N'-propan-2-ylpropane-1,3-diamine

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: A solution of N-isopropyl-1,3-propanediamine (116 g, 1 M) in isopropyl alcohol (1 l ) maintained ca 10° was treated dropwise with 40% aqueous HCHO solution (75 ml, 1 M). After 1 hour the solvents were evaporated under reduced pressure and the residue distilled to give N-isopropylhexahydropyrimidine (100 g, 78%), Bp 65° /20 mbar. After 1 hour the solvents were evaporated under reduced pressure the residue distilled

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

Procedure: A solution of N-isopropyl-1,3-propanediamine (116 g, 1 M) in isopropyl alcohol (1 l ) maintained ca 10° was treated dropwise with 40% aqueous HCHO solution (75 ml, 1 M). After 1 hour the solvents were evaporated under reduced pressure and the residue distilled to give N-isopropylhexahydropyrimidine (100 g, 78%), Bp 65° /20 mbar. After 1 hour the solvents were evaporated under reduced pressure the residue distilled

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

Procedure: Sulphanilyl fluoride (6.5 g, 37.1 mmol), N-isopropyl-1,3-propanediamine (5.71 ml, 40.8 mmol) and triethylamine (5.69 ml, 40.8 mmol) in N-butanol (15 ml) was heated at reflux for 10 hours. The mixture was allowed to cool, silica was added and the volatiles were evaporated. The residue was purified by chromatography eluting with DCM/methanolic ammonia (100:0) increasing in polarity to (90:10) to give the title compound as a clear oil which crystallized on standing (8.81 g, 88%). NMR: 0.89 (d, 6H), 1.43 (m, 2H), 2.41 (t, 2H), 2.58 (m, 1H), 2.68 (t, 2H), 3.16 (s, 2H), 5.85 (s, 2H), 6.58 (d, 2H), 7.38 (d, 2H); m/z: 272. at reflux for 10 hours to cool silica was added the volatiles were evaporated The residue was purified by chromatography eluting with DCM/methanolic ammonia (100:0) increasing in polarity to (90:10)

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

Procedure: Following the procedure of Example 1, m-nitrobenzenesulfonyl chloride was reacted with N-isopropyl propane-1,3-diamine to provide the free base, m.r. 57°-59° C., converted to the hydrochloride salt, m.r. 184°-188° C. to provide the free base, m.r 57°-59° C. 184°-188° C.

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

Procedure: Following the procedure of Example 1, m-nitrobenzenesulfonyl chloride was reacted with N-isopropyl propane-1,3-diamine to provide the free base, m.r. 57°-59° C., converted to the hydrochloride salt, m.r. 184°-188° C. to provide the free base, m.r 57°-59° C. 184°-188° C.

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

Procedure: The title compound was prepared from [4-carbamoyl-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazol-5-yl]-carbamic acid phenyl ester and N-isopropyl-propane-1,3-diamine by the procedure analogous to Example 1. MS (APCl, m/z): 460 [M+H]+.

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

Procedure: A mixture of 2-chloro-5-formyl-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.244 g, Example 25b), N-isopropyl-1,3-propanediamine (0.211 g), p-toluenesulfonic acid (0.005 g) and toluene (30 ml) were refluxed together under Dean-Stark conditions for 3 h. The mixture was cooled and concentrated under reduced pressure to an oil. This was dissolved in ethanol (30 ml) and cooled to 0° C. under a nitrogen atmosphere. Solid sodium borohydride (0.040 g) was added portionwise and the mixture stirred at room temperature for 30 min, then concentrated under reduced pressure and the residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia) to give the title compound (0.015 g) and a by-product (see Example 27). were refluxed together under Dean-Stark conditions for 3 h The mixture was cooled concentrated under reduced pressure to an oil This was dissolved in ethanol (30 ml) Solid sodium borohydride (0.040 g) was added portionwise concentrated under reduced pressure the residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia)

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

Procedure: A mixture of 2-chloro-5-formyl-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.244 g, Example 25b), N-isopropyl-1,3-propanediamine (0.211 g), p-toluenesulfonic acid (0.005 g) and toluene (30 ml) were refluxed together under Dean-Stark conditions for 3 h. The mixture was cooled and concentrated under reduced pressure to an oil. This was dissolved in ethanol (30 ml) and cooled to 0° C. under a nitrogen atmosphere. Solid sodium borohydride (0.040 g) was added portionwise and the mixture stirred at room temperature for 30 min, then concentrated under reduced pressure and the residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia) to give the title compound (0.015 g) and a by-product (see Example 27). were refluxed together under Dean-Stark conditions for 3 h The mixture was cooled concentrated under reduced pressure to an oil This was dissolved in ethanol (30 ml) Solid sodium borohydride (0.040 g) was added portionwise concentrated under reduced pressure the residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia)

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

Procedure: The title compound was prepared from 3-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methyl-N-1,3-thiazol-2-ylbenzamide and N-(1-methylethyl)-1,3-propanediamine by following the procedures in Example 79c. LC-MS m/z 590 (M+H)+; 1H-NMR (MeOD) 1.02 (m, 6H), 1.68 (m, 2H), 2.32 (m, 3H), 2.46 (m, 1H), 2.66 (m, 1H), 2.82 (m, 1H), 3.11 (m, 1H), 3.46 (m, 1H), 6.35 (d, J=8.8 Hz, 1H), 7.11 (m, 1H), 7.24 (m, 2H), 7.46 (m, 2H), 7.55 (m, 2H), 8.02 (m, 1H), 8.11 (d, J=7.6 Hz, 1H).

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

Procedure: A solution of 16.7 g. of 2-methyl-5-chlorophenylisocyanate and 50 ml. of dichloromethane was added to a stirred, cooled solution of 35 g. of N-isopropyl-1,3-diaminopropane and 250 ml. of dichloromethane. The temperature was kept at -5° to 0° C. during addition. Stirring was continued at room temperature for 20 minutes. The precipitated solid was separated by filtration. The filtrate was extracted with water, then with 200 ml. of 15% hydrochloric acid (v/v). The acid extract was made basic with saturated sodium carbonate solution, then extracted with dichloromethane. The dichloromethane solution was dried over magnesium sulfate, then evaporated to dryness. The residue was dissolved in ethanol and saturated with hydrogen chloride. The solution was evaporated to dryness in vacuo. The residue was triturated with ether until it solidified. The solid was recrystallized from EtOH/Et2O to obtain N-[3-(isopropylamino)propyl]-N'-(5-chloro-2-methylphenyl)urea hydrochloride, m.p. 180°-183° C. cooled solution of 35 g The temperature was kept at -5° to 0° C. during addition The precipitated solid was separated by filtration The filtrate was extracted with water The acid extract extracted with dichloromethane The dichloromethane solution was dried over magnesium sulfate evaporated to dryness The residue was dissolved in ethanol and saturated with hydrogen chloride The solution was evaporated to dryness in vacuo The residue was triturated with ether until it The solid was recrystallized from EtOH/Et2O