2,2-dimethylpropane-1,3-diamine

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

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

Procedure: A mixture of 2-fluoropyridine and 2,2-dimethyl-1,3-propanediamine (2 eq) in pyridine (0.3M) was refluxed for 18 hrs. and then concentrated by rotary evaporation. The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The product was purified by flash chromatography using 10:1:1 EtOH/NH4OH/H2O as eluent. EI-MS m/z 180 (M+H)+. was refluxed for 18 hrs and then concentrated by rotary evaporation The solution was then concentrated in vacuo the residue was partitioned between ethyl acetate and 10% sodium carbonate The phases were separated the organic phase was washed with brine dried over magnesium sulfate filtered concentrated in vacuo The product was purified by flash chromatography

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

Procedure: A mixture of 2-fluoropyridine and 2,2-dimethyl-1,3-propanediamine (2 eq) in pyridine (0.3M) was refluxed for 18 hrs. and then concentrated by rotary evaporation. The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The product was purified by flash chromatography using 10:1:1 EtOH/NH4OH/H2O as eluent. EI-MS m/z 180 (M+H)+. was refluxed for 18 hrs and then concentrated by rotary evaporation The solution was then concentrated in vacuo the residue was partitioned between ethyl acetate and 10% sodium carbonate The phases were separated the organic phase was washed with brine dried over magnesium sulfate filtered concentrated in vacuo The product was purified by flash chromatography

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

Procedure: To a solution of 12.45 g of potassium tetrachloroplatinate in 60 ml of water was added 3.06 g of 2,2-dimethyl-1,3-propanediamine. This mixture was allowed to stand overnight and then the solid was collected, giving 7.0 g of 2,2-dimethyl-1,3-propanediamine compound with platinum chloride (1:1). the solid was collected

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

Procedure: To a solution of 2,2-dimethyl-1,3-propane diamine (69 g, 0.75 mole) in dry methanol (100 mL), 3-chloro-3-methyl-2-nitrosobutane (20.55 g, 0.15 mole, Example 1) was added in portions at 0° C. over a period of 2 hours. The reaction mixture was then stirred at room temperature for 20 hours. The solvent was removed under reduced pressure to give a paste. Water (50 mL) was added, and the solution was cooled in an ice bath. The solution was filtered and the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide. The solution was cooled again and filtered. The filtrate was concentrated under reduced pressure to a paste and then extracted with ether repeatedly (10×50 mL). The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether to yield the title A compound as a colorless crystalline solid (20.0 g), m.p. 58-60° C. 1H NMR [CDCl3]: δ 0.85 (s, 6H, C-Me2), 1.28 (s, 6H, N—CMe2), 1.9 (s, 3H, N═CMe), 2.2 (s, 2H, NCH2) and 2.6 (s, 2H, N—CH2). The solvent was removed under reduced pressure to give a paste the solution was cooled in an ice bath The solution was filtered the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide The solution was cooled again filtered The filtrate was concentrated under reduced pressure to a paste extracted with ether repeatedly (10×50 mL) The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether

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

Procedure: To a solution of 2,2-dimethyl-1,3-propane diamine (69 g, 0.75 mole) in dry methanol (100 mL), 3-chloro-3-methyl-2-nitrosobutane (20.55 g, 0.15 mole, Example 1) was added in portions at 0° C. over a period of 2 hours. The reaction mixture was then stirred at room temperature for 20 hours. The solvent was removed under reduced pressure to give a paste. Water (50 mL) was added, and the solution was cooled in an ice bath. The solution was filtered and the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide. The solution was cooled again and filtered. The filtrate was concentrated under reduced pressure to a paste and then extracted with ether repeatedly (10×50 mL). The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether to yield the title A compound as a colorless crystalline solid (20.0 g), m.p. 58-60° C. 1H NMR [CDCl3]: δ 0.85 (s, 6H, C-Me2), 1.28 (s, 6H, N—CMe2), 1.9 (s, 3H, N═CMe), 2.2 (s, 2H, NCH2) and 2.6 (s, 2H, N—CH2). The solvent was removed under reduced pressure to give a paste the solution was cooled in an ice bath The solution was filtered the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide The solution was cooled again filtered The filtrate was concentrated under reduced pressure to a paste extracted with ether repeatedly (10×50 mL) The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether

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

Procedure: To a solution of 2,2-dimethyl-1,3-propane diamine (69 g, 0.75 mole) in dry methanol (100 mL), 3-chloro-3-methyl-2-nitrosobutane (20.55 g, 0.15 mole, Example 1) was added in portions at 0° C. over a period of 2 hours. The reaction mixture was then stirred at room temperature for 20 hours. The solvent was removed under reduced pressure to give a paste. Water (50 mL) was added, and the solution was cooled in an ice bath. The solution was filtered and the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide. The solution was cooled again and filtered. The filtrate was concentrated under reduced pressure to a paste and then extracted with ether repeatedly (10×50 mL). The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether to yield the title A compound as a colorless crystalline solid (20.0 g), m.p. 58-60° C. 1H NMR [CDCl3]: δ 0.85 (s, 6H, C—Me2), 1.28 (s, 6H, N—CMe2), 1.9 (s, 3H, N=CMe) 2.2 (s, 2H, NCH2) and 2.6 (s, 2H, N—CH2). The solvent was removed under reduced pressure to give a paste the solution was cooled in an ice bath The solution was filtered the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide The solution was cooled again filtered The filtrate was concentrated under reduced pressure to a paste extracted with ether repeatedly (10×50 mL) The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether

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

Procedure: To a solution of 2,2-dimethyl-1,3-propane diamine (69 g, 0.75 mole) in dry methanol (100 mL), 3-chloro-3-methyl-2-nitrosobutane (20.55 g, 0.15 mole, Example 1) was added in portions at 0° C. over a period of 2 hours. The reaction mixture was then stirred at room temperature for 20 hours. The solvent was removed under reduced pressure to give a paste. Water (50 mL) was added, and the solution was cooled in an ice bath. The solution was filtered and the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide. The solution was cooled again and filtered. The filtrate was concentrated under reduced pressure to a paste and then extracted with ether repeatedly (10×50 mL). The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether to yield the title A compound as a colorless crystalline solid (20.0 g), m.p. 58-60° C. 1H NMR [CDCl3]: δ 0.85 (s, 6H, C—Me2), 1.28 (s, 6H, N—CMe2), 1.9 (s, 3H, N=CMe) 2.2 (s, 2H, NCH2) and 2.6 (s, 2H, N—CH2). The solvent was removed under reduced pressure to give a paste the solution was cooled in an ice bath The solution was filtered the filtrate was adjusted to pH 10-11 by the addition of sodium hydroxide The solution was cooled again filtered The filtrate was concentrated under reduced pressure to a paste extracted with ether repeatedly (10×50 mL) The combined ether solution was concentrated to give an oil which was recrystallized twice from petroleum ether

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

Procedure: The title compound was prepared in analogy to Example 9-1 in Scheme 5 by using 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (prepared in analogy to the one in Example 2-1) and 2,2-dimethylpropane-1,3-diamine. MS obsd. (ESI+) [(M+H)+] 439, 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (d, J=1.2 Hz, 1 H), 7.99 (s, 1 H), 7.88 (d, J=7.2 Hz, 1 H), 7.73-7.70 (m, 2 H), 7.61-7.57 (m, 2 H), 6.07 (s, 1 H), 5.31 (s, 2 H), 4.50 (s, 2 H), 3.73 (s, 2 H), 3.49 (s, 2 H), 2.99 (s, 2 H), 2.47 (s, 3 H), 1.10 (s, 6 H).

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

Procedure: The title compound was prepared in analogy to Example 9-1 in Scheme 5 by using 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (prepared in analogy to the one in Example 2-1) and 2,2-dimethylpropane-1,3-diamine. MS obsd. (ESI+) [(M+H)+] 439, 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (d, J=1.2 Hz, 1 H), 7.99 (s, 1 H), 7.88 (d, J=7.2 Hz, 1 H), 7.73-7.70 (m, 2 H), 7.61-7.57 (m, 2 H), 6.07 (s, 1 H), 5.31 (s, 2 H), 4.50 (s, 2 H), 3.73 (s, 2 H), 3.49 (s, 2 H), 2.99 (s, 2 H), 2.47 (s, 3 H), 1.10 (s, 6 H).

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

Procedure: The process according to claim 1 wherein a mixture of neopentyldiamine and guanidine hydrohalide is initially reacted to form 5,5-dimethyl-2-amino-1,4,5,6-tetrahydropyrimidine hydrohalide and further reacting the latter with the hydrazine reactant. is initially reacted

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

Procedure: A mixture of 2-chloro-4-methoxyquinoline (0.63 g, 3.25 mmol) and 2,2-dimethyl-1,3-propanediamine (2.00 g, 19.5 mmol) was stirred for 16 h at 75° C. in a sealed propanediamine (2.00 g, 19.5 mmol) was stirred for 16 h at 75° C. in a sealed NaHCO3 and ethyl acetate. The organic layer was dried (MgSO4) and concentrated onto silica, then chromatographed eluting with 5% then 10% methanol/CH2Cl2+0.5% 880 aqueous ammonia to give the title compound as a white solid (0.19 g, 23%). δH (CDCl3) 0.99 (6H, s, C(CH3)2), 2.57 (2H, s, 2′-H), 3.41 (2H, s, 4′-H), 3.96 (3H, s, OCH3), 5.98 (1H, s, 3-H), 7.12-7.93 (4H, m, ArH). MS (ES+) 260 (MH+). The organic layer was dried (MgSO4) concentrated onto silica chromatographed eluting with 5%