquor was carefully concentrated to leave a cloudy brown oil. This oil was dissolved in DCM (15 volumes), dried (Na2SO4), filtered and carefully concentrated in vacuo to leave an orange oil. Yield: 101% of theoretical. The mixture was filtered through a glass fibre filter paper washed with EtOH (2×3 volumes) the mother liquor was carefully concentrated to leave a cloudy brown oil dried (Na2SO4) filtered carefully concentrated in vacuo to leave an orange oil

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

Procedure: To a solution of butan-1-amine (limiting reagent) in EtOH (5 volumes) was added 2,2-dimethoxyacetaldehyde (60%) in water (1 molar equivalent) and the mixture was stirred at room temp for 4 clays. A slurry of 5% palladium on carbon (0.01 molar equivalent) in EtOH (1 volume) was added and the mixture was hydrogenated at 3 bar pressure for 20 hours. The mixture was filtered through a glass fibre filter paper, washed with EtOH (2×3 volumes) and the mother liquor was carefully concentrated to leave a cloudy brown oil. This oil was dissolved in DCM (15 volumes), dried (Na2SO4), filtered and carefully concentrated in vacuo to leave an orange oil. Yield: 101% of theoretical. The mixture was filtered through a glass fibre filter paper washed with EtOH (2×3 volumes) the mother liquor was carefully concentrated to leave a cloudy brown oil dried (Na2SO4) filtered carefully concentrated in vacuo to leave an orange oil

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

Procedure: T3P (15.67 mL of 1.57M solution in THF) was added dropwise over 15 minutes to a stirred solution of 3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanoic acid trifluoroacetate salt [Example 34a, step c] (14.4 g) and N-(2,2-dimethoxyethyl)butan-1-amine [J. Am. Chem. Soc. 1949, 71(6), 2272] (3.97 g) and triethylamine (21.83 mL) in DMF (180 mL). The mixture was stirred at 20° C. for 3 hours and then partitioned between ethyl acetate and aqueous brine. The organic layer was washed with aqueous brine (×2), dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to give the subtitled compound. Yield 15.00 g. partitioned between ethyl acetate and aqueous brine The organic layer was washed with aqueous brine (×2) dried over sodium sulphate filtered the solvent evaporated under reduced pressure

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

Procedure: T3P (15.67 mL of 1.57M solution in THF) was added dropwise over 15 minutes to a stirred solution of 3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanoic acid trifluoroacetate salt [Example 34a, step c] (14.4 g) and N-(2,2-dimethoxyethyl)butan-1-amine [J. Am. Chem. Soc. 1949, 71(6), 2272] (3.97 g) and triethylamine (21.83 mL) in DMF (180 mL). The mixture was stirred at 20° C. for 3 hours and then partitioned between ethyl acetate and aqueous brine. The organic layer was washed with aqueous brine (×2), dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to give the subtitled compound. Yield 15.00 g. partitioned between ethyl acetate and aqueous brine The organic layer was washed with aqueous brine (×2) dried over sodium sulphate filtered the solvent evaporated under reduced pressure

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

Procedure: 3-(3-(2-(4-(2-Isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanoic acid [Example 34, step c] (0.50 g), Hunig's base (0.58 mL), and N-(2,2-dimethoxyethyl)butan-1-amine [J. Am. Chem. Soc. 1949, 71(6), 2272] (0.12 g) were dissolved in dichloromethane (10 mL). HATU (0.33 g) was then added and the mixture was stirred at room temperature for 24 hours. The mixture was poured into water and extracted with dichloromethane. The organic extracts were combined and evaporated under reduced pressure to give the subtitled compound. Yield 0.45 g. extracted with dichloromethane evaporated under reduced pressure

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

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

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