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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
IR-780 iodide is a near-infrared lipophilic cation heptamethine fluorescent dye for the exclusive characterization of human CSCs through the HIF‐1α/glycolysis dependent mitochondrial transporter ABCB10's activity.
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| CAS No. : | 207399-07-3 |
| Formula : | C36H44ClIN2 |
| M.W : | 667.11 |
| SMILES Code : | C(N1/C(/C(C2=CC=CC=C12)(C)C)=C/C=C1\CCCC(=C\1Cl)C=CC1C(C2=CC=CC=C2[N+]=1CCC)(C)C)CC.[I-] |
| MDL No. : | MFCD00191907 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | In butan-1-ol; benzene; at 160℃; for 10h;Inert atmosphere; | la (500 mg, 2.9 mmol, lequiv) and lb (1.91g, 5.81 mmol, 2 equiv) were dissolved in n-butanol (BuOH)-benzene (7:3) under N2 atmosphere, and refluxed at 160 C for 10 hours with a Dean-Stark condenser. Afterwards, the solvent was evaporated, and the resulting green solid was washed with Et20 and purified by flash chromatography (DCM-MeOH, 50:1) to obtain 1 as a green solid (1.8 g, 96%). 1H- NMR (300 MHz, CDC13) 5=1.06 (t, 6H, J=7.5 Hz), 1.31 (m, 4H), 1.64 (s, 12H), 1.95 (m, 2H), 2.73 (m, 4H), 4.15 (t, 4H, J=6.9Hz), 6.23 (d, 2H, J=14.2 Hz), 7.15-7.72 (m, 8H), 8.19 (d, 2H, J=13.8 Hz). tR: 5.64 min, ESI m/z (C36H44C1N2+), calc: 539.4; found: 539.1. |
| 85.3% | With sodium acetate; In toluene;Inert atmosphere; Reflux; Dean-Stark; | Compound 3 (0.5 g, 2.9 mmol) and compound 4 (1.91 g, 5.81 mmol) were dissolved in BuOH-toluene (25 mL, 7:3, v:v) under Ar, and the solution was refluxed overnight in a 100-mL flask with three necks installed with a Dean-Stark condenser to remove generated water. Then, all solvents were removed under vacuum and the residual solid was purified with a flash chromatography (DCM:MeOH, 50:1 to 20:1, v:v) to give compound 4 (IR780, 1.6 g, 85.3%) as a dark green solid. |
| 71.17% | In cyclohexane; butan-1-ol; at 100℃; for 10h;Inert atmosphere; | Starting material A (0.86 g, 5 mmol), starting material B (3.29 g, 10 mmol),Add 28 mL of n-butanol and 12 mL of cyclohexaneIn a 100 mL round bottom flask, replace N2 three times with vacuum.The temperature was raised to 100 C and refluxed for 10 hours.After cooling the reaction solution to room temperature,A large amount of metallic luster green solid is produced in the system, suction filtration, petroleum ether,The filter cake was rinsed with ethyl acetate to give 2.37 g of a gold-green solid powder.The yield was 71.17%. |
| In toluene; butan-1-ol; at 120℃; for 12h;Darkness; | Under ice bath conditions, POCl3 (10.5 mL, 115 mmol)Methylene chloride solution (5 mL) was slowly added to DMF (20 mL, 258 mmol)The mixture was mixed with dichloromethane (15 mL) and stirred for 0.5 h.Cyclohexanone (5 g, 50 mmol) was added dropwise to the solution.The mixed solution was refluxed for 6 hours and poured into an ice water mixture.After 12 hours, the resulting yellow crystals were filtered to give a yellow solid powder, Compound a.Dissolve in 50ml acetonitrile at room temperature2,3,3-trimethylhydrazine(2g, 12.5mmol) and propyl iodide(10.6g, 62mmol),Stir at 85 C for 15 h in the dark.The solvent was recrystallized from anhydrous diethyl ether to give a purple powder, Compound b.Compound a (0.52 g, 3 mmol, 1 equiv.), b (1.97 g, 6 mmol, 2 equiv.)The mixed solution of butanol and toluene (20 mL, 3:7, v/v) was stirred at 120 C for 12 h in the dark.After cooling to room temperature, the solvent was evaporated under reduced pressure to give a crude product, which was crystallised twice from diethyl ether.A green powder, Cy7-Cl, was obtained. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 45% | 1 (20 mg, 30 μιηο, 1 equiv) and a primary amine building block selected from FIG. 4 (120 μιηο, 4 equiv) were dissolved in ACN, and DIEA (7.7 μΙ_, 60 μϖιο, 2 equiv) was added. The reaction mixture was heated at 80 C for 10-60 minutes, depending on the reactivity of the amine. The resulting blue mixtures were neutralized with 0.1 N HC1, and concentrated under vacuum. The blue mixtures were then dissolved in DCM under N2 atmosphere, and treated with excess DIEA (96.2 μ, 750 μϖιο, 25 equiv) and acetyl chloride (11.7 μ., 150 μϖιο, 5 equiv) at 0 C for 15 minutes. The final green products were washed with 0.1 N HC1 to remove excess DIEA, concentrated under vacuum, and purified by a normal-phase silica short column using DCM-MeOH (ranging from 100:0 to 97:3) as the eluting solvent. The characterization of the whole library was performed by LCMS (Table 1 ), and selected compounds were also characterized by NMR and high-resolution mass spectrometry (HRMS). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1 (300 mg, 0.45 mmol, 1 equiv) and l-(3-aminopropyl)-2-pipecoline (170 mg, 0.9 mmol, 2 equiv) were dissolved in ACN (2 mL), and DIEA (87 iL, 0.67 mmol, 1.5 equiv) was added. The reaction mixture was heated at 80 C for 40 minutes, and the resulting blue mixture was neutralized with 0.1 N HCl and concentrated under vacuum. The blue mixture was dissolved in DCM under N2 atmosphere, and treated with excess DIEA (700 iL, 5.39 mmol, 12 equiv) and methyl 4- (chloroformyl)butyrate (110 μ, 0.67 mmol, 1.5 equiv) at 0 C for 15 minutes. The resulting green product 2 was washed with 0.1 N HCl and brine, concentrated under vacuum, and used without further purification. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | Compound 4 (126 mg, 0.60 mmol) was dissolved in DMF (15 mL), the solution was added with sodium hydride (60% in oil, 24 mg, 0.60 mmol), and the mixture was stirred at room temperature for 10 minutes under an argon atmosphere. The reaction solution was added with <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> (200 mg, 0.30 mmol) dissolved in DMF (15 mL), and the mixture was further stirred at room temperature for 16 hours. After the solvent was evaporated, the residue was purified by silica gel column chromatography (NH silica, dichloromethane/methanol, 19:1) to obtain Compound 5 (184 mg, 73%) as green solid.1H-NMR (300 MHz, CDCl3): δ 1.05 (t, J=7.4 Hz, 6H), 1.36 (s, 12H), 1.50 (s, 9H), 1.87 (sex, J=7.4 Hz, 4H), 2.05 (t, J=5.5 Hz, 2H), 2.72 (t, J=5.5 Hz, 4H), 4.05 (t, J=7.4 Hz, 4H), 6.05 (d, J=14.3 Hz, 2H), 6.80 (br s, 1H), 6.99 (d, J=9.0 Hz, 2H), 7.09 (d, J=7.7 Hz, 2H), 7.20 (d, J=7.7 Hz, 2H), 7.27 (d, J=6.8 Hz, 2H), 7.34 (d, J=6.8 Hz, 2H), 7.47 (d, J'29.0 Hz, 2H), 7.91 (d, J=14.3 Hz, 2H)LRMS (ESI+): m/z 712 (M-I)+ |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium tetrahydroborate; In methanol; at 20℃; for 0.333333h;Inert atmosphere; | Synthesis of H-IR 780: To an oven-dried 250-mL round-bottomed flask with a stir-bar and septum under N2 were added <strong>[207399-07-3]IR-780</strong> (100 mg, 0.125 mmol), followed by methanol (100 mL). To the resulting green solution, sodium borohydride (19.0 mg, 5.0 mmol) was slowly added over 5 min. The solution turned light yellow, and the mixture was stirred (at) ambient temperature for an additional 15 min. The solvent was removed under reduced pressure, and the product was purified by CombiFlash system (i.e., automated flash chromatography) using hexane/ethyl acetate as eluent. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium borodeuteride; In methanol; at 20℃; for 0.333333h;Inert atmosphere; | Synthesis of H-IR 780: To an oven-dried 250-mL round-bottomed flask with a stir-bar and septum under N2 were added <strong>[207399-07-3]IR-780</strong> (100 mg, 0.125 mmol), followed by methanol (100 mL). To the resulting green solution, sodium borohydride (19.0 mg, 5.0 mmol) was slowly added over 5 min. The solution turned light yellow, and the mixture was stirred (at) ambient temperature for an additional 15 min. The solvent was removed under reduced pressure, and the product was purified by CombiFlash system (i.e., automated flash chromatography) using hexane/ethyl acetate as eluent. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; water; at 115℃; for 2h;Inert atmosphere; | To an oven dried pressure tube with a magnetic stir-bar were added <strong>[207399-07-3]IR-780</strong> (400 mg, 0.74 mmol), 2,3-difluoro phenyl boronic acid (1.17 g, 6.23 mmol), palladium (0) tetrakis (222 mg), 4.5 mL THF and 1.5 mL nano-pure water followed by 1.44 mL DIPEA. The reaction mixture was flashed with N2 and was heated to 115 C for 2 h. Mass spectral analysis indicated only the desired product with a very little peak corresponding to the decholinated starting material (m/z = 506). The product was purified using Teledyne's Isco CombiFlash system using dichloromethane/methanol as eluent. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87.4% | In N,N-dimethyl-formamide; at 80℃; for 4h; | A convenient synthetic route for compound 1 from commercially available compounds was provided and depicted in Fig. 1. Compound 1: <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> (52.2 mg, 0.08 mmol) and piperazine (36.4 mg, 0.4 mmol) were dissolved in dry DMF (10 mL). The reaction mixture was stirred and refluxed for 4 h at 80 C. After the solvent was evaporated under reduced pressure, the crude product was purified by silica gel column chromatography using CH2Cl2/C2H5OH (20:1, v/v) as eluent to afford a golden solid product. Yield: 41.2 mg (87.4%). 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 12.80 Hz, 2H), 7.33 (d, J = 12.4, 2H), 7.27 (d, J = 8.2 Hz, 2H) 7.14 (d, J = 5.4 Hz, 2H), 6.96 (d, J = 6.0 Hz, 2H), 5.78 (d, J = 12.6 Hz, 2H) 4.02 (s, 4H) 3.89 (s, 4H) 3.31 (s, 4H) 2.93 (m, 2H) 2.47 (s, 4H) 1.72 (s, 12H) 1.32 (t,J = 7.3, 4H) 1.06 (t, J = 6.7 6H) 13C NMR (100 MHz, CDCl3): δ.169.1, 142.9, 141.0, 140.3, 128.3, 123.6, 123.5, 122.2, 109.2, 95.6, 55.8, 47.4, 45.2, 29.7, 28.7, 25.8, 22.6, 21.8, 11.7. MS (TOF) m/z 589.5. Anal. calcd. for C40H53N4 (1): C, 81.45; H, 9.06; N, 9.50. Found: C, 81.35; H, 9.09; N, 9.57. |
| In N,N-dimethyl-formamide; at 85℃; for 4h;Inert atmosphere; | (1) 0.3mmol compound of formula II is dissolved in 15 ml of anhydrous dimethylformamide (DMF), under a nitrogen atmosphere, added the 1.2mmol of piperazine to the above solution, stirred at 85 C for 4 hours, and then the mixture is cooled at room temperature. The solvent has been removed by distillation under reduced pressure; the distillation residue is purified by silica gel column chromatography under reduced pressure, the eluent is a mixture of dichloromethane and methanol with a volume ratio of 40: 1, and then obtained compound of formula III |
[ 207399-07-3 ]
[ 1377297-20-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 22% | With N-ethyl-N,N-diisopropylamine; In ethanol; dimethyl sulfoxide; at 70℃; for 3h; | 2-((E)-2-((E)-2-((19-((2-carbamoyl-5-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-lH- indazol-l-yl)phenyl)amino)-4,7,10,13,16-pentaoxanonadecyl)amino)-3-((E)-2-(3,3- dimethyl-l-propylindolin-2-ylidene)ethylidene)cyclohex-l-en-l-yl)vinyl)-3,3-dimethyl-l- [00233] Amine 8 (12.1 mg, 20 μιηο) was dissolved in DMSO (200 L) and added to <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> (7 mg, 10 μιηο) and treated with Hunig's base (15 μ) followed by ethanol (100 μ). The sample was heated for 3 h at 70 C. The entire sample was added to a silica gel column (2.5 x 20 cm) and chromatographed with CH2C12 (200 mL), CH2Cl2/MeOH/NH3 39/0.9/0.1 (240 mL), 19/0.9/0.1 (240 mL) and 12.3/0.9/0.1 (240 mL). The blue band was concentrated to give product 14 (2.4 mg, 22%) as a blue solid. MS (ESI): m/z 554.1 [M+H]2+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 16% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 16h;Inert atmosphere; | CS788 To a mixture of NaH (60% oil dispersion, 4.0 mg, 94 mmol) and compound 6 (38 mg, 94 mmol) in DMF (5 mL) was added <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> (52 mg, 78 mmol). After stirring at room temperature for 16 h, the reaction mixture was diluted with a mixture of AcOEt-toluene (3:1, 30 mL), and then washed with water (10 mL×5) and brine (10 mL). The organic layer was dried over Na2SO4 and then evaporated. Purification by column chromatography (MeOH-dichloromethane, 1:20) afforded CS-788 as a green film (13 mg, 16%). 1H-NMR (CDCl3, 400 MHz): δ 7.93 (2H, d, J=14.2 Hz), 7.33 (2H, t, J=7.4 Hz), 7.27 (2H, d, J=6.2 Hz), 7.18 (2H, t, J=7.4 Hz), 7.09 (2H, d, J=8.0 Hz), 6.97 (2H, d, J=9.1 Hz), 6.68 (2H, d, J=9.1 Hz), 6.07 (2H, d, J=14.2 Hz), 4.07 (4H, t, J=7.2 Hz), 3.47 (4H, t, J=7.0 Hz), 2.75-2.65 (16H, m), 2.55 (4H, q, J=7.4 Hz), 2.04 (2H, m), 1.85 (4H, m), 1.38 (12H, s), 1.22 (6H, t, J=7.4 Hz), 1.05 (6H, t, J=7.5 Hz). 13C-NMR (CDCl3, 100 MHz): δ 171.7, 165.0, 152.7, 142.3, 142.2, 142.1, 140.9, 128.6, 124.9, 122.8, 122.1, 115.6, 14.7, 110.6, 100.0, 52.3, 48.9, 46.1, 32.5, 31.8, 29.6, 27.9, 26.1, 24.6, 20.8, 14.8, 11.7. LRMS (ESI): calculated for [(M-I)+] 908.5. found 908.5. HRMS (ESI): calculated for C54H7401N3S4 [(M-I)+] 908.4709. found 908.4740. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | In N,N-dimethyl-formamide; at 85℃; for 4h;Inert atmosphere; | The specific synthesis steps are as follows: 1) Under inert anaerobic Condition , <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> (0.5 mmol), Piperazine (2 mmol) and dried water-removed N, N-dimethylformamide were placed in a two-necked flask and reacted at 85 C for 4 hours. After the reaction was completed, Extract with CH2Cl2, dry the organic layer over anhydrous Na2SO4, The solvent was removed by rotary evaporation and the residue was separated by column chromatography The blue solid piperazine-substituted cyanine dye intermediate was obtained. Yield: 85%; |
| In N,N-dimethyl-formamide; for 4h;Inert atmosphere; | After purging the two-necked 50ml flask with nitrogen three times, <strong>[207399-07-3]IR-780</strong> (300mg, 0.45mmol), piperazine (155mg, 1.8mmol) and 10mL double distilled DMF were added under nitrogen for 4 hours. At the end of this time, excess DMF was removed and the residue was separated by column chromatography to give a blue solid. | |
| In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Darkness; | Cy7-Cl (668 mg, 1 mmol, 1 equiv.) was dissolved in anhydrous N,N-dimethylformamide (10 mL).Piperazine (345 mg, 4 mmol, 4 equiv.) was added under a nitrogen atmosphere.The mixed solution was stirred overnight at room temperature in the dark. Column chromatography (SiO2; CH2Cl2/CH3OH, 40:1, v/v)Purification gave a blue solid, Cy-NH. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | In acetonitrile; at 70℃; for 2h;Sealed tube; | To a solution of <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> 3 (100 mg, 0.150 mmol) in methyl cyanide (MeCN, 5 mL) was added N-methylethanolamine 7 (60 0.750 mmol). The solution was heated to 70 C in a sealed vial for 2 hours as the reaction color transitioned from green to dark blue. After this time LC/MS analysis showed complete consumption of 3. The reaction mixture was concentrated in vacuo, and the residue was purified by silica gel chromatography (100% EtOAc, then 0→10% MeOH/DCM) afforded 6 (85 mg, 80%) as a dark blue iridescent solid. Compound 6 had a broad hypsochromic absorbance with a maximum at 687 nm. 1H NMR (CDC13, 400 MHz) δ 7.69 (d, J = 13.0 Hz, 2H), 7.30 (t, J = 1.5 Hz, 4H), 7.09 (d, J = 1.5 Hz, 2H), 6.89 (d, J = 1.9 Hz, 2H), 5.69 (d, J = 13.03 Hz, 2H), 4.12 - 3.94 (m, 4H), 3.81 (t, J = 7.4 Hz, 4H), 3.55 (s, 3H), 2.47 (t, J = 6.6 Hz, 4H), 1.90 - 1.76 (m, 6H), 1.67 (s, 12H), 1.04 (t, J = 1.4 Hz, 6H); 13C NMR (CDCI3, 100 MHz) δ 176.9, 168.5, 143.0, 142.2, 140.5, 128.1, 123.5, 123.0, 122.2, 108.7, 95.0, 60.0, 59.3, 48.1, 45.3, 44.9, 29.4, 24.9, 21.9, 20.2, 11.7; IR (thin film) 1544, 1509, 1444, 1345 cm"1; HRMS (ESI) calculated for C39H52N3O (M+) 578.4110, observed 578.4096. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 84% | In acetonitrile; at 80℃; for 0.166667h;Sealed tube; | To a solution of <strong>[207399-07-3]<strong>[207399-07-3]IR-780</strong> iodide</strong> 3 (315 mg, 0.472 mmol) in MeCN (3 mL) was added 3-methylamino-l-propanol (230 μ, 2.36 mmol). The solution was heated to 80 C in a sealed vial for 10 minutes as the reaction color transitioned from green to dark blue. After this time LC/MS analysis showed complete consumption of 3. The reaction mixture was concentrated in vacuo, and the residue was purified by silica gel chromatography (0→10% MeOH/DCM) to afford 18 (285 mg, 84%) as a dark blue iridescent solid. 1H NMR (CD3CN, 400 MHz) δ 7.51 (d, J = 13.3 Hz, 2H), 7.38 (d, J = 7.3 Hz, 2H), 7.33 - 7.25 (m, 2H), 7.13 - 7.03 (m, 4H), 5.83 (d, J = 13.4 Hz, 2H), 3.86 (m, 6H), 3.55 (q, J = 5.6 Hz, 2H), 3.40 (s, 3H), 3.02 (t, J = 4.9 Hz, 1H), 2.47 (t, J = 6.6 Hz, 4H), 2.01 - 1.93 (m, 2H), 1.83 - 1.69 (m, 6H), 1.59 (s, 12H), 0.98 (t, J = 7.4 Hz, 6H); 13C NMR (CD3CN, 125 MHz) δ 176.8, 169.4, 144.2, 142.2, 141.3, 129.1, 124.3, 123.8, 122.9, 110.3, 95.9, 59.6, 56.8, 48.6, 45.7, 45.4, 32.5, 29.4, 25.4, 22.6, 20.8, 11.6; IR (thin film) 3339, 1540, 1508, 1449, 1344, 1256 cm"1; HRMS (ESI) calculated for C4oH54N30 (M+) 592.4261, observed 592.4255. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 60% | In N,N-dimethyl-formamide; at 25℃; for 10h;Inert atmosphere; Schlenk technique; | A mixture of compounds <strong>[207399-07-3]IR-780</strong> (333.65mg, 0.5mmol) and 4-amino thiophenol (69mg, 0.55mmol) were stirred in DMF (5mL) for 10h under an argon atmosphere at 25C. After completion of present reaction, the solvent was removed under reduced pressure. The crude mixture was purified by flash chromatography on silica gel using dichloromethane/methanol (60: 1) to give 3 (223mg, 60%).1H NMR (400MHz, CDCl3): δ ppm=1.06 (t, J=16Hz, 6H, CH3), 1.52 (s, 12H, CH3), 1.91 (q, 4H, CH2), 2.04 (t, J=12Hz, 2H, CH2), 2.78 (t, J=12Hz, 4H, CH2), 4.09 (t, J=16Hz, 4H, CH2), 6.19 (d, J=16Hz, 2H, CH2=CH-H), 6.56 (s, 1H, Ar-H), 6.63 (d, J=12Hz, 2H, Ar-H), 6.99 (q, 1H, Ar-H), 7.10 (d, J=8Hz, 2H, Ar-H). 7.19 (t, J=16Hz, 3H, Ar-H). 7.32 (t, J=20Hz, 5H, Ar-H), 8.68 (d, J=12Hz, 2H, CH2=CH-H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | In N,N-dimethyl-formamide; at 25℃; for 10h;Inert atmosphere; Schlenk technique; | A mixture of compounds <strong>[207399-07-3]IR-780</strong> (333.65mg, 0.5mmol) and thiophenol (60.6mg, 0.55mmol) were stirred in DMF (5mL) for 10h under an argon atmosphere at 25C. After completion of present reaction, the solvent was removed under reduced pressure. The crude mixture was purified by flash chromatography on silica gel using dichloromethane/methanol (60: 1) to give 1 (330mg, 87%).1H NMR (400MHz, CDCl3): δ ppm=1.06 (t, J=12Hz, 6H, CH3), 1.48 (s, 12H, CH3), 1.89 (q, 4H, CH2), 2.06 (t, J=12Hz, 2H, CH2), 2.79 (t, J=12Hz, 4H, CH2), 4.13 (t, J=12Hz, 4H, CH2), 6.22 (d, J=12Hz, 2H, CH2=CH-H), 7.08 (t, J=16Hz, 1H, Ar-H), 7.12 (d, J=8Hz, 2H, Ar-H), 7.28 (d, J=8Hz, 3H, Ar-H), 7.36 (t, J=16Hz, 2H, Ar-H), 8.66 (d, J=12Hz, 2H, CH2=CH-H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79.4% | In N,N-dimethyl-formamide; at 20℃; | The main process for chemical synthesis in thisexample was shown in FIG. 2. The synthesis steps were asfollows. IR780 iodide (2-[2-[2-Chloro-3-(1,3-dihydro-3,3-dimethyl-1-propyl-2H -indol-2-ylidene) ethylidene ]-1-cyclohexen-1-yl]etheny 1]-3,3 -dimethy 1-1-propy lindoliumiodide) (120 mg, 143.2 flillOl) and 4-aminothiophenol (300mg, 958 flillOl) were dissolved in anhydrous DMF (5 ml),and reacted overnight at room temperature. The obtainedcrude product was purified by preparative HPLC coupledwith a C-18 colunm, to obtain a pure target product IR780-NH2. A green solid (120 mg, 79.4%) was obtained afterdrying, which was then analyzed by HPLC, and identified bynuclear magnetic resonance spectrometry and mass spectrometry.IR780-NH2 (75.5 mg, 100 f.tmol) was dissolved inanhydrous DMF (5 ml), and triethyl amine (20 mg, 200f.tmol) was added. Then, a solution ofDOTA-NHS (153 mg,200 flillOl) dissolved in DMF (1 ml) was added to thereaction mixture, and stirred for 3 days at room temperature.The obtained crude product was purified by preparativeHPLC coupled with a C-18 colunm using, as a mobile phase,60% CAN and 40% H20 containing 0.1% TFA which wasgradient to 100% ACN in 15 min, to obtain a pure targetproduct. A green solid (21 mg, 17.2%) was obtained afterdrying, and the structure of the multi-functional probe of thepresent invention was determined after analysis by HPLCand identification by nuclear magnetic resonance spectrometryand mass spectrometry. |
| 75% | In N,N-dimethyl-formamide; at 25℃; for 10h;Inert atmosphere; Schlenk technique; | A mixture of compounds <strong>[207399-07-3]IR-780</strong> (333.65mg, 0.5mmol) and 4-amino thiophenol (69mg, 0.55mmol) were stirred in DMF (5mL) for 10h under an argon atmosphere at 25C. After completion of present reaction, the solvent was removed under reduced pressure. The crude mixture was purified by flash chromatography on silica gel using dichloromethane/methanol (60: 1) to give 2 (278mg, 75%).1H NMR (400MHz, CDCl3): δ ppm=1.06 (t, J=16Hz, 6H, CH3), 1.56 (s, 12H, CH3), 1.89 (q, 4H, CH2), 2.00 (t, J=12Hz, 2H, CH2), 2.71 (t, J=12Hz, 4H, CH2), 4.08 (t, J=16Hz, 4H, CH2), 6.14 (d, J=16Hz, 2H, CH2=CH-H), 6.64 (d, J=8Hz, 2H, Ar-H), 7.00 (d, J=12Hz, 2H, Ar-H), 7.11 (d, J=8Hz, 2H, Ar-H), 7.21 (t, J=12Hz, 3H, Ar-H). 7.31 (d, 1H, Ar-H). 7.33 (d, J=4Hz, 2H, Ar-H). 7.36 (d, J=8Hz, 2H, Ar-H). 8.74 (d, J=16Hz, 2H, CH2=CH-H). |
[ 207399-07-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 60% | With sodium acetate; In N,N-dimethyl-formamide; at 80℃; for 6h; | IR780 (1 g, 1.5 mmol) and 2 g of sodium acetate were dissolved in 20 ml of DMF and reacted at 80 C for 6 hours.The reaction solution was extracted with ethyl acetate and washed with water three times.Dichloromethane / methanol = 20: 1 as the eluent passed through the column to give 600mgRed solid metal I-2 with a metallic luster, yield 60%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 2h;Reflux; | CD123 antibody probe conjugates were synthesized as fluorescent probes for in vitro cellular uptake studies. <strong>[207399-07-3]IR-780</strong> dye was synthesized according to previously reported method.26 Then <strong>[207399-07-3]IR-780</strong> dye was further modified with pyridyl disulfide reactive group. <strong>[207399-07-3]IR-780</strong> (51.0mg) and 4-(pyridin-2-yldisulfanyl)butanoic acid (30.0mg) were dissolved in acetonitrile. Then DIEA (27.0mg) was added and the resulting mixture was refluxed for 2h. The resulting mixture was condensed under vacuum. And intermediate 3 was purified to afford as a blue solid. The remaining procedures were similar with the synthesis of CD123-CPT. |