2-propan-2-yl-2,5-diazabicyclo[2.2.1]heptane

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:; See reaction.notes.procedure_details.

Procedure: 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) (35 μL, ca. 0.249 mmol) and diisopropylethylamine (32 mg, 0.249 mmol) were added to a mixture of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-sulfonyl chloride (103 mg, 0.166 mmol) (COMPOUND CCC8) in 2 mL THF at 0° C. The mixture was warmed to rt, stirred at this temperature for 0.5 h, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and added to 6 mL of 1M aqueous HCl The phases were separated and the aqueous was extracted with 3×15 mL of ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by preparative thin-layer chromatography, eluting with 93:7 CH2Cl2-methanol to yield the 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one. Mass spectrum (ESI) 725 (M+1). concentrated under reduced pressure The residue was diluted with ethyl acetate added to 6 mL of 1M aqueous HCl The phases were separated the aqueous was extracted with 3×15 mL of ethyl acetate The combined organic layers were washed with brine dried (Na2SO4) concentrated under reduced pressure The product was purified by preparative thin-layer chromatography eluting with 93:7 CH2Cl2-methanol

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

Procedure: The title compound was prepared from 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-iodo-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (EXAMPLE CCC34) and using 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) as described in EXAMPLE 80. Mass spectrum (ESI): 661.3 (M+1).

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

Procedure: The 5-bromo-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one was prepared from 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carbaldehyde (EXAMPLE AAA16, STEP B) and 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) as described in EXAMPLE AAA1, STEP A. 1H NMR (CDCl3, 500 MHz): δ 1.15 (brs, 3H), 1.22 (brs, 3H), 1.74 (brs, 1H), 1.90 (brs, 1H), 243 (brs, 2H), 2.72 (brs, 1H), 2.88 (brs, 1H), 3.07 (brs, 1H), 3.16 (s, 2H), 3.53 (abq, 2H, J=14.2 Hz), 3.72 (brs, 1H), 3.83 (s, 3H), 4.48 (s, 2H), 4.68 (s, 2H), 6.05 (s, 1H), 6.91 (d, 2H, J=8.5 Hz), 7.17 (s, 1H), 7.36 (d, 2H, J=8.4 Hz), 7.38 (t, 1H, J=8.0 Hz), 7.52 (d, 2H, J=8.0 Hz). MS (API-ES+): 645 (M+H).

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

Procedure: 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) (35 μL, ca. 0.249 mmol) and diisopropylethylamine (32 mg, 0.249 mmol) were added to a mixture of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-sulfonyl chloride (103 mg, 0.166 mmol) (COMPOUND CCC8) in 2 mL THF at 0° C. The mixture was warmed to rt, stirred at this temperature for 0.5 h, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and added to 6 mL of 1M aqueous HCl The phases were separated and the aqueous was extracted with 3×15 mL of ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by preparative thin-layer chromatography, eluting with 93:7 CH2Cl2-methanol to yield the 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one. Mass spectrum (ESI) 725 (M+1). concentrated under reduced pressure The residue was diluted with ethyl acetate added to 6 mL of 1M aqueous HCl The phases were separated the aqueous was extracted with 3×15 mL of ethyl acetate The combined organic layers were washed with brine dried (Na2SO4) concentrated under reduced pressure The product was purified by preparative thin-layer chromatography eluting with 93:7 CH2Cl2-methanol

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

Procedure: 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) (35 μL, ca. 0.249 mmol) and diisopropylethylamine (32 mg, 0.249 mmol) were added to a mixture of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-sulfonyl chloride (103 mg, 0.166 mmol) (COMPOUND CCC8) in 2 mL THF at 0° C. The mixture was warmed to rt, stirred at this temperature for 0.5 h, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and added to 6 mL of 1M aqueous HCl The phases were separated and the aqueous was extracted with 3×15 mL of ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by preparative thin-layer chromatography, eluting with 93:7 CH2Cl2-methanol to yield the 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one. Mass spectrum (ESI) 725 (M+1). concentrated under reduced pressure The residue was diluted with ethyl acetate added to 6 mL of 1M aqueous HCl The phases were separated the aqueous was extracted with 3×15 mL of ethyl acetate The combined organic layers were washed with brine dried (Na2SO4) concentrated under reduced pressure The product was purified by preparative thin-layer chromatography eluting with 93:7 CH2Cl2-methanol

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

Procedure: The title compound was prepared from 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-iodo-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (EXAMPLE CCC34) and using 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) as described in EXAMPLE 80. Mass spectrum (ESI): 661.3 (M+1).

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

Procedure: The 5-bromo-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one was prepared from 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carbaldehyde (EXAMPLE AAA16, STEP B) and 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) as described in EXAMPLE AAA1, STEP A. 1H NMR (CDCl3, 500 MHz): δ 1.15 (brs, 3H), 1.22 (brs, 3H), 1.74 (brs, 1H), 1.90 (brs, 1H), 243 (brs, 2H), 2.72 (brs, 1H), 2.88 (brs, 1H), 3.07 (brs, 1H), 3.16 (s, 2H), 3.53 (abq, 2H, J=14.2 Hz), 3.72 (brs, 1H), 3.83 (s, 3H), 4.48 (s, 2H), 4.68 (s, 2H), 6.05 (s, 1H), 6.91 (d, 2H, J=8.5 Hz), 7.17 (s, 1H), 7.36 (d, 2H, J=8.4 Hz), 7.38 (t, 1H, J=8.0 Hz), 7.52 (d, 2H, J=8.0 Hz). MS (API-ES+): 645 (M+H).

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

Procedure: The 5-bromo-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one was prepared from 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carbaldehyde (EXAMPLE AAA16, STEP B) and 2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) as described in EXAMPLE AAA1, STEP A. 1H NMR (CDCl3, 500 MHz): δ 1.15 (brs, 3H), 1.22 (brs, 3H), 1.74 (brs, 1H), 1.90 (brs, 1H), 243 (brs, 2H), 2.72 (brs, 1H), 2.88 (brs, 1H), 3.07 (brs, 1H), 3.16 (s, 2H), 3.53 (abq, 2H, J=14.2 Hz), 3.72 (brs, 1H), 3.83 (s, 3H), 4.48 (s, 2H), 4.68 (s, 2H), 6.05 (s, 1H), 6.91 (d, 2H, J=8.5 Hz), 7.17 (s, 1H), 7.36 (d, 2H, J=8.4 Hz), 7.38 (t, 1H, J=8.0 Hz), 7.52 (d, 2H, J=8.0 Hz). MS (API-ES+): 645 (M+H).

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