3-(dimethylamino)-2,2-dimethylpropan-1-ol

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

Procedure: The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and 3-dimethylamino-2,2-dimethyl-1-propanol as starting materials to give the aimed compound.

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

Procedure: The title compound was prepared following a similar procedure to the previous example with 4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile, using 3-(dimethylamino)-2,2-dimethylpropan-1-ol. 1H NMR (400 MHz, d6-DMSO) δ 12.78 (s, 1H), 8.99 (d, J=0.8, 1H), 8.55 (d, J=5.7, 1H), 8.39 (d, J=0.8, 1H), 7.06 (d, J=5.8, 1H), 4.12 (s, 2H), 2.41 (s, 2H), 2.24 (s, 6H), 1.10 (s, 6H). LCMS (Method E): RT=3.58 min, M+H+=324.1.

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

Procedure: The title compound was prepared following a similar procedure to the previous example with 4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile, using 3-(dimethylamino)-2,2-dimethylpropan-1-ol. 1H NMR (400 MHz, d6-DMSO) δ 12.78 (s, 1H), 8.99 (d, J=0.8, 1H), 8.55 (d, J=5.7, 1H), 8.39 (d, J=0.8, 1H), 7.06 (d, J=5.8, 1H), 4.12 (s, 2H), 2.41 (s, 2H), 2.24 (s, 6H), 1.10 (s, 6H). LCMS (Method E): RT=3.58 min, M+H+=324.1.

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

Procedure: A suspension of 114 mg (0.5 mmol) of 2-methyl-4-pyrrolidin-1-yl-quinolin-7-ol, product of example 2, 71 mg (0.53 mmol) of 3-dimethylamino-2,2-dimethyl-1-propanol, 196.7 mg (0.75 mmol) of triphenyl phosphine in THF (4 ml) was treated at RT with 123 μl (0.75 mmol) of diethyl azodicarboxylate and stirred at RT for 48 h. The precipitate that had formed was removed by filtration, the filtrate was concentrated in vacuo and the oily residue obtained was applied to silica gel column with CH2Cl2/MeOH/NH4OH (90:10:1) as eluent. The purified fractions were combined and concentrated in vacuo. The residue was taken up in ether, the crystalline solid that formed was filtered off by suction and dried in a high vacuum to give 24 mg (23%) of the desired [2,2-dimethyl-3-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-yloxy)-propyl]-dimethyl-amine as an off-white solid. ISP mass spectrum, m/e: 342.4 (M+1 calculated for C21H31N3O: 342). (Further material, 30 mg, 29%, was obtained on concentration of the mother liquid and collection of the product as hydrochloride salt). The precipitate that had formed was removed by filtration the filtrate was concentrated in vacuo the oily residue obtained concentrated in vacuo the crystalline solid that formed was filtered off by suction dried in a high vacuum

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

Procedure: A suspension of 114 mg (0.5 mmol) of 2-methyl-4-pyrrolidin-1-yl-quinolin-7-ol, product of example 2, 71 mg (0.53 mmol) of 3-dimethylamino-2,2-dimethyl-1-propanol, 196.7 mg (0.75 mmol) of triphenyl phosphine in THF (4 ml) was treated at RT with 123 μl (0.75 mmol) of diethyl azodicarboxylate and stirred at RT for 48 h. The precipitate that had formed was removed by filtration, the filtrate was concentrated in vacuo and the oily residue obtained was applied to silica gel column with CH2Cl2/MeOH/NH4OH (90:10:1) as eluent. The purified fractions were combined and concentrated in vacuo. The residue was taken up in ether, the crystalline solid that formed was filtered off by suction and dried in a high vacuum to give 24 mg (23%) of the desired [2,2-dimethyl-3-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-yloxy)-propyl]-dimethyl-amine as an off-white solid. ISP mass spectrum, m/e: 342.4 (M+1 calculated for C21H31N3O: 342). (Further material, 30 mg, 29%, was obtained on concentration of the mother liquid and collection of the product as hydrochloride salt). The precipitate that had formed was removed by filtration the filtrate was concentrated in vacuo the oily residue obtained concentrated in vacuo the crystalline solid that formed was filtered off by suction dried in a high vacuum

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

Procedure: A suspension of 114 mg (0.5 mmol) of 2-methyl-4-pyrrolidin-1-yl-quinolin-7-ol, product of example 2, 71 mg (0.53 mmol) of 3-dimethylamino-2,2-dimethyl-1-propanol, 196.7 mg (0.75 mmol) of triphenyl phosphine in THF (4 ml) was treated at RT with 123 μl (0.75 mmol) of diethyl azodicarboxylate and stirred at RT for 48 h. The precipitate that had formed was removed by filtration, the filtrate was concentrated in vacuo and the oily residue obtained was applied to silica gel column with CH2Cl2/MeOH/NH4OH (90:10:1) as eluent. The purified fractions were combined and concentrated in vacuo. The residue was taken up in ether, the crystalline solid that formed was filtered off by suction and dried in a high vacuum to give 24 mg (23%) of the desired [2,2-dimethyl-3-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-yloxy)-propyl]-dimethyl-amine as an off-white solid. ISP mass spectrum, m/e: 342.4 (M+1 calculated for C21H31N3O: 342). (Further material, 30 mg, 29%, was obtained on concentration of the mother liquid and collection of the product as hydrochloride salt). The precipitate that had formed was removed by filtration the filtrate was concentrated in vacuo the oily residue obtained concentrated in vacuo the crystalline solid that formed was filtered off by suction dried in a high vacuum

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

Procedure: From intermediate 21 and 3-(dimethylamino)-2,2-dimethylpropan-1-ol, reacted in an analogous manner to the preparation of intermediate 68. UPLC-MS 3: Rt=0.40 min; MS m/z [M+H]+ 249.2.

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

Procedure: Using an analogous procedure to that described in Example 8, 2-chloro-4-[5-(4-dibenzofuranylcarbonylamino)-2-methylanilino]pyrimidine was reacted with 3-dimethylamino-2,2-dimethylpropanol. The reaction mixture was evaporated and the residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent followed by increasingly polar mixtures of methylene chloride and methanol containing 1% aqueous ammonium hydroxide solution. There was thus obtained the title compound; NMR Spectrum: (DMSOd6) 0.85 (s, 6H), 2.14 (s, 6H), 2.18 (s, 2H), 3.94 (s, 2H), 6.22 (d, 1H), 7.23 (d, 1H), 7.4-7.58 (m, 4H), 7.78 (d, 1H), 7.84 (d, 1H), 7.96 (m, 2H), 8.2 (d, 1H), 8.31 (d, 1H); Mass Spectrum: M+H+ 524. The reaction mixture was evaporated the residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent by increasingly polar mixtures of methylene chloride and methanol containing 1% aqueous ammonium hydroxide solution

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

Procedure: The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and 3-dimethylamino-2,2-dimethyl-1-propanol as starting materials to give the aimed compound.

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

Procedure: The title compound was prepared following a similar procedure to the previous example with 4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile, using 3-(dimethylamino)-2,2-dimethylpropan-1-ol. 1H NMR (400 MHz, d6-DMSO) δ 12.78 (s, 1H), 8.99 (d, J=0.8, 1H), 8.55 (d, J=5.7, 1H), 8.39 (d, J=0.8, 1H), 7.06 (d, J=5.8, 1H), 4.12 (s, 2H), 2.41 (s, 2H), 2.24 (s, 6H), 1.10 (s, 6H). LCMS (Method E): RT=3.58 min, M+H+=324.1.