3-(diethylamino)propan-1-ol

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:; See reaction.notes.procedure_details.

Procedure: 6-Methoxy-4-[(5-nitro-2-thienyl)sulfanyl]-7-quinolinol (500 mg), 3-diethylaminopropanol (290 mg), diethyl azodicarboxylate (390 mg), triphenylphosphine (590 mg), tetrahydrofuran (30 ml), 1-methyl-2-pyrrolidinone (2 ml) and dimethylsulfoxide (10 ml) were stirred together at 0° C. for 5 hours and then at room temperature for 10 hours. Water was added, extraction was performed with ethyl acetate, and the extract was back extracted with 2N aqueous hydrochloric acid. After adding 5N aqueous sodium hydroxide to the hydrochloric acid extract and performing extraction with ethyl acetate, the extract was washed with water and then with saline and dried over magnesium sulfate. NH type silica gel was coated onto a glass filter, the ethyl acetate layer was passed through the filter, and the solvent was distilled off under reduced pressure to obtain 500 mg of a reddish-brown oil. extraction the extract was back extracted with 2N aqueous hydrochloric acid After adding 5N aqueous sodium hydroxide to the hydrochloric acid extract extraction with ethyl acetate the extract was washed with water with saline and dried over magnesium sulfate filter the solvent was distilled off under reduced pressure

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

Procedure: A solution of 3-diethylamino-1-propanol (Aldrich) (10 g, 76 mmol) in DCM was stirred at 0° C. A solution of thionyl chloride (DCM 30 mL) was then added drop-wise such that the reaction temperature remained at 0° C. Once addition is complete, the reaction was refluxed for one hour. The reaction was allowed to cool and the excess DCM and thionyl chloride were removed under vacuum. The residue was basified (pH8–9) using 2N NaOH and the aqueous mixture extracted with DCM (3×100 mL). The organic extracts were combined, dried (MgSO4) and evaporated to give a brown oil. The oil was distilled (160°–165° C.) to give the product as a clear oil (4.2 g 36.9%). remained at 0° C Once addition the reaction was refluxed for one hour to cool the excess DCM and thionyl chloride were removed under vacuum the aqueous mixture extracted with DCM (3×100 mL) dried (MgSO4) evaporated to give a brown oil The oil was distilled (160°–165° C.)

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

Procedure: To a solution of 4-(3-chloro-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indol-6-yl)phenol (180 mg, 0.41 mmol, 1 eq.), triphenylphosphine (430 mg, 1.64 mmol, 4 eq.) and 3-(diethylamino)propan-1-ol (264 mg, 2.05 mmol, Seq.) in THF (10 ml) was added diisopropyldiazodicarboxylate (DIAD, 332 mg, 1.64 mmol, 4 eq.). The resulting solution was stirred at room temperature under Ar for 20 h and concentrated under reduced pressure. The crude residue was chromatographed over silica gel column (eluted with mixtures of AcOEt and EP and then AcOEt and MeOH). The product was then dissolved in dichloromethane and precipitated with EP. The solid was then filtered and washed with EP to give 3-(4-(3-chloro-9-(benzenesulfonyl)-9H-pyrido[2,3-b]indol-6-yl)phenoxy)-N,N-diethylpropan-1-amine (113 mg, 0.21 mmol, 51% yield). 1H NMR (CDCl3 300 MHz) δ ppm 8.47 (dd, 2H, J=2.6 Hz, 8.3 Hz), 8.18 (d, 1H, J=2.3 Hz), 8.13 (d, 2H, J=7.4 Hz), 8.01 (d, 1H, J=1.5 Hz), 7.77 (dd, 1H, J=1.8 Hz, 8.7 Hz), 7.54 (dd, 3H, J=8.7 Hz, 9.0 Hz), 7.42 (dd, 2H, J=7.3 Hz, 7.9 Hz), 7.01 (d, 2H, J=8.6 Hz), 4.08 (t, 2H, J=6.1 Hz), 2.58-2.72 (m, 6H), 2.00 (dd, 2H, J=6.8 Hz, 7.5 Hz), 1.08 (t, 6H, J=7.2 Hz). NMR 13C 75 MHz CDCl3 δ ppm 162.5 (C), 158.9 (C), 149.3 (C), 145.6 (CH), 138.6 (C), 137.5 (C), 137.4 (C), 134.3 (CH), 129.1 (2×CH), 128.3 (2×CH), 128.3 (C), 128.1 (CH), 127.6 (2×CH), 122.4 (C), 120.1 (C), 118.8 (CH), 115.5 (CH), 115.1 (2×CH), 66.5 (CH2), 49.5 (CH2), 47.1 (2×CH2), 26.8 (CH2), 11.6 (2×CH3). MS [ESI] 548 [M+H 35Cl], 550 [M+H 37Cl]. concentrated under reduced pressure The crude residue was chromatographed over silica gel column ( eluted with mixtures of AcOEt and EP The product was then dissolved in dichloromethane precipitated with EP The solid was then filtered washed with EP

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-fluoro-4-hydroxy-5-methoxy-benzaldehyde (39, 1.20 g, 7.05 mmol, prepared as described in Scheme 12 of Example 15) in tetrahydrofuran (60.0 mL) were added triphenylphosphine (1.93 g, 7.35 mmol) and 3-(diethylamino)-propan-1-ol, (0.96 g, 7.30 mmol). The reaction was cooled to 0° C., followed by slow addition of diethyl azodicarboxylate (1.28 g, 7.35 mmol). The reaction was allowed to warm to room temperature overnight. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10% methanol in dichloromethane to give a colorless oil (102, 0.90 g, 45.0%). to warm to room temperature overnight extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered The filtrate was concentrated purified by silica gel column chromatography eluting with 10% methanol in dichloromethane to give a colorless oil (102, 0.90 g, 45.0%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-fluoro-4-hydroxy-5-methoxy-benzaldehyde (39, 1.20 g, 7.05 mmol, prepared as described in Scheme 12 of Example 15) in tetrahydrofuran (60.0 mL) were added triphenylphosphine (1.93 g, 7.35 mmol) and 3-(diethylamino)-propan-1-ol, (0.96 g, 7.30 mmol). The reaction was cooled to 0° C., followed by slow addition of diethyl azodicarboxylate (1.28 g, 7.35 mmol). The reaction was allowed to warm to room temperature overnight. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10% methanol in dichloromethane to give a colorless oil (102, 0.90 g, 45.0%). to warm to room temperature overnight extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered The filtrate was concentrated purified by silica gel column chromatography eluting with 10% methanol in dichloromethane to give a colorless oil (102, 0.90 g, 45.0%)

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

Procedure: Additional 5-substituted 7-azaindoles were prepared following the protocol of Scheme 31, replacing 4-morpholineethanol with either 2-diethylamino-ethanol, 3-diethylamino-propan-1-ol, 2-piperidin-1-yl-ethanol, or 2-pyrrolidin-1-yl-ethanol to provide diethyl-[2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-ethyl]-amine, Diethyl-[3-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-propyl]-amine, 5-(2-piperidin-1-yl-ethoxy)-1H-pyrrolo[2,3-b]pyridine, and 5-(2-pyrrolidin-1-yl-ethoxy)-1H-pyrrolo[2,3-b]pyridine, respectively.

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

Procedure: Additional 5-substituted 7-azaindoles were prepared following the protocol of Scheme 31, replacing 4-morpholineethanol with either 2-diethylamino-ethanol, 3-diethylamino-propan-1-ol, 2-piperidin-1-yl-ethanol, or 2-pyrrolidin-1-yl-ethanol to provide diethyl-[2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-ethyl]-amine, Diethyl-[3-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-propyl]-amine, 5-(2-piperidin-1-yl-ethoxy)-1H-pyrrolo[2,3-b]pyridine, and 5-(2-pyrrolidin-1-yl-ethoxy)-1H-pyrrolo[2,3-b]pyridine, respectively.