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[ CAS No. 1255942-06-3 ] {[proInfo.proName]}

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Chemical Structure| 1255942-06-3
Chemical Structure| 1255942-06-3
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Product Details of [ 1255942-06-3 ]

CAS No. :1255942-06-3 MDL No. :MFCD22380759
Formula : C18H16N2O Boiling Point : -
Linear Structure Formula :- InChI Key :OCCYFTDHSHTFER-UHFFFAOYSA-N
M.W : 276.33 Pubchem ID :77078258
Synonyms :

Calculated chemistry of [ 1255942-06-3 ]

Physicochemical Properties

Num. heavy atoms : 21
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.17
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 86.57
TPSA : 46.33 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.66 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.47
Log Po/w (XLOGP3) : 1.87
Log Po/w (WLOGP) : 1.83
Log Po/w (MLOGP) : 2.64
Log Po/w (SILICOS-IT) : 3.01
Consensus Log Po/w : 2.36

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.96
Solubility : 0.306 mg/ml ; 0.00111 mol/l
Class : Soluble
Log S (Ali) : -2.46
Solubility : 0.948 mg/ml ; 0.00343 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.44
Solubility : 0.000999 mg/ml ; 0.00000361 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.54

Safety of [ 1255942-06-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1255942-06-3 ]

* 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 [ 1255942-06-3 ]

[ 1255942-06-3 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 756525-91-4 ]
  • [ 1255942-06-3 ]
  • [ 1255942-12-1 ]
YieldReaction ConditionsOperation in experiment
Aza-dibenzocyclooctyne-PEG4-amine (ADIBO-PEG4-amine, 9). EDC (0.75 g, 4.68 mmol) was added to a solution of Boc-NH-(CH2CH2O)4-CH2CH2CO2H (PCT International Application Publication No. WO 2009/053339 A2; Pessi et al.) (1.57 g, 4.32 mmol) in CH2Cl2 (15 mL) and DTRA (0.7 g, 5.4 mmol) at room temperature and stirred for 15 minutes. A solution of ADIBO-amine 7 (1 g, 3.6 mmol) in CH2Cl2 (1 mL) was added to the reaction mixture and stirred for 4 hours, at which time the solvent was removed under reduced pressure and the crude product purified by chromatography (ethyl acetate:hexanes 1:1 to 9:1) to provide 1.8 g (2.8 mmol, 80%) of crude N-Boc-protected ADIBO-PEG4-amine (9-Boc) as yellow oil.A solution of TFA (0.48 g, 4.2 mmol) in THF (15 mL) was added to a solution of 9-Boc (1.8 g, 2.8 mmol) in THF (30 mL) at room temperature. The reaction mixture was stirred overnight and the solvent was removed under reduced pressure. The residue was purified by chromatography (CH2Cl2:MeOH 10:1 to 10:4) to provide 1.15 g (2.2 mmol, 79%) of ADIBO-PEG4-amine (9) as slightly yellow oil. 1H-NMR (500 MHz): 7.67 (d, J=7.5 Hz, 1H), 7.43-7.34 (m, 5H), 7.31 (t, J=7.5 Hz, 1H), 7.29-7.24 (m, 1H), 6.95-6.88 (m, 1H), 5.13 (d, J=14 Hz, 1H), 4.45-4.2 (br s, 2H), 3.7-3.5 (m, 22H), 3.37-3.2 (m, 3H), 2.68 (t, J=5 Hz, 2H), 2.57-2.42 (m, 1H), 2.4-2.32 (m, 2H), 2.02-1.92 (1H); 13C-NMR (100 MHz, CDCl3): 172.13, 171.21, 151.20, 148.16, 129.3, 129.2, 128.78, 128.44, 128.31, 127.9, 127.29, 127.25, 125.68, 123.16, 122.55, 114.81, 107.92, 70.46, 70.39, 70.35, 70.32, 70.30, 70.26, 70.1, 55.62. 48.86, 36.69, 35.41, 34.67; FIRMS (ESI+) m/z calcd for C29H38N3O6 [M+H] 524.2761. found 524.2756.
  • 2
  • [ 1255942-06-3 ]
  • 1 7-oxo-21-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3 ,4-d]imidazol-4-yl)-4,7,10,13-tetraoxa-16-azahenicosan-1-oic acid [ No CAS ]
  • [ 1255942-07-4 ]
  • 3
  • N-(3-trifluoroacetamidopropanoyl)-5,6-Dihydro-11,12-Didehydrodibenzo[b,f]azocine [ No CAS ]
  • [ 1255942-06-3 ]
  • 4
  • [ 23194-93-6 ]
  • [ 1255942-06-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: pyridine / dichloromethane / 0.5 h / 20 °C 2: pyridinium perbromide hydrobromide / dichloromethane / 20 °C 3: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 4: potassium carbonate / methanol; water / 20 °C
  • 5
  • [ 1021-91-6 ]
  • [ 1255942-06-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: polyphosphoric acid / 1 h / 125 °C 2: lithium aluminium tetrahydride / diethyl ether / 15 h / Reflux 3: pyridine / dichloromethane / 0.5 h / 20 °C 4: pyridinium perbromide hydrobromide / dichloromethane / 20 °C 5: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 6: potassium carbonate / methanol; water / 20 °C
  • 6
  • [ 66134-67-6 ]
  • [ 1255942-06-3 ]
  • 5,6-dihydro-11,12-didehydrodibenz[b,f ]azocino-3-oxopropyl-4-fluorobenzamide [ No CAS ]
  • 7
  • [ 1255942-06-3 ]
  • [ 77744-44-6 ]
  • [ 1350811-68-5 ]
YieldReaction ConditionsOperation in experiment
87% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; ADIBO amine 1 was synthesized following the procedure reported previously.i TBDMS-protected 6-hydroxyhexanoic acid (2, 118 mg, 0.48 mmol), EDC (100 mg, 0.52 mmol), and catalytic amount of DMAP were added to a solution of ADIBO amine 1 (120 mg, 0.43 mmol) in 5 mL DMF. The reaction mixture was stirred overnight at RT, the solvent was removed under reduced pressure, and the residue was taken in 50 mL of dichloromethane. The dichloromethane solution was washed with brine (3 X 25 mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified using silica gel column chromatography using 2% methanol in dichloromethane to yield 190 mg (87%) of amide 3 as yellow oil.
78.2% With dmap; 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; Compound 3 (187 mg, 0.76 mmol), EDC (58.3 mg, 0.30 mmol),and DMAP (3.1 mg, 0.03 mmol) were added to a solution ofADIBO-amine (70 mg, 0.25 mmol) in 5 mL DMF. The reaction mixturewas stirred overnight at 20 C. The solvent was removed undervacuum and the residue dissolved in 50 mL dichloromethane. Theresultant solution was washed with brine (3 50 mL), dried overNa2SO4, and dichloromethane removed using a rotary evaporator.The residue was purified by chromatography using 2% methanolin dichloromethane to obtain 100 mg (0.20 mmol, 78.2%) of compound4 as a yellow oil: 1H NMR (CDCl3) d 0.05 (s, 6H), 0.90 (s,9H), 0.90 (s, 9H), 1.25-1.35 (m, 2H), 1.45-1.55 (m, 4H), 1.95-2.05(m, 3H), 2.40-2.50 (m, 1H), 3.27-3.37 (m, 2H), 3.60 (t, 2H), 3.70(d, 1H), 5.15 (d, 1H), 6.00 (t, 1H), 7.26-7.42 (m, 7H), 7.68 (d, 1H).LRMS (LCMS-ESI) m/z: 505.2 (M+H)+.
  • 8
  • [ 1255942-06-3 ]
  • biotin-PEG4-acid [ No CAS ]
  • ADIBO-biotin [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% Aza-dibenzocyclooctyne-biotin conjugate (ADIBO-biotin, 8). HBTU (1.916 g, 5.05 mmol) was added to a solution of biotin-PEG4-acid (1.9 g, 3.74 mmol) and DIEA (0.647 g, 5.61 mmol) in CH2Cl2 (15 mL) at room temperature and stirred for 15 minutes. A solution of 7 (1.238 g, 4.12 mmol) in CH2Cl2 (2 mL) was added dropwise, the reaction mixture was stirred for 3 hours, and concentrated under reduced pressure. The product was purified by chromatography (CH2Cl2 to CH2Cl2:MeOH 20:1 to 100:15) to provide 2.44 g (3.32 mmol, 89%) of 8 as colorless semi-solid. 1H NMR (500 MHz, CDCl3): δ 7.66 (d, J=7 Hz, 1H), 7.42-7:3 (m, 7H), 7.28-7.25 (m, 1H), 7.05-6.99 (m, 1H), 6.79-6.75 (m, 1H), 6.61 (br s, 1H), 5.13 (d, J=14 Hz, 1H), 4.5-4.45 (m, 1H), 4.32-4.25 (m, 1H), 3.68 (d, J=14 Hz, 1H), 3.65-3.45 (m, 17H), 3.44-3.36 (m, 2H), 3.32-3.22 (m, 2H), 3.15-3.07 (m, 2H), 2.9-2.82 (m, 1H), 2.75-2.65 (m, 1H), 2.55-2.46 (m, 1H), 2.33 (q, J=6 Hz, 2H), 2.2 (t, J=7.5 Hz, 2H), 2.0-1.92 (m, 1H), 1.75-1.6 (m, 4H), 1.45-1.35 (m, 5H); 13C, 173.51, 171.99, 171.13, 164.01, 151.1, 148.09, 132.13, 129.14, 128.68, 128.21, 127.83, 127.19, 125.58, 123.07, 122.45, 114.72, 107.86, 70.45, 70.43, 70.39, 70.3, 70.17, 70.03, 69.98, 97.17, 61.83, 60.26, 55.69, 55.52, 53.67, 42.0, 40.52, 39.14, 36.79, 35.89, 35.26, 34.71, 28.29, 28.11, 25.63, 18.59, 17.44, 11.88; HRMS (ESI+) m/z calcd for C39H53N5O8S [M+H]+ 750.3537. found 750.3542.
  • 9
  • [ 1255942-06-3 ]
  • sodium 3,3'-(2-((E)-2-((E)-3-((E)-2-(3-(6-(2,5-dioxopyrrolidin-1-yloxy)-6-oxohexyl)-1,1-dimethyl-7-sulfonato-1H-benzo[e]indol-2(3H)-ylidene)ethylidene)-2-(2-fluorophenyl)cyclohex-1-enyl)vinyl)-3,3-dimethyl-1-(3-sulfonatopropyl)-3H-indolium-5-ylazanediyl)dipropane-1-sulfonate [ No CAS ]
  • C73H77FN5O14S4(3-)*3Na(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 2h; Example 98[0495] Example 98 illustrates the synthesis of a strained cycloalkyne-containing Compound 79 derivative for click chemistry (Compound 79-DBCO, 66).66 [0496] To a solution of Compound 64 (Example 96, 0.8 mg, 6.1 x 10-4 mmol) and N,N- diisopropylethylamine (0.001 mL, 5.7 x 10-3 mmol) in anhydrous dimethylsulfoxide (0.8 mL) was added DBCO-Amine (from Jena Bioscience, 0.5 mg, 1.8 x 10-3 mmol) in one portion. The reaction was allowed to proceed at ambient temperature for 2 h, with periodic agitation at 15-min intervals. After HPLC analysis indicated complete consumption of Compound 64, the crude product was precipitated in anhydrous diethyl ether (10 mL). The ethereal supernatant was decanted and the precipitate was purified by prep-HPLC to afford the desired product Compound 87 as a teal solid (0.8 mg, 90%). UV/Vis (acetonitrile/water = 1 : 1) = 790 nm; LRMS (ES/water), m/z calculated for C73H81FN5014S4 [M + H]+ 1398.46, found 1398.5.
  • 10
  • [ 1255942-06-3 ]
  • [ 25357-95-3 ]
  • C63H54N6O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
48.1% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 24h; 1,3,5-Cyclohexanetricarboxylic acid (3.47 mg, 16.08 μηιοεβ), l-ethyl-3-(3'- dimethylaminopropyl)carbodiimide hydrochloride (14.1 mg, 73.55 μηιοεβ) and hydroxybenzotriazole hydrate (11 mg, 71.89 μιηοεβ) were added to a 140 μ solution of Ν,Ν-dimethylformamide (DMF). It was shaken until everything was dissolved. To this added DBCO amine (20.2 mg, 73.1 μιηοεβ) and shaken for 24 hours. The desired product was purified by reversed phase HPLC (flow rate 2 mL/min, runtime 40 minutes), solvent A (0.1% trifluoroacetic acid (TFA) in water), solvent B (0.1% TFA in acetonitrile (ACN)), gradient 0% B to 100% B over 30 minutes, isocratic 100% B for next 10 minutes, C 18 column with TMS endcapping (5 μιη, 250 χ 10 mm, Phenomenex): the crude reaction mixture was run multiple times and the fractions(or peak) at 34-35 minutes were collected, combined, dried and analyzed using HPLC and mass spectrometry. Yield 7.6 mg (48.1% yield), Purity (95%, HPLC). TLC (EtOAc/MeOH, 50:50 v/v): Rf = 0.82; UV/vis (methanol) (ελ): 310 nm (36000 M-l cm-1), reversed phase HPLC (flow rate 1 mL/min, runtime 30 minutes), solvent A (0.1% TFA in water), solvent B (0.1% TFA in ACN), gradient 0% B to 100% B over 25 minutes, isocratic 100% B for 5 minutes, CI 8 with Hypersil column (5 μηι, 250 χ 4.6 mm, Agilent Microsorb): retention time (min) 21.41, ESI-MS {mlz): [MH]+ calculated for 991.4; found, 991.3. See FIG. 12D for HPLC and MS.
  • 11
  • [ 1255942-06-3 ]
  • [ 35013-72-0 ]
  • [ 1418217-95-4 ]
YieldReaction ConditionsOperation in experiment
49% With triethylamine; In N,N-dimethyl-formamide; for 3h; To a solution of amine 29, commercially available from ClickChemistryTools (50 mg, 0.18 mmol) in DMF (2 mL) was added biotin-OSu (62 mg, 0.18 mmol) and Et3N (50 μΕ, 0.36 mmol). The reaction mixture was stirred for 3 h followed by concentration under reduced pressure. Flash column chromatography (DCM:MeOH 99: 1-90: 10) afforded DIBAC-biotin 30 (44 mg, 0.09 mmol, 49%). 1H-NMR (300 MHz, CDC13): δ 7.66-7.62 (m, 1H), 7.40-7.24 (m, 7H), 6.67-6.60 (m, 1H), 6.53-6.49 (m, 1H), 5.75 (d, J = 8.8 Hz, 1H), 5.13 (dd, J = 2.9, 14.0 Hz, 1H), 4.47-4.43 (m, 1H), 4.29-4.28 (m, 1H), 3.68 (d, J = 13.9 Hz, 1H), 3.34-3.30 (m, 1H), 3.17-3.08 (m, 2H), 2.92-2.67 (m, 3H), 2.50-2.42 (m, 1H), 2.10-1.95 (m, 2H), 1.73-1.24 (m, 6H). LRMS (ESI+) calcd for C28H30N4O3S ( +H+) 503.2, found 503.1.
  • 12
  • [ 108-55-4 ]
  • [ 74124-79-1 ]
  • [ 1255942-06-3 ]
  • [ 1269997-07-0 ]
YieldReaction ConditionsOperation in experiment
48% DIBAC-amine 29, commercially available from ClickChemistryTools (430 mg, 1.50 mmol) was dissolved in DCM (15 mL) and treated with glutaric acid anhydride (213 mg, 1.87 mmol) and Et3N (647 μ., 4.67 mmol)_at rt. The reaction was stirred for 2h, followed by the addition of DSC (478 mg, 1.87 mmol). After another 2 h of stirring at rt, DCM (30 mL) was added and the reaction was washed with H20 (3 x 20 mL). The organic phase was dried over Na2S04and the solvent removed under reduced pressure. Flash chromatography (0: 100-2:98 EtOAc:MeOH) afforded the DIBAC-OSu ester (368 mg, 0.75 mmol, 48%).Next, to a solution of the DIBAC-OSu ester (1 mg, 0.003 mmol) in DMF (0.2 mL) was added vc-PABA-MMAF (2 mg, 0.002 mmol) and triethylamine (1 μ, 0.007 mmol). The solution was stirred overnight followed by concentration. Purification with HPLC (reversed phase, MeCN:H20 + 0.1% TFA) gave 41 (0.9 mg, 0.0006 mmol, 33%). LCMS analysis gave one peak with mass 1510.40 (expected for C8iHn3Ni20i6 = 1510.83).
  • 13
  • [ 1255942-06-3 ]
  • BODIPY FL NHS ester [ No CAS ]
  • C32H29BF2N4O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine; In N,N-dimethyl-formamide; General procedure: We chose BODIPY as our fluorescent probe.29 This probe isneutral, and its fluorescence is not sensitive to pH. BODIPY-Fl succinimidylester (2.5 mg; 6.4 lmol) was dissolved in 0.23 mL of0.025 M DMF containing <strong>[1255942-06-3]dibenzocyclooctyne-amine</strong> (1.1 equiv)and triethylamine (3 equiv). Amide-bond formation was monitoredby TLC (10% v/v MeOH in DCM). Upon completion of the reaction,the product was purified by preparative TLC to removeremaining reactants and filtration through cotton using MeOH asthe solvent to give 3.5 mg (95%) of cyclooctyne-BODIPY. m/z568.4 [calc’d for C32H33BF2N5O2 (M+NH4) 568.5). 1H NMR(500 MHz, CD3OD) d 7.65 (dd, J = 7.6, 1.3 Hz, 1H), 7.45 (s, 4H),7.42 (s, 1H), 7.36 (td, J = 7.5, 1.5 Hz, 1H), 7.31 (td, J = 7.6, 1.4 Hz,1H), 7.24 (dd, J = 7.5, 1.5 Hz, 1H), 6.96 (d, J = 4.1 Hz, 1H), 6.25-6.18 (m, 2H), 5.13 (d, J = 14.0 Hz, 1H), 3.70 (d, J = 14.0 Hz, 1H),3.27-3.20 (m, 2H), 3.16-3.07 (m, 2H), 2.50 (s, 3H), 2.47-2.40 (m,2H), 2.28 (s, 3H), 2.07-1.98 (m, 2H).
  • 14
  • [ 108-30-5 ]
  • [ 1255942-06-3 ]
  • C22H20N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
74.7% 220 mg of the aza-dibenzo cyclooctyne (ADIBO) was dissolved in 15 ml of chloroform, Add dropwise 0.2 ml of triethylamine, The reaction was carried out for 0.5 hour at room temperature. 105 mg of succinic anhydride, Reaction overnight at room temperature. After the reaction is completed, Dilute hydrochloric acid washed twice, Washed with saturated saline once, Dried over anhydrous sodium sulfate, The organic layer was concentrated. Dichloromethane / methanol column chromatography, A yellow oil (ADIBO-COOH, 224 mg, 74.7%) was obtained, 124 mg ADIBO-COOH And 37.9 mg of N-hydroxysuccinimide (NHS) were dissolved in 5 mL In chloroform, 60.3 mg dicyclohexylcarbodiimide (DCC) was added, Stir overnight at room temperature. After the reaction is completed, Suction filtration, The resulting full name (DCU) precipitate was removed, The filtrate spin dry. Dichloromethane / methanol column chromatography, To give a pale yellow solid (ADIBO -NHS, 101mg, 64.7%).74.8 mg of distearoyl phosphatidylethanolamine (DSPE) was dissolved in 4 mL of chloroform, 30.36 mg of triethylamine was added dropwise. After stirring at room temperature for 1 hour, 47.34 mg of ADIBO-NHS, Stir overnight. Dichloromethane / methanol column chromatography, A white solid (azabicyclooctynated distearoyl phosphatidylethanolamine, 72 mg, 72.1%).
  • 15
  • [ 876752-68-0 ]
  • [ 1255942-06-3 ]
  • C39H28N2O5 [ No CAS ]
  • 16
  • [ 1255942-06-3 ]
  • [ 108-24-7 ]
  • N-(3-N'-acetyl-3-aminopropanoyl)dibenzoazacyclooctyne [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With dmap; triethylamine; In dichloromethane; at 20℃; for 16h; Example 13. Synthesis of compound 26b To a solution of DIBAC-NH2 26a (100 mg, 0.362 mmol) in DCM (5 mL) was added Ac20 (51 μ, 0.543 mmol), NEt3 (101 μ, 0.724 mmol) and a cat. amount of DMAP. After stirring for 16 h at rt water (5 mL) was added and the mixture was extracted with DCM (3 x 10 mL). The organic layer was dried (Na2S04), filtered and concentrated in vacuo. The residue was purified by column chromatography (MeOH/DCM, 1 : 19) to afford 26b (106 mg, 92%) as a white solid. Rf 0.32 (MeOH/DCM, 1 : 19). 1H NMR (CDC13, 400 MHz): δ 7.68 (d, J = 7.5 Hz, 1H), 7.42-7.26 (m, 7H), 6.07-6.02 (m, 1H), 5.14 (d, J = 13.9 Hz, 1H), 3.70 (d, J = 13.9 Hz, 1H), 3.38-3.30 (m, 1H), 3.24-3.16 (m, 1H), 2.46 (ddd, J= 16.6, 7.7, 4.0 Hz, 1H), 1.96 (ddd, J= 16.6, 7.3, 3.7 Hz, 1H), 1.81 (s, 3H) ppm. 13C NMR (CDC13, 125 MHz): δ 172.5, 170.0, 151.2, 148.1, 132.2, 129.2, 128.7, 128.6, 128.5, 128.0, 127.4, 125.7, 123.1, 122.7, 114.9, 107.9, 55.7, 35.4, 34.9, 23.3. HRMS (ESI+) m/z calcd for C20Hi8N2NaO2 (M + Na)+: 341.1266, found: 341.1275.
92% With dmap; triethylamine; In dichloromethane; at 20℃; for 16h; To a solution of DIBAC-NH2 26a (100 mg, 0.362 mmol) in DCM (5 mL) was added Ac2O (51 μL, 0.543 mmol), NEt3 (101 μL, 0.724 mmol) and a cat. amount of DMAP. After stirring for 16 h at rt water (5 mL) was added and the mixture was extracted with DCM (3×10 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (MeOH/DCM, 1:19) to afford 26b (106 mg, 92%) as a white solid. Rf 0.32 (MeOH/DCM, 1:19). 1H NMR (CDCl3, 400 MHz): δ 7.68 (d, J=7.5 Hz, 1H), 7.42-7.26 (m, 7H), 6.07-6.02 (m, 1H), 5.14 (d, J=13.9 Hz, 1H), 3.70 (d, J=13.9 Hz, 1H), 3.38-3.30 (m, 1H), 3.24-3.16 (m, 1H), 2.46 (ddd, J=16.6, 7.7, 4.0 Hz, 1H), 1.96 (ddd, J=16.6, 7.3, 3.7 Hz, 1H), 1.81 (s, 3H) ppm. 13C NMR (CDCl3, 125 MHz): δ 172.5, 170.0, 151.2, 148.1, 132.2, 129.2, 128.7, 128.6, 128.5, 128.0, 127.4, 125.7, 123.1, 122.7, 114.9, 107.9, 55.7, 35.4, 34.9, 23.3. HRMS (ESI+) m/z calcd for C20H18N2NaO2 (M+Na)+: 341.1266. found: 341.1275.
90% With dmap; triethylamine; In dichloromethane; water; at 20℃; for 16h; Synthesis of N-(3-N'-acetyl-3-aminopropanoyl)-dibenzoazacyclooctyne (DIBAC-NHAc) (14): To a solution of DIBAC-NH2 (80% purity, 90 mg, 0.33 mmol) in DCM (5 mL) was added Ac2O (46 μL, 0.49 mmol, 1.5 eq.), TEA (91 μL, 0.652 mmol, 2 eq.) and a cat. amount of 4-dimethylaminopyridine (DMAP). After stirring for 16 h at rt water (5 mL) was added and the mixture was extracted with DCM (3 * 10 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (MeOH/DCM, 1:19) to afford 14 (93 mg, 90%) as a white solid. RF 0.32 (MeOH/DCM, 1/19). 1H NMR (CDCl3, 400 MHz): δ 7.68 (d, J = 7.5 Hz, 1H), 7.42-7.26 (m, 7H), 6.07-6.02 (m, 1H), 5.14 (d, J = 13.9 Hz, 1H), 3.70 (d, J = 13.9 Hz, 1H), 3.38-3.30 (m, 1H), 3.24-3.16 (m, 1H), 2.46 (ddd, J = 16.6, 7.7, 4.0 Hz, 1H), 1.96 (ddd, J = 16.6, 7.3, 3.7 Hz, 1H), 1.81 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ 172.5, 170.0, 151.2, 148.1, 132.2, 129.2, 128.7, 128.6, 128.5, 128.0, 127.4, 125.7, 123.1, 122.7, 114.9, 107.9, 55.7, 35.4, 34.9, 23.3. HRMS (ESI) m/z for C20H18N2NaO2: (M + Na+), calcd: 341.1266, found: 341.1275.
  • 17
  • [ 1255942-06-3 ]
  • C15H21(125)IN4O4 [ No CAS ]
  • C33H37(125)IN6O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 20℃; for 0.5h; To a solution of <strong>[1255942-06-3]DBCO-amine</strong> 4 (2 μL), solution of 125I-labeledazide ([125I]1, 0.16 MBq, 18 μL) which was dissolved in DMSO or DMSO/mouse serum (1:1) was added. Total volume of the reaction mixture was 20 lL and final concentrations of <strong>[1255942-06-3]DBCO-amine</strong> 4 were1 mM, 100 lM and 10 μM. The labeling reaction was conducted at room temperature or 37 C for 30 min. Radiochemical yields of[125I]5 were determined by analytical HPLC (eluent gradient: 40%solvent B for 0-2 min; 40-100% solvent B for 2-22 min, retentiontime of [125I]5: 5.38 min). The results were shown in Table 1.
  • 18
  • [ 1255942-06-3 ]
  • N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-4-iodobenzamide [ No CAS ]
  • N-(2-(2-(2-(2-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)ethoxy)ethoxy)ethoxy)ethyl)-4-iodobenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% In dimethyl sulfoxide; at 20℃; for 0.5h; 4.2.3 N-(2-(2-(2-(2-(8-(3-Propanoyl)-8,9-dihydro-1H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-1-yl)ethoxy)ethoxy)ethoxy)ethyl)-4-iodobenzamide (5) To a solution of the azide 1 (13.5 mg, 0.03 mmol) in DMSO (1 mL), <strong>[1255942-06-3]DBCO-amine</strong> 4 (11.2 mg, 0.03 mmol) was added. The reaction solution was stirred for 0.5 h at room temperature. The crude mixture was purified with preparative-HPLC (eluent gradient: 20% solvent B for 0-2 min; 20-80% solvent B for 2-22 min; 80-100% solvent B for 22-23 min; 100% solvent B for 23-28 min, retention time: 10.3 min) to give the product 5 (16 mg, 69%). HRMS ([M+H]+) Calcd for C33H38IN6O5+: 725.1943; Found 725.1951.
  • 19
  • [ 1255942-06-3 ]
  • 2-((2-azidoethoxy)methyl)-4-bromo-1-fluorobenzene [ No CAS ]
  • C27H25Br(19)FN5O2 [ No CAS ]
  • 20
  • [ 1255942-06-3 ]
  • 2-((2-azidoethoxy)methyl)-4-bromo-1-fluorobenzene [ No CAS ]
  • C27H25Br(18)FN5O2 [ No CAS ]
  • 21
  • [ 1255942-06-3 ]
  • [ 152711-55-2 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% In dimethylsulfoxide-d6; at 20℃; for 0.5h; 2 mg of 3-azidocoumarin was shaken with 3 mg of DBCO amine (1:1 mole ratio) in 0.5 ml of DMSO-d6 at room temperature for 30 minutes at 1000 rpm. The reaction was completed within 30 minutes and we performed the NMR of this solution.3-(8-(3-Aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-2H-chromen-2-one (4a): yellow powder; yield 95%; 1H NMR (400 MHz, DMSO-d6): σ 1.83-1.90 (m, 2H, CH2), 3.05-3.10 (m, 2H, CH2), 3.66 (d, 2H, J=13Hz, NH2), 5.06 (s, 2H, CH), 6.68-6.74 (m, 2H, ArH), 6.97 (t, 1H, J=6.0Hz), 7.10-7.36 (m, 2H, ArH), 7.38-7.46 (m, 5H, ArH), 7.47-7.51 (m, 2H, ArH), 7.64 (t, 1H, J=7.2Hz, ArH); ESI-MS (MeOH): m/z: 464.1 [M+H]+; HRMS (ESI): m/z calcd for C27H21N5O3+H+: 464.1644 [M+H]+; found: 464.1638 [M+H]+.
  • 22
  • [ 1255942-06-3 ]
  • C10H7N3O3 [ No CAS ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-8-methoxy-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e) were shaken with of DBCO (3) (1:1 mole ratio) in 0.5 ml of DMSO-d6 at room temperature for 30 minutes at 1000 rpm. The reaction was completed within 30 minutes which was confirmed by TLC. Consequently, NMR was performed with this solution.
  • 23
  • [ 1255942-06-3 ]
  • [ 817638-68-9 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-7-hydroxy-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e) were shaken with of DBCO (3) (1:1 mole ratio) in 0.5 ml of DMSO-d6 at room temperature for 30 minutes at 1000 rpm. The reaction was completed within 30 minutes which was confirmed by TLC. Consequently, NMR was performed with this solution.
  • 24
  • [ 1255942-06-3 ]
  • C9H3Cl2N3O2 [ No CAS ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-6,8-dichloro-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e) were shaken with of DBCO (3) (1:1 mole ratio) in 0.5 ml of DMSO-d6 at room temperature for 30 minutes at 1000 rpm. The reaction was completed within 30 minutes which was confirmed by TLC. Consequently, NMR was performed with this solution.
  • 25
  • [ 1255942-06-3 ]
  • [ 817638-73-6 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-6-bromo-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e) were shaken with of DBCO (3) (1:1 mole ratio) in 0.5 ml of DMSO-d6 at room temperature for 30 minutes at 1000 rpm. The reaction was completed within 30 minutes which was confirmed by TLC. Consequently, NMR was performed with this solution.
  • 26
  • [ 1255942-06-3 ]
  • 4-azido-2-(methylthio)pyrimidine [ No CAS ]
  • C23H21N7OS [ No CAS ]
  • 27
  • [ 1255942-06-3 ]
  • 4-azidopyrimidin-2(1H)-one [ No CAS ]
  • C22H19N7O2 [ No CAS ]
  • 28
  • [ 1255942-06-3 ]
  • 4-azido-N-methylpyrimidin-2-amine [ No CAS ]
  • C23H22N8O [ No CAS ]
  • 29
  • [ 1189-71-5 ]
  • [ 1255942-06-3 ]
  • N-(2-hydroxyethyl)pyrene-1-carboxamide [ No CAS ]
  • C38H30N4O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% Compound 65 (26 mg, 0.09 mmol) was dissolved in DCM (2 mL) followed by the addition of CSI (8 tL, 0.09 mmol). After 5 mi Et3N (37 tL, 0.27 mmol) and 64 (26 mg, 0.09 mmol) were added and the reaction was stirred for 2 h at rt, after which the reaction was quenched through the addition of aqueous NH4C1 (sat., 5 mL). The organic layer was washed with water (3 x 5 mL), dried over Na2504, filtrated and concentratedin vacuo. Purification via gradient flash column chromatography (DCM - DCM:MeOH95:5) yielded product 29 (10 mg, 17%). ‘H NIVIR (400 MHz, CDC13) (ppm) 8.49 (d,1H, J= 9.2 Hz), 8.25-8.18 (m, 3H), 8.11-7.95 (m, 5H), 7.38-7.00 (m, 8H), 6.05 (m, 1H),5.96 (m, 1H), 4.62-4.58 (m, 1H). 4.52-4.47 (m, 1H), 4.11-4.08 (m, 1H), 3.81-3.78 (m,1H), 3.64-3.60 (m, 1H), 3.06 (d, 1H, J= 14Hz), 2.90-2.87 (m, 2H), 2.17-2.09 (m, 1H),1.62-1.56 (m, 2H).
  • 30
  • [ 1255942-06-3 ]
  • C32H34N2O9 [ No CAS ]
  • C46H45N3O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
12 mg With triethylamine; for 1h; Compound 45 (75 mg, 0.22 mmol) was dissolved in DCM (3 mL) followed by the addition of amino-PEG4-carboxylic acid (53 mg, 0.20 mmol) and Et3N (83 tL, 0.6 mmol). After stirring overnight additional 45 (25 mg, 0.07 mmol) was added and thereaction mixture was stirred for an additional 1 h. After complete conversion (based on TLC-analysis), N-hydroxysuccinimide (5 mg, 0.04 mmol) and EDC.HC1 (70 mg, 0.36 mmol) were added and the reaction was stirred overnight at rt. To the reaction mixture was added 64 (60 mg, 0.2 mmol) and Et3N (50 tL, 0.36 mmol) were added and after 1 h the reaction mixture was concentrated under reduced pressure. Purification via gradientflash column chromatography (DCM -* DCM:MeOH 9:1) yielded product 27 (12 mg,8%). ‘HNIVIR (400 IVIFIz, CDC13) (ppm) 8.61 (d, 1H, J= 9.2 Hz), 8.23-8.21 (m, 2H),8.17-8.10 (m, 4H), 8.07-8.02 (m, 3H), 7.59 (d, 1H, J= 7.2 Hz), 7.38-7.18 (m, 7H), 7.06(bs, 1H), 6.45 (m, 1H), 5.00 (d, 1H, J= 13.6), 3.86-3.79 (m, 3H), 3.70-3.19 (m, 14H),2.42-2.38 (m, 1H), 2.19-2.15 (m, 2H), 1.89-1.85 (m, 1H).
  • 31
  • [ 1255942-06-3 ]
  • C40H50N2O13 [ No CAS ]
  • C54H61N3O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
8 mg With triethylamine; for 4h; Compound 45 (24 mg, 0.07 mmol) was dissolved in DCM (1 mL) followed by the addition of amino-PEG8-carboxylic acid (27 mg, 0.06 mmol) and Et3N (14 tL, 0.10 mmol). After stirring for 2 h, additional 45 (10 mg, 0.03 mmol) was added and thereaction mixture was stirred for on. Subsequently, NHS (10 mg, 0.08 mmol) andEDC.HC1 (17 mg, 0.09 mmol) were added and the reaction was stirred for 2h. Next 64(21 mg, 0.08 mmol) and Et3N (14 tL, 0.10 mmol) were added and after 4 h the reactionwas quenched by the addition of water (3 mL). The organic layer was washed with water(2 x 3 mL), dried over Na2504, filtrated and concentrated under reduced pressure.Purification via flash column chromatography (DCM -* DCM:MeOH 93:7) yielded theproduct (8 mg, 14%). ‘H NIVIR (400 MHz, CDC13) (ppm) 8.55 (d, 1H, J = 9.2 Hz), 8.19-7.86 (m, 7H), 7.59 (d, 1H, J= 6.8 Hz), 7.33-7.18 (m, 8H), 6.99 (m, 1H), 6.45 (m, 1H), 5.03 (d, 1H, J= 14.0), 3.78-3.74 (m, 3H), 3.65-3.29 (m, 29H), 2.43-2.37 (m, 1H)2.25-2.21 (m, 2H), 1.91-1.84 (m, 1H).
  • 32
  • [ 1255942-06-3 ]
  • C10H20O8S [ No CAS ]
  • C28H34N2O8S [ No CAS ]
  • 33
  • [ 1255942-06-3 ]
  • C16H24O8S [ No CAS ]
  • C34H38N2O8S [ No CAS ]
  • 34
  • [ 1255942-06-3 ]
  • 4-((6-amino-2-butoxy-8-hydroxy-9H-purin-9-yl)methyl)benzoic acid [ No CAS ]
  • C35H33N7O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With 1-[(1-(cyano-​2-​ethoxy-​2-​oxoethylidenaminooxy)​dimethylamino-​morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 2h;Cooling with ice; <strong>[1255942-06-3]DBCO-amine</strong> (50 mg, 0.18 mmol) and N,N-diisopropylethylamine (42 μL, 0.24 mmol) were added to a solution of3b (43 mg, 0.12 mmol) in DMSO (1.4 ml). After placing the reaction flask in ice, COMU (77 mg, 0.18 mmol) wasadded. The flask was allowed to warm to room temperature while stirring and the reaction was continued for 2hours. The reaction mixture was poured into ethyl acetate (12 ml) and refrigerated (4C) for an hour. The mixturewas then poured into a 100 ml glass-capped round-bottom flask. 1N sodium bicarbonate (7.8 ml) was added and thecontents were mixed and allowed to settle. After concentrating the mixture in vacuo, the flask was cooled at 0C for onehour. The solid obtained was filtered under vacuum and purified by flash chromatography (7% methanol/CH2Cl2) togive the product in 70% yield. 1H NMR (600 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.20 (t, J = 5.6 Hz, 1H), 7.68 - 7.52(m, 4H), 7.50 - 7.46 (m, 1H), 7.46 - 7.36 (m, 3H), 7.34 - 7.25 (m, 3H), 7.20 (dd, J = 7.5, 1.1 Hz, 1H), 6.47 (s,2H), 5.05 (d, J = 14.1 Hz, 1H), 4.87 (s, 2H), 4.11 (t, J = 6.6 Hz, 2H), 3.62 (d, J = 14.0 Hz, 1H), 3.33 - 3.29 (m,1H), 3.10 (dt, J = 13.7, 6.0 Hz, 1H), 2.56 - 2.52 (m, 1H), 2.00 - 1.94 (m, 1H), 1.64 - 1.56 (m, 2H), 1.35 (dq, J =14.8, 7.4 Hz, 2H), 0.88 (t, J = 7.4 Hz, 3H); 13C NMR (126 MHz, DMSO-d6) δ 170.2, 165.7, 160.1, 152.2, 151.4,149.2, 148.3, 147.8, 140.1, 133.5, 132.4, 129.5, 128.9, 128.2, 128.0, 127.7, 127.3, 127.1, 126.8, 125.2, 122.5,121.4, 114.33, 108.1, 98.3, 65.9, 54.8, 48.0, 42.1, 35.8, 34.2, 30.6, 18.8, 13.7; HRMS (+ESI) calcd for C35H34N7O4(MH+) 616.2667, found 616.2676; (-ESI) calcd for C35H32N7O4 (M-H+) 614.2521, found 614.2534.
  • 35
  • [ 1255942-06-3 ]
  • 8-azidotoyocamycin [ No CAS ]
  • C30H28N10O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% In water; acetonitrile; at 20℃; for 4h;Inert atmosphere; Cyclooctyne 6 (16.6 mg, 0.06 mmol) was added to a stirred solution of 3b (20 mg, 0.06 mmol) in ACN and H2O (3:1) in a flask and the resulting clear, pale red solution was stirred at room temperature for 4 h, by which time TLC showed >80% conversion to a more polar product almost on the baseline. Volatiles were removed using high vacuum rotary evaporator on a ho twater bath (<80 oC). The resulting pale red oily gum was then injected into a semi-preparative HPLC column (Phenomenex Gemini RP-C18 column; 5µ, 25 cm x 1 cm) via a 2.5 mL loop and was eluted with an isocratic mobile phase mixture 40% CH3CN in H2O at a flow rate of 1.0 mL/min to give isomers of 7 [~1:1; 17.1 mg, 47%; Rf (EtOAc:iPrOH:H2O,4:1:2, upper layer) 0.13] as an off-white gummy solid: UV (MeOH) λmax 290 nm (ε 12 600) λmin 260 nm (ε 9500); 1H NMR (DMSO-d6/D2O) δ 8.38 (s, 0.5H, H2), 8.33 (s, 0.5H, H2), 7.75-7.05 (m, 8H, Har), 6.20-6.10 (m, 0.5H, H1'), 5.85-5.80 (m, 0.5H, H1'), 5.25-5.15 (m, 1H, H2'), 4.62-4.50 (m, 2H, CH2), 4.11-3.38 (m, 4H, H3', H4', H5', H5"), 2.73-2.65 (m,2H, CH2NH2), 2.60-2.49 (m, 2H, CH2CO), 1.96-1.55 (m, 2H, NH2); HRMS (ESI) m/z[M+H]+ calcd for [C30H29N10O5]+609.2317; found 609.2332.
  • 36
  • [ 1255942-06-3 ]
  • C15H19N3O5S [ No CAS ]
  • C33H33N5O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24h; Compound 7 (370 mg, 1.23 mmol),Compound 8a (434 mg, 1.23 mmol), Diisopropylethylamine (DIPEA, 0.322 mL, 1.85 mmol) toIn dichloromethane (10 mL) Melted and EDCI (259 mg, 1.35 mmol) to Put at room temperature for 24 hoursAfter stirring water was added. After washing the reaction mixture with water and saturated aqueous sodium bicarbonate solution over anhydrous sodium sulfateTo remove the water.After the removal of the solvent under reduced pressure was purified by column chromatographyUsed to obtain a white solid product 6e (555mg, 74%)
  • 37
  • [ 1255942-06-3 ]
  • [ 817638-68-9 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-7-hydroxy-2H-chromen-2-one [ No CAS ]
  • C27H21N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield. Characterization of Compound 5a-f: Compound 5a: 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-7-hydroxy-2H-chromen-2-one(5a): Yield: 95%; mp: 128-130C;Rf (2% MeOH in EA): 0.36; 1H NMR (400 MHz, DMSO-d6): σ 1.86-1.88 (m, 2H, CH2),2.62 (brs, 2H, CH2), 3.18 (s, 2H, CH2), 5.04-5.07 (m, 2H,NH2), 7.23-7.40 (m, 7H, ArH), 7.48-7.51 (m, 3H, ArH), 7.63-7.65 (m,2H, ArH); 13C NMR (125 MHz, DMSO-d6): σ 33.4 (CH2),35.8 (CH2), 54.9 (CH2), 101.8 (CH), 107. 9 (CH), 109.0(CH), 113.0 (CH), 114.3 (CH), 121.5 (CH), 122.3 (CH), 125.2 (CH), 125.7 (C),126.9 (CH), 127.8 (C), 128.1 (CH), 128.4 (C), 128.8 (C), 129.1 (CH), 129.6(CH), 130.3 (C), 132.4 (CH), 148.2 (C), 149.3 (C), 150.9 (C), 156.2 (-COH),159.0 (-OCO), 169.8 (-NCO); ESI-MS (MeOH): 480 [M+H]+.
  • 38
  • [ 1255942-06-3 ]
  • C10H7N3O3 [ No CAS ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-8-methoxy-2H-chromen-2-one [ No CAS ]
  • C28H23N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield.
  • 39
  • [ 1255942-06-3 ]
  • [ 817638-73-6 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-6-bromo-2H-chromen-2-one [ No CAS ]
  • C27H20BrN5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield.
  • 40
  • [ 1255942-06-3 ]
  • C9H3Cl2N3O2 [ No CAS ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-6,8-dichloro-2H-chromen-2-one [ No CAS ]
  • C27H19Cl2N5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield.
  • 41
  • [ 1255942-06-3 ]
  • [ 152711-55-2 ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-2H-chromen-2-one [ No CAS ]
  • C27H21N5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield.
  • 42
  • [ 1255942-06-3 ]
  • 3-azido-7-(2-bromoethoxy)chromen-2-one [ No CAS ]
  • 3-(8-(3-aminopropanoyl)-8,9-dihydro-3H-dibenzo[b,f][1,2,3]triazolo[4,5-d]azocin-3-yl)-7-(2-bromoethoxy)-2H-chromen-2-one [ No CAS ]
  • C29H24BrN5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethylsulfoxide-d6; at 20℃; for 0.5h; General procedure: 3-Azidocoumarin derivatives (2a-e, 3f) wereshaken with DBCO (4) (1:1 moleratio) in 0.5 ml of DMSO-d6at room temperature for 30 minutes at 1000 rpm. The reaction was completedwithin 30 minutes which was confirmed by TLC. Consequently, NMR was performedwith the solution. The Solvent has been evaporated and a mixture ofregioisomers (1:1) was formed with high yield.
  • 43
  • [ 1255942-06-3 ]
  • C13H19(125)IN4O4 [ No CAS ]
  • C31H35(125)IN6O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% In dimethyl sulfoxide; at 37℃; for 0.5h; To asolution of <strong>[1255942-06-3]DBCO-amine</strong> 4 (2 mL in DMSO), 125I-labeledazide pyridine ([125I]1, 1.5 MBq, 18 mL in DMSO) wasadded. Total reaction mixture was 20 mLand the final concentration of <strong>[1255942-06-3]DBCO-amine</strong> was 1 mM (20 nmol) or 100 mM (2 nmol). Thelabeling reaction was conducted at 37 C for 60 min. Radiochemicalyields of [125I]-<strong>[1255942-06-3]DBCO-amine</strong> were determined by integration ofanalytical radio-HPLC chromatogram (eluent gradient: 40% solvent B in solvent Afor 0-2 min; 40-100% solvent B in solvent A for 2-22 min; 100% solvent B insolvent A for 22-28 min, retention time of [125I]7 was 6.9 min).
  • 44
  • [ 1120-71-4 ]
  • [ 1255942-06-3 ]
  • C21H22N2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% In dichloromethane; at 20℃; A solution of DECO-Amine (4 g, 14.48 mmol) (Click Chemistry Tools, Scottsdale, Ariz.) and 1,2-oxathio- lane 2,2-dioxide (1.591 g, 13.03 mmol) in DCM (20 mE) was stirred overnight at room temperature. A white precipitate was filtered, washed with a small amount of THF-Et20, and dried on an oil pump to provide 3.53 g (8.86 mmol, 61%) of Compound 16.
  • 45
  • [ 1255942-06-3 ]
  • DM1-SMCC [ No CAS ]
  • DBCO-MCC-DM1 [ No CAS ]
  • 46
  • [ 1255942-06-3 ]
  • C39H46N3O10S2(1-)*Na(1+) [ No CAS ]
  • DBCO-Cy5 [ No CAS ]
  • 47
  • [ 1255942-06-3 ]
  • [ 1375413-67-4 ]
  • C31H31N3O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 0.5h; DECO-Amine (0.877 g, 3.17 mmol) (Click Chemistry Tools, Scottsdale, Ariz.) was added to a solution of 2,5-dioxopyrrolidin- 1 -yl 4-(4-(1 -hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanoate (4) in DCM (25 ml) at room temperature. The reaction mixture was stirred for ca. 30 mm. According to TLC analysis, all NHS ester was consumed. The reaction mixture was transferred into a separatory thnnel, washed with 5% HC1, dried over Na2504 and concentrated. The crude product was purified on silica gel to provide PC-DECO-OH 15 as a yellow solid.
  • 48
  • [ 1255942-06-3 ]
  • [ 1610596-19-4 ]
  • C47H43N5O4 [ No CAS ]
  • 49
  • [ 1255942-06-3 ]
  • [ 127985-74-4 ]
  • C42H49N7O9S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In N,N-dimethyl-formamide; at 40℃; for 12h; P-SCN-Bn-DOTA (0.05 mmol, 34 mg) and <strong>[1255942-06-3]DBCO-amine</strong> (0.05 mmol, 14 mg) were suspended in anhydrous DMF (1 mL). Triethylamine (0.2 mmol, 20 mg) was added and the mixture was stirred at 40oC. HPLC measurements showed complete reaction after 12 h. The solvent was removed under reduced pressure and the product was used without further purification. LRMS (ESI) m/z: calculated forC42H50N7O9S [M + H]+828.3, found 828.2.
  • 50
  • [ 1255942-06-3 ]
  • [ 1510-21-0 ]
  • C49H64N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
40.3% 5 g of cholesterol and 1.55 g of succinic anhydride were dissolved in 90 mL of pyridine,90 reflux 24h,Cool to room temperature,Dilute hydrochloric acid (pH 1.0, 100 mL)Produce a white precipitate,filter,After the filter cake was washed with ethyl acetate dissolved in water,Dichloromethane / methanol column chromatography,A white solid (cholesterol succinate, 5.24 g, 85.3%) was obtained.100 mg of cholesterol succinate monoester was dissolved in 10 mL of chloroform,Stirred at room temperature,65 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI) was added,46 mg of 1-hydroxybenzotriazole (HOBt) and 150 μL of triethylamine,After 1 h 62.5 mg of ADIBO,After stirring at room temperature overnight,After completion of the reaction, wash with water (10 mL × 3)The organic layer was concentrated,Dichloromethane / methanol column chromatography,Obtained as a light yellow solid (azabicyclooctynecholesterol, 64 mg, 40.3%).
  • 51
  • [ 1255942-06-3 ]
  • [ 1332724-68-1 ]
  • C61H40N6O3S [ No CAS ]
  • C46H31N5O4S [ No CAS ]
  • 52
  • [ 38862-24-7 ]
  • [ 1255942-06-3 ]
  • C21H18N2O2 [ No CAS ]
  • 53
  • [ 616-91-1 ]
  • [ 1255942-06-3 ]
  • C23H25N3O4S [ No CAS ]
  • C23H25N3O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water-d2; dimethyl sulfoxide; for 0.333333h; To a vial, solution 1 (0.5 mL, 0.02 mmol 9) was added followed by H2O2 (7 μL, 30 wt% in H2O). Thesolution was then stirred for a few seconds before dropwise addition of solution 2 (0.5 mL, 0.06 mmol 9)over 1 minute. The reaction mixture was stirred for 20 minutes before analysing directly by LC-MS.
  • 54
  • [ 1255942-06-3 ]
  • C105H196N10O21S [ No CAS ]
  • C123H210N12O21S [ No CAS ]
YieldReaction ConditionsOperation in experiment
50.16% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 6.5h;Inert atmosphere; Compound 5 ( 60 mg, 30 μπιο) and <strong>[1255942-06-3]DBCO-amine</strong> (10 mg, 33 μπιο) were dissolved in DCM (4 ml) followed by addition of propylphosphonic anhydride (T3P) (27 μ, 45 μπιο) and DIPEA (9 μ, 45 μπιο). The reaction mixture was stirred under N2 atmosphere at RT. The reaction was monitored by TLC (CHCl3:EtOH) and appeared complete after 6.5 h. The reaction mixture was diluted with DCM (5 ml) and washed with saturated NaHC03 (5 ml) and water (5 ml). The organic layer was separated, dried over Na2S04, and evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (CHCl3:EtOH) to obtain compound 6 as a white powder (33 mg, 50.16%). HR-MALDI- MS: [M+Na] m/z calcd for Ci23H2ioNi2Na02iS, 2248.16; found, 2248.899. FIG. 16 shows the HRMS spetrum of side -chain protected Parri3CysSK4-DBCO conjugate 6 ("CysSILt" disclosed as SEQ ID NO: 16).
  • 55
  • [ 1255942-06-3 ]
  • C105H196N10O21S [ No CAS ]
  • C123H210N12O21S [ No CAS ]
  • 56
  • [ 1255942-06-3 ]
  • Pha-GSGRSAG [ No CAS ]
  • Pha-GSGRSAG-DBCO [ No CAS ]
  • 57
  • [ 1255942-06-3 ]
  • [ 114932-60-4 ]
  • C38H30N2O2 [ No CAS ]
  • 58
  • [ 1255942-06-3 ]
  • C54H71N16O11(1+)*C2F3O2(1-) [ No CAS ]
  • [ 76-05-1 ]
  • BHQ3-GSGRSAG-DBCO TFA salt [ No CAS ]
  • 59
  • [ 1255942-06-3 ]
  • C60H83N20O10(1+)*C2F3O2(1-) [ No CAS ]
  • [ 76-05-1 ]
  • BHQ3-GAGRRAAG-DBCO TFA salt [ No CAS ]
  • 60
  • [ 1255942-06-3 ]
  • C62H84N18O13 [ No CAS ]
  • Pha-GAGRRAAG-DBCO [ No CAS ]
  • 61
  • [ 108-55-4 ]
  • [ 1255942-06-3 ]
  • [ 1337920-25-8 ]
YieldReaction ConditionsOperation in experiment
45% In dichloromethane; at 20℃; for 2h; To a solution of <strong>[1255942-06-3]DBCO-amine</strong> (50 mg, 180.9 pmol) in DCM (2 mL) was added glutaricanhydride (21.1 mg, 180.9 pmol). The reaction medium was stirred for 2 h at RT,concentrated in vacuo and purified by flash chromatography on 4 g of silica gel(gradient elution DCM/MeOH) to give 32.6 mg of compound 84 (45%).RMN 1H (400 MHz, ö in ppm, DMSO-d6): 1.59 (m, 2 H) ; 1.81 (m, 1 H); 1.94 (t, J =7.4 Hz, 2 H); 2.11 (t, J = 7.4 Hz, 2 H); 2.40 (m, 1 H); 2.91 (m, 1 H); 3.09 (m, 1 H);3.62 (d, J = 14.2 Hz, 1 H); 5.13 (d, J = 14.2 Hz, 1 H); 7.38 to 7.53 (m, 6 H); 7.56 to7.67 (m, 3 H); 12.05 (broad m, 1 H).
  • 62
  • [ 1255942-06-3 ]
  • 4-carboxy-2-(7-(dimethylamino)-3-(dimethyliminio)-5,5-dimethyl-3,5-dihydrodibenzo[b,e]silin-10-yl)benzoate [ No CAS ]
  • C45H42N4O4Si [ No CAS ]
  • 63
  • [ 161621-25-6 ]
  • [ 1255942-06-3 ]
  • C29H23FeN3O5 [ No CAS ]
  • 64
  • [ 24424-99-5 ]
  • [ 1255942-06-3 ]
  • [ 1539290-74-8 ]
  • 65
  • [ 1255942-06-3 ]
  • [ 107-19-7 ]
  • 2-propyn-1-yl N-(3-(5H,6H-11,12-didehydrodibenzo[b,f]azocin-5-yl)-3-oxopropyl)carbamate [ No CAS ]
  • 66
  • [ 1255942-06-3 ]
  • C14H19N3O10(4-)*Tb(3+) [ No CAS ]
  • C32H33N5O10(4-)*Tb(3+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 4-morpholineethanesulfonic acid; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dimethyl sulfoxide; at 20℃; for 2h;pH 5.5;Darkness; Metalation of DTPA with terbium exposed DTPA’s central carboxylic acid moiety foramide coupling with the <strong>[1255942-06-3]DBCO-amine</strong> (Fig 1B) to generate the clickable lanthanide chelator(CLC, Fig 1D). Amide coupling was performed by combining <strong>[1255942-06-3]DBCO-amine</strong> dissolved inDMSO (8.33% (v/v)) in 100 mM MES, pH 5.5, with 10 mM DTPA:Tb to achieve a final concentrationof 50 mM <strong>[1255942-06-3]DBCO-amine</strong>. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)was added to the amide coupling reaction until a final concentration of 50 mM was reached.The reaction was gently rocked, protected from light, at room temperature for 120 minutes.Upon completion, the entire reaction mixture was applied to a pre-equilibrated size-exclusioncolumn containing G10 Sephadex resin (GE Healthcare, Chicago, IL), which excludesparticles 700 Da, and therefore also the CLC (806.2 Da). Approximately 3.5-mL fractionswere eluted from the G10 column using 100 mM MES, pH 5.5. Each fraction was evaluatedusing a Fluoromax 4 FluoroHub spectrofluorometer (HORIBA Jobin Yvon, Edison, NJ), withthe Origin FluorEssence software package (HORIBA Jobin Yvon). Fractions were analyzed forfluorescence as follows: 1) excitation at 350 nm with emission monitored from 400-800 nmand 2) excitation at 259 nm with emission monitored from 300-800 nm. Fractions containingsubstantial fluorescence were lyophilized, reconstituted in mobile phase, and analyzed byUPLC-MS.
  • 67
  • [ 1255942-06-3 ]
  • C50H59N5O29 [ No CAS ]
  • C62H70N6O27 [ No CAS ]
  • 68
  • [ 1255942-06-3 ]
  • C14H12N3O(1+)*I(1-) [ No CAS ]
  • C32H28N5O2(1+)*I(1-) [ No CAS ]
  • 69
  • [ 1255942-06-3 ]
  • 3-(2-(2-fluoroethoxy)ethoxy)propanoic acid [ No CAS ]
  • C25H27FN2O4 [ No CAS ]
  • 70
  • [ 1255942-06-3 ]
  • 3-(2-(2-(tosyloxy)ethoxy)ethoxy)propanoic acid [ No CAS ]
  • C32H34N2O7S [ No CAS ]
  • 71
  • [ 1255942-06-3 ]
  • (3,9-dihydro-1,3-dioxopyrido[3,4,5-gh][1,2,4]triazolo[1,5-a]perimidine-2(1h)-hexanoic acid) [ No CAS ]
  • C38H31N7O4 [ No CAS ]
  • 72
  • [ 1255942-06-3 ]
  • 1-((2S,3S,6S,7R,10R,E)-7-acetoxy-10-hydroxy-2-((R,2E,4E)-6- hydroxy-7-((2R,3R)-3-((2R,3S)-3-hydroxypentan-2-yl)oxiran-2-yl)-6-methylhepta-2,4- dien-2-yl)-3,7-dimethyl-12-oxooxacyclododec-4-en-6-yl) 4-(4-((S)-2-((S)-2-amino-3- methylbutanamido)-5-ureidopentanamido)benzyl) piperazine-1,4-dicarboxylate [ No CAS ]
  • [ 7693-46-1 ]
  • 1-((2S,3S,6S,7R,10R,E)-7-acetoxy-10-hydroxy-2-((R,2E,4E)-6-hydroxy-7-((2R,3R)-3-((2R,3S)-3-hydroxypentan-2-yl)oxiran-2-yl)-6-methylhepta-2,4-dien-2-yl)-3,7-dimethyl-12-oxooxacyclododec-4-en-6-yl) 4-(4-((9S,12S)-9-isopropyl-3,7,10-trioxo-12-(3-ureidopropyl)-2,6,8,11-tetraazatridecan-13-dibenzenecyclooctyneamido)benzyl) piperazine-1,4-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
8.27% To a solution of 3-amino-1-(11,12-dihydrodibenzo[b,f]azocin-5(6H)-yl)propan-1-one (19.36 mg, 0.07 mmol) in DCM (5 ml_) at 0C was added Hunig’s base (10.26 mg, 0.079 mmol) followed by 4-nitrophenyl carbonochloridate (14.12 mg, 0.07 mmol). The reaction was warmed to 20C and stirred for 2 h. The mixture was then concentrated to dryness and diluted with DMF. The resulting mixture was charged Hunig’s base (10.26 mg, .079 mmol) and 1-((2S,3S,6S,7R,10R,E)-7-acetoxy-10-hydroxy-2-((R,2E,4E)-6- hydroxy-7-((2R,3R)-3-((2R,3S)-3-hydroxypentan-2-yl)oxiran-2-yl)-6-methylhepta-2,4- dien-2-yl)-3,7-dimethyl-12-oxooxacyclododec-4-en-6-yl) 4-(4-((S)-2-((S)-2-amino-3- methylbutanamido)-5-ureidopentanamido)benzyl) piperazine-1,4-dicarboxylate (50 mg, .047 mmol) and sitrred for 1 h. The mixture was then concentrated to dryness and purified by column chromatography followed by reverese-phase purification to afford 1- ((2S,3S,6S,7R,10R,E)-7-acetoxy-10-hydroxy-2-((R,2E,4E)-6-hydroxy-7-((2R,3R)-3- ((2R,3S)-3-hydroxypentan-2-yl)oxiran-2-yl)-6-methylhepta-2,4-dien-2-yl)-3, 7-dimethyl- 12-oxooxacyclododec-4-en-6-yl) 4-(4-((9S,12S)-9-isopropyl-3,7,10-trioxo-12-(3-ureidopropyl)-2,6,8,1 1-tetraazatridecan-13-dibenzenecyclooctyneamido)benzyl) piperazine-1,4-dicarboxylate (5.3mg, 8.27%) LCMS (ESI, m/z) 1372.7 [M]+
  • 73
  • [ 1255942-06-3 ]
  • C12H18FNO8 [ No CAS ]
  • C30H32FN3O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; Scheme El-2: 1 mmol 6-succinyl-4-F-GlcNAc, 10 molar excess of DBCO- amine, 5 molar excess of HBTU, 1 m DIPEA and 108 μl DMF were stirred at RT overnight. The products were purified by Akta purifier (GE Healthcare) HPLC instrument with Gemini 5 mm NX-C18 reverse phase column (4.6 x 250 mm, 110 A (Phenomenex) ) eluted with acetonitrile gradient in aqueous ammonium acetate buffer. The fractions were analysed by MALDI-TOF MS similarly as above, showing expected mass for DBCO-6- succinyl-4-F-GlcNAc (Figure 3, m/z 604 [M+Na]+) .
  • 74
  • [ 1255942-06-3 ]
  • C16H15F5N2O5S [ No CAS ]
  • C28H30N4O5S [ No CAS ]
  • 75
  • [ 1255942-06-3 ]
  • [(1,2,3,4,5-pentamethylcyclopentadiene)Ir(4-methyl-4′-carboxy-2,2′-bipyridine)Cl]PF6 [ No CAS ]
  • C40H39ClIrN4O2(1+)*F6P(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Complex Ir-I (26 mg, 0.036 mmol) was dissolved in anhydrousDCM (10 mL) in a two-neck round-bottomed flask to obtain a clearyellow solution. Oxalyl chloride (0.5 mL 2.0 M) was injected slowlyunder nitrogen into the solution which was cooled over an ice bath. Acatalytic amount of anhydrous DMF was then added and the solutioncolour changed from yellow to red due to the carboxylic acid group ofcomplex Ir-I being converted to the acyl chloride. The reaction mixturewas further stirred for 2 h at 298 K and the solvent was taken off undervacuum to obtain a yellow residue. In a new two-neck flask, anhydrousDCM (10 mL), TEA (0.2 mL) and <strong>[1255942-06-3]dibenzocyclooctyne-amine</strong> (DBCONH2)(10 mg, 0.036 mmol) were added. The acid chloride was resuspendedin anhydrous DCM (8 mL) and added dropwise to the icecooled mixture in the new flask within 0.5 h. The final mixture wasstirred at 298 K for 4 h under nitrogen and dark conditions. The solventwas evaporated under vacuum and the crude solid obtained was purifiedon an Al2O3 column with MeOH/DCM (1/4 v/v). Yield 23 mg,yellow solid, 65%; 1H NMR (400 MHz, d4-MeOD, 298 K): δ 9.09 (d,0.5H, J = 5.8 Hz), 9.00 (d, 0.5H, J = 5.9 Hz), 8.86 (d, 0.5H,J = 4.3 Hz), 8.83 (d, 0.5H, J = 4.2 Hz), 8.72 (s, 0.5H), 8.57 (s, 0.5H),8.47 (s, 0.5H), 8.33 (s, 0.5H), 8.05 (d, 0.5H, J = 5.9 Hz), 7.86 (d, 0.5H,J = 5.8 Hz), 7.75-7.73 (m, 1H), 7.65 (d, 0.5H, J = 7.5 Hz), 7.62 (d,0.5H, J = 7.6 Hz), 7.51-7.41 (m, 4H), 7.32 (t, 0.5H, J = 7.6 Hz); 7.20(t, 0.5H, J = 7.4 Hz), 7.14 (t, 0.5H, J = 7.4 Hz), 6.72-6.86 (m, 1H),6.75 (d, 0.5H, J = 7.5 Hz), 5.13 (d, 1H, J = 14.0 Hz), 3.66 (d, 1H, J = 13.7 Hz), 3.48 (m, 2H), 2.61-2.54 (m, 1H), 2.73 (s, 1.5H), 2.72 (s,1.5H), 2.47-2.39 (m, 1H), 1.73 (s, 15H); 13C NMR (125 MHz, d4-MeOD,298 K): 173.35, 164.65, 156.07, 154.87, 153.72, 152.75, 152.58,149.52, 145.82, 133.59, 131.27, 130.56, 130.22, 129.91, 129.07,128.37, 127.97, 127.46, 126.47, 126.58, 126.53, 126.28, 124.19,123.64, 122.76, 122.26, 115.62, 91.17, 38.22, 34.96, 21.55, 8.73; highresolution ESI-MS m/z calcd for [M-PF6]+ 835.2379, found 835.2383.
  • 76
  • [ 1255942-06-3 ]
  • C36H38F2N6O14S [ No CAS ]
  • C72H66F2N10O14S [ No CAS ]
  • C54H52F2N8O14S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; 2 pmol di-6-succinyl-33DFTG, 3 molar excess of DBCO- amine, 5 molar excess of HBTU, 2 m DIPEA and 100 m DMF were stirred at RT for overnight. The DBCO-di-6-succinyl-33DFTG products were purified by Akta purifier (GE Healthcare) HPLC instrument with Gemini 5 pm NX-C18 reverse phase column (4.6 x 250 mm, 110 A (Phenomenex) ) eluted with acetonitrile gradient in aqueous ammonium acetate. The fractions were analysed by MALDI- TOF MS similarly as above, showing expected masses for mono-DBCO- di-6-succinyl-33DFTG (m/z 1129 [M+Na]+) and di-DBCO-di-6-succinyl- 33DFTG (Figure 3, m/z 1387 [M+Na]+) .
  • 77
  • [ 1255942-06-3 ]
  • C56H86N2O7S3 [ No CAS ]
  • C71H97N3O8S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 1h; (0489) Compound 54, referred to as NH2-Pam2Cys-DBCO, was synthesized using Compound 26 and DBCO-Amine as starting materials. 30 mg of Compound 26 (0.03 mmol, 1 eq) was prepared as a 100 mg/mL stock solution in DCM. To this stock solution was added 8.34 mg of DBCO-Amine (0.03 mmol, 1 eq) also as a 100 mg/mL stock solution in DCM. The reaction mixture was stirred for 1 hour at room temperature then injected on a flash chromatography column and purified. The gradient used was a stepwise gradient from 0-5% methanol in DCM (5CV hold, 1CV to increase methanol concentration by 1%). The fractions were collected and dried to provide the DBCO intermediate. 26 mg of Fmoc-Pam2Cys-DBCO (0.023 mmol, 1 eq) was dissolved in 1 mL of 20% Piperidine in DMF and stirred for 30 minutes at room temperature. The reaction mixture was diluted with DCM and washed three times with DI water. The organic layer was dried with sodium sulfate and evaporated. The solid was taken up in 0.5 mL of DCM and injected on a flash chromatography column and purified. The gradient used was a stepwise gradient from 0-5% methanol in DCM. The fractions were collected and dried to provide NH2-Pam2Cys-DBCO. Product molecular weight verified based on the MS (ESI+) for peptide antigen conjugates of Compound 54.
  • 78
  • [ 1255942-06-3 ]
  • [ 112-64-1 ]
  • C32H42N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 1h; (0483) Compound 49, referred to as Myr-DBCO or C14-DBCO was prepared from Myristoyl Chloride and DBCO-Amine 50 mg of DBCO-Amine (0.18 mmol, 1 eq) was dissolved in 0.5 mL of DCM. TEA (0.22 mmol, 1.2 eq) was added and the solution was stirred for 5 minutes at room temperature. Myristoyl Chloride (0.16 mmol, 0.9 eq) was added and the reaction mixture was stirred for 1 hour at room temperature. TLC (2.5% methanol in DCM) showed a new spot with rf of 0.5 for Myr-DBCO. The reaction mixture was injected on a flash chromatography column and purified using a gradient of 0-3% methanol in DCM over 12 CVs. The fractions were collected and dried to provide 86 mg of Myr-DBCO in quantitative yield. MS (ESI) calculated for C32H42N2O2 m/z 486.32 found 487.3 (m+H)+.
  • 79
  • [ 1255942-06-3 ]
  • C34H53NO3S2 [ No CAS ]
  • C49H64N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% In dichloromethane; at 20℃; for 1h; (0492) Compound 57, referred to as Chol-DBCO, was prepared from Compound 56 and DBCO-Amine 106.28 mg of Compound 56 (0.18 mmol, 1 eq) and 50 mg of DBCO-Amine (0.18 mmol, 1 eq) were dissolved in 0.5 mL of DCM and stirred at room temperature. Over the course of an hour the bright yellow color of the solution faded and TLC in DCM indicated complete absence of Compound 56. The reaction mixture was injected on a flash chromatography column and purified using a gradient of 0-3% methanol in DCM over 12 CVs. The fractions were collected and dried to provide 139 mg of Chol-DBCO in quantitative yield. Product molecular weight verified based on the MS (ESI+) for peptide antigen conjugates of Compound 57.
  • 80
  • [ 1255942-06-3 ]
  • (4-cyano-4-(phenylcarbono-thioylthio))pentanoic acid N-succinimidyl ester [ No CAS ]
  • C31H27N3O2S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 20℃; for 2h; (0497) Compound 62, referred to as CTA-DBCO, was synthesized from “CTA-NHS” (4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid N-succinimidyl ester, Sigma-Aldrich) and DBCO-Amine (Click Chemistry Tools). 210 mg of CTA-NHS (0.56 mmol, 1 eq) and 167.8 mg of DBCO-Amine (0.61 mmol, 1.1 eq) were dissolved in 2 mL of dry DMSO and stirred at room temperature for 2 hours. The reaction mixture was diluted with DCM and washed twice with 1M HCl and once with DI water. The organic layer was dried with sodium sulfate and evaporated. Compound 62 was purified on a preparatory HPLC system using a gradient of 50-70% acetonitrile/H2O (0.05% TFA) over 10 minutes on an Agilent Prep-C18 column, 30×100 mm, 5 μm. MS (ESI) calculated for C31H127N3O2S2 m/z 537.7, found 538.2 (M+H)+.
  • 81
  • [ 1255942-06-3 ]
  • [ 870779-03-6 ]
  • ACVA-DBCO [ No CAS ]
YieldReaction ConditionsOperation in experiment
95.1% In dichloromethane; at 20℃; for 1h; ACVA-DBCO is a DBCO functionalized initiator, which is an example of a strained-alkyne functionalized initiator that can be used to incorporate strained-alkynes to the ends of polymer arms (A) during polymerization or capping (i.e. by replacing the CTA of a living polymer). ACVA-DBCO was synthesized by reacting ACVA-TT with <strong>[1255942-06-3]DBCO-amine</strong>. To a 20 mL scintillation vial, ACVA-TT (201.4 mg, 0.417 mmol), <strong>[1255942-06-3]DBCO-amine</strong> (229.2 mg, 0.829 mmol), and 1 mL of DCM were added. The reaction was allowed to proceed for 1 h at r.t. before solvent was removed. The crude product was purified by flash chromatography using a silica gel column and a gradient of 0-5% MeOH in DCM to yield white solid (314.4 mg, 95.1 %). ESI-MS: m/z = 797.3 (M-H)+. [00445] Compound 10
In dimethyl sulfoxide; at 20℃; for 1h; General procedure: (0495) Compound 60, referred to as LA-2BXy, was synthesized using Compound 59 and Compound 2 as starting materials. 50 mg of Compound 59 (0.23 mmol, 1 eq) and 82.62 mg of Compound 2 (0.23 mmol, 1 eq) were dissolved in 1 mL of DMSO. The reaction mixture was stirred at room temperature for 1 hour. TLC (35% ethyl acetate in hexane) showed disappearance of both starting materials. Compound 60 was purified on a preparatory HPLC system using a gradient of 15-30% acetonitrile/H2O (0.05% TFA) over 10 minutes on an Agilent Prep-C18 column, 30×100 mm, 5 μm. MS (ESI) calculated for C27H31N5O2, m/z, 457.25, found 458.3 (M+H)+.
  • 82
  • fluorescein isothiocyanate [ No CAS ]
  • [ 1255942-06-3 ]
  • C39H27N3O6S [ No CAS ]
  • 83
  • [ 1255942-06-3 ]
  • dithiobis(succinimidyl) propionate [ No CAS ]
  • C24H24N2O4S2 [ No CAS ]
  • 84
  • [ 1255942-06-3 ]
  • C21H15O2P [ No CAS ]
  • N-(3-(5H,6H-11,12-didehydrodibenzo[b,f]azocin-5-yl)-3-oxopropyl)-3-ethynyl-5-(diphenylphosphino)benzamide [ No CAS ]
  • 85
  • [ 1255942-06-3 ]
  • [ 55804-65-4 ]
  • C34H29N3O4 [ No CAS ]
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[ 1255942-06-3 ]

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