3-Amino-1-butanol

General Procedure for the Synthesis of Compounds Starting from β-Amino Acids.; A solution of borane:tetrahydrofurane complex (1M, 3-4 mL per mmol=3-11 equiv. of β-amino acid) was added dropwise over a period of 1 hour to a cold (0° C.) suspension of beta amino acid (1 equiv.) in THF (1 mL per mmol). The mixture was stirred 20 minutes at room temperature at the end of the addition. It was then heated at reflux for 22 hours. The mixture was then cooled to 0° C.; and methanol (2 mL per mmol) was added over a period of 30 minutes. The mixture was then heated at reflux for 20 minutes and concentrated to a thick oil. The oil was co-evaporated with methanol (3.x.200 mL). The solid obtained was dried in vacuo to afford the coresponding 3-substituted 3-amino-1-propanol derivative as a white waxy solid (quantitative yield). An aqueous solution of HBr (48percent, 2 mL per equiv. of the alcohol) was added slowly to a flask containing a 3-substituted 3-amino-1-propanol (1 equilv.). The mixture was heated at reflux for 6 hours, and then concentrated to dryness. The crude material was used directly in the next step. The 1-substituted 3-bromo-1-propylamine hydrobromide (obtained in step 2) was added to a solution of sodium sulfite (1.0 equiv. of the 1-substituted 3-bromo-1-propylamine) in water and 1, 4-dioxane. The mixture was heated under reflux for 6 h then concentrated to dryness. The residual material was treated with concentrated HCl. The inorganic material was removed by filtration; and the filtrate was treated ethanol, causing precipitation of the corresponding sulfonic acid. The crude sulfonic acid was suspended in ethanol and the mixture was heated at reflux for 1 hour. After cooling to room temperature, the solid material was collected by filtration, rinsed with ethanol and dried overnight in the vacuum oven at 60° C., giving the corresponding 3-substituted 3-amino-1-propanesulfonic acid as a fine white crystalline solid.Reference Example 257 Step A: A. Step-iii: Preparation of (R, S)-3-amino-l-butanol : 4-Hydroxy-2-butanone oxime was dissolved ( 10.0 g, 0.097 mol) in methanol (100 ml). 8.0 ml of Raney nickel was added to the reaction mixture and hydrogenated under 10 kg/cmTo a solution of 4-hydroxy-2-butanone (5) (250.0 g, 2.84 mol) in methanol (2500 mL) at 20-25 °C, hydroxylamine hydrochloride (207.05 g, 2.9792 mol) was added. Afterwards sodium carbonate (180.45 g, 1.7024 mol) was added portionwise to the reaction mixture so as to maintain the temperatureat 25-30 °C. The mixture was then stirred for 2 h by keeping the temperature of about 45-50 °C. After the disappearance of the starting material which was monitored by TLC, the reaction mixture was filtered to remove inorganic salts which were washed with chilled methanol (250 mL). Then the combined filtrate and washed ones were transferred into a suitable vessel, and reduced using hydrogen in the presence of Raney Nickel at about 40-45 °C. The hydrogen pressure during reduction was maintained at 5-6 Kg/cmTo a solution of 3-aminobutan-1 -ol (500 mg, 5.61 mmol, 1 eq) in anhydrous DCM (25 ml_), cata- lytic amount of DMF (43 mI_, 0.56 mmol, 0.1 eq) was added, followed by dropwise addition of thionyl chloride (610 mI_, 8.414 mmol, 1.5 eq). The reaction was carried out 40C for 1 h, and continued at rt for further 16 h. The solvents were removed in vacuo. The residue was triturated using Et2A mixture of 4-chloro-1-methyl-6-nitroquinolin-2(1/-/)-one (Intermediate F1 ; 250 mg, 1.05 mmol) and 3-aminobutan-1-ol (280 mg, 3.14 mmol) and DIPEA (0.36 mL, 2.10 mmol) in NMP (1.9 mL) was stirred at 160 C for 20h. The reaction mixture was allowed to cool to rt. The reaction mixture was diluted with water and extracted with EtOAc. The organic extracts were combined, washed with water and brine, dried (Na2S04) and concentrated in vacuo. Purification by flash chromatography (50 g KP-sil; 0% to 10% MeOH in CH2CI2, afforded 4- ((4-hydroxybutan-2-yl)amino)-1-methyl-6-nitroquinolin-2(1/-/)-one (200 mg, 66%). 1H NMR (500 MHz, CDCb) d 8.48 (d, J = 2.5 Hz, 1 H), 8.36 (dd, J = 9.3, 2.5 Hz, 1 H), 7.38 (d, J = 9.3 Hz, 1 H), 6.05 (d, J = 6.6 Hz, 1 H), 5.80 (s, 1 H), 4.10 - 3.97 (m, 1 H), 3.96 - 3.82 (m, 2H), 3.68 (s, 3H), 2.08 - 1.95 (m, 2H), 1.89 (dtd, J = 14.8, 6.3, 3.5 Hz, 1 H), 1.35 (d, J = 6.4 Hz, 3H). LCMS (Method T2) RT 1.21 min, m/z 292.13 [M+H]+.General procedure: Compound 1: A mixture solution of 3-aminopropanol (0.52 mL, 6.77 mmol) and triethylamine (2.0 mL, 9.0 x 10-5 mol) in CH2Cl2was added dropwise to a solution of phenylthiono phosphonicdichloride (1 mL, 6.77 mmol) in CH2Cl2 with stirring. The mixturewas stirred for 12 h in room temperature, the precipitate wasfiltered off, the filtrate was washed with cold water (3 20 mL), dried with Na2SO 4, and the solvent was removed in vacuum. Thecrude productwas chromatographed on a silica gel (PE/EA 3:1), anda white granular solid was obtained. Yield: 37.4%.[00409] To a solution of Example 67a (10 g, 38mmol) in CH3CN/AcOH (80 mL/20 mL) was added Example 67b (5.1 g, 57 mmol). The mixture was heated at reflux for 5 h. After cooling to r.t., the mixture was concentrated under reduced pressure. The residue was dissolved in water and IN aqueous NaOH was added to adjust pH to 8. The resulting mixture was concentrated under reduced pressure and purified by silica gel chromatography (DCM/MeOH= 10/1) to give the desired product ( Example 67c , 5.5 g, yield 62%) as yellow oil. LCMS [M+l]+ = 234

Molecular Weight:89.14
XLogP3:-0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:89.084063974
Monoisotopic Mass:89.084063974
Topological Polar Surface Area:46.2
Heavy Atom Count:6
Complexity:30.7
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes