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CAS No. : | 477293-60-0 |
Formula : | C10H19NO3 |
M.W : | 201.26 |
SMILES Code : | O=C(N1[C@@H](C)C[C@H](O)C1)OC(C)(C)C |
MDL No. : | MFCD20278358 |
InChI Key : | BXZADLGAYWRZCR-YUMQZZPRSA-N |
Pubchem ID : | 56846373 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
* 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 |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 20.5h;Inert atmosphere; | Mesyl chloride (0.125 mL, 1.61 mmol) was added to a stirred solution of (2LU)-4- hydroxy-2-methyl-pyrrolidine-l -carboxylic acid tert- butyl ester (CAS: 477293-60-0; 250 mg, 1.24) in DCM (5 mL) at 0 C under nitrogen atmosphere. Then, DIPEA (0.368 mL, 2.11 mmol) was added at 5 C over 5 min. The mixture was stirred at 5 C for 30 min, then was stirred at rt for 20 h. The mixture was diluted with an NaHC03 aq. sat. sol and extracted with DCM. The organic layer was separated, dried (MgS04), filtered and the solvents evaporated in vacuo to yield intermediate (350 mg, 100%) as a brown sticky solid. |
87% | With triethylamine; In dichloromethane; at 0 - 18℃; for 2.0h; | To a solution of tert-butyl (2S,4S)-4-hydroxy-2-methylpyrrolidine-l-carboxylate (200 mg, 0.994 mmol) and TEA (201 mg, 1.99 mmol) in DCM (10 mL) was added methanesulfonyl chloride (228 mg, 1.99 mmol) at 0C. After addition, the mixture was stirred at 18C for 2 h. The reaction was quenched with aq. NaHCCL (8 mL) and extracted with DCM (10 mL x 3). The combined organics were dried (I^SCL) and evaporatedScheme to dryness to give the title compound as a yellow oil (243 mg, 87%) which was used without further purification. LCMS: ([M-Boc+H] = 163.0). |
67% | With triethylamine; In dichloromethane; at 0℃; for 1.5h;Inert atmosphere; | The reaction was performed in anhydrous conditions under Argon atmosphere. To a solution of <strong>[477293-60-0]tert-butyl (2S,4S)-4-hydroxy-2-methylpyrrolidine-1-carboxylate</strong> (2 g, 9.94 mmol) in DCM (32 mL) cooled at 0 C were added Et3N (2.67 mL, 19.2 mmol) and methanesulfonyl chloride (1.11 mL, 14.4 mmol) and the reaction mixture was stirred at 0 C for 1.5 h. Water (55 mL) was added and the aqueous layer was extracted with DCM (2 x 75 mL). The combined organic layers were washed with HC1 (IN, aq., 50 mL), NaHCCb (sat., aq., 50 mL), dried (NaiSCL), filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, mobile phase: cyclohexane/EtOAc, gradient from 80/20 to 40/60) to afford tert-butyl (2S,4S)-2-methyl-4-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate 131 (1.97 g, 67%) as a colorless oil. |
With triethylamine; In dichloromethane; at 0℃; for 16.0h; | Intermediate 81,1 -dimethylethyl (2S,4S)-2-methyl-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate1 ,1-dimethylethyl (2S,4S)-4-hydroxy-2-methyl-1-pyrrolidinecarboxylate (1.0326 g,5.13 mmol) in DCM (~2 mL) was placed under argon and cooled to 0 0C. To the reaction mixture was added triethylamine (1.2973 g, 12.8 mmol) and methanesulfonyl chloride (1.1753 g, 10.3 mmol). The resultant mixture was stirred for 16 hours and diluted in ether (-100 mL) and water (-60 mL). The aqueous layer was extracted with ethyl acetate (x2). The organic layers were combined, washed with 1 N HCI and NaHCO3 solution, dried on MgSO4 and the solvent evaporated under vacuum to afford the title compound as a yellow liquid (0.6395 g). LC-MS: m/z, 280 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; for 10.0h;Cooling with ice; | Step 2 [0412] Compound iv-8 (2.52g, 7.99mmol) was dissolved in THF (13mL). To the solution was added 1mol/L tetra butylammonium fluoride in THF (15.97mL, 15.97mmol) under ice-cooling, and the mixture was stirred for 10 hours under ice-cooling. To the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed by water and brine, and concentrated in vacuo to give Compound IV-4 (1.6g, Yield 99.5%). [0413] 1H-NMR (CDCl3) δ: 4.42-4.39 (1H, m), 4.02-3.99 (1H, m), 3.49-3.46 (2H, m), 2.11-2.08 (1H, m), 1.76-1.73 (1H, br m), 1.57-1.53 (1H, m), 1.47 (9H, s), 1.24 (3H, t, J = 5.26 Hz). |
With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20℃; for 3.0h; | Intermediate 7 1,1 -dimethylethyl-(2S,4S)-4-hydroxy-2-methyl-1 -pyrrolidinecarboxylateTo 1 ,1-dimethylethyl (2S,4S)-4-[(1 ,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-1- pyrrolidinecarboxylate (0.19201 g, 6.08 mmol) in THF (~1 ml.) was added TBAF (12 ml_,12.17 mmol) under argon. The resultant mixture was stirred at room temperature for 3 hours and purified by flash chromatography (silica gel) with gradient ethyl acetate:hexanes(1 :2) to (2:1 ) to afford the title compound (1.0326 g). LC-MS: m/z, 202 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.387 g | With di-isopropyl azodicarboxylate; In tetrahydrofuran; at 20℃;Cooling with ice; | (Step 1) Synthesis of (2S,4R)-tert-butyl 4-(3-iodo-4-((triphenylphosphoranylidene)amino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpyrrolidine-1-carboxylate tert-Butyl (2S,4S)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylate (0.30 g), triphenylphosphine, and 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine were dissolved in THF (7 mL). To the solution, diisopropyl azodicarboxylate (0.443 mL) was added under ice cooling. The solution was stirred at room temperature for 2 hours, and then, THF (10 mL) was further added thereto. After overnight stirring, triphenylphosphine (0.117 g) and diisopropyl azodicarboxylate (0.089 mL) were further added thereto, and the mixture was further stirred for 1 hour. After concentration of the solution, the residue was suspended in ethyl acetate, and the resulting insoluble matter was removed. Then, the filtrate was concentrated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate) to obtain the title compound (0.387 g) as a colorless amorphous. |
0.387 g | With di-isopropyl azodicarboxylate; In tetrahydrofuran; at 20℃; for 3.0h;Cooling with ice; | tert-Butyl (2S,4S)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylate (0.30 g), triphenylphosphine, and 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine were dissolved in THF (7 mL). To the solution, diisopropyl azodicarboxylate (0.443 mL) was added under ice cooling. The solution was stirred at room temperature for 2 hours, and then, THF (10 mL) was further added thereto. After overnight stirring, triphenylphosphine (0.117 g) and diisopropyl azodicarboxylate (0.089 mL) were further added thereto, and the mixture was further stirred for 1 hour. After concentration of the solution, the residue was suspended in ethyl acetate, and the resulting insoluble matter was removed. Then, the filtrate was concentrated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate) to obtain the title compound (0.387 g) as a colorless amorphous. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 60℃; for 2.0h; | To a solution of 6-fluoropyridin-3-ol (185 mg, 1.64 mmol) and ieri-butyl (2S,4S)-4-hydroxy-2- methylpyrrolidine- 1 -carboxylate (300 mg, 1.49 mmol) in THF (15.0 mL) were added DIAD (603 mg, 2.98 mmol) and triphenylphosphine (782 mg, 2.98 mmol). The mixture was stirred at 60C for 2 hrs. The solvent was removed and the residue was purified by column chromatograph on silica gel eluted (Petroleum ether/EtOAc = 3/1) to provide the title compound (92.0 mg, 21% yield). 1HNMR: (400 MHz, CDCl3) d 7.78-7.79 (m, 1H), 7.27-7.31 (m, 1H), 6.87 (dd, 7=8.8, 3.2 Hz, 1H), 4.82-4.84 (m, 1H), 4.03-4.09 (m, 1H), 3.75-3.76 (m, 1H), 3.62-3.64 (m, 1H), 2.33-2.36 (m, 1H), 1.93-1.96 (m, 1H), 1.47 (s, 9H), 1.32 (d, 7=6.4 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 55℃; for 12.0h; | A mixture of pyrazolo[l,5-a]pyridin-6-ol (240 mg, 1.79 mmol), tert-butyl (2S,4S)-4-hydroxy-2-methylpyrrolidine-l-carboxylate (300 mg, 1.49 mmol), DIAD (603 mg, 2.98 mmol, 585.27 uL) and triphenylphosphine (782 mg, 2.98 mmol) in THF (5 mL) was stirred at 55C for 12 hours. The mixture was evaporated to dryness in vacuo and the residue purified by column chromatography on silica gel (petroleum ether/EtOAc; 10: 1) to give the title compound as a yellow oil (220 mg, 46%). H NMR (400MHz, CDCI3) d: 8.03 (s, 1H), 7.86 (d, 7=2.4 Hz, 1H), 7.45 (d, 7=9.6 Hz, 1H), 6.90 (d, 7=9.6 Hz, 1H), 6.47 (s, 1H), 4.76- 4.79 (m, 1H), 3.95-4.10 (m, 1H), 3.62-3.81 (m, 2H), 2.31-2.37 (m, 1H), 1.97-2.05 (m, 1H), 1.47 (s, 9H), 1.34-1.35 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
180 mg | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 10.0h; | DIAD (241.1 mg, 1.19 mmol) was added to a mixture of 7-chloro-l,8- naphthyridin-2-ol (107.7 mg, 0.596 mmol), tert-butyl (2S,4S)-4-hydroxy-2- methylpyrrolidine-l-carboxylate (120 mg, 0.596 mmol) and PPI13(312.8 mg, 1.19 mmol) in THF (5 mL) and the mixture was stirred at 20C for 10 hours. The mixture was evaporated to dryness in vacuo and the residue was purified by column chromatography on silica gel (petroleum ether/EtOAc; 3: 1) to give the title compound as a white solid (180 mg). LCMS (ESI): [M+H] = 364.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 40℃; | To a solution of triphenylphosphine (350 mg, 1.33 mmol) in THF (6.0 mL) was dropwise added DIAD (1.33 mmol, 262 uL). Light yellow ppt formedafter 5min. The reaction mixture was stirred at rt for 30min. A solution of tert-butyl ( 2S,4S )- 4-hydro xy-2-methyl-pyrrolidine- l-carboxy late (223 mg, 1.11 mmol) in THF (2.0 mL) and added dropwise to the reaction, followed by a mixture of 2-methyloxazolo[4,5-b]pyridin-6-ol (200 mg, 1.33 mmol) in THF (2.0 mL). The reaction was then stirred at 40C overnight. The reaction mixture was concentrated down and the crude was purified by chromatography on silica gel (0-60%EtOAc-EtOH 3: 1 with 2% NH40H in heptane) to give the title compound (252 mg, 68% yield). LCMS (ESI): [M+H] 334;8.17 (d, / = 2.51 Hz, 1H), 7.73 (d, / = 2.51 Hz, 1H), 5.05-5.13 (m, 1H), 3.99-4.08 (m, 1H), 3.78 (dd, / = 5.02, 12.55 Hz, 1H), 3.57-3.66 (m, 1H), 2.67 (s, 3H), 2.44 (br s, 1H), 1.94-2.02 (m, 1H), 1.48 (s, 9H), 1.35 (d, / = 6.27 Hz, 3H). |
Tags: 477293-60-0 synthesis path| 477293-60-0 SDS| 477293-60-0 COA| 477293-60-0 purity| 477293-60-0 application| 477293-60-0 NMR| 477293-60-0 COA| 477293-60-0 structure
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H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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