Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 1286281-32-0 | MDL No. : | MFCD13184944 |
Formula : | C19H39NO8 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QGSFECNPSLZGGT-UHFFFAOYSA-N |
M.W : | 409.51 | Pubchem ID : | 51340920 |
Synonyms : |
|
Num. heavy atoms : | 28 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.95 |
Num. rotatable bonds : | 22 |
Num. H-bond acceptors : | 9.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 103.99 |
TPSA : | 107.7 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -9.36 cm/s |
Log Po/w (iLOGP) : | 4.81 |
Log Po/w (XLOGP3) : | -0.79 |
Log Po/w (WLOGP) : | 0.78 |
Log Po/w (MLOGP) : | -0.83 |
Log Po/w (SILICOS-IT) : | 3.1 |
Consensus Log Po/w : | 1.41 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 1.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.43 |
Solubility : | 152.0 mg/ml ; 0.372 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.99 |
Solubility : | 41.6 mg/ml ; 0.102 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -4.45 |
Solubility : | 0.0147 mg/ml ; 0.0000359 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 3.72 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
100% | With palladium on activated charcoal; hydrogen; In methanol; at 20℃; | Example A82 Preparation of Ar-(24-bromo-23-oxo-4,7,10,13,16,19-hexaoxa-22-azatetracosan-l-oyl)-L-valyl-Ar- {4-[([2^[(3i?,55',7i?,8i?)-7-{(l£,3^-5-[(25',35',5JR,6JR)-5-[(2Z,41S)-4-(acetyloxy)pent-2- enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-l,3-dien-l-yl}-8-hydroxy- l,6-dioxaspiro[2.5]oct-5-yl]acetyl}amino)ethyl]carbamoyl}oxy)methyl]phenyl}-A^-carbamoyl-L- ornithinamide (B245). r Step 1. Synthesis of tert-butyl l-hydroxy-3,6,9,12,15,18-hexaoxahenicosan-21-oate (B246). A mixture of 3,6,9,12,15-pentaoxaheptadecane-l,17-diol (25 g, 88.7 mmol, 1 eq.), tert-butyl prop-2- enoate (11.3 g, 88.7 mmol, 1 eq.) and benzyltrimethylammonium hydroxide (2.5 mL) was stirred at 50 C overnight. The reaction mixture was purified by silica gel chromatography eluting with ethyl acetate:dichloromethane (4%~10%) to afford B246 (9.63 g, 25.7%) as a yellow oil. Step 2. Synthesis of teri-butyl l -[(4-methylphenyl)sulfonyl]oxy}-3,6,9,12,15,18- hexaoxahenicosan-21-oate (B247). To a solution of B246 (9.63 g, 23.5 mmol, 1 eq.) and triethylamine (3.56 g, 35.2 mmol, 1.5 eq.) in dichloromethane (150 mL) was added 4- methylbenzenesulfonyl chloride (6.69 g, 35.2 mmol, 1.5 eq.) at 0 C, and the solution was stirred at rt overnight. The reaction mixture was washed with aqueous NaHCC>3 (150 mL), and the aqueous phase was re-extracted with ethyl acetate (200 mL x 3). The combined organic layers were dried over sodium sulfate and concentrated in vacuo, and the residue was purified by silica column chromatography eluting with methanol: dichloromethane (0.5%~0.8%) to afford B247 (9.21 g, 69.7%>) as a yellow oil. Step 3. Synthesis of teri-butyl l-azido-3, 6,9,12,15, 18-hexaoxahenicosan-21 -oate (B248). To a solution of B247 (13.0 g, 23.0 mmol, 1 eq.) in acetone/water (150 mL/150 mL) was added sodium azide (3.20 g, 49.2 mmol, 2.1 eq.) and sodium iodide (621 mg, 3.45 mmol, 0.15 eq.), and the reaction was stirred at reflux overnight. The reaction mixture was extracted with ethyl acetate (150 mL x 3), and the organic phases were concentrated in vacuo. The residue was purified by silica column chromatography eluting with ethyl acetate:petroleum ether (12-35%) to afford B248 (8.30 g, 83. 1%) as a yellow oil. Step 4. Synthesis of teri-butyl l -amino-3, 6,9,12,15, 18-hexaoxahenicosan-21-oate (B249). A suspension of B248 (8.30 g, 19.1 mmol, 1 eq.) and Pd/C (1.0 g) in methanol was stirred under hydrogen balloon at rt overnight. The reaction mixture was filtered, and the filtrate was concentrated in vacuo to afford B249 (7.80 g, 100%) as a yellow oil, which was directly used for the next step. Step 5. Synthesis of teri-butyl l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3-azatetracosan-24- oate (B250). To a solution of B249 (5.80 g, 14.1 mmol, 1 eq.) in dichloromethane (300 mL) was added NN-diisopropylethylamine (5.50 g, 42.6 mmol, 3 eq.) and bromoacetyl bromide (4.24 g, 21.3 mmol, 1.5 eq.) at 0 C, and the reaction was stirred at 0 C for 15 min. The reaction mixture was concentrated to dryness, and the residue was purified by silica column chromatography eluting with methano dichloromethane (0.5-0.8%) to afford B250 (5.20 g, 69. 3%) as a yellow solid. Step 6. Synthesis of l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3-azatetracosan-24-oic acid (B251). To a solution of B250 (5.20 g, 9.80 mmol, 1 eq.) in dichloromethane (100 mL) was added trifluoroacetic acid (100 mL) at 0 C, and the solution was stirred at rt for 3 h. The reaction mixture was concentrated in vacuo to afford B251 (6.00 g, 100%) as a yellow oil. Step 7. Synthesis of pentafluorophenyl l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3- azatetracosan-24-oate (B252). To a solution of B251 (4.65 g, 9.80 mmol, 1 eq.) and pentafluorophenyl trifluoroacetate (4.12 g, 14.7 mmol, 1.5 eq.) in dichloromethane (150 mL) was added dropwise pyridine (4.65 g, 9.80 mmol, 1.5 eq.) at 0 C, and the solution was stirred at for 30 min. The reaction mixture was washed with 2 M HC1 (150 mL x 2), and the aqueous phase was extracted dichloromethane (150 mL x 2). The combined organic layers were dried over sodium sulfate and concentrated in vacuo, and the residue was purified by silica column chromatography eluting with methano dichloromethane (1.5-2%) to afford a yellow oil, which was further purified by prep-HPLC to afford B252 (1.20 g, 19.1%) as a yellow oil. lH NMR (400 MHz, CDC13) 7.06 (br, 1 H), 3.89 (m, 4 H), 3.69-3.59 (m, 22 H), 3.58 (m, 2 H), 2.96 (m, 2 H). Step 8. Synthesis of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl-N- {4-[( [2- ([(3R,5S,7R,8R)-7- {(l£,3JE)-5-[(2S,3S,5R,6R)-5-[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6- dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-l,3-dien-l -yl}-8-hydroxy-l,6-dioxaspiro[2.5]oct-5- yl] acetyl} amino)ethyl]carbamoyl}oxy)methyl]phenyl}-N5-carbamoyl-L-ornithinamide (B253). To a solution of B51 (18.5 mg, 0.032 mmol, 1 eq.) in NN-dimethylformamide (0.8 mL) at rt was added NN-diisopropylethylamine (22.5 muL, 0.128 mmol, 4 eq.) followed by N-[(9H-fluoren-9- ylmethoxy)carbonyl]... |
With triphenylphosphine; In tetrahydrofuran; water; at 20℃; | The product 4-23 (1.74 g, 4 mmol) obtained in the previous step was dissolved in 30 mL THF and 5 mL water, PPh3 (1.31 g, 5 mmol) was added. The reaction mixture was stirred overnight at room temperature. THF was removed under reduced pressure, 1 N dilute hydrochloric acid 10 mL was added, the mixture was washed with EtOAc for 3 times (20 mL×3), the aqueous phase was freeze-drying to give 1.5 g crude product 5-23 as light yellow oil. LCMS (ESI) m/z 410.3 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.3% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; for 0.25h; | Example A82 Preparation of Ar-(24-bromo-23-oxo-4,7,10,13,16,19-hexaoxa-22-azatetracosan-l-oyl)-L-valyl-Ar- {4-[([2^[(3i?,55',7i?,8i?)-7-{(l£,3^-5-[(25',35',5JR,6JR)-5-[(2Z,41S)-4-(acetyloxy)pent-2- enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-l,3-dien-l-yl}-8-hydroxy- l,6-dioxaspiro[2.5]oct-5-yl]acetyl}amino)ethyl]carbamoyl}oxy)methyl]phenyl}-A^-carbamoyl-L- ornithinamide (B245). r Step 1. Synthesis of tert-butyl l-hydroxy-3,6,9,12,15,18-hexaoxahenicosan-21-oate (B246). A mixture of 3,6,9,12,15-pentaoxaheptadecane-l,17-diol (25 g, 88.7 mmol, 1 eq.), tert-butyl prop-2- enoate (11.3 g, 88.7 mmol, 1 eq.) and benzyltrimethylammonium hydroxide (2.5 mL) was stirred at 50 C overnight. The reaction mixture was purified by silica gel chromatography eluting with ethyl acetate:dichloromethane (4%~10%) to afford B246 (9.63 g, 25.7%) as a yellow oil. Step 2. Synthesis of teri-butyl l -[(4-methylphenyl)sulfonyl]oxy}-3,6,9,12,15,18- hexaoxahenicosan-21-oate (B247). To a solution of B246 (9.63 g, 23.5 mmol, 1 eq.) and triethylamine (3.56 g, 35.2 mmol, 1.5 eq.) in dichloromethane (150 mL) was added 4- methylbenzenesulfonyl chloride (6.69 g, 35.2 mmol, 1.5 eq.) at 0 C, and the solution was stirred at rt overnight. The reaction mixture was washed with aqueous NaHCC>3 (150 mL), and the aqueous phase was re-extracted with ethyl acetate (200 mL x 3). The combined organic layers were dried over sodium sulfate and concentrated in vacuo, and the residue was purified by silica column chromatography eluting with methanol: dichloromethane (0.5%~0.8%) to afford B247 (9.21 g, 69.7%>) as a yellow oil. Step 3. Synthesis of teri-butyl l-azido-3, 6,9,12,15, 18-hexaoxahenicosan-21 -oate (B248). To a solution of B247 (13.0 g, 23.0 mmol, 1 eq.) in acetone/water (150 mL/150 mL) was added sodium azide (3.20 g, 49.2 mmol, 2.1 eq.) and sodium iodide (621 mg, 3.45 mmol, 0.15 eq.), and the reaction was stirred at reflux overnight. The reaction mixture was extracted with ethyl acetate (150 mL x 3), and the organic phases were concentrated in vacuo. The residue was purified by silica column chromatography eluting with ethyl acetate:petroleum ether (12-35%) to afford B248 (8.30 g, 83. 1%) as a yellow oil. Step 4. Synthesis of teri-butyl l -amino-3, 6,9,12,15, 18-hexaoxahenicosan-21-oate (B249). A suspension of B248 (8.30 g, 19.1 mmol, 1 eq.) and Pd/C (1.0 g) in methanol was stirred under hydrogen balloon at rt overnight. The reaction mixture was filtered, and the filtrate was concentrated in vacuo to afford B249 (7.80 g, 100%) as a yellow oil, which was directly used for the next step. Step 5. Synthesis of teri-butyl l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3-azatetracosan-24- oate (B250). To a solution of B249 (5.80 g, 14.1 mmol, 1 eq.) in dichloromethane (300 mL) was added NN-diisopropylethylamine (5.50 g, 42.6 mmol, 3 eq.) and bromoacetyl bromide (4.24 g, 21.3 mmol, 1.5 eq.) at 0 C, and the reaction was stirred at 0 C for 15 min. The reaction mixture was concentrated to dryness, and the residue was purified by silica column chromatography eluting with methano dichloromethane (0.5-0.8%) to afford B250 (5.20 g, 69. 3%) as a yellow solid. Step 6. Synthesis of l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3-azatetracosan-24-oic acid (B251). To a solution of B250 (5.20 g, 9.80 mmol, 1 eq.) in dichloromethane (100 mL) was added trifluoroacetic acid (100 mL) at 0 C, and the solution was stirred at rt for 3 h. The reaction mixture was concentrated in vacuo to afford B251 (6.00 g, 100%) as a yellow oil. Step 7. Synthesis of pentafluorophenyl l-bromo-2-oxo-6,9,12,15,18,21-hexaoxa-3- azatetracosan-24-oate (B252). To a solution of B251 (4.65 g, 9.80 mmol, 1 eq.) and pentafluorophenyl trifluoroacetate (4.12 g, 14.7 mmol, 1.5 eq.) in dichloromethane (150 mL) was added dropwise pyridine (4.65 g, 9.80 mmol, 1.5 eq.) at 0 C, and the solution was stirred at for 30 min. The reaction mixture was washed with 2 M HC1 (150 mL x 2), and the aqueous phase was extracted dichloromethane (150 mL x 2). The combined organic layers were dried over sodium sulfate and concentrated in vacuo, and the residue was purified by silica column chromatography eluting with methano dichloromethane (1.5-2%) to afford a yellow oil, which was further purified by prep-HPLC to afford B252 (1.20 g, 19.1%) as a yellow oil. lH NMR (400 MHz, CDC13) 7.06 (br, 1 H), 3.89 (m, 4 H), 3.69-3.59 (m, 22 H), 3.58 (m, 2 H), 2.96 (m, 2 H). Step 8. Synthesis of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl-N- {4-[( [2- ([(3R,5S,7R,8R)-7- {(l£,3JE)-5-[(2S,3S,5R,6R)-5-[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6- dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-l,3-dien-l -yl}-8-hydroxy-l,6-dioxaspiro[2.5]oct-5- yl] acetyl} amino)ethyl]carbamoyl}oxy)methyl]phenyl}-N5-carbamoyl-L-ornithinamide (B253). To a solution of B51 (18.5 mg, 0.032 mmol, 1 eq.) in NN-dimethylformamide (0.8 mL) at rt was added NN-diisopropylethylamine (22.5 muL, 0.128 mmol, 4 eq.) followed by N-[(9H-fluoren-9- ylmethoxy)carbonyl]... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Preparation of tert-butyl 1-(9H-fluoren-9-yl)-3,6-dioxo-2,10,13,16,19,22,25- heptaoxa-4,7-diazaoctacosan-28-oate (FMOC G PEG6 CO2tBu) (Compound 27) To a dried 20 mL glass scintillation vial containing a dried pea stir bar was added FMOC G CO2H (297.6 mg, 1.0 mmol), HATU (381.0 mg, 1.0 mmol), and anhydrous DMF (3 mL). The clear, colorless solution was stirred at room temperature for 15 min. H2N PEG6 CO2tBu (415.7 mg, 1.0 mmol), DIPEA (387.7 mg, 522.5 uL, 3.0 mmol), and anhydrous DMF (1 mL) were combined in a separate, dried 4 mL glass scintillation vial and added dropwise, slowly, to the stirring solution. The reaction was stirred at room temperature for 2 h, adsorbed directly onto a Biotage KP C18 HS 12 g samplet, and purified on a Biotage KP C18 HS 60 g cartridge using a gradient of 0-100% CH3CN in H2O, giving the title compound as a pale yellow, viscous oil (669.0 mg, 97% yield). HPLC retention time 12.481 min. Method A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | 2- (2, 5-Bis ( (3S, 4S) -3, 4-bis (((is, 2R) -2- phenylcyclopropyl) carbamoyl)pyrrolidine-i-carbonyl)- phenoxy)acetic acid (S-86, 15 mg, 0.0153 mmol, 1.00 equiv), tert-butyl 1-amino-3,6,9,12,15,18- hexaoxahenicosan-2i-oate (9.4 mg, 0.0230 mmol, 1.50 equiv), DMAP (trace amount), and i-Pr3NEt (4.0 mg, 0.0306 mmoi, 2.00 equiv) were dissolved in anhydrous DMF (0.1 mL) . Upon dissolution of the reagents (ca. 5 mm), EDCIOHC1 (5.9 mg, 0.0306 mmol, 2.00 equiv) was added in one portion at room temperature, and the reaction mixture was stirred for 20 hours. 1-lOAt (2.3 mg, 0.0168 rnmol, 1.10 equiv), 2,6-lutidine (1 drop) and EDCI0HC1 (5.9 mg, 0.0306 mmol, 2.00 equiv) was added. The reaction mixture was stirred for 4 hours, after which it was poured into aqueous 1 N HC1 (1 mL) and EtOAc (4 mL) . The aqueous phase was extracted twice with EtOAc (2 mL), and the combined organic phases were washed with aqueous 1 N HC1 (1 mL), saturated aqueous NaHCO3 (1 mL), and saturated aqueous NaC1 (1 ml), sequentially. The organic phase was dried over Na2SO4, filtered and concentrated. Flash column chromatography (SiC2, 6% MeOH/CH2C12) provided 9.3 mg (44%) of 153. ?H NMR (500 MHz, DMSO-d6) 8.40 (d, J = 4.5 Hz, 2H), 8.28 (d, J = 4.5 Hz, 1H), 8.25 (d, J = 4.5 Hz, 1H), 8.05 (t, J = 5.5 Hz, 111), 7.32 (d, J = 8.0 Hz, 1H) , 7.28 - 7.20 (m, 9H) , 7.18 - 7.04 (m, 13H), 4.66 (s, 2H), 3.79 (td, J 12.0, 9.0 Hz, 2H), 3.66 - 3.55 (m, 5H), 3.54 - 3.41 (m, 23H), 3.39- 3.28 (m, 2H), 3.27 - 3.15 (m, 4R), 3.13 - 3.05 (m, 2H), 2.87 - 2.81 (m, 2H), 2.80 - 2.74 (m, 2H), 2.40 (t, J = 6.0 Hz, 2H), 1.99 - 1.94 (m, 2H), 1.90 - 1.84 (m, 2H) , 1.38 (s, 9H) , 1.20 - 1.07 (m, 8H) . HRMS (ESI-TOF) rn/z calcd foi C77H96N70,6 [M+H] 1374.6908, found 1374.6936. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.8% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | To a stirred solution of 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)- picolinic acid (08) (200 mg, 0.44 mmol, 1.0 equiv) in DMF (5.0 mL, 25.0 vol. equiv), were added <strong>[1286281-32-0]tert-butyl 2-(3-(2-aminoethoxy)propoxy)acetate</strong> (19) (218.0 mg, 0.53 mmol, 1.2 equiv), HATU (505 mg, 1.33 mmol, 3.0 equiv) and DIPEA (68.50 mg, 0.53 mmol, 1.20 equiv). The reaction mixture was stirred for 12 h at RT. Completion of reaction was monitored by TLC. The Reaction mixture was quenched with DMW (100 mL) and extracted with EtOAc (100 mL x 3). The combined organic extract was washed with brine (100 mL), dried over Na2S04 and concentrated under vacuum to afford titled compound (20) (350 mg, 93.80%) brownish gum. MR (300 MHz, OMSO-d6) delta 9.30 (s, IH), 9.10 (s, IH), 8.70 (s, IH), 8.60 (d, IH), 8.13-8.12 (d, IH), 7.70-7.65 (m, 4H), 7.50 (s, IH), 7.21-7.18 (m, 3H), 3.58-3.44 (m, 26H), 2.51-2.49 (t, 2H). MS (ES+): 843 (M+l); MS (ES-): 841.2 (M-l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoroacetic acid; In dichloromethane; at 0 - 20℃; for 1h; | The crude product 5-23 (818 mg, 2 mmol) obtained in the previous step was dissolved in 4 mL dry DCM, the mixture was cooled to 0 C. in an ice bath, 0.8 mL TFA was added dropwise slowly, the reaction mixture was gradually warmed to room temperature and stirred for 1 hour, after the starting material was completely consumed as monitored by LCMS, DCM and TFA were removed under reduced pressure at ambient temperature to give 700 mg crude product 6-23 as light yellow solid, which was used directly for the next step. LCMS (ESI) m/z 354.2 (M+H)+. |