3-bromopropan-1-amine;hydrochloride

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture wws dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture wws dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture wws dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture wws dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure

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

Procedure: To a solution of 2,4,6-trichloropyrimidine (10 g, 54.5 mmol) in acetonitrile (200 mL) was added triethylamine (22.80 mL, 164 mmol) at 0° C., stirred for 5 min at r.t., and then added dropwise a solution of 3-bromopropan-1-amine hydrochloride (12 g, 68.8 mmol) in N, N-dimethylformamide (5 mL). The reaction mixture was stirred for 1 h at r.t., filtered, and concentrated. Purification via FC afforded the title compound (5.6 g). The reaction mixture was stirred for 1 h at r.t. filtered concentrated Purification via FC

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

Procedure: To a solution of 2,4,6-trichloropyrimidine (10 g, 54.5 mmol) in acetonitrile (200 mL) was added triethylamine (22.80 mL, 164 mmol) at 0° C., stirred for 5 min at r.t., and then added dropwise a solution of 3-bromopropan-1-amine hydrochloride (12 g, 68.8 mmol) in N, N-dimethylformamide (5 mL). The reaction mixture was stirred for 1 h at r.t., filtered, and concentrated. Purification via FC afforded the title compound (5.6 g). The reaction mixture was stirred for 1 h at r.t. filtered concentrated Purification via FC

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture was dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture was dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture was dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture was dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure

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

Procedure: 3-Bromopropylamine hydrochloride (2.189 g, 10 mmol) was suspended in 15 ml of dry dichloromethane, and to the suspension were added triethylamine (7 ml, 50 mmol) and methyl 2(chlorosulfonyl)benzoate (2.738 g, 10.5 mmol). The mixture was stirred at room temperature for 66 hours, poured into ice water, extracted with dichloromethane, washed with water, dried over sodium sulfate, and concentrated. The residue was purified by flash chromatography on silica gel to give 617 mg of 1,1-Dihydroxy-3-oxo-3H-benzo[d]isothiazole (20%). The isothiazole was etherified with Deg. B-Bh-Ester by the NaH/DMF method described above, and the compound was subjected to deprotection to remove the Bh group by the TFA/Anisole method described above, providing 309 mg of the desired compound 120 (97%). extracted with dichloromethane washed with water dried over sodium sulfate concentrated The residue was purified by flash chromatography on silica gel

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

Procedure: In a mixture of 100 ml of water and 100 ml of tetrahydrofuran are dissolved 8.76 g of 3-bromopropylamine hydrochloride and 6.72 ml of triethylamine. After addition of 8.73 g of di-tert-butyl bicarbonate, the mixture is stirred at room temperature for 16 hours. The reaction mixture is extracted with ethyl acetate, and the extract is washed with water, 5% aqueous citric acid solution and aqueous sodium chloride solution in that order and then dried over magnesium sulfate. The solvent is then distilled off under reduced pressure to give a light yellow oil. This is dissolved in 80 ml of dimethyl sulfoxide. To the solution are added 8.12 g of ethyl 2-(2-aminothiazol-4-yl)-(Z)-2-hydroxyiminoacetate and 16.56. g of potassium carbonate, and the mixture is stirred at 60° C. for 5 hours. After cooling, the reaction mixture is poured into 800 ml of ice-water and extracted with dichloromethane. The extract is washed with aqueous potassium carbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue is subjected to silica gel (250 g) column chromatography, elution being carried out with hexane-ethylacetate (2:3). The fractions rich in the desired compound are collected and concentrated under reduced pressure to give 5.27 g of ethyl 2-(2-aminothiazol-4-yl)-(Z)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetate as a yellow foamy product. The reaction mixture is extracted with ethyl acetate the extract is washed with water, 5% aqueous citric acid solution and aqueous sodium chloride solution in that order dried over magnesium sulfate The solvent is then distilled off under reduced pressure to give a light yellow oil After cooling extracted with dichloromethane The extract is washed with aqueous potassium carbonate solution and aqueous sodium chloride solution dried over magnesium sulfate concentrated under reduced pressure The residue is subjected to silica gel (250 g) column chromatography, elution The fractions rich in the desired compound are collected concentrated under reduced pressure

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

Procedure: Methyl 2-formylphenylcarbamate (7, 2.5 g, 14 mmol) and magnesium sulfate (5 g) were added to a solution of 3-bromopropylamine hydrochloride (3.68 g, 16.8 mmol) and triethylamine in chloroform (30 mL) and mixture was stirred for 24 h. The mixture was filtered and the residue was washed with chloroform (2×30 mL). The combined filtrates were washed with water (2×30 mL), brine (30 mL), dried with sodium sulfate, and concentrated to afford 21 as a yellow oil (3.95 g, 94.5%). IR (film) 1730, 1638 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.38 (d, J=8.4 Hz, 1 H), 8.30 (s, 1 H), 7.35 (t, J=7.7 Hz, 2 H), 7.26 (d, J=7.7 Hz, 1 H), 7.00 (t, J=7.4 Hz, 1 H), 3.74 (s, 3 H), 3.69 (t, J=6.3 Hz, 2 H), 3.50 (t, J=6.6 Hz, 2 H), 2.20 (pent, J=6.3 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 164.74, 154.30, 140.07, 133.00, 131.32, 121.25, 119.79, 117.69, 58.17, 52.87, 33.16, 31.15; ESIMS m/z (rel intensity) 299/301 (MH+, 100/99); EIHRMS m/z M+ calcd. for C12H15BrN2O2, 298.0317; found, 298.0320. The mixture was filtered the residue was washed with chloroform (2×30 mL) The combined filtrates were washed with water (2×30 mL), brine (30 mL) dried with sodium sulfate concentrated

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture wws dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture wws dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure

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

Procedure: To a solution of 2,4,6-trichloropyrimidine (10 g, 54.5 mmol) in acetonitrile (200 mL) was added triethylamine (22.80 mL, 164 mmol) at 0° C., stirred for 5 min at r.t., and then added dropwise a solution of 3-bromopropan-1-amine hydrochloride (12 g, 68.8 mmol) in N, N-dimethylformamide (5 mL). The reaction mixture was stirred for 1 h at r.t., filtered, and concentrated. Purification via FC afforded the title compound (5.6 g). The reaction mixture was stirred for 1 h at r.t. filtered concentrated Purification via FC

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

Procedure: A flask fitted with a dry ice condenser was charged with liquid ammonia (250 ml). To this was added sodium (0.24 mol) in portions together with a few grains of ferric nitrate; subsequently dimethylaminoprop-2-yne (0.24 mol) was added. The reaction mixture was stirred for one hour, 3-bromopropylamine hydrochloride (0.24 mol) was added in portions and the mixture stirred for a further two hours. Anhydrous diethyl ether (150 ml) was added and excess ammonia was allowed to evaporate overnight. The reaction mixture was dissolved in methanol and evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water. The aqueous layer was washed with chloroform (5×150 ml). The chloroform extracts were combined, dried over MgSO4, filtered and evaporated under reduced pressure to give 6-dimethylaminohex-4-ynylamine as an oil (5.4 g). A flask fitted with a dry ice condenser the mixture stirred for a further two hours to evaporate overnight The reaction mixture was dissolved in methanol evaporated under reduced pressure to afford a residue, which was partitioned between chloroform and water The aqueous layer was washed with chloroform (5×150 ml) dried over MgSO4 filtered evaporated under reduced pressure