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Chemical Structure| 1174020-25-7

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Product Details of [ 1174020-25-7 ]

CAS No. :1174020-25-7
Formula : C14H16N2O4
M.W : 276.29
SMILES Code : O=C([C@H](CC[C@@]1([H])N2OCC3=CC=CC=C3)[N@@](C1)C2=O)O
MDL No. :MFCD28502389
InChI Key :UMHGLONVYIYIOU-NEPJUHHUSA-N
Pubchem ID :57389355

Safety of [ 1174020-25-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 1174020-25-7 ]

* 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.

  • Downstream synthetic route of [ 1174020-25-7 ]

[ 1174020-25-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 75051-55-7 ]
  • [ 1174020-25-7 ]
  • [ 1452466-19-1 ]
YieldReaction ConditionsOperation in experiment
89% With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; Step 1. tert-Butyl {2-[([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)oxy]ethyl}carbamate (42) To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.150 g, 0.543 mmol, US 2005/20572 A1) in DCM (4.0 mL) was added tert-butyl[2-(aminooxy)ethyl]carbamate 41 (0.143 g, 0.814 mmol, US 2005/54701 A1), 1-hydroxybenzotriazole (0.110 g, 0.814 mmol), 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.156 g, 0.814 mmol) and DMAP (0.100 g, 0.814 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue which was subjected to chromatography to give 42 (0.21 g, 89%) as a white foam. 1H NMR (400 MHz, CDCl3): δ 1.44 (9H, s), 1.65 (1H, m), 1.93 (2H, m), 2.31 (1H, m), 2.76 (1H, d, J=12 Hz), 3.04 (1H, d, J=11.2 Hz), 3.26 (2H, m), 3.38 (1H, m), 3.91 (2H, m), 3.98 (1H, d, J=12 Hz), 4.89 (1H, d, J=11.2 Hz), 5.07 (1H, d, J=11.2 Hz), 5.41 (1H, br s), 7.41 (5H, m), 9.30 (1H, br s). MS (ES+): m/z [M+H]+ calcd for C21H31N4O6: 435.22. Found: 435.02.
89% With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.1.50 g, 0.543 mmol, US 2005/20572 A1 ) in DCM (4.0 mL) was added tert-butyl [2-(aminooxy)ethyl]carbamate 41 (0.143 g, 0.814 mmol, US 2005/54701 A1 ), 1-hydroxybenzotriazole (0.1 10 g, 0.814 mmol), 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.156 g, 0.814 mmol) and DMAP (0.100 g, 0.814 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue which was subjected to chromatography to give 42 (0.21 g, 89 %) as a white foam. 1H NMR (400 MHz, CDCl3): δ 1.44 (9H, s), 1.65 (1 H, m), 1.93 (2H, m), 2.31 (1 H, m), 2.76 (1 H, d, J = 12 Hz), 3.04 (1 H, d, J = 11.2 Hz), 3.26 (2H, m), 3.38 (1 H, m), 3.91 (2H, m), 3.98 (1 H, d, J = 12 Hz), 4.89 (1 H, d, J = 11.2 Hz), 5.07 (1 H, d, J = 1 1.2 Hz), 5.41 (1 H, br s), 7.41 (5H, m), 9.30 (1 H, br s). MS (ES+): m/z [M+H]+ calcd for C21H31N406: 435.22. Found: 435.02.
84% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; Step 1 tert-Butyl {2-[([(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)oxy]ethyl}carbamate [0439] methylene chloride (35 mL) were added triethylamine (2.71 mL), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.41 g), 1-hydroxybenzotriazole · monohydrate (1.15 g), and tert-butyl 2-(aminooxy)ethylcarbamate (1.12 g) described in Reference Example 9, followed by agitating at room temperature overnight. To the residue resulting from concentrating the reaction solution under reduced pressure was added water, followed by extracting with ethyl acetate. The resulting organic layer was washed with 0.1M hydrochloric acid, saturated sodium bicarbonate aqueous solution, and a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtrated, and concentrated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 8/2-0/10) to afford 1.77 g of the title compound (yield 84%). [α]D20 -0.08 (c 0.29, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 1.56-1.70 (m, 1H), 1.90-2.09 (m, 2H), 2.25-2.38 (m, 1H), 2.76 (d, J = 11.6 Hz, 1H), 3.03 (br d, J = 11.6 Hz, 1H), 3.24-3.47 (m, 3H), 3.84-4.01 (m, 3H), 4.90 (d, J = 11.6 Hz, 1H), 5.05 (d, J = 11.6 Hz, 1H), 5.44 (br s, 1H), 7.34-7.48 (m, 5H), 9.37 (br s, 1H); MS m/z 435 [M+H]+; enantiomeric excess 99.9% ee or more (CHIRALPAK AD-H, 4.6 x 150mm, hexane/ethanol = 2/1, UV 210 nm, flow rate 1 mL/min., retention time 4.95 min. (2R,5S), 6.70 min. (2S,5R).
79% With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid (20a) (3.19 g, 11.6 mmol), <strong>[75051-55-7]tert-butyl (2-(aminooxy)ethyl)carbamate</strong> (27b) (2.06 g, 11.7 mmol) in DCM (20 mL) was added HATU (4.39 g, 11.6 mmol) and DIPEA (2.02 mL, 11.6 mmol). The reaction was stirred at room temperature overnight. The mixture was washed with saturated NH4Cl solution, water and brine. The organic layer was dried with anhydrous Na2SO4, filtered, and concentrated under vacuum to give a crude residue. The residue was purified by silica gel column chromatography using EtOAc/ hexane (1:1 to 3:1) as an eluent to give the product (27c) as a white paste (4.0 g, yield 79%). 1H NMR (300 MHz, CDCl3): δ 9.46 (br, s, 1H), 7.26-7.43 (m, 5H), 5.46 (t, 1H), 4.80-5.10 (dd, 2H, J=11.1 Hz), 2.75-3.97 (m, 8H), 1.61-2.33 (m, 4H), 1.43 (t, 9H). MS (ESI) C21H30N4O6=435 (M+1)+.
76% 10335] A solution of (2S,5R)-6-(benzyloxy)-7-oxo- 1 ,6-di- azabicyclo[3.2. l]octane-2-carboxylic acid (4.80 kg, 17.373 mol) in dehydrated ethyl acetate (62 L) was cooled to -30 C., isobutyl chloroformate (2.52 kg) and triethylamine (1.85 kg) were sequentially added dropwise, followed by stirring at -30 C. for 15 minutes. To the reaction solution was added a solution of tert-butyl 2-(aminooxy)ethylcarbamate in dehydrated ethyl acetate (15 wt %, 23.45 kg) over 30 minutes (washed with 2 L of dehydrated ethyl acetate), and the temperature was elevated to 0 C. over 1 hour. The mixture was washed sequentially with 8% citric acid (65 L), 5% sodium bicarbonate (60 L), and water (60 L), and concentrated to 24 L. To the concentrate was added ethyl acetate (24 L), and the mixture was substitution-concentrated twice to 24 L. To the resulting concentrate was added ethyl acetate (29 L) and hexane (72 L), followed by stirring overnight. To the mixture was added dropwise hexane (82 L), followed by stirring for 2 hours. The precipitated crystals were filtered, washed with hexane, and dried in vacuo to afford 5.51 kg of the title compound (yield 76%). Instrumental data were consistent with those of ReferenceExample 5, Step 1.
76% A solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid (4.80 kg, 17.373 mol) in dehydrated ethyl acetate (62 L) was cooled to -30 C., to which isobutyl chloroformate (2.52 kg) and then triethylamine (1.85 kg) were added dropwise, and was stirred at -30 C. for 15 minutes. To the reaction mixture was added a solution of tert-butyl 2-(aminooxy)ethylcarbamate in dehydrated ethyl acetate (15 wt %, 23.45 kg) over 30 minutes (the residue washed with 2 L of dehydrated ethyl acetate), and the temperature was raised to 0 C. over 1 hour. The mixture was washed sequentially with an 8% solution of citric acid (65 L), a 5% solution of sodium bicarbonate (60 L), and water (60 L), and concentrated to 24 L. A step of adding ethyl acetate (24 L) to the concentrated mixture, followed by concentration to 24 L for solvent displacement was performed twice, and to the resultant concentrated solution, ethyl acetate (29 L) and hexane (72 L) were added, and stirred overnight. To the mixture, hexane (82 L) was added dropwise and stirred tier 2 hours. The precipitated crystals were separated by filtration, washed with hexane, and vacuum-dried to give 5.51 kg of the title compound (yield 76%). HPLC:COSMOSIL 5C18 MS-II 4.6*150 mm, 33.3 mM phosphate buffer/MeCN=50/50, 1.0 mL/min, UV 210 nm, RT 4.4 min; 1H NMR (400 MHz, CDCl) δ 1.44 (s, 9H), 1.56-1.70 (m, 1H), 1.90-2.09 (m, 2H), 2.25-2.38 (m, 1H), 2.76 (d, J=11.6 Hz, 1H), 3.03 (br.d., J=11.6 Hz, 1H), 3.24-3.47 (m, 3H), 3.84-4.01 (m, 3H), 4.90 (d, J=11.6 Hz, 1H), 5.05 (d, J=11.6 Hz, 1H), 5.44 (br.s., 1H), 7.34-7.48 (m, 5H), 9.37 (br.s., 1H); MS m/z 435 [M+H]+.
74% A solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid (4.30 g, 15.56 mmol) in dehydrated ethyl acetate (47 mL) was cooled to -30 C., and isobutyl chloroformate (2.17 g, washed with dehydrated ethyl acetate 1 mL) and triethylamine (1.61 g, washed with 1 mL of dehydrated ethyl acetate) were sequentially added dropwise at -30 C., followed by stirring for 1 hour. To the reaction solution was added a solution of tert-butyl 2-(aminooxy)ethylcarbamate (3.21 g) in dehydrated ethyl acetate (4 mL) (washed with 1 mL of dehydrated ethyl acetate), and the temperature of the mixture was elevated to 0 C. over 1.5 hours, followed by stirring overnight. The mixture was washed sequentially with 8% aqueous citric acid (56 mL), saturated sodium bicarbonate (40 mL), and saturated brine (40 mL), and dried over anhydrous magnesium sulfate. The mixture was then filtered, concentrated to 5 mL, and further substitution-concentrated with ethanol (10 mL) to 6 mL. To the resulting solution was added ethanol (3 mL) and hexane (8 mL), and the mixture was ice-cooled and seeded with crystals, followed by stirring for 15 minutes. To the mixture was added dropwise hexane (75 mL) over 2 hours, followed by stirring overnight. The crystalline material was filtered, washed with hexane, and dried in vacuo to afford 5.49 g of the title compound (net 4.98 g, yield 74%).
73% To a clear solution of sodium (2S,5R)-6-(benzyloxy)-7 -oxo- 1 ,6-diazabicyclo [3.2.1 ]octane-2- carboxylate (II, 42.67 g, 0.143 mol; prepared according to the procedure disclosed in hidian Patent Application No. 6991MUM/2013) in water (426 ml) was added EDC.HC1 (67.1 g, 0.349 mol) at 15Cunder stirring. After 10 minutes, a solution of tert-butyl-[2-(aminooxy) ethyl]carbamate (III, 28.Og, 0.159 mol; prepared as per the literature procedure depicted in Scheme 2) in dimethylformamide (56 ml) was added drop wise at 10C under continuous stirring. The temperature of the reaction mass was allowed to warm to 25C and then HOBt (21.5g, 0.159 mol) was added in small portions over a period of 15 minutes and the resulting mixture was further stirred at room temperature for 16 hours. The reaction was continuously monitored using thin layer chromatography using mixture of acetone and hexane (35:65) as solvent system. After completion of reaction, the resulting mixture was filtered and the residue was washed with water (130 ml). The obtained white residue was suspended in water (130 ml) and the mixture stined at 50C for 3 hours. The resulting suspension was filtered, the residue dried under reduced pressure to obtain 51 g of (2S ,5R)-N-(2-Boc-aminoethoxy)-6-(benzyloxy)-7-oxo- 1,6- diaza-bicyclo [3.2.1 ]octane-2-carboxamide (IV) as off white solid in 73% yield.Analysis:Mass: 433.4 (M-1); for Molecular Weight of 434.5 and Molecular Formula of C21H30N4061H-NMR (400MHz, CDC13): 5 9.32 (br s, 1H), 7.41-7.26(m,5H), 5.41(br s, 1H), 5.06-4.88(dd,2H), 3.98-3.96(d,1H), 3.91-3.90(m,2H), 3.39(m, 1H), 3.31-3.26(m, 2H), 3.04-3.01(d,1H), 2.77-2.74(d,1H), 2.33-2.28(m, 1H), 2.03-1.93(m, 2H), 1.67-1.64(m, 1H), 1.44(s, 9H); Purity as determined by HPLC: 99.4%.
The (2S, 5R) -6- (benzyloxy) -7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylic acid (4.30g, 15.56mmol) dehydrated ethyl acetate (47mL) was cooled to -30 , successively added isobutylchloroformate (2.17g, dehydrated and washed with ethyl acetate 1mL), triethylamine (1.61g, dehydrated and washed with ethyl acetate 1mL), in stirred at -30 1 hour. Was added to the reaction mixture2- (aminooxy) ethylcarbamateTert-butyl ester (3.21 g) in dehydrated ethyl acetate (4mL) solution of (ethyl acetate, washed with dehydrated 1mL), spending 1.5 hours warmed to 0 , and further stirred overnight. The mixture was washed with 8% aqueous citric acid (56mL), saturated aqueous sodium bicarbonate solution (40 mL), saturated brine (40 mL) successively, dried over anhydrous magnesium sulfate, filtered, and concentrated to 5mL, further washed with ethanol (10 mL) replacement concentrate to 6mL. Was added ethanol (3mL) in the resulting solution, hexane (8mL), cooled on ice, seeded and stirred for 15 minutes. It takes two hours the mixture was added dropwise hexane (75mL), stirred overnight. Precipitated crystal was filtered out, washed with hexane, and dried in vacuo to give 5.49 g of the title compound (4.98g essence, yield 74%).

  • 2
  • [ 118753-66-5 ]
  • [ 1174020-25-7 ]
  • [ 1452467-34-3 ]
YieldReaction ConditionsOperation in experiment
88% With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; Step 1. tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate (206) To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added <strong>[118753-66-5]tert-butyl 4-aminopiperazine-1-carboxylate</strong> 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4-dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1H, m), 1.95 (2H, m), 2.38 (1H, m), 2.70 (1H, d, J=12.0 Hz), 2.76 (4H, m), 2.99 (1H, d, J=12.0 Hz), 3.30 (1H, m), 3.57 (4H, m), 3.89 (1H, d, J=8.0 Hz), 4.90 (1H, d, J=11.6 Hz), 5.04 (1H, d, J=12.0 Hz), 7.21 (5H, m), 8.90 (1H, br s).
88% With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added te/f-butyl 4-aminopiperazine-1-carboxylate 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4- dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give terf-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo- 1 ,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1 H, m), 1.95 (2H, m), 2.38 (1 H, m), 2.70 (1 H, d, J = 12.0Hz), 2.76 (4H, m), 2.99(1H, d, J = 12.0 Hz), 3.30 (1 H, m), 3.57 (4H, m), 3.89 (1 H, d, J = 8.0 Hz), 4.90 (1H, d, J = 11.6 Hz), 5.04 (1 H, d, J = 12.0 Hz), 7.21 (5H, m), 8.90 (1 H, br s).
  • 3
  • [ 1174020-25-7 ]
  • [ 20605-41-8 ]
  • [ 1452467-43-4 ]
YieldReaction ConditionsOperation in experiment
82% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; Step 1. (2S,5R)-6-(benzyloxy)-N'-(methoxyacetyl)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide (219) To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.250 g, 0.905 mmol) in DCM (15.0 mL) were added <strong>[20605-41-8]2-<strong>[20605-41-8]methoxyacetohydrazide</strong></strong> 218 (0.141 g, 1.358 mmol), 1-hydroxybenzotriazole (0.186 g, 1.358 mmol) and 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.260 g, 1.358 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue, which was subjected to chromatography to give 219 (0.27 g, 82percent) as a white foam. 1H NMR (400 MHz, CDCl3): 1.60 (1H, m), 1.99 (2H, m), 2.40 (1H, m), 3.10 (2H, s), 3.32 (1H, s), 3.46 (3H, s), 3.04 (2H, s), 4.06 (1H, m), 4.90 (1H, d, J=11.2 Hz), 5.05 (1H, d. J=11.2 Hz), 7.42 (5H, m). MS (ES-) m/z; [M-H]- calcd for C10H15N4O6: 347.2. Found: 361.1.
82% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.250 g, 0.905 mmol) in DCM (15.0 ml_) were added <strong>[20605-41-8]2-<strong>[20605-41-8]methoxyacetohydrazide</strong></strong> 218 (0.141 g, 1.358 mmol), 1-hydroxybenzotriazole (0.186 g, 1.358 mmol) and 1 -ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.260 g, 1.358 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue, which was subjected to chromatography to give 219 (0.27 g, 82 percent) as a white foam. 1H NMR (400 MHz, CDCI3): delta 1.60 (1 H, m), 1.99 (2H, m), 2.40 (1 H, m), 3.10 (2H, s), 3.32 (1 H, s), 3.46 (3H, s), 3.04 (2H, s), 4.06 (1 H, m), 4.90 (1 H, d, J = 1 1.2 Hz), 5.05 (1 H, d, J = 1 1.2 Hz), 7.42 (5H, m). MS (ES-) m/z: [M-H]- calcd for C10H15N4O6: 347.2. Found: 361.1
 

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