4-(3-chloropropylsulfonyl)morpholine

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

Procedure: The procedure used for the preparation of Example 24, Step 2 was used to prepare the title compound from 5-amino-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol (Intermediate I) and 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). Yield 190 mg (61%). Rf=0.68 in 10% MeOH/CH2Cl2, HPLC MS RT=1.13 min, MH+=394.4. The procedure used for the preparation of Example 24, Step 2

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To N-(8-hydroxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide (Example 2-5 in WO2004029055, 250 mg, 0.001 mol) and K2CO3 (1.1 g, 0.008 mol) in DMF (5 ml) was added 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E, 204.0 mg, 0.001 mol) to a sealed tube and heated to 120° C. for 3 h. The reaction was poured into water and extracted with CH2Cl2. Organic layers dried with MgSO4, filtered and concentrated. The residue was purified using silica gel flash chromatography (100% EtOAc, then 0-20% MeOH/CH2Cl2) to provide the title compound (130 mg, 33%). TLC: Rf=0.21 in 10% MeOH/CH2Cl2, HPLC MS RT=1.81 min., MW=499.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.22 (2H, m), 3.17 (4H, m), 3.26 (2H, m), 3.64 (4H, m), 4.18-4.29 (4H, m), 4.56 (2H, m), 7.22 (1H, d), 7.74 (1H, s), 7.89 (1H, m), 8.12 (1H, d), 8.81 (1H, m), 8.95 (1H, dd), 9.44 (1H, s). extracted with CH2Cl2 Organic layers dried with MgSO4 filtered concentrated The residue was purified

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 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). High vacuum drying gave the title compound (100%): 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.17-2.22 (2H, m), 3.14-3.17 (4H, m), 3.22-3.27 (2H, m), 3.61-64 (4H, m), 3.83 (3H, s), 4.16-4.20 (2H, m), 4.28-4.35 (4H, m), 7.30 (1H, d), 7.89 (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 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). High vacuum drying at 60° C. gave the title compound (42 mg, 34%): HPLC MS RT=1.82 min, MH+=499.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.26-2.31 (2H, m), 3.13-3.24 (4H, m), 3.37-3.43 (2H, m), 3.60-3.63 (4H, m), 4.27-4.34 (2H, m), 4.43 (2H, t), 4.58-4.65 (2H, m), 7.58 (1H, t), 7.73 (1H, d), 7.84 (1H, d), 7.94 (1H, dd), 8.86 (1H, d), 8.98 (1H, dd), 9.46 (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 Intermediate D was used to prepare the title compound from 3-chloropropanesulfonyl chloride and morpholine. High vacuum drying gave the title compound (1.3 g, 104%): 1H NMR (CDCl3) δ: 2.20-2.29 (2H, m), 3.02 (2H, dd), 3.20-3.23 (4H, m), 3.64 (2H, t), 3.68-3.72 (4H, m).

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 morpholine. High vacuum drying gave the title compound (1.3 g, 104%): 1H NMR (CDCl3) δ: 2.20-2.29 (2H, m), 3.02 (2H, dd), 3.20-3.23 (4H, m), 3.64 (2H, t), 3.68-3.72 (4H, m).

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

Procedure: The procedure used for the preparation of Example 24, Step 2 was used to prepare the title compound from 5-amino-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol (Intermediate I) and 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). Yield 190 mg (61%). Rf=0.68 in 10% MeOH/CH2Cl2, HPLC MS RT=1.13 min, MH+=394.4. The procedure used for the preparation of Example 24, Step 2

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To N-(8-hydroxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide (Example 2-5 in WO2004029055, 250 mg, 0.001 mol) and K2CO3 (1.1 g, 0.008 mol) in DMF (5 ml) was added 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E, 204.0 mg, 0.001 mol) to a sealed tube and heated to 120° C. for 3 h. The reaction was poured into water and extracted with CH2Cl2. Organic layers dried with MgSO4, filtered and concentrated. The residue was purified using silica gel flash chromatography (100% EtOAc, then 0-20% MeOH/CH2Cl2) to provide the title compound (130 mg, 33%). TLC: Rf=0.21 in 10% MeOH/CH2Cl2, HPLC MS RT=1.81 min., MW=499.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.22 (2H, m), 3.17 (4H, m), 3.26 (2H, m), 3.64 (4H, m), 4.18-4.29 (4H, m), 4.56 (2H, m), 7.22 (1H, d), 7.74 (1H, s), 7.89 (1H, m), 8.12 (1H, d), 8.81 (1H, m), 8.95 (1H, dd), 9.44 (1H, s). extracted with CH2Cl2 Organic layers dried with MgSO4 filtered concentrated The residue was purified

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 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). High vacuum drying gave the title compound (100%): 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.17-2.22 (2H, m), 3.14-3.17 (4H, m), 3.22-3.27 (2H, m), 3.61-64 (4H, m), 3.83 (3H, s), 4.16-4.20 (2H, m), 4.28-4.35 (4H, m), 7.30 (1H, d), 7.89 (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 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E). High vacuum drying at 60° C. gave the title compound (42 mg, 34%): HPLC MS RT=1.82 min, MH+=499.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.26-2.31 (2H, m), 3.13-3.24 (4H, m), 3.37-3.43 (2H, m), 3.60-3.63 (4H, m), 4.27-4.34 (2H, m), 4.43 (2H, t), 4.58-4.65 (2H, m), 7.58 (1H, t), 7.73 (1H, d), 7.84 (1H, d), 7.94 (1H, dd), 8.86 (1H, d), 8.98 (1H, dd), 9.46 (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 Intermediate D was used to prepare the title compound from 3-chloropropanesulfonyl chloride and morpholine. High vacuum drying gave the title compound (1.3 g, 104%): 1H NMR (CDCl3) δ: 2.20-2.29 (2H, m), 3.02 (2H, dd), 3.20-3.23 (4H, m), 3.64 (2H, t), 3.68-3.72 (4H, m).