3-chloro-N,N-dimethylpropane-1-sulfonamide

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:

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

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of dimethylamine hydrochloride are placed in 60 ml of water, a nitrogen atmosphere is applied and the solution is cooled to between 0° C. and −5° C., and then 18 ml of 3-chloro-1-propanesulphonyl chloride are added dropwise. 10.6 g of sodium hydroxide in 40 ml of water are added while maintaining at −5° C., then the mixture is allowed to return to AT and stirring is maintained for 1 hour. 1 ml of concentrated HCl is added and then extraction is carried out with DCM. The organic phase is washed with a 10% NaOH solution and then with an NaCl solution. 15.1 g of the expected compound are obtained. the solution is cooled to between 0° C. and −5° C. is maintained for 1 hour extraction The organic phase is washed with a 10% NaOH solution

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of dimethylamine hydrochloride are placed in 60 ml of water, a nitrogen atmosphere is applied and the solution is cooled to between 0° C. and −5° C., and then 18 ml of 3-chloro-1-propanesulphonyl chloride are added dropwise. 10.6 g of sodium hydroxide in 40 ml of water are added while maintaining at −5° C., then the mixture is allowed to return to AT and stirring is maintained for 1 hour. 1 ml of concentrated HCl is added and then extraction is carried out with DCM. The organic phase is washed with a 10% NaOH solution and then with an NaCl solution. 15.1 g of the expected compound are obtained. the solution is cooled to between 0° C. and −5° C. is maintained for 1 hour extraction The organic phase is washed with a 10% NaOH solution

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

Procedure: The procedure used for the preparation of Example 1 was used to prepare the title compound from 5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol bistrifluoroacetate salt (Intermediate A) and 3-chloro-N,N-dimethylpropane-1-sulfonamide (Intermediate F). High vacuum drying gave the title compound (1.12 g, 86%): HPLC MS RT=1.28 min, MH+=382.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.15-2.20 (2H, m), 2.77 (6H, s), 3.18-3.23 (2H, m), 3.84 (3H, s), 4.18-4.21 (2H, m), 4.29-4.35 (4H, m), 7.30 (1H, d), 7.90 (1H, d). The procedure used for the preparation of Example 1

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

Procedure: The procedure used for the preparation of Example 1 was used to prepare the title compound from N-[7-hydroxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide (Intermediate H) and 3-chloro-N,N-dimethylpropane-1-sulfonamide (Intermediate F). High vacuum drying gave the title compound (15 mg, 15%): HPLC MS RT=0.24 min, MH+=600.4; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 1.07 (6H, t), 2.18-2.27 (4H, m), 3.04-3.13 (2H, m), 3.27-3.36 (4H, q), 3.51 (2H, d), 3.66 (2H, t), 3.98-4.02 (2H, m), 4.21-4.36 (6H, m), 4.56-4.59 (2H, m), 7.49 (1H, d), 8.02 (1H, dd), 8.08 (1H, d), 8.96 (1H, d), 9.04 (1H, dd), 9.50 (1H, d). The procedure used for the preparation of Example 1

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

Procedure: The procedure used for the preparation of Example 1 was used to prepare the title compound from N-[7-hydroxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide (Intermediate H) and 3-chloro-N,N-dimethylpropane-1-sulfonamide (Intermediate F). High vacuum drying gave the title compound (15 mg, 15%): HPLC MS RT=0.24 min, MH+=600.4; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 1.07 (6H, t), 2.18-2.27 (4H, m), 3.04-3.13 (2H, m), 3.27-3.36 (4H, q), 3.51 (2H, d), 3.66 (2H, t), 3.98-4.02 (2H, m), 4.21-4.36 (6H, m), 4.56-4.59 (2H, m), 7.49 (1H, d), 8.02 (1H, dd), 8.08 (1H, d), 8.96 (1H, d), 9.04 (1H, dd), 9.50 (1H, d). The procedure used for the preparation of Example 1

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

Procedure: The procedure used for the preparation of Example 1 was used to prepare the title compound from N-(7-hydroxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide (Intermediate C) and 3-chloro-N,N-dimethylpropane-1-sulfonamide (Intermediate F). High vacuum drying at 60° C. gave the title compound (44 mg, 39%): HPLC MS RT=0.68 min, MH+=457.3; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.27 (2H, bs), 2.84 (6H, s), 3.36-3.37 (2H, m), 4.31 (2H, bs), 4.43 (2H, bs), 4.62 (2H, bs), 7.59-7.61 (1H, m), 7.71 (1H, bs), 7.83-7.86 (1H, m), 7.97-7.98 (1H, m), 8.89 (1H, bs), 9.00 (1H, m), 9.47 (1H, bs). The procedure used for the preparation of Example 1

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

Procedure: The procedure used for the preparation of Intermediate D was used to prepare the title compound from 3-chloropropanesulfonyl chloride and dimethylamine. High vacuum drying gave the title compound (2.1 g, 100%): 1H NMR (DMSO-d6) δ: 2.06-2.11 (2H, m), 2.75 (6H, s), 3.10-3.15 (2H, m), 3.72 (2H, t).