Structure of 871022-62-7
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CAS No. : | 871022-62-7 |
Formula : | C11H21FN2O2 |
M.W : | 232.30 |
SMILES Code : | O=C(OC(C)(C)C)NCC1(F)CCNCC1 |
MDL No. : | MFCD11973738 |
InChI Key : | QBENUNRDGNUPQJ-UHFFFAOYSA-N |
Pubchem ID : | 53415226 |
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 |
---|---|---|
58% | With sodium hydroxide; In ethanol; water; for 15h;Heating / reflux; | A mixture of N-benzoyl-4-tert-butoxycarbonylaminomethyl-4-fluoropiperidine (step 3 of Example 15) (4.42 g, 13.1 mmol), NaOH (2.62 g, 65.5 mmol), H2O (9.00 mL) and ethanol (90.0 mL) was refluxed for 15 h and concentrated in vacuo. To the resulting residue were added water and chloroform. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. Recrystallization of the resulting solid with hexane-CH2Cl2 afforded a colorless solid 1.77 g (58%) as the titled compound. MS (ESI) m/z: 233 (M+H)+. 1H NMR (CDCl3) d 4.93 (1H, m), 3.30 (2H, dd, J=21.5, 6.3 Hz), 2.91 (4H, m), 1.88-1.34 (4H, m), 1.45 (9H, s), The signal which correspond to amino group was not observed. |
58% | With sodium hydroxide; ethanol; water; for 15h;Heating / reflux; | Step 2. 4-tert-Butoxycarbonylaminomethyl-4-fluoropiperidine; A mixture of N-benzoyl-4-tert-butoxycarbonylaminomethyl-4-fluoro piperidine (step 3 of Example 15) (4.42 g, 13.1 mmol), NaOH (2.62 g, 65.5 mmol), H2O (9.00 mL) and ethanol (90.0 mL) was refluxed for 15 h and concentrated in vacuo. To the resulting residue were added water and chloroform. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. Recrystallization of the resulting solid with hexane-CH2Cl2 afforded colorless solid 1.77 g (58%) as the title compound. MS (ESI) m/z: 233 (M+H)+. 1H NMR (CDCl3) delta 4.93 (1H, m), 3.30 (2H, dd, J=21.5, 6.3 Hz), 2.91 (4H, m), 1.88-1.34 (4H, m), 1.45 (9 H, s). A signal due to NH and was not observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
285 mg | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 150℃; for 16h; | [00344] Step a: A mixture of 3-((3-amino-2-chlorophenyl)thio)-6-chloropyrazin-2- amine (200 mg, 0.696 mmol) and <strong>[871022-62-7]tert-butyl ((4-fluoropiperidin-4-yl)methyl)carbamate</strong> (243 mg, 1.045 mmol), and DIPEA (0.6 mL, 3.48 mmol) in NMP (2 mL) was stirred for 16 h at 150 C. After cooling to RT, the reaction mixture was poured into a separation funnel containing brine and it was extracted with EtOAc (3 x 5 mL). The combined organic phases were dried over MgS04, filtered and the volatiles were removed under reduced pressure. The resulting residue was purified by silica chromatography (0 to 10% gradient of MeOH DCM) to give tert-butyl ((l-(6-amino-5- ((3-amino-2-chlorophenyl)thio)pyrazin-2-yl)-4-fluoropiperidin-4-yl)methyl)carbamate (285 mg, 0.590 mmol). MS m/z 483.1 (M+H)+. |
285 mg | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 15℃; for 16h; | A mixture of 3-((3-amino-2-chlorophenyl)thio)-6-chloropyrazin-2-amine (200 mg, 0.696 mmol) and <strong>[871022-62-7]tert-butyl ((4-fluoropiperidin-4-yl)methyl)carbamate</strong> (243 mg, 1.045 mmol), and DIPEA (0.6 mE, 3.48 mmol) in NMP (2 mE) was stirred for 16 h at 1500 C. After cooling to RT, the reaction mixture was poured into a separation flannel containing brine and it was extracted with EtOAc (3x5 mE). The combined organic phases were dried over Mg504, filtered and the volatiles were removed under reduced pressure. The resulting residue was purified by silica chromatography (0 to 10% gradient of MeOH/DCM) to give tert-butyl ((1 -(6-amino-5-((3-amino-2-chlorophenyl)thio) pyrazin-2-yl)-4-fluoropiperidin-4-yl)methyl)carbamate (285 mg, 0.590 mmol). MS m/z 483.1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.54% | With sodium hydrogencarbonate; In tetrahydrofuran; water; at 15℃; for 14h;Inert atmosphere; | The mixture of tert-butyl N-[(4-fluoro-4- piperidyl)methyl]carbamate (150.00 mg, 645.74 //mol, 1.00 eq) and 9H-fluoren-9-ylmethyl carbonochloridate (250.58 mg, 968.61 //mol, 1.50 eq) were dissolved in THF (20.00 mP) and H20 (4.00 mP), to which NaHCCp (162.75 mg, 1.94 mmol, 75.35 //F, 3.00 eq) was added in one portion. The resulting mixture was then stirred at 15 C for 14 h. The reacting solution was diluted with water (50 mP) and extracted with EA (50 mP x 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (pure PE to PE:EA = 5:1) to afford 9H-fluoren-9-ylmethyl 4-[(tert- butoxycarbonylamino)methyl]-4-fluoro-piperidine-l -carboxylate (163.00 mg, 358.61 //mol, 55.54% yield) as an off-white solid. The product was confirmed by PC-MS and used directly for the next step without further purification |
With sodium hydrogencarbonate; In tetrahydrofuran; water; at 15℃; for 14h; | The mixture of tert-butyl N-[(4-fluoro-4- piperidyl)methyl]carbamate (150.00 mg, 645.74 mupiiotaomicron, 1.00 eq) and 9H-fluoren-9-ylmethyl carbonochloridate (250.58 mg, 968.61 mupiiotaomicron, 1.50 eq) were dissolved in THF (20.00 mL) and H20 (4.00 mL), to which NaHC03 (162.75 mg, 1.94 mmol, 75.35 /L, 3.00 eq) was added in one portion. The resulting mixture was then stirred at 15 C for 14 h. The reacting solution was diluted with water (50 mL) and extracted with EA (50 mL x 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (pure PE to PE:EA = 5: 1) to afford 9H-fluoren-9-ylmethyl 4-[(tert- butoxycarbonylamino)methyl]-4-fluoro-piperidine- l -carboxylate (163.00 mg, 358.61 mupiiotaomicron, 55.54% yield) as an off-white solid. The product was confirmed by LC-MS and used directly for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.91% | A mixture of <strong>[871022-62-7]tert-butyl ((4-fluoropiperidin-4-yl)methyl)carbamate</strong> (330.00 mg, 1.42 mmol, 1.00 eq) and aq. HCHO (37%, 172.88 mg, 2.13 mmol, 158.61 /L, 1.50 eq) in CH3CN (10.00 mL) was stirred at 30 C for 30 min, and then NaBH3CN (178.47 mg, 2.84 mmol, (0315) 2.00 eq) and AcOH (104.88 mg, 1.75 mmol, 99.89 /L, 1.23 eq) were added in portions. The mixture was stirred at 15 C for 13.5 h. The reacting solution was diluted with water (100 mL) and extracted with EA (100 mL x 4). The combined organic layers were concentrated under reduced pressure and purified by silica gel chromatography (PE:EA = 1 : 1 to (0316) EA:MeOH = 5: 1) to afford tert-butyl ((4-fluoro- l-methylpiperidin-4-yl)methyl)carbamate (290.00 mg, 1.18 mmol, 82.91% yield) as a colorless oil, which was confirmed by LC-MS. | |
82.91% | A mixture of <strong>[871022-62-7]tert-butyl ((4-fluoropiperidin-4-yl)methyl)carbamate</strong> (330.00 mg, 1.42 mmol, 1.00 eq) and aq. HCHO (37%, 172.88 mg, 2.13 mmol, 158.61 //L, 1.50 eq) in CH3CN (10.00 mL) was stirred at 30 C for 30 min, and then NaBH3CN (178.47 mg, 2.84 mmol, 2.00 eq) and AcOH (104.88 mg, 1.75 mmol, 99.89 //L, 1.23 eq) were added in portions. The mixture was stirred at 15 C for 13.5 h. The reacting solution was diluted with water (100 mL) and extracted with EA (100 mL x 4). The combined organic layers were concentrated under reduced pressure and purified by silica gel chromatography (PE:EA = 1:1 to EA:MeOH = 5:1) to afford tert-butyl ((4-fluoro-l-methylpiperidin-4-yl)methyl)carbamate (290.00 mg, 1.18 mmol, 82.91% yield) as a colorless oil, which was confirmed by LC-MS |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
718 mg | With palladium 10% on activated carbon; hydrogen; In tetrahydrofuran; methanol; for 8h; | To a solution of benzyl 4-(((tert-butoxycarbonyl)amino)methyl)-4-fluoropiperidine-1-carboxylate (1.10 g, 3.0 mmol) in THF (15 mL) and MeOH (15 mL) was added 10% palladium on carbon (46.7% wet, 345 mg, 0.15 mmol) and stirred for 8 h under hydrogen atmosphere. After the reaction mixture was filtered by celite, the solvent was removed at reduced pressure to give the title compound (718 mg). MS: [M+H] + = 233. |