Structure of 15518-10-2
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CAS No. : | 15518-10-2 |
Formula : | C4H11NO |
M.W : | 89.14 |
SMILES Code : | OCC(C)CN |
MDL No. : | MFCD03412698 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(i) Resolution of 3-amino-2-methyl propan-1-ol To a solution of racemic 3-amino-2-methyl propan-1-ol (4) (3.0 g) in methyl ethyl ketone (65 ml) was added (-) N-(1-phenylethyl)-succinamic acid (7.6 g) (E. Felder, D. Pitre and S. Boveri, Helv. Chim. Acta, 1969, 52, 329) at 60 C. and the mixture stirred until dissolved. On cooling the stirred solution to ambient temperature, the desired salt was precipitated. This was filtered, washed with ether and dried in vacuo to yield 3.7 g of crystalline material. On recrystallisation from methylethyl ketone the optical rotation remained constant; [alpha]D20 =-64.2 (C=1, ethanol); m.p. 112-115 C.; Found: C, 61.59; H, 8.29; N, 8.95%, C16 H26 N2 O4 requires C, 61.94; H, 8.39; N, 9.03%. A solution of the salt in methanol was applied to strongly basic ion-exchange column (alphaAmberlystalpha A-26 resin) Elution with methanol followed by evaporation of solvent gave the optically active amino alcohol; [alpha]D20 =+7.8 (C=1.7, chloroform). | ||
...sulting amino amide has at least two labile-non-amido hydrogens, for example STR20 Aromatic polyamines can also be employed, for example: STR21 Also included are substituted amines, for example hydroxylamines, such as hydroxyalkyl amines, having 2-10 or more carbons, monoethanol amine ... 2-amino-2-methyl-1-propanol 2-amino-2-methyl-1,3-propanediol 2-amino-2-ethyl-1,3-propanediol 3-amino-2-methyl-1-propanol 2-amino-1-butanol 3-amino-2,2-dimethyl-1-propanol 2-amino-2,3-dimethyl-1-propanol ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; thionyl chloride; In potassium hydroxide; diethyl ether; dichloromethane; | A. 2-(4-Fluorophenyl)4,4-dimethyl-4,5-dihydro-oxazole To a stirred solution of 2-amino-methylpropanol (0.378 mol, 33.64 gm) in 300 ml of methylene chloride at about 0 C. was added a solution of 4-fluorobenzoyl chloride (0.189 mol, 22.35 mL) in 100 mL of methylene chloride over about 0.5 hr. The mixture was allowed to warm to room temperature and stirred for about 3 hrs. The mixture was then poured into water and the layers were separated. The organic phase was washed with two portions of 10% HCl, one portion of saturated sodium chloride solution and dried over anhydrous MgSO4. Removal of the solvent in vacuo afforded a colorless solid which was stirred while SOCl2 (0.567 mol. 41 mL) was added dropwise over about 30 min. The resulting solution was stirred for about 0.5 hr, at which time diethyl ether was added while the solution was stirred rapidly. During this procedure, a colorless precipitate was produced. The slurry was filtered and the solid was washed with three 250 mL portions of diethyl ether. The solid was then dissolved in 300 mL of 3N KOH and the resulting solution was extracted with ethyl acetate. The organic extracts were washed with saturated aqueous NaCl solution and dried over MgSO4. Removal of the solvent in vacuo afforded 32 gm of the title compound of this Example 1A: 1 H-NMR (250 MHz., CDCl3) delta:8.00-7.91 (m, 2H), 7.10-7.02 (m, 2H), 4.11 (s, 2H), 1.39 (s, 6H). | |
With hydrogenchloride; thionyl chloride; In potassium hydroxide; diethyl ether; dichloromethane; | A. 2-(4-Fluorophenyl)-4,4-dimethyl-4,5-dihydro-oxazole To a stirred solution of 2-amino-methylpropanol (0.378 mol, 33.64 gm) in 300 ml of methylene chloride at about 0 C. was added a solution of 4-fluorobenzoyl chloride (0.189 mol, 22.35 mL) in 100 mL of methylene chloride over about 0.5 hr. The mixture was allowed to warm to room temperature and stirred for about 3 hrs. The mixture was then poured into water and the layers were separated. The organic phase was washed with two portions of 10% HCl, one portion of saturated sodium chloride solution and dried over anhydrous MgSO4. Removal of the solvent in vacuo afforded a colorless solid which was stirred while SOCl2 (0.567 mol, 41 mL) was added dropwise over about 30 min. The resulting solution was stirred for about 0.5 hr, at which time diethyl ether was added while the solution was stirred rapidly. During this procedure, a colorless precipitate was produced. The slurry was filtered and the solid was washed with three 250 mL portions of diethyl ether. The solid was then dissolved in 300 mL of 3N KOH and the resulting solution was extracted with ethyl acetate. The organic extracts were washed with saturated aqueous NaCl solution and dried over MgSO4. Removal of the solvent in vacuo afforded 32 gm of the title compound of this Example 1A: 1 H-NMR (250 MHz., CDCl3) delta: 8.00-7.91 (m, 2H), 7.10-7.02 (m, 2H), 4.11 (s, 2H), 1.39 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; N,N-dimethyl-formamide; | EXAMPLE I N-(2-Hydroxy-1,1-dimethylethyl)-2,4,5-trifluorobenzamide A solution of 19.4 g (110 mmol) of 2,4,5-trifluorobenzoic acid (JP 58,150,543 (Cl. C07C69) Sept. 7, 1983). 15.2 g (120 mmol) of oxalyl chloride and 250 ml of dichloromethane was treated with four drops of DMF, and the mixture was stirred at room temperature for four hours. The mixture was concentrated to a oil and was redissolved in 100 ml of dichloromethane. This solution was added dropwise to a solution of 19.6 g (240 mmol) of <strong>[15518-10-2]3-amino-2-methyl-1-propanol</strong> in 200 ml of dichloromethane at 5 C., and the reaction mixture was stirred at room temperature overnight. The solids were filtered, and the filtrate was washed with 5% sodium bicarbonate, 1N hydrochloric acid, and water. The organic layer was dried over magnesium sulfate and concentrated to give 24.5 g of the title compound, mp 114-116 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydride; In toluene; at 0 - 20℃; for 0.5h; | A 50 mL round bottom flask was flame dried and a stir bar was placed in it and cooled under a stream of nitrogen. This flask was then charged with 3, 6- dichloropyridazine (5.0 g, 33.6 mmol) and sodium hydride (967 mg, 40.3 mmol). Toluene (25 mL) was then added to this mixture and the flask cooled to 0 0C. 2- Amino-2-methyl-l-propanol (3.15 g, 35.3 mmol) dissolved in 5 mL toluene was then added drop-wise to the above at such a rate so as to keep gas evolution under control. The reaction mixture was then stirred for 30 minutes at room temperature after which it was filtered and the solid was washed with toluene (20 mL) and dichloromethane (20 mL). The filtrates were combined and concentrated under reduced pressure. The mixture so obtained was purified by silica gel flash chromatography (9:0.9:0.1 dichloromethane:methanol:NH3) to obtain the title compound (5.86 g, 86%) as a semi-solid. 1H NMR (600 MHz, OMSO-d6): delta 7.77 (d, IH, J = 9.0 Hz), 7.47 (d, IH, J = 9.0 Hz), 4.10 (s, 2H), 1.10 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
147 mg | In an ice bath, 44.5 mg (1.11 mmol) sodium hydride (60% dispersion in mineral oil) were dispensed in 8 mL of anhydrous THF. 99.2 mg (1.11 mmol) 3-amino-2-methyl- propan-1 -ol were slowly added. After complete addition, stirring at 0C was continued for 15 min. 150 mg (0.556 mmol) of 3-(1 -benzofur-2-yl)-6- chloroimidazo[1 ,2-b]pyridazine were added, the ice bath was removed and the resulting mixture was stirred for 72 h at 40 C. The reaction mixture was carefully poured into water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, and concentrated. The crude product was purified by HPLC to give 147 mg of the title compound as a solid material. 1H-NMR (300 MHz, DMSO-de), delta [ppm] = 1.12 (3H), 2.22-2.32 (1 H), 2.74-2.82 (1 H), 2.87-2.96 (1 H), 4.40-4.54 (2H), 7.03-7.11 (1 H), 7.26-7.42 (2H), 7.68 (2H), 7.73-7.80 (1 H), 8.16-8.23 (2H). LC-MS (Method 3): Rt = 0.76 min; MS (ESIpos) m/z = 323 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
122 mg | At 0C 96 mg (1.1 mmol) 3-amino-2-methylpropan-1 -ol were added to 43 mg (1.1 mmol) sodium hydride (60% in mineral oil) in 8 mL anhydrous THF. After 15 min of stirring on the ice bath, 250 mg (0.54 mmol) of 6-chloro-3-(4-methoxyfuro[3,2- c]pyridin-2-yl)imidazo[1 ,2-b]pyridazine were added. The ice bath was removed and the mixture was stirred for 72 h at 40 C. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and concentrated. The residue was purified by HPLC to give 122 mg of the title compound as solid material. 1H-NMR (300 MHz, DMSO-d6), delta [ppm]= 1.07 (3H), 4.01 (3H), 4.41 (2H), 7.04 (1 H), 7.36 (1 H), 7.50 (1 H), 8.04 (1 H), 8.12-8.20 (2H). LC-MS (Method 3): Rt = 0.70 min; MS (ESIpos) m/z = 354 [M+H]' |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.5% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; | K3P04 (6.1 g, 28.8 mmol), BINAP (0.44 g, 0.72 mmol) and Pd2(dba)3 (0.32.0 g, 0.36 mmol) was added to the degassed suspension of 6-bromo-1 -cyanoisoquinoline A3 (1.7 g, 7.2 mmol), D2 (1.2 g, 14.5 mmol) in DMSO at room temperature. The reaction mixture was heated at 105 C for 2 h. The reaction was cooled to room temperature, water (500 ml_) followed by EtOAc (100 ml_) were added, and the mixture was stirred for 10 minutes. The biphasic mixture was filtered through a Celite pad and washed with EtOAc (100 ml_). The organic layer was separated, and the aqueous layer was extracted with EtOAc (3 x 100 ml_). The combined organic layers were dried over anhydrous Na2S04, concentrated under reduced pressure to get a crude material. This was purified by column chromatography on 100 - 200 mesh silica gel, using 50 - 70% EtOAc in petroleum ether as the eluent to obtain D3 (0.5 g, 48.5%) as a yellow solid. Rf: 0.4 (60% EtOAC in petroleum ether). LCMS m/z = 242.0 (M + H). 1 H NMR (400 MHz, cf6-DMSO): delta 0.97 (d, J = 6.4 Hz, 3H), 1.87 - 1.99 (m, 1 H), 2.92 - 2.99 (m, 1 H), 3.20 - 3.27 (m, 1 H), 3.38 - 3.42 (m, 2H), 4.59 (t, J = 5.2 Hz, 1 H), 6.77 (d, J = 2.0, 1 H), 7.01 (t, J = 5.6 Hz, 1 H), 7.34 (dd, J = 9.2 Hz, J = 2.0 Hz, 1 H), 7.73 (d, J = 6.0 Hz, 1 H), 7.88 (d, J = 8.8 Hz, 1 H), 8.312 (d, J = 6.0 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(3-hydroxy-2-methylpropyl)-2-oxo-1-[2-(2-oxo-1-piperidinyl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1-[2-(2-oxo-1-piperidinyl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate and <strong>[15518-10-2]3-amino-2-methyl-1-propanol</strong> using methods similar to Example 563 to provide an orange solid: 1H NMR (300 MHz, DMSO-d6) delta ppm 0.89 (d, J=6.95 Hz, 3H) 1.52-1.65 (m, 4H) 1.79-1.88 (m, 1H) 2.03 (t, J=6.00 Hz, 2H) 3.20-3.47 (m, 6H) 3.51 (t, J=6.00 Hz, 2H) 4.16 (s, 2H) 4.40 (t, J=6.11 Hz, 2H) 4.64 (s, 1H) 7.11-7.17 (m, 2H) 7.38-7.43 (m, 2H) 8.20 (d, J=1.47 Hz, 1H) 8.56 (d, J=1.47 Hz, 1H) 10.38 (t, J=5.90 Hz, 1H) 17.24 (s, 1H); ES+MS: 511 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 3h;Inert atmosphere; Reflux; | D1 (2.0 g, 13.0 mmol) was added portionwise to a suspension of LiAIH4 (1.4 g, 39.2 mmol) in THF (75 ml_) under nitrogen atmosphere at 0 C. The reaction mixture was stirred for 30 minutes and then allowed to stir at room temperature for another 30 minutes. The reaction mixture was refluxed for 2 h, and then it was cooled to -10 C and quenched carefully with ice cold water (1.4 ml_). 10% NaOH solution (2.8 ml_) and ice cold water (4.2 ml_) were added, and the mixture was stirred for 15 minutes. It was filtered, and the filtrate washed with EtOAc (3 x 100 ml_), dried over anhydrous Na2S04 and concentrated under vacuum to obtain D2 (1.2 g, 86%) as a pale yellow liquid. Rf: 0.2 (20% MeOH in DCM). 1H NMR (400 MHz, cf6-DMSO): delta 0.78 (d, J = 6.8 Hz, 3H), 1.46 - 1.54 (m, 1 H), 2.41 - 2.45 (m, 2H), 2.50 - 2.54 (m, 1 H), 3.22 - 3.34 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; | 6-(4-Chlorophenyl)-2-(3-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (70 mg, 0.20 mmol) was dissolved in anhydrous DMF (1.5 ml_). (2RS)-3-Amino-2-methylpropan-1 -ol (36.2 mg, 0.41 mmol), N-ethyl-N-isopropylpropan-2-amine (0.159 ml_, 0.91 mmol), and propane phosphonic acid anhydride (T3P, 178 muIota_, 50% in DMF, 305mueta-iotaomicronIota) were successively added. It was stirred at rt overnight. The crude reaction mixture was purified by RP-HPLC (column: X-Bridge C18 5muetaiota 100x30mm, mobile phase: (water + 0.2 vol% aqueous ammonia (32%)) / acetonitrile, gradient) to yield 40 mg (47%) of the title compound. 1H-NMR (400MHz, DMSO-d6): delta [ppm] = 0.87 (d, 3H), 1.74 - 1.86 (m, 1 H), 3.22 - 3.42 (m, 4H and water signal), 4.62 (t, 1 H), 7.35 - 7.42 (m, 1 H), 7.53 - 7.66 (m, 5H), 7.97 - 8.02 (m, 2H), 8.63 (s, 1 H), 9.44 (t, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; | 2-(3-Fluorophenyl)-3-oxo-6-[4-(trifluoromethyl)phenyl]-2,3-dihydropyridazine-4-carboxylic acid (100 mg, 0.26 mmol) was dissolved in anhydrous DMF (2 mL). (2RS)-3-Amino-2- methylpropan-1 -ol (47.1 mg, 0.53 mmol), N-ethyl-N-isopropylpropan-2-amine (0.207 mL, 1.19 mmol), and propane phosphonic acid anhydride (T3P, 231 muIota_, 50% in DMF, 397 muetaetaomicronIota) were successively added. It was stirred at rt overnight. The crude reaction mixture was purified by RP-HPLC (column: X-Bridge C18 5muetaiota 100x30mm, mobile phase: (water + 0.2 vol% aqueous ammonia (32%)) / acetonitrile, gradient) to yield 87.4 mg (74%) of the title compound. 1H-NMR (400MHz, DMSO-d6): delta [ppm] = 0.88 (d, 3H), 1.75 - 1.87 (m, 1 H), 3.23 - 3.42 (m, 4H and water signal), 4.62 (t, 1 H), 7.36 - 7.43 (m, 1 H), 7.55 - 7.59 (m, 1 H), 7.60 - 7.67 (m, 2H), 7.88 (d, 2H), 8.20 (d, 2H), 8.70 (s, 1 H), 9.43 (t, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; at 20℃; for 0.5h; | General procedure: Lambda-[Ir(ppy)2(MeCN)2](PF6) (0.0072g, 0.01mmol), 3-hydroxypyridine-2-carboxaldehyde (0.0012g, 0.01mmol) and amine or amino derivative (0.01mmol) was added to a CHCl3 (3 mL) solution sequentially. The solution was stirred at room temperature for 30min. Then the solvent was removed and the mixture was transferred to a NMR tube with 0.5mL CDCl3 for 1H NMR determination. For 3-aminopropane-1,2-diol experiment, CH3OH and CD3OD solvents were used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With chlorosulfonic acid; In tetrachloromethane; at 0 - 20℃; for 16h; | To a solution of <strong>[15518-10-2]3-amino-2-methylpropan-1-ol</strong> (1 , 4.4 g, 49.36 mmol) in carbon tetrachloride (18 mL) cooled to 0 C was added chloro sulphonic acid (3.31 mL, 49.85 mmol) drop wise using an addition funnel (highly exothermic) and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated, the residue was suspended in methanol, triturated, filtered and dried to afford the title compound 3-amino-2-methylpropyl hydrogen sulfate (2, 5.6 g, 67% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-cfe) _ (ppm): 7.63 (bs, 3H), 3.74-3.70 (m, 1H), 3.65-3.61 (m, 1H), 2.87-2.80 (m, 1H), 2.70-2.64 (m, 1H), 2.05-1 .97 (m, 1H), 0.88 (d, J = 7.2 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In N,N-dimethyl-formamide; at 50℃; for 1h; | 3-chloro-4-(2,6-difluoro-4-isothiocyanatophenoxy)-1 -[2-(trimethylsilyl)ethoxy]methyl}-1 H- pyrrolo[2,3-b]pyridine (1 10 mg, 235 muetaetaomicronIota, intermediate 323) was dissolved in DMF (5.0 mL) and (+/-)-3-amino-2-methylpropan-1 -ol (41 .9 mg, 470 muetaetaomicronIota) was added. The mixture was stirred at 50 C for 1 hour. After cooling to room temperature ethyl acetate and brine were added to the mixture and the mixture was extracted with ethyl acetate (3x). The organic layers were combined, dried with magnesium sulfate, filtered and solvent evaporated to afford a crude product, which was purified by reverse phase chromatography on Biotage isolera, 30 g C-18 column (eluent: 50-90% acetonitrile in NH4HC03 pH 10 aqueous buffer) to obtain the desired titled compound (72 mg, 55% yield) as a white solid. 1H-NMR (400 MHz, CDCI3) delta [ppm]: -0.05 (s, 9H), 0.87 - 1 .00 (m, 5H), 2.01 (br s, 1 H), 3.49 - 3.58 (m, 5H), 3.75 - 3.82 (m, 1 H), 5.63 (s, 2H), 6.29 (d, 1 H), 6.91 - 7.07 (m, 1 H), 7.27 (s, 1 H), 7.60 (br s, 1 H), 8.15 (d, 1 H). |