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Chemical Structure| 330194-76-8 Chemical Structure| 330194-76-8

Structure of 330194-76-8

Chemical Structure| 330194-76-8

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Product Details of [ 330194-76-8 ]

CAS No. :330194-76-8
Formula : C8H16N2O2
M.W : 172.23
SMILES Code : NCC(NCC1)CC21OCCO2
MDL No. :MFCD20664342

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Application In Synthesis of [ 330194-76-8 ]

* 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 [ 330194-76-8 ]

[ 330194-76-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 330194-76-8 ]
  • [ 26638-43-7 ]
  • [ 330194-77-9 ]
YieldReaction ConditionsOperation in experiment
51% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 25℃; for 24h; To a solution of 2-aminomethyl-4-(2-spiro[1,3]dioxolane)-piperidine (193 mg, 1.12 mmol) and diisopropyl ethylamine (0.46 ml, 2.55 mmol) in acetonitrile (10 ml) cooled to 0 C was added 2-chlorosulfonyl-benzoic acid methyl ester (278 mg. 1.18 mmol). The solution was stirred at 25 C for 24 hours. Solvent was removed in vacuo and the residue was chromatographed using a mixture of ethyl acetate/hexane (1:3) as eluent, which afforded 199 mg (51 %) of 2-(4-(2-spiro[1,3]dioxolane)piperidin-2-ylmethyl)-1,1-dioxo-1,2-dihydro-1H-benzo[d]isothiazol-3-one as a solid. 1H-NMR (CDCl3): delta 7.99-7.96 (m, 1H), 7.66-7.53 (m, 3H), 5.01 (s, 1H), 4.73 (dm, 1H, J = 14.4 Hz), 4.06-3.93 (m, 6H), 3.25 (dd, 1H, J = 12.6 Hz), 3.06 (td, 1H, J = 13.5 Hz and J = 3.6 Hz), 1.93 (dd, 1H, J = 14.1 Hz and J = 5.7 Hz), 1.87 (dd, 1H, J = 14.1 Hz and J = 3.0 Hz), 1.76 (dd, 1H, J = 13.5 Hz and J = 5.1 Hz). LC-MS: Rt = 1.78; m/z: 339 [M+H]+. 2-(4-(2-Spiro[1,3]dioxolane)piperidin-2-ylmethyl)-1,1-dioxo-1,2-dihydro-1H-benzo[d]isothiazol-3-one (199 mg, 0.588 mmol) was dissolved in 2 M hydrochloric acid (12 ml) and the solution was heated to 50 C for 24 hours. The volatiles were removed in vacuo and the residue (341 mg) was treated without further purification with saturated sodium carbonate (12 ml), dichloromethane (8 ml) and di-t-butyl dicarbonate (1.64 g, 7.5 mmol). The mixture was stirred at 35 C for 3 days and extracted with dichloromethane (30 ml). The organic solution was washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1:3) as eluent, which afforded 115 mg (50 %) of 4-oxo-2-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazo)-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester as an oil. 1H-NMR (CDCl3): delta 8.06 (dd, 1H, J = 6.0, 1.8 Hz), 7.95-7.80 (m, 3H), 5.02 (bs, 1H), 4.35 (bs, 1H), 3.91 (dd, 1H, J = 15.0 Hz and J = 8.4 Hz), 3.78 (dd, 1H, J =14.7 Hz and J = 5.7 Hz), 3.53 (t, 1H, J = 10.8 Hz), 2.74 (dd, 1H, J = 15.0 Hz and J = 7.5 Hz), 2.60-2.38 (m, 3H), 1.32 (s, 9H). To a solution of 4-oxo-2-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester (115 mg, 0.292 mmol) in absolute ethanol (5 ml) was added t-butyl cyanoacetate (57 l, 0.41 mmol), sulfur (13 mg, 0.41 mmol) and morpholine (55 mul, 0.63 mmol). The solution was stirred at 50 C for 14 hours. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1:4) as eluent, which afforded 100 mg (62 %) of 2-amino-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-y)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-amino-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester as a mixture. 1H-NMR (CDCl3): delta 8.10-8.00 (m, 1H), 7.98-7.77 (m, 2.8H), 7.66-7.58 (m, 0.2H), 6.11 (s, 0.4H), 6.06 (s, 0.6H), 5.59 (m, 0.2H), 5.39 (t, 0.3H, J= 5.7 Hz) 5.23 (bs, 0.3H), 5.04 (bs, 0.4H), 4.77 (d, 0.4H, J= 14.4 Hz), 4.60 (d, 0.4H, J= 14.4 Hz), 4.45-4.18 (m, 1H), 4.02-3.82 (m, 1.5H), 3.64 (dd, 0.5H, J= 14.7 Hz and J= 5.2 Hz), 3.30-2.60 (m, 2H), 1.54 (s, 7H), 1.53 (s, 2H), 1.26 (s, 7H), 1.21 (s, 2H). To a stirred solution of the above 2-amino-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-amino-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester mixture (100 mg, 0.18 mmol) in acetonitrile (7 ml) was added imidazol-1-yl-oxo-acetic acid tert-butyl ester (290 mg, 1.46 mmol) in acetonitrile (1 ml). The mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was taken into ethyl acetate. The solution was washed with 0.5 N hydrochloric acid solution, saturated sodium bicarbonate, brine, dried MgSO4) and filtered. The solvent was removed in vacuo and the residue was chromatographed on silicagel using a mixture of ethyl acetate/hexane (1:4) as eluent, which provided 98 mg (80 %) of a mixture of 2-(tert-butoxyoxalyl-amino)-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-(tert-butoxyoxalyl-amino)-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester as a solid. 1H-NMR (CDCl3): delta 12.60 (s, 0.3H), 12.54 (s, 0.7H), 8.12-8.06 (m, 1H), 7.98-7.80 (m, 2.8H), 7.66-7.58 (m, 0.2H), 5.83 (bs, 0.1H), 5.61 (t, 0.2H), 5.40-4.54 (m, 0.9H), 4.53-4.40 (m, 0.8H), 4.02-3.70 (m, 1.42H), 3.66 (dd, 0.58H, J= 14.7 Hz and J= 5.2 Hz), 3.30-2.99 (m, 3H), 1.68 (s, 6H), 1.62 (s, 6H), 1.60 (s, 6H), 1.31 (s, 4.5H), 1.25 (...
51% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 25℃; for 24h; Example 111 2-(Oxalyl-amino)-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3-carboxylic acid and2-(Oxalyl-amino)-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3-carboxylic acid; To a solution of 2-aminomethyl-4-(2-spiro[1,3]dioxolane)-piperidine (193 mg, 1.12 mmol) and diisopropyl ethylamine (0.46 ml, 2.55 mmol) in acetonitrile (10 ml) cooled to 0 C. was added 2-chlorosulfonyl-benzoic acid methyl ester (278 mg. 1.18 mmol). The solution was stirred at 25 C. for 24 hours. Solvent was removed in vacuo and the residue was chromatographed using a mixture of ethyl acetate/hexane (1:3) as eluent, which afforded 199 mg (51%) of 2-(4-(2-spiro[1,3]dioxolane)piperidin-2-ylmethyl)-1,1-dioxo-1,2-dihydro-1H-benzo[d]isothiazol-3-one as a solid.1H-NMR (CDCl3): delta 7.99-7.96 (m, 1H), 7.66-7.53 (m, 3H), 5.01 (s, 1H), 4.73 (dm, 1H, J=14.4 Hz), 4.06-3.93 (m, 6H), 3.25 (dd, 1H, J=12.6 Hz), 13.06 (td, 1H, J=13.5 Hz and J=3.6 Hz), 1.93 (dd, 1H, J=14.1 Hz and J=5.7 Hz), 1.87 (dd, 1H, J=14.1 Hz and J=3.0 Hz), 1.76 (dd, 1H, J=13.5 Hz and J=5.1 Hz).LC-MS: Rt=1.78; m/z: 339 [M+H]+.2-(4-(2-Spiro[1,3]dioxolane)piperidin-2-ylmethyl)-1,1-dioxo-1,2-dihydro-1H-benzo[d]isothiazol-3-one (199 mg, 0.588 mmol) was dissolved in 2 M hydrochloric acid (12 ml) and the solution was heated to 50 C. for 24 hours. The volatiles were removed in vacuo and the residue (341 mg) was treated without further purification with saturated sodium carbonate (12 ml), dichloromethane (8 ml) and di-t-butyl-dicarbonate (1.64 g, 7.5 mmol). The mixture was stirred at 35 C. for 3 days and extracted with dichloromethane (30 ml). The organic solution was washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1:3) as eluent, which afforded 115 mg (50%) of 4-oxo-2-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester as an oil.1H-NMR (CDCl3): delta 8.06 (dd, 1H, J=6.0, 1.8 Hz), 7.95-7.80 (m, 3H), 5.02 (bs, 1H), 4.35 (bs, 1H), 3.91 (dd, 1H, J=15.0 Hz and J=8.4 Hz), 3.78 (dd, 1H, J=14.7 Hz and J=5.7 Hz), 3.53 (t, 1H, J=10.8 Hz), 2.74 (dd, 1H, J=15.0 Hz and J=7.5 Hz), 2.60-2.38 (m, 3H), 1.32 (s, 9H).To a solution of 4-oxo-2-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester (115 mg, 0.292 mmol) in absolute ethanol (5 ml) was added t-butyl cyanoacetate (57 mul, 0.41 mmol), sulfur (13 mg, 0.41 mmol) and morpholine (55 mul, 0.63 mmol). The solution was stirred at 50 C. for 14 hours. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1:4) as eluent, which afforded 100 mg (62%) of 2-amino-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-amino-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester as a mixture.1H-NMR (CDCl3): delta 8.10-8.00 (r, 1H), 7.98-7.77 (m, 2.8H), 7.66-7.58 (m, 0.2H), 6.11 (s, 0.4H), 6.06 (s, 0.6H), 5.59 (m, 0.2H), 5.39 (t, 0.3H, J=5.7 Hz) 5.23 (bs 0.3H), 5.04 (bs, 0.4H), 4.77 (d, 0.4H, J=14.4 Hz), 4.60 (d, 0.4H, J=14.4 Hz), 4.45-4.18 (m, 1H), 4.02-3.82 (m, 1.5H), 3.64 (dd, 0.5H, J=14.7 Hz and J=5.2 Hz), 3.30-2.60 (m, 2H), 1.54 (s, 7H), 1.53 (s, 2H), 1.26 (s, 7H), 1.21 (s, 2H).To a stirred solution of the above 2-amino-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-amino-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester mixture (100 mg, 0.18 mmol) in acetonitrile (7 ml) was added imidazol-1-yl-oxo-acetic acid tert-butyl ester (290 mg, 1.46 mmol) in acetonitrile (1 ml). The mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was taken into ethyl acetate. The solution was washed with 0.5 N hydrochloric acid solution, saturated sodium bicarbonate, brine, dried MgSO4) and filtered. The solvent was removed in vacuo and the residue was chromatographed on silicagel using a mixture of ethyl acetate/hexane (1:4) as eluent, which provided 98 mg (80%) of a mixture of 2-(tert-butoxyoxalyl-amino)-5-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-(tert-butoxyoxalyl-amino)-7-(1,1,3-trioxo-1,3-dihydro-1H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester as a solid.1H-NMR (CDCl3): delta 12.60 (s, 0.3H), 12.54 (s, 0.7H), 8.12-8.06 (m, 1H), 7.98-7.80 (m, 2.8H), 7.66-7.5...
 

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