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Structure of 870812-94-5

Chemical Structure| 870812-94-5

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Product Details of [ 870812-94-5 ]

CAS No. :870812-94-5
Formula : C14H20N2O2S
M.W : 280.39
SMILES Code : O=C(N1CCOCC1)C[C@@H](N)CSC2=CC=CC=C2
MDL No. :MFCD26967948

Safety of [ 870812-94-5 ]

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

Application In Synthesis of [ 870812-94-5 ]

* 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 [ 870812-94-5 ]

[ 870812-94-5 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 870812-93-4 ]
  • [ 870812-94-5 ]
YieldReaction ConditionsOperation in experiment
~ 100% A suspension of (R)-benzyl 4-morpholino-4-oxo-1-(phenylthio)butan-2-ylcarbamate (INTERMEDIATE 71, 25 g, 60 mmol) in 40% HBr in acetic acid (500 ml) was stirred at room temperature for 50 hrs. The reaction mixture became homogeneous during this time. The reaction mixture was concentrated to dryness, diluted with water (400 ml) and 5% aq. HCl (200 ml) and washed with diethyl ether (3*100 ml). The aqueous phase was brought to pH ~8-9 with solid Na2CO3 and extracted vigorously with CH2Cl2 (5*). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give the title product (16.9 g, yield: almost quantitative), which was used in the preparation of Intermediate 73 without further purification. 1H-NMR (300 MHz, DMSO-d6) delta 2.42 (dd, 1H), 2.57 (dd, 1H), 2.77 (m 3H), 2.97-3.02 (m, 1H), 3.06-3.14 (m, 1H), 3.37 (m, 2H), 3.59 (m, 6H), 7.18 (t, 1H), 7.27 (d, 2H), 7.37 (d, 2H). LCMS: (ESI) m/z 281 (M+H)+.
98% With hydrogen bromide; acetic acid; at 20℃; for 24h; EXAMPLE 21E (1R)-3-(4-morpholinyl)-3-oxo-1-((phenylsulfanyl)methyl)propylamine A solution of EXAMPLE 21D (18.0 g, ~39 mmol) in 30% HBr in acetic acid (250 mL) was stirred for 24 hours at room temperature, concentrated to half its volume, poured into 1M HCl (300 mL), washed with diethyl ether (3*200 mL), and extracted with 1M HCl (150 mL). The combined aqueous layers were cooled to 0 C., adjusted to pH ~12 with solid KOH, and extracted with dichloromethane (5*100 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated to provide the desired product (10.8 g, 98%).
93% A solution of intermediate g 4g, 9.7 mmol) in 30% HBr in acetic acid (40 ml) was stirred for 24 hours at room temperature, concentrated to half its volume, poured into IM HCl (40 ml) . The combined aqueous layers were washed with ether (3X50 mL) and cooled to 0 0C, adjusted to 12 with solid KOH, and extracted with CH2Cl2. The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated to provide the desired product h (2.5g, yield:93%). MS (ESI) m/e (M+H^):281; 1H- NMR (CDCl3, 400 MHz): delta 7.31 (d, J= 8.0 Hz, 2H), 7.21 (t, J= 7.6 Hz, 2H), 7.12 (t, J = 7.6 Hz, IH), 3.58-3.50 (m, 6H), 3.38-3.30 (m, 3H), 3.05 (m, IH), 2.87 (m, IH), 2.50 (m, IH), 2.28 (m, IH).
  • 2
  • [ 870812-94-5 ]
  • [ 870812-95-6 ]
YieldReaction ConditionsOperation in experiment
73% EXAMPLE 21F (1R)-3-(4-morpholinyl)-1-((phenylsulfanyl)methyl)propylamine A solution of EXAMPLE 21E (6.00 g, 21.4 mmol) in THF (80 mL) was heated to 55 C. and treated dropwise with a solution of 1M borane in THF (85 mL, 85.0 mmol) over a 1 hour period. The resulting reaction mixture was stirred at 55 C. for 18 hours, cooled to 0 C., treated dropwise with methanol (10 mL), treated with 150 mL additional methanol, and concentrated. The crude residue was dissolved in methanol (70 mL), treated with methanolic HCl (100 mL), and heated to reflux for 24 hours. The mixture was allowed to cool to room temperature, concentrated, diluted with 2M NaOH (200 mL), and extracted with ethyl acetate (3*250 mL). The combined extracts were washed with 1M NaOH and brine, dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography eluding with 5% triethylamine/10% methanol/0% acetonitrile/ethyl acetate to provide the desired product (3.45 g, 73%).
  • 3
  • [ 406233-31-6 ]
  • [ 870812-94-5 ]
  • [ 872866-27-8 ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine; In 1,4-dioxane;Heating / reflux; A solution of intermediate h (2.5g, 8.9 mmol) and intermediate i (1.96g, 8.9 mmol) in 100 ml of dioxane was treated with Et3N (1.8g, 17.8mmol) heated to reflux overnight, concentrated, and purified by silica gel chromatography eluting with PE:EA=(1 :1) to provide the desired product] (3.6g, yield:84%) . MS (ESI) m/e (M-I-H+): 481; 1H-NMR (DMSO, 400 MHz): delta 8.66 (d, J = 9.6 Hz, IH), 8.35 (s, IH), 7.69 (d, J = 8.8 Hz, IH), <n="35"/>7.41-7.21 (m, 5H), 7.15 (m, IH), 7.05 (d, J= 9.6 Hz, IH), 4.39 (m, IH), 3.52-3.36 (m, 10H), 2.96 (m, IH), 2.76 (m, IH).
83% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃;Inert atmosphere; To a solution of <strong>[870812-94-5](R)-3-amino-1-morpholino-4-(phenylthio)butan-1-one</strong> (INTERMEDIATE 72, 375.5 mg, 1.34 mmol) in DMF (2.5 ml) and DIPEA (1.20 Ml, 6.87 mmol) was added 4-fluoro-3-nitrobenzenesulfonamide (INTERMEDIATE 18, 325.8 mg, 1.48 mmol), and the resulting dark solution was stirred at 50 C. overnight, under a nitrogen atmosphere. The mixture was diluted with EtOAc (50 ml) and washed with water and brine (30 ml each), dried (Na2SO4), filtered, and evaporated under reduced pressure. The concentrate was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0?100% EtOAc/DCM) to give the title product (532.5 mg, yield: 83%).1H NMR (400 MHz, DICHLOROMETHANE-d2) delta ppm 2.72 (dd, 1H) 2.85-2.97 (m, 1H) 3.25-3.44 (m, 4H) 3.48-3.68 (m, 6H) 4.26-4.39 (m, 1H) 4.96 (s, 2H) 6.76 (d, 1H) 7.23-7.37 (m, 3H) 7.37-7.46 (m, 2H) 7.74 (dd, 1H) 8.61 (d, 1H) 9.08 (d, 1H).LCMS: (ESI) m/z 481 [M+H]+.Optical Rotation:Concentration: 0.1 g/dLLamp: SodiumWavelength: 589 nmTemperature: 20 C.Path length: 10 cm Cell volume: 1 ml Solvent: CH2Cl2 [alpha]=-212
  • 4
  • [ 870812-94-5 ]
  • [ 1027345-08-9 ]
  • [ 1027345-11-4 ]
YieldReaction ConditionsOperation in experiment
77% With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 50℃; for 4h; Example 4 4-((R)-3-morpholin-4-yl-l-phenylsulfanylmethyl-propylamino)-3- trifluoromethanesulfonyl-benzenesulfonamideThe sulfonamide a (1.63 mmol), amine b (1.63 mmol) and diisopropylethylamine (3.26 mmol) in dioxane was stirred at 50 0C for 4 h. The mixture was treated 10% sodium hydrogen carbonate solution (30 ml) and the aqueous solution was then extracted with ethyl acetate (2 x 20 ml). The organic layer was dried (MgSO4) and concentrated in vacuo. The resulting residue was applied to silica chromatography gradient eluting with 100% dichloromethane to 5% methanol/dichloromethane to yield 4-((i?)-3- morpholin-4-yl-3 -oxo- 1 -phenylsulfanylmethyl-propylamino)-3 - trifluoromethanesulfonyl-benzenesulfonamide c as a white solid (77%). 1H NMR (300 MHz, DMSO) delta 7.97 (IH, d, J 2.2 Hz), 7.83 (IH, dd, J 9.2 and 2.2 Hz), 7.39-7.27 (7H, m, ArH), 7.21 (IH, tt, J 6.8 and 1.65 Hz), 7.00 (IH, bd, J 9.5 Hz), 4.38-4.25 (IH, m), 3.40-3.27 (2H, m), 3.50-3.37 (1OH, m), 2.94 (IH, dd, J 16.8 and 5.8 Hz), 2.71 (IH, dd, J 16.8 and 5.1 Hz). LCMS- rt 7.17, M+H 568.
  • 5
  • [ 406233-31-6 ]
  • [ 870812-94-5 ]
  • [ 872866-28-9 ]
  • 6
  • [ 870812-92-3 ]
  • [ 870812-94-5 ]
 

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