3-(methylamino)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:

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

Procedure: Using a procedure analogous to that described for the starting material in Example 46, 4-chloropyridine (885 mg, 59 mmol) and 3-(methylamino)propanol (2.1 g, 0.23 mmol), (Tetrahedron Lett. 1994, 35, 1545-1548), were heated for 8 hours to give 3-(N-methyl-N-(4-pyridyl)amino)propanol (979 mg, 61%). were heated for 8 hours

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

Procedure: Using a procedure analogous to that described for the starting material in Example 46, 4-chloropyridine (885 mg, 59 mmol) and 3-(methylamino)propanol (2.1 g, 0.23 mmol), (Tetrahedron Lett. 1994, 35, 1545-1548), were heated for 8 hours to give 3-(N-methyl-N-(4-pyridyl)amino)propanol (979 mg, 61%). were heated for 8 hours

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

Procedure: The title compound was prepared from 8-(6-chlorohexyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one (Intermediate 6) and 3-(methylamino)propan-1-ol following the procedure outlined in Example 18, Step 2 (modifications: 22° C., 60 h). 1H NMR (300 MHz, DMSO-d6):):δ: 9.64 (s, 1H), 8.41 (s, 3H), 7.90 (d, J=9 Hz, 1H), 7.04 (d, J=9 Hz, 1H), 4.54 (s, 2H), 3.98 (t, J=6.9 Hz, 2H), 3.43 (t, J=6 Hz, 3H), 2.37-2.25 (4H, m), 2.14 (d, J=9.3 Hz, 8H), 1.76 (t, J=6.9 Hz, 2H), 1.37 (m, 6H). MS (ESI): 483. outlined in Example 18, Step 2 (modifications: 22° C., 60 h)

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

Procedure: The title compound was prepared from 8-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one (Intermediate 4) and 3-(methylamino)propan-1-ol following the procedure outlined in Example 18, Step 2 (modifications: 40° C., 24 h). 1H NMR (400 MHz, DMSO-d6): δ 9.95 (s, 1H), 8.83 (s, 1H), 8.75 (s, 2H), 7.87 (d, 1H), 7.04 (d, 1H), 4.76 (s, 1H), 4.52 (br, 1H), 3.95 (t, 2H), 3.89 (s, 3H), 3.40 (t, 2H), 2.31 (t, 2H), 2.25 (t, 2H), 2.09 (s, 3H), 1.74 (m, 2H), 1.52 (m, 2H), 1.39 (m, 4H), 1.29 (m, 2H); MS (ESI): 523.3. outlined in Example 18, Step 2 (modifications: 40° C., 24 h)

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

Procedure: A solution of 1.02 g (3.00 mmol) of trans-4-{2-[(4-chloro-phenoxycarbonyl)-methyl-amino]-ethyl}-cyclohexanecarboxylic acid in 30 mL of CH42Cl2 was treated at RT with 2 drops of DMF, followed by 0.28 mL (3.30 mmol, 1.1 eq) of oxalyl chloride within 5 min, and stirring was continued for 90 min. The solution was evaporated, redissolved in 15 mL of CH2Cl2 and added to a solution of 0.80 g (9.00 mmol, 3 eq) of 3-(methylamino)-1-propanol [Powell et al., Synthesis (4) 338-340 (1986)]and 2.09 mL (15.00 mmol, 5 eq) of Et3N in 12 mL of CH2Cl2 at 0° C. The reaction was kept at RT for 1 h then partitioned between Et2O (×3)/ aqueous saturated NaHCO3. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1) gave 0.95 g (77%) of pure trans-(2-{4-[(3-hydroxy-propyl)-methyl-carbamoyl]-cyclohexyl}-ethyl)-methyl-carbamic acid 4-chloro-phenyl ester, MS: 411 (MH+, 1Cl). The solution was evaporated redissolved in 15 mL of CH2Cl2 The reaction was kept at RT for 1 h then partitioned between Et2O (×3)/ aqueous saturated NaHCO3 The organic phases were washed once with aqueous 10% NaCl dried over Na2SO4 evaporated Purification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1)

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

Procedure: A solution of 1.02 g (3.00 mmol) of trans-4-{2-[(4-chloro-phenoxycarbonyl)-methyl-amino]-ethyl}-cyclohexanecarboxylic acid in 30 mL of CH42Cl2 was treated at RT with 2 drops of DMF, followed by 0.28 mL (3.30 mmol, 1.1 eq) of oxalyl chloride within 5 min, and stirring was continued for 90 min. The solution was evaporated, redissolved in 15 mL of CH2Cl2 and added to a solution of 0.80 g (9.00 mmol, 3 eq) of 3-(methylamino)-1-propanol [Powell et al., Synthesis (4) 338-340 (1986)]and 2.09 mL (15.00 mmol, 5 eq) of Et3N in 12 mL of CH2Cl2 at 0° C. The reaction was kept at RT for 1 h then partitioned between Et2O (×3)/ aqueous saturated NaHCO3. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1) gave 0.95 g (77%) of pure trans-(2-{4-[(3-hydroxy-propyl)-methyl-carbamoyl]-cyclohexyl}-ethyl)-methyl-carbamic acid 4-chloro-phenyl ester, MS: 411 (MH+, 1Cl). The solution was evaporated redissolved in 15 mL of CH2Cl2 The reaction was kept at RT for 1 h then partitioned between Et2O (×3)/ aqueous saturated NaHCO3 The organic phases were washed once with aqueous 10% NaCl dried over Na2SO4 evaporated Purification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1)

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

Procedure: A solution of 0.09 g (0.276 mmol) of trans-4-{[(4-chloro-phenoxycarbonyl)-methyl-amino]-methyl}-cyclohexanecarboxylic acid in 2.5 mL of CH2Cl2 was treated at RT with 1 drop of DMF. 0.026 mL (0.304 mmol, 1.1 eq) of oxalyl chloride was added within 5 min and stirring was continued for 90 min. The solution was evaporated, redissolved in 2.5 mL of CH2Cl2 and added to a solution of 0.197 mL (2.21 mmol, 7.2 eq) of 3-(methylamino)-1-propanol [Powell et al., Synthesis (1986), (4), 338-40]at 0° C. The reaction was kept over night at RT, then partitioned between Et2O (×3)/aqueous saturated NaHCO3. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 5 g silica gel (EtOAc:CH2Cl2 1:9 to 9:1) gave 0.064 g (58%) of pure trans-{4-[(3-hydroxy-propyl)-methyl-carbamoyl]-cyclohexylmethyl}-methyl-carbamic acid 4-chloro-phenyl ester, MS: 397 (MH+, 1Cl). The solution was evaporated redissolved in 2.5 mL of CH2Cl2 Powell et al., Synthesis (1986), (4), 338-40]at 0° C The reaction was kept over night at RT partitioned between Et2O (×3)/aqueous saturated NaHCO3 The organic phases were washed once with aqueous 10% NaCl dried over Na2SO4 evaporated Purification by flash-chromatography on 5 g silica gel (EtOAc:CH2Cl2 1:9 to 9:1)