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Chemical Structure| 125559-00-4 Chemical Structure| 125559-00-4

Structure of LC-SMCC
CAS No.: 125559-00-4

Chemical Structure| 125559-00-4

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Product Details of [ 125559-00-4 ]

CAS No. :125559-00-4
Formula : C22H29N3O7
M.W : 447.48
SMILES Code : O=C(ON1C(CCC1=O)=O)CCCCCNC(C2CCC(CN3C(C=CC3=O)=O)CC2)=O
English Name :2,5-Dioxopyrrolidin-1-yl 6-(4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)cyclohexanecarboxamido)hexanoate
MDL No. :MFCD01863459

Safety of [ 125559-00-4 ]

Application In Synthesis of [ 125559-00-4 ]

* 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 [ 125559-00-4 ]

[ 125559-00-4 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 701-54-2 ]
  • [ 125559-00-4 ]
  • [ 951792-85-1 ]
YieldReaction ConditionsOperation in experiment
In water; N,N-dimethyl-formamide at 20℃; for 4.08333h; I.3.4 A solution of succinimidyl 4-[iV-maleimidomethyl]cyclohexane-l-carboxy-[6- amidocaproate]) (PIERCE Ref: 22362) (25 mmol) in DMF (100 mL) was stirred for 5 min, and was added at room temperature to a solution of trans-A-(aminomethyl)cyclohexanecarboxylic acid (50 mmol) (SIGMA ref: 08455) in H2O (50 mL).The mixture was stirred for 4h at room temperature. Dichloromethane was added (100 mL) and the organic layer was washed with water (3x150 mL) and then with 5% aqueous citric acid (3x150 mL) to remove trørcs-4-(aminomethyl)cyclohexanecarboxylic acid excess. The organic layer was dried under vacuum and the resulting white powder was stored at -20°C.
  • 2
  • [ 125559-00-4 ]
  • [ 1020412-43-4 ]
  • [ 2101204-35-5 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; Inert atmosphere; 10.A Step A: Preparation of ATAC33 To a stirred solution of 1 -(4-amino-2-((ethylamino )methyl)- 1 H-imidazo [4,5-cj quinolin- 1-yl)-2-methylpropan-2-ol (100 mg, 0.3 19 mmol) in DCM (10 mL) under nitrogen was added via asyringe pump a solution of 2,5-dioxopyrrolidin- 1 -yl 6-(4-((2,5-dioxo-2,5-dthydro- 1H-pyrrol- 1-yl)methyl)cyclohexane-1-carboxamido)hexanoate (143 mg, 0.3 19 mmol) in DCM (5 mL) over a period of 3.5 h. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was purified by reverse phase column chromatography. Pure fractions identified by HPLC analysis were pooled and concentrated. The residue was lyophilized from CH3CN to provide a white solid (52.8, mg) as the TFA salt of ATAC33 as a mixture of cis and trans isomers. ‘H NMR (400 MHz, (CD3OD) ö 8.54 and 8.48 (d, 1=8.3 Hz, 1H), 7.81-7.71 (m, 2H), 7.62-7.55 (m, 1H), 6.80 (s, 2H), 3.66 (q, 1=7.0 Hz, 2H), 3.13 and 3.08 (t, 1=7.0 Hz, 2H), 2.45 and 2.38 (t, 1=7.5 Hz, 2H), 2.1-2.0 (m, 1H), 1.8-1.47 (m, 1OH), 1.46-1.15 (m, 16H), 1.54-1.41 (m, 4H), 1.25-1.00 (m, 1OH). LCMS [M + Hj = 646.3.
  • 3
  • [ 125559-00-4 ]
  • [ 2244133-42-2 ]
  • [ 2241495-10-1 ]
YieldReaction ConditionsOperation in experiment
49 mg Stage #1: 2,5-dioxopyrrolidin-1-yl 6-(4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)cyclohexane-1-carboxamido)hexanoate; C29H38N6O4 With triethylamine In dichloromethane for 16h; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 2h; 6.A Step A:
Preparation of Compound-Linker 2.2 Step A: Preparation of Compound-Linker 2.2 50 mg (0.11 mmol) of N-succinimidyl 6-[[4-(maleimidomethyl)cyclohexyl]carboxamido]caproate (CAS No. 125559-00-4) was added to a solution containing 60 mg (0.11 mmol) of 2-amino-N8-(5-(aminomethyl)pyridin-3-yl)-N4,N4-dipropyl-3H-benzo[b]azepine-4,8-dicarboxamide in 2.0 mL of DCM and 15 μL (0.11 mmol) of triethylamine. The reaction mixture was stirred for 16 h and then purified directly by reverse phase chromatography (no TFA). The clean fractions were lyophilized to afford the desired product which was dissolved in 5 mL of DCM and treated with 1 mL of TFA at room temperature. The mixture was stirred for 2 h and then evaporated. The resulting residue was purified by reverse phase chromatography (no TFA) to afford 49 mg of Compound-Linker 2.2 as a white solid. 1H NMR (CD3OD) δ 8.78 (s, 1H), 8.25 (s, 2H), 7.70 (d, J=1.8 Hz, 1H), 7.58 (dd, J=1.8, 8.1 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 6.91 (s, 1H), 6.77 (s, 2H), 4.42 (s, 2H), 3.43 (m, 4H), 3.13 (t, J=6.9 Hz, 2H), 2.85 (d, J=16.6 Hz, 1H), 2.29 (t, J=7.3 Hz, 2H), 2.05 (m, 1H), 1.8-1.6 (m, 12H), 1.51 (m, 1H), 1.37 (m, 4H), 1.11-0.84 (m, 9H). LCMS (M+H)=767.
  • 4
  • [ 125559-00-4 ]
  • [ 2254678-02-7 ]
  • [ 2254702-81-1 ]
YieldReaction ConditionsOperation in experiment
31.8 mg With N-ethyl-N,N-diisopropylamine In dichloromethane 1.1.G Step G: Preparation of Compound 1-1 A solution containing 43 mg (0.037 mmol) of (S)-2-amino-N1-(4-(5-amino-6-((4- morpholinopyridin-3-yl)carbamoyl)pyrazin-2-yl)benzyl)-N5-(2-(3-(((S)-l-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3,3-dimethyl-l- oxobutan-2-yl)amino)-3-oxopropoxy)ethyl)pentanediamide trihydrochloride was combined with (16 mg, 0.037 mmol) of LC-smcc (succinimidyl 4-(N-maleimidomethyl)cyclohexane-l- carboxy-(6-amidocaproate)) in 1.5 mL of DCM and DIPEA (0.064 mL, 0.36 mmol). After stirring overnight, the reaction became cloudy and LCMS indicated the presence of product. The reaction was concentrated then taken up in a minimum amount of THF and water. The mixture was neutralized with saturated NaHC03 and the mixture was chromatographed (30 g, C18, H20 to CH3CN, liquid load) to provide Compound 1-1 (31.8, mg) as a yellow solid after lyophilization from CH3CN/H20. 1H NMR (CD3OD) δ 9.46 (s, 1H), 8.84 (s, 1H), 8.78 (s, 1H), 8.26 (d, J=8.5Hz, 1H), 8.03 (d, J=8.5Hz, 2H), 7.44 (d, J=8.5Hz, 2H), 7.41 (d, J=8.4Hz, 2H), 7.35 (d, J=8.4Hz, 2H), 7.26 (d, J=5.5Hz, IH), 6.78 (s, 2H), 4.66 (s, IH), 4.59 (m, 2H), 4.46 (t, J=7.0Hz, 4H), 4.37 (m, 2H), 3.88 (d, J=11.5Hz, IH), 3.81-3.70 (m, 5H), 3.69 (t, J=5.5Hz, 2H), 3.55-3.49 (m, 3H), 3.11 (t, J=11.5Hz, 2H), 3.10-3.01 (m, 5H), 2.50 (t, J=15.0Hz, 2H), 2.33 (s, 3H), 2.35-2.22 (m, 6H), 2.11-2.01 (m, 4H), 1.94 (m, IH), 1.76-1.58 (m, 8H), 1.50-1.25 (m, 8H), 1.11 (s, 9H), 1.05-0.95 (m, 4H). LCMS (M+H) = 1395.6.
31.8 mg With N-ethyl-N,N-diisopropylamine In dichloromethane 1.G Step G: Preparation of Compound 1-1 A solution containing 43 mg (0.037 mmol) of (S)-2-amino-N1-(4-(5-amino-6-((4- morpholinopyridin-3-yl)carbamoyl)pyrazin-2-yl)benzyl)-N5-(2-(3-(((S)-l-((2S,4R)-4-hydroxy-2- ((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3,3-dimethyl-l-oxobutan-2- yl)amino)-3-oxopropoxy)ethyl)pentanediamide trihydrochloride was combined with (16 mg, 0.037 mmol) of LC-smcc (succinimidyl 4-(N-maleimidomethyl)cyclohexane-l-carboxy-(6- amidocaproate)) in 1.5 mL of DCM and DIPEA (0.064 mL, 0.36 mmol). After stirring overnight, the reaction became cloudy and LCMS indicated the presence of product. The reaction was concentrated then taken up in a minimum amount of THF and water. The mixture was neutralized with saturated NaHC03 and the mixture was chromatographed (30 g, CI 8, H20 to CH3CN, liquid load) to provide Compound 1-1 (31.8, mg) as a yellow solid after lyophilization from CH3CN/H20. 1H NMR (CD3OD) δ 9.46 (s, IH), 8.84 (s, IH), 8.78 (s, IH), 8.26 (d, J=8.5Hz, IH), 8.03 (d, J=8.5Hz, 2H), 7.44 (d, J=8.5Hz, 2H), 7.41 (d, J=8.4Hz, 2H), 7.35 (d, J=8.4Hz, 2H), 7.26 (d, J=5.5Hz, IH), 6.78 (s, 2H), 4.66 (s, IH), 4.59 (m, 2H), 4.46 (t, J=7.0Hz, 4H), 4.37 (m, 2H), 3.88 (d, J=11.5Hz, IH), 3.81-3.70 (m, 5H), 3.69 (t, J=5.5Hz, 2H), 3.55-3.49 (m, 3H), 3.11 (t, J=11.5Hz, 2H), 3.10-3.01 (m, 5H), 2.50 (t, J=15.0Hz, 2H), 2.33 (s, 3H), 2.35- 2.22 (m, 6H), 2.11-2.01 (m, 4H), 1.94 (m, 1H), 1.76-1.58 (m, 8H), 1.50-1.25 (m, 8H), 1.11 (s, 9H), 1.05-0.95 (m, 4H). LCMS (M+H) = 1395.6
  • 5
  • [ 125559-00-4 ]
  • [ CAS Unavailable ]
  • [ 2254657-57-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane 1.2.E Step E: Preparation of Compound 2-1 To a solution containing 43 mg (0.05 mmol) of (S)-2-amino-N1-(4-(5-amino-6-((4- morpholinopyridin-3-yl)carbamoyl)pyrazin-2-yl)benzyl)-N5-(2-(3-(((S)-l-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3,3-dimethyl-l- oxobutan-2-yl)amino)-3-oxopropoxy)ethyl)pentanediamide trihydrochloride as bright yellow crystalline solid which was combined with (32 mg, 0.07 mmol) of LC-smcc (succinimidyl 4- (N-maleimidomethyl)cyclohexane-l-carboxy-(6-amidocaproate)) in 3 niL of DCM and DIPEA (0.13 mL, 0.7 mmol). After stirring overnight, the reaction became cloudy and LCMS indicated the presence of product. The reaction was concentrated then taken up in a minimum amount of THF and water. The mixture was neutralized with saturated NaHC03 and the mixture was chromatographed (30 g, CI 8, H20 to CH3CN, liquid load) to provide Compound 2-1 as a yellow solid after lyophilization from CH3CN/H20. LCMS (M+H) = 1194.3.
  • 6
  • [ 125559-00-4 ]
  • [ 2254678-03-8 ]
  • [ 2254657-57-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane 2.E Step E: Preparation of Compound 2-1 To a solution containing 43 mg (0.05 mmol) of (S)-2-amino-N1-(4-(5-amino-6-((4- morpholinopyridin-3-yl)carbamoyl)pyrazin-2-yl)benzyl)-N5-(2-(3-(((S)-l-((2S,4R)-4-hydroxy-2- ((4-(4-methylthiazol-5-yl)benzyl)carbam yl)amino)-3-oxopropoxy)ethyl)pentanediamide trihydrochloride as bright yellow crystalline solid which was combined with (32 mg, 0.07 mmol) of LC-smcc (succinimidyl 4-(N- maleimidomethyl)cyclohexane-l-carboxy-(6-amidocaproate)) in 3 mL of DCM and DIPEA (0.13 mL, 0.7 mmol). After stirring overnight, the reaction became cloudy and LCMS indicated the presence of product. The reaction was concentrated then taken up in a minimum amount of THF and water. The mixture was neutralized with saturated NaHC03 and the mixture was chromatographed (30 g, CI 8, H20 to CH3CN, liquid load) to provide Compound 2-1 as a yellow solid after lyophilization from CH3CN/H20. LCMS (M+H) = 1194.3
  • 7
  • [ 125559-00-4 ]
  • [ 1998726-22-9 ]
  • [ 2241495-10-1 ]
YieldReaction ConditionsOperation in experiment
49 mg With triethylamine In dichloromethane for 16h; 7.A Step A: Preparation of Compound 2.2 50 mg (0.11 mmol) of N-succinimidyl 6-[[4-(maleimidomethyl)cyclohexyl]carboxamido] caproate (CAS No. 125559-00-4) was added to a solution containing 60 mg (0.11 mmol) of 2- amino-N8-(5-(aminomethyl)pyridin-3-yl)-N4,N4-dipropyl-3H-benzo[b]azepine-4,8- dicarboxamide in 2.0 mL of DCM and 15 pL (0.1 1 mmol) of triethylamine. The reaction mixture was stirred for 16 h and then purified directly by reverse phase chromatography (no TFA). The clean fractions were lyophilized to afford the desired product which was dissolved in 5 mL of DCM and treated with 1 mL of TFA at room temperature. The mixture was stirred for 2 h and then evaporated. The resulting residue was purified by reverse phase chromatography (no TFA) to afford 49 mg of Compound-Linker 2.2 as a white solid. 1H NMR (CD3OD) d 8.78 (s, 1H), 8.25 (s, 2H), 7.70 (d, J=l.8Hz, 1H), 7.58 (dd, J=L8, 8.1Hz, 1H), 7.46 (d, J=8.3Hz, 1H), 6.91 (s, 1H), 6.77 (s, 2H), 4.42 (s, 2H), 3.43 (m, 4H), 3.13 (t, J=6.9Hz, 2H), 2.85 (d, J=l6.6Hz, 1H), 2.29 (t, J=7.3Hz, 2H), 2.05 (m, 1H), 1.8-1.6 (m, 12H), 1.51 (m, 1H), 1.37 (m, 4H), 1.11- 0.84 (m, 9H). LCMS (M+H) = 767.
49 mg Stage #1: 2,5-dioxopyrrolidin-1-yl 6-(4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)cyclohexane-1-carboxamido)hexanoate; 2-amino-N8-(5-(aminomethyl)pyridin-3-yl)-N4,N4-dipropyl-3H-benzo[b]azepine-4,8-dicarboxamide With triethylamine In dichloromethane for 16h; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 2h; 6.A Step A:
Preparation of Compound 2.2 Step A: Preparation of Compound 2.2 50 mg (0.11 mmol) of N-succinimidyl 6-[[4-(maleimidomethyl)cyclohexyl]carboxamido]caproate (CAS No. 125559-00-4) was added to a solution containing 60 mg (0.11 mmol) of 2-amino-N8-(5-(aminomethyl)pyridin-3-yl)-N4,N4-dipropyl-3H-benzo[b]azepine-4,8-dicarboxamide in 2.0 mL of DCM and 15 μL (0.11 mmol) of triethylamine. The reaction mixture was stirred for 16 h and then purified directly by reverse phase chromatography (no TFA). The clean fractions were lyophilized to afford the desired product which was dissolved in 5 mL of DCM and treated with 1 mL of TFA at room temperature. The mixture was stirred for 2 h and then evaporated. The resulting residue was purified by reverse phase chromatography (no TFA) to afford 49 mg of Compound-Linker 2.2 as a white solid. 1H NMR (CD3OD) δ 8.78 (s, 1H), 8.25 (s, 2H), 7.70 (d, J=1.8 Hz, 1H), 7.58 (dd, J=1.8, 8.1 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 6.91 (s, 1H), 6.77 (s, 2H), 4.42 (s, 2H), 3.43 (m, 4H), 3.13 (t, J=6.9 Hz, 2H), 2.85 (d, J=16.6 Hz, 1H), 2.29 (t, J=7.3 Hz, 2H), 2.05 (m, 1H), 1.8-1.6 (m, 12H), 1.51 (m, 1H), 1.37 (m, 4H), 1.11-0.84 (m, 9H). LCMS (M+H)=767.
 

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