2-bromopropan-2-ylbenzene

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

Procedure: When n is the bridging group --C(CH3)2 --, an appropriately substituted or unsubstituted phenyl methyl ketone, for example, methyl (3-chlorophenyl) ketone, is prepared by the reaction of methylmagnesium bromide and an appropriate benzonitrile in tetrahydrofuran. The ketone is in turn treated with methylmagnesiun bromide in tetrahydrofuran, yielding the corresponding 2-phenylpropan-2-ol, which is then converted to the 2-bromo-2-phenylpropane by the treatment of the alcohol with lithium bromide and trimethylsilyl chloride in acetonitrile. The Grignard reagent of the 2-bromo-2-phenylpropane is then prepared and reacted with 1,4-cyclohexanedione mono-ethylene ketal in tetrahydrofuran, yielding the corresponding 1-(2-phenylpropan-2-yl)-1-cyclohexen-4-one. The so-prepared cyclohexenone is reduced with hydrogen gas in the presence of 10% palladium on charcoal, yielding the 4-(2-phenylpropan-2-yl)cyclohexanone, which is in turn reacted with cyanoguanidine, as previously described, yielding the targeted 2,4-diamino-6-(2-phenylpropan-2-yl)-5,6,7,8-tetrahydroquinazoline. Example 7 provides a detailed description of how this reaction is conducted.

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

Procedure: The title compound was prepared from 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid benzylamide and 2-(bromo-1-methyl-ethyl)-benzene as described in Example 90 and isolated by chiral separation (90:10, heptane:isopropyl alcohol). 1H NMR (400 MHz, CDCl3) δ 7.20-7.39 (m, 8H), 7.13 (d, J=4 Hz, 2H), 7.04 (d, J=2 Hz, 1H), 6.68 (d, J=2 Hz, 1H), 5.98-6.04 (bm, 1H), 4.62 (d, J=8 Hz, 2H), 4.17-4.32 (m, 2H), 3.33-3.44 (m, 1H), 2.75 (s, 3H), 1.29 (d, J=4 Hz, 3H); MS (M+H)+=417.2; Rt=1.32 min; HRMS (M+H)+=417.17.

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

Procedure: The title compound was prepared from 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid benzylamide and 2-(bromo-1-methyl-ethyl)-benzene as described in Example 90 and isolated by chiral separation (90/10, heptane/isopropyl alcohol). 1H NMR (400 MHz, CDCl3) δ 7.35-7.41 (m, 5H), 7.20-7.35 (m, 3H), 7.14 (d, J=4 Hz, 2H), 7.08 (d, J=2 Hz, 1H), 6.75-6.82 (bs, 1H), 6.66 (d, J=2 Hz, 1H), 4.60 (d, J=8 Hz, 2H), 4.20-4.32 (m, 2H), 3.38-3.46 (m, 1H), 2.73 (s, 3H), 1.30 (d, J=4 Hz, 3H); MS (M+H)+=417.2; Rt=1.32 min; HRMS (M+H)+=417.17.

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

Procedure: When n is the bridging group --C(CH3)2 --, an appropriately substituted or unsubstituted phenyl methyl ketone, for example, methyl (3-chlorophenyl) ketone, is prepared by the reaction of methylmagnesium bromide and an appropriate benzonitrile in tetrahydrofuran. The ketone is in turn treated with methylmagnesium bromide in tetrahydrofuran, yielding the corresponding 2-phenylpropan-2-ol, which is then converted to the 2-bromo-2-phenylpropane by the treatment of the alcohol with lithium bromide and trimethylsilyl chloride in acetonitrile. The Grignard reagent of the 2-bromo-2-phenylpropane is then prepared and reacted with 1,4-cyclohexanedione mono-ethylene ketal in tetrahydrofuran, yielding the corresponding 1-(2-phenylpropan-2-yl)-1-cyclohexen-4-one. The so-prepared cyclohexenone is reduced with hydrogen gas in the presence of 10% palladium on charcoal, yielding the 4-(2-phenylpropan-2-yl)cyclohexanone, which is in turn reacted with cyanoguanidine, as previously described, yielding the targeted 2,4-diamino-6-(2-phenylpropan-2-yl)-5,6,7,8-tetrahydroquinazoline. Example 7 provides a detailed description of how this reaction is conducted.

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

Procedure: When n is the bridging group --C(CH3)2 --, an appropriately substituted or unsubstituted phenyl methyl ketone, for example, methyl (3-chlorophenyl) ketone, is prepared by the reaction of methylmagnesium bromide and an appropriate benzonitrile in tetrahydrofuran. The ketone is in turn treated with methylmagnesiun bromide in tetrahydrofuran, yielding the corresponding 2-phenylpropan-2-ol, which is then converted to the 2-bromo-2-phenylpropane by the treatment of the alcohol with lithium bromide and trimethylsilyl chloride in acetonitrile. The Grignard reagent of the 2-bromo-2-phenylpropane is then prepared and reacted with 1,4-cyclohexanedione mono-ethylene ketal in tetrahydrofuran, yielding the corresponding 1-(2-phenylpropan-2-yl)-1-cyclohexen-4-one. The so-prepared cyclohexenone is reduced with hydrogen gas in the presence of 10% palladium on charcoal, yielding the 4-(2-phenylpropan-2-yl)cyclohexanone, which is in turn reacted with cyanoguanidine, as previously described, yielding the targeted 2,4-diamino-6-(2-phenylpropan-2-yl)-5,6,7,8-tetrahydroquinazoline. Example 7 provides a detailed description of how this reaction is conducted.