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. : | 1186-73-8 | MDL No. : | MFCD02178862 |
Formula : | C7H10O6 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BNOIMFITGLLJTH-UHFFFAOYSA-N |
M.W : | 190.15 | Pubchem ID : | 136922 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.57 |
Num. rotatable bonds : | 6 |
Num. H-bond acceptors : | 6.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 39.62 |
TPSA : | 78.9 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) : | -7.28 cm/s |
Log Po/w (iLOGP) : | 2.11 |
Log Po/w (XLOGP3) : | 0.26 |
Log Po/w (WLOGP) : | -0.88 |
Log Po/w (MLOGP) : | -0.33 |
Log Po/w (SILICOS-IT) : | -0.13 |
Consensus Log Po/w : | 0.21 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.79 |
Solubility : | 31.1 mg/ml ; 0.163 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.48 |
Solubility : | 6.33 mg/ml ; 0.0333 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.16 |
Solubility : | 131.0 mg/ml ; 0.69 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.53 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-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 |
---|---|---|
96.6% | Embodiment 3; A. Synthesis of (3aS,4S,6aR)-1,3-dibenzyl-4-(omega,omega,omega-methoxycarbonyl buty)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)-ketone; Put 300 ml methylbenzene and 60% sodium hydride 3.3 g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8 g (0.085 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80 C. and protected for 2 h by heat preservation; add 33.3 g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 70 C. for a 10 h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-1.0 g tri-ester dibenzyl biotin (96.6% of the theoretical value), and the HPLC measured content is 98.4% with no impurity 5 (hereinafter to be referred as dicarboxylic ester). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.3% | Embodiment 2; A. Synthesis of (3aS,4S,6aR)-1,3-dibenzyl-4-(omega,omega,omega-3-methoxycarbonyl butyl)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)- ketone; Put 300 ml methylbenzene and 60% sodium hydride 3.3 g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8 g (0.083 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80 C. and protected for 2 h by heat preservation; add 33.3 g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 80 C. for a 15 h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-0.2 g tri-ester dibenzyl biotin (95.3% of the theoretical value), and the HPLC measured content is 98.0% with no impurity 5 (hereinafter to be referred as dicarboxylic ester). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.3% | Put 300 ml methylbenzene and 60% sodium hydride 3.3g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8g(0.083 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80C and protected for 2h by heat preservation; add 33.3g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 80C for a 15h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-0.2g tri-ssterdibanzyl biotin (95.3% of the theoretical value), and the HPLC measured content is 98.0% with no impurity 5 (hereinafter to be referred as dicarboxylic ester). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.13 g | In diphenylether; at 230℃; for 0.166667h; | Step 9; methyl 7-((tert-butyldimethylsilyl)oxy)-9-chloro-l-(2,4-dimethoxybenzyl)-4- hydroxy-2-oxo-2,5,6,7-tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3- carboxylate To a suspension of the intermediate obtained above in Ph20 (10 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.6 g, 8.4 mmol, 1.7 eq) at room temperature. A short-path distillation apparatus was attached to the flask and the reaction mixture was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature and then purified by flash column chromatography (0- 25% EtOAc in CH2C12) to give the product (1.13 g, 1.9 mmol, 37%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm -0.13 (s, 3 H) -0.03 (s, 3 H) 0.90 (s, 9 H) 1.51 (td, J=13.87, 7.25 Hz, 1 H) 1.66 - 1.77 (m, 1 H) 2.36 (tdd, J=13.28, 13.28, 7.49, 6.31 Hz, 1 H) 2.94 (dd, J=14.50, 5.36 Hz, 1 H) 3.56 (s, 3 H) 3.73 (s, 3 H) 4.01 (s, 3 H) 4.31 - 4.40 (m, 1 H) 5.10 (d, J=16.08 Hz, 1 H) 5.25 (d, J=16.08 Hz, 1 H) 6.28 (d, J=2.21 Hz, 1 H) 6.34 (dd, J=8.51, 2.21 Hz, 1 H) 6.73 (d, J=8.51 Hz, 1 H) 7.1 1 (d, .7=8.51 Hz, 1 H) 7.25 (dd, J=8.20, 2.21 Hz, 3 H) 7.64 (d, J=2.21 Hz, 1 H) 13.78 (s, 1 H). LC-MS 598.5/600.4 [M-H]", 600.4 [M+H]+, RT 1.95 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.15 g | In diphenylether; for 0.166667h;Heating; | The intermediate N-(l-methyl-6,7-dihydrocyclohepta[fJindol-5(lH)-ylidene)prop-2-en- 1 -amine obtained above (ca. 8.46 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (2.75 g, 14.46 mmol) were mixed together in PI12O (17 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-80% gradient) to provide the product as a yellow solid (2.15 g, 56% overall). ^ MR ^OO MHz, CHCl3-i/) 8 ppm 2.1 1 (ddd, J=14.1, 5.8, 2.0 Hz, 1 H) 3.51 (dd, J=14.1, 8.0 Hz, 1 H) 3.86 (s, 3 H) 4.01 (s, 3 H) 4.38 (dd, J=15.1, 5.9 Hz, 1 H) 4.53 (ddt, J=15.1, 4.6, 2.1 Hz, 1 H) 4.75 (dd, J=17.2, 1.1 Hz, 1 H) 5.05 (dd, J=10.4, 1.1 Hz, 1 H) 5.90 (dddd, J=17.2, 10.4, 5.9, 4.6 Hz, 1 H) 6.37 (ddd, J=9.8, 8.0, 5.8 Hz, 1 H) 6.53 (dd, J=3.2, 0.9 Hz, 1 H) 6.76 (dd, J=9.8, 2.0 Hz, 1 H) 7.20 (d, J=3.2 Hz, 1 H) 7.29 (s, 1 H) 7.85 (s, 1 H) 13.72 (br. s., 1 H). LC-MS 375.3 [M+H]+, 377.3 [M+H]+, RT 1.40 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diphenylether; at 230℃; for 0.166667h; | Step 11; 8-fluoro-4-hvdroxv-9-methyl-2-oxo-l,2,5,6,7,9- hexahydropyrido [3',2' :6,7] cyclohepta [l,2-f]indole-3-carboxylic acid The N-(10-fluoro-l-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(lH)-ylidene)-2- methylpropan-2-amine obtained above (ca. 2.22 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.72 g, 3.79 mmol) were mixed together in Ph20 (5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min. The reaction mixture was cooled to room temperature. The precipitate was filtered, then washed with ether, to give a crude product (22 mg, 3%) which was used directly in the next step without further purification. LC-MS 357.1 [M+H]+, RT 1.38 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
404 mg | In diphenylether; for 0.166667h;Heating; | Step 12; methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2,4-dimethoxybenzyl)-8- hydroxy-l-methyl-6-oxo-l,5,6,9-tetrahydropyrido[3',2':4,5]cyclopenta[l,2- f] indole-7-carboxylate The crude product obtained above (1.09 g, ca. 2.04 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.68 g, 3.58 mmol) were mixed together in Pl^O (6.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature) under a blanket of Argon. The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 25-60% gradient ) to yield the product as a yellow foam (404 mg, 33% 2 steps). LC-MS 605.3 [M+H]+, RT 1.80 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.158 g | In diphenylether; for 0.166667h;Heating; | Step 5; methyl 9-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-8-methyl-2-oxo-2,5,6,8-tetrahydro-lH-indolo[6,5-h]quinoline-3- carboxylate The N-(2-(((tert-butyldimethylsilyl)oxy)methyl)- 1 -methyl-7,8-dihydro- 1H- benzo[f]indol-5(6H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (1.40 g, 2.84 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.95 g, 5.00 mmol) were mixed together in PI12O (7.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature) under a blanket of Argon. The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 25-60% gradient) to yield the product as a yellow foam (1.158 g, 63% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.06 (s, 6 H) 0.90 (s, 9 H) 2.58 - 2.72 (m, 2 H) 2.89 (t, J=6.6 Hz, 2 H) 3.62 (s, 3 H) 3.78 (s, 3 H) 3.80 (s, 3 H) 3.97 (s, 3 H) 4.77 (s, 2 H) 5.37 (s, 2 H) 6.19 (s, 1 H) 6.42 (d, J=2.4 Hz, 1 H) 6.46 (dd, J=8.4, 2.4 Hz, 1 H) 7.14 (d, J=8.4 Hz, 1 H) 7.18 (s, 1 H) 7.63 (s, 1 H) 13.60 (s, 1 H). LC-MS 619.6 [M+H]+, RT 1.76 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.44 g | In diphenylether; for 0.166667h;Heating; | Step 6; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-9-methyl-2-oxo-l,2,5,6,7,9-hexahydropyrido[3',2':6,7]cyclohepta[l,2- f] indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)-l-methyl-6,7,8,9- tetrahydrocyclohepta[fJindol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (10.6 g, 20.91 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (6.80 g, 35.76 mmol) were mixed together in PI12O (40 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (7.44 g, 56%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.08 (s, 3 H) 0.09 (s, 3 H) 0.90 (s, 9 H) 1.45 - 1.55 (m, 1 H) 1.85 - 1.95 (m, 1 H) 1.96 - 2.05 (m, 1 H) 2.32 - 2.44 (m, 1 H) 2.58 (dd, J=13.4, 6.1 Hz, 1 H) 2.96 (dd, J=13.4, 5.4 Hz, 1 H) 3.33 (s, 3 H) 3.76 (s, 3 H) 3.78 (s, 3 H) 4.00 (s, 3 H) 4.80 (s, 2 H) 5.13 - 5.37 (m, 2 H) 6.22 (d, J=2.2 Hz, 1 H) 6.28 (s, 1 H) 6.34 (dd, J=8.4, 2.2 Hz, 1 H) 6.81 (d, J=8.4 Hz, 1 H) 7.06 (s, 1 H) 7.32 (s, 1 H) 13.66 (br. s, 1 H). LC-MS 633.5 [M+H]+, RT 1.85 min. |
7.44 g | With diphenylether; at 230℃; for 0.166667h; | Step 2: Methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)- l-(2,4-dimethoxybenzyl)-4-hydroxy-9-methyl-2-oxo- 1,2,5, 6,7, 9-hexahydropyrido[3',2':6,7]cyclohepta[l,2-f]indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)- l-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (10.6 g, 20.91 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (6.80 g, 35.76 mmol) were mixed together in Ph20 (40 mL). The stirred mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after initial bubbling of MeOH was observed (occurs at approx. 160 C internal reaction temperature). The reaction mixture was cooled to room temperature, loaded directly on a silica column, eluted first with hexanes to separate Ph20 and then anEtOAc/hexanes gradient (0-80%) to yield the product as a yellow foam (7.44 g, 56% 2 steps). LC-MS: 633.5 [M+H]+, RT 1.85 min. 1H NMR (500 MHz, CDC13) 5 ppm 0.08 (s, 3H), 0.09 (s, 3H), 0.90 (s, 9H), 1.45 - 1.55 (m, IH), 1.85 - 1.95 (m, IH), 1.96 - 2.05 (m, IH), 2.32 -2.44 (m, IH), 2.58 (dd, J=13.4, 6.1 Hz, IH), 2.96 (dd, J=13.4, 5.4 Hz, IH), 3.33 (s, 3H), 3.76 (s, 3H), 3.78 (s, 3H), 4.00 (s, 3H), 4.80 (s, 2H), 5.13 - 5.37 (m, 2H), 6.22 (d, J=2.2 Hz, IH), 6.28 (s, IH), 6.34 (dd, J=8.4, 2.2 Hz, IH), 6.81 (d, J=8.4 Hz, IH), 7.06 (s, IH), 7.32 (s, IH), 13.66 (br. s, IH) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | In diphenylether; for 0.25h;Heating; | Step 1; methyl l-(2,4-dimethoxybenzyl)-9-(dimethylamino)-4-hydroxy-2-oxo-2,5,6,7- tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate The previously obtained product 5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl-6,7,8,9- tetrahydro-5H-benzo[7]annulen-2-amine (Example 1, step 6, 0.85 g, 2.41 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.87 g, 4.58 mmol) were mixed together in PI12O (5.5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 220 C and heated for 15 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 40-90% gradient) to provide the product as a yellow foam (0.525 g, 45% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 1.58 (td, J=13.6, 6.9 Hz, 1 H) 1.86 - 2.08 (m, 2 H) 2.33 (td, J=12.7, 7.7 Hz, 1 H) 2.45 (dd, J=13.1, 6.1 Hz, 1 H) 2.97 - 3.01 (m, 1 H) 3.00 (s, 6 H) 3.61 (s, 3 H) 3.76 (s, 3 H) 3.97 (s, 3 H) 5.14 (br. s., 2 H) 6.33 (d, J=2.2 Hz, 1 H) 6.36 (dd, J=8.4, 2.2 Hz, 1 H) 6.50 (br. s., 2 H) 6.79 (d, J=8.4 Hz, 1 H) 7.00 (d, J=8.4 Hz, 1 H) 13.65 (s, 1 H). LC-MS 477.4 [M-H]", 479.4 [M+H]+, RT 1.46 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.375 g | In diphenylether; for 0.166667h;Heating; | Step 9; methyl ll-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-10-methyl-2-oxo-2,5,6,7,8,10-hexahydro-lH- pyrido [3 ',2' : 7,8] cycloocta [1,2-f] indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)- 1 -methyl-7,8,9, 10-tetrahydro- 1 H- cycloocta[f]indol-5(6H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (-0.60 g, 1.17 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.37 g, 1.95 mmol) were mixed together in Ph 0 (2.5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-60% gradient) to yield the product as a yellow foam (0.3750 g, 51%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.10 (s, 3 H) 0.11 (s, 3 H) 0.91 (s, 9 H) 1.33 - 1.51 (m, 3 H) 1.80 - 1.90 (m, 1 H) 2.02 (t, J=7.7 Hz, 1 H) 2.13 (t, J=12.0 Hz, 1 H) 2.55 (dd, J=13.6, 7.3 Hz, 1 H) 2.82 (dd, J=13.2, 7.6 Hz, 1 H) 3.10 (s, 3 H) 3.76 (s, 3 H) 3.77 (s, 3 H) 4.03 (s, 3 H) 4.80 (d, J=13.2 Hz, 1 H) 4.82 (d, J=13.2 Hz, 1 H) 4.96 - 5.26 (m, 2 H) 6.12 (d, J=2.5 Hz, 1 H) 6.24 (s, 1 H) 6.32 (dd, J=8.5, 2.2 Hz, 1 H) 6.81 (d, J=8.5 Hz, 1 H) 7.04 (s, 1 H) 7.11 (s, 1 H) 13.73 (s, 1 H). LC-MS 647.5 [M+H]+, RT 1.90 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | In diphenylether; at 230℃; for 0.166667h; | 2-(((tert-Butyldimethylsilyl)oxy)methyl)-N-(2,4-dimethoxybenzyl)-3-methyl-7, 8,9,10- tetrahydrocyclohepta[e]indol-6(3H)-imine was divided into two batches for the annulation reaction. The crude imine (2.6 g, 5.12 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.66 g, 8.73 mmol) were mixed together in Ph20 (10 mL). The stirred mixture was placed onto a heat block pre-heated to 230 C and heated for 10 minutes. Initial bubbling of MeOH was observed (occuring at approx.. 160 C internal reaction temperature). The reaction mixture was cooled to room temperature, loaded directly on a column, eluted first with hexanes to separate Ph20 and then an EtOAc/hexanes gradient (0-50%) to yield the title compound as a yellow foam (3.093 g, 48% 2 steps). LC-MS 633.5 [M+H]+, RT 1.85 min. 1H NMR (500 MHz, CDC13 delta ppm 0.09 (s, 3H), 0.12 (s, 3H), 0.92 (s, 9H), 1.49 (td, J=13.6, 7.3 Hz, IH), 1.97 - 2.17 (m, 2H), 2.41 (td, J=12.9, 7.9 Hz, IH), 2.99 (dd, J=13.9, 6.0 Hz, 2H), 3.48 (s, 3H), 3.75 (s, 3H), 3.78 (s, 3H), 3.99 (s, 3H), 4.84 (d, J=13.2 Hz, IH), 4.84 (d, J=13.2 Hz, IH), 5.18 (br. s, 2H), 6.27 (d, J=2.4 Hz, IH), 6.35 (dd, J=8.2, 2.4 Hz, IH), 6.45 (s, IH), 6.82 (d, J=8.2 Hz, IH), 7.00 (d, J=8.8 Hz, IH), 7.11 (d, J=8.8 Hz, IH), 13.68 (s, IH). |
0.5425 g | In diphenylether; for 0.166667h;Heating; | Step 13; methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-10-(2,4-dimethoxybenzyl)-7- hydroxy-l-methyl-9-oxo-l,4,5,6,9,10- hexahydropyrido [2',3' :3,4] cyclohepta [l,2-e]indole-8-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)-3-methyl-7,8,9, 10- tetrahydrocyclohepta[e]indol-6(3H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (0.858 g, 1.69 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.55 g, 2.89 mmol) were mixed together in Rho12theta (4 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (0.5425 g, 50%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.09 (s, 3 H) 0.12 (s, 3 H) 0.92 (s, 9 H) 1.49 (td, J=13.6, 7.3 Hz, 1 H) 1.97 - 2.17 (m, 2 H) 2.41 (td, J=12.9, 7.9 Hz, 1 H) 2.99 (dd, J=13.9, 6.0 Hz, 2 H) 3.48 (s, 3 H) 3.75 (s, 3 H) 3.78 (s, 3 H) 3.99 (s, 3 H) 4.84 (d, J=13.2 Hz, 1 H) 4.84 (d, J=13.2 Hz, 1 H) 5.18 (br. s., 2 H) 6.27 (d, J=2.4 Hz, 1 H) 6.35 (dd, J=8.2, 2.4 Hz, 1 H) 6.45 (s, 1 H) 6.82 (d, J=8.2 Hz, 1 H) 7.00 (d, J=8.8 Hz, 1 H) 7.11 (d, J=8.8 Hz, 1 H) 13.68 (s, 1 H). LC-MS 633.5 [M+H]+, RT 1.85 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.41 g | In diphenylether;Heating; | Step 7; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-7,9-dimethyl-2-oxo-l,2,5,6,7,9- hexahydropyrido[3',2':6,7]cyclohepta[l,2-f|indole-3-carboxylate Crude N-(2-(((tert-butyldimethylsilyl)oxy)methyl)-l,9-dimethyl-6,7,8,9- tetrahydrocyclohepta[fJindol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (ca 3.63 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.20 g, 6.31 mmol) were mixed together in Pl^O (7 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (1.41 g, 60% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.09 (s, 3 H) 0.10 (s, 3 H) 0.91 (s, 9 H) 1.23 (d, J=6.9 Hz, 3 H) 1.37 - 1.52 (m, 2 H) 2.00 - 2.12 (m, 1 H) 2.33 - 2.47 (m, 1 H) 2.89 (dd, J=13.4, 5.5 Hz, 1 H) 3.21 (s, 3 H) 3.74 (s, 3 H) 3.80 (s, 3 H) 4.02 (s, 3 H) 4.82 (s, 2 H) 5.09 (d, J=15.4 Hz, 1 H) 5.39 - 5.58 (m, 1 H) 6.14 (d, J=1.9 Hz, 1 H) 6.27 (dd, J=8.4, 1.9 Hz, 1 H) 6.31 (s, 1 H) 6.69 (d, J=8.4 Hz, 1 H) 7.04 (s, 1 H) 7.35 (s, 1 H) 13.64 (s, 1 H) LC-MS 647.4 [M+H]+, RT 1.92 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
210 mg | In diphenylether; for 0.166667h;Heating; | Step 7; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-5,9-dimethyl-2-oxo-l,2,5,6,7,9- hexahydropyrido[3',2':6,7]cyclohepta[l,2-f|indole-3-carboxylate The crude product obtained above (450 mg, ca. 0.88 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (380 mg, 2.0 mmol) were mixed together in Ph20 (2 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (210 mg, 37% 2 steps) LC-MS 645.3 [M-H]", 647.3 [M+H]+, RT 1.87 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.4 g | In diphenylether; for 0.166667h;Heating; | The crude product obtained above (ca. 16.31 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (5.20 g, 27.35 mmol) were mixed together in Pl^O (32 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (5.40 g, 52% overall). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.10 (s, 3 H) 0.10 (s, 3 H) 0.91 (s, 9 H) 2.09 (ddd, J=14.1, 5.9, 2.0 Hz, 1 H) 3.35 (s, 3 H) 3.50 (dd, J=14.1, 7.9 Hz, 1 H) 3.74 (s, 3 H) 3.79 (s, 3 H) 3.99 (s, 3 H) 4.82 (s, 2 H) 4.91 (d, J=15.4 Hz, 1 H) 5.20 (br. s., 1 H) 6.19 (d, J=2.2 Hz, 1 H) 6.24 - 6.36 (m, 3 H) 6.60 - 6.68 (m, 2 H) 7.14 (s, 1 H) 7.57 (s, 1 H) 13.72 (br. s., 1 H). LC- MS 629.3 [M+H]+, 631.3 [M+H]+, RT 1.84 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.322 g | In diphenylether; for 0.166667h;Heating; | The crude product obtained above (ca. 1.47 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.50 g, 2.63 mmol) were mixed together in Pl^O (3 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (0.322 g, 34% overall). LC-MS 645.6 [M+H]+, RT 2.04 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.6 g | In diphenylether; at 230℃; for 0.25h; | Step 5; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-l,2,5,6- tetrahydrobenzo [2,3] oxepino [4,5-b] pyridine-3-carboxylate A solution of N-(8-chloro-3 ,4-dihydrobenzo [b] oxepin-5 (2H)-ylidene)- 1 -(2,4- dimethoxyphenyl)methanamine (4.4 g crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (4.9 g, 25.6 mmol) in Pl^O (13 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature, and purified on silica gel using EtO Ac/Hex (0-60% gradient) to afford the product (2.6 g, 43%) as a yellow foam. XH NMR (500 MHz, CHCl3-i/) delta ppm 2.06 - 2.17 (m, 1 H) 3.18 (dd, J=15.09, 3.90 Hz, 1 H) 3.63 - 3.68 (m, 3 H) 3.75 - 3.79 (m, 3 H) 3.99 (s, 3 H) 4.37 (dd, J=9.81, 6.34 Hz, 1 H) 4.41 - 4.50 (m, 1 H) 4.93 - 5.04 (m, 1 H) 5.15 (d, J=15.76 Hz, 1 H) 6.32 - 6.44 (m, 2 H) 6.94 (d, J=8.35 Hz, 1 H) 7.06 - 7.12 (m, 2 H) 7.17 (s, 1 H) 13.80 (s, 1 H). LC-MS: 470.1 [M-H]", RT 1.45 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.6 g | In diphenylether; at 230℃; for 0.25h; | Step 7; methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-l,2,5,6- tetrahydrobenzo [2,3] oxepino [4,5-b] pyridine-3-carboxylate A solution of N-(8-bromo-3-methyl-3,4-dihydrobenzo[b]oxepin-5(2H)-ylidene)-l-(2,4- dimethoxyphenyl)methanamine (3.7 g, crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (3.4 g, 18 mmol) in PI12O (10 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature and purified on silica gel using EtOAc/Hex (0-60% gradient) to afford the product methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-l, 2,5,6- tetrahydrobenzo[2,3]oxepino[4,5-b]pyridine-3-carboxylate (2.6 g, 43%) as a brown foam. XH NMR (500 MHz, DMSO-i) delta ppm 0.56 (d, J=7.72 Hz, 3 H) 3.57 - 3.66 (m, 4 H) 3.68 - 3.72 (m, 3 H) 3.85 (s, 3 H) 4.14 (d, J=10.96 Hz, 1 H) 4.60 (dd, J=11.07, 6.66 Hz, 1 H) 4.90 (d, J=15.68 Hz, 1 H) 5.13 (br. s., 1 H) 6.35 - 6.46 (m, 2 H) 6.74 (d, J=8.43 Hz, 1 H) 7.31 - 7.51 (m, 3 H) 13.51 (br. s, 1 H).LC-MS: 530.2 [M-H]", RT 0.92 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
480 mg | In diphenylether; at 230℃; for 0.25h; | A solution of the crude product obtained above and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.0 g, 5.6 mmol) in Pl^O (5 mL) was heated at 230 C for 15 min. The reaction mixture was then cooled to room temperature at which point the product precipitates. The solid was filtered and rinsed with Et20 (20 mL) to afford the title compound as a brown solid (480 mg, 38%). XH NMR (500 MHz, DMSO-i) delta ppm 2.56 (t, J=6.46 Hz, 2 H) 3.79 (s, 3 H) 4.38 (t, J=6.34 Hz, 2 H) 6.52 (dd, J=3.1 1, 0.75 Hz, 1 H) 7.29 (s, 1 H) 7.37 - 7.39 (m, 1 H) 7.74 (s, 1 H) 11.72 (br. s., 1 H) 13.59 (br. s., 1 H). LC-MS: 341.3 [M+H]+, 0.68 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2 g | In diphenylether; at 230℃; for 0.25h; | Step 13; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-9-methyl-2-oxo-2,5,6,9-tetrahydro-lH-pyrido[2',3':4,5]oxepino[3,2- f] indole-3-carboxylate A solution of N-(8-((tert-butyldimethylsilyloxy)methyl)-9-methyl-3,4-dihydro-2H- oxepino[3,2-f]indol-5(9H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (3.81 g crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (2.9 g, 15.0 mmol) in Ph20 (15 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature and purified on silica gel using EtO Ac/Hex (0-60% gradient) to afford the product (2.0 g, 43%) as a yellow foam. XH NMR (500 MHz, DMSO-i) delta ppm 0.00 (d, J=0.95 Hz, 6 H) 0.77 - 0.83 (m, 9 H) 1.87 - 1.96 (m, 2 H) 2.88 - 2.96 (m, 1 H) 3.48 (s, 3 H) 3.64 (d, J=1.89 Hz, 6 H) 3.77 (s, 3 H) 4.21 (br. s., 2 H) 4.74 (s, 2 H) 4.98 - 5.07 (m, 1 H) 6.24 (s, 1 H) 6.37 (s, 2 H) 6.61 - 6.68 (m, 1 H) 7.21 (s, 1 H) 7.31 - 7.40 (m, 1 H) 13.28 - 13.36 (m, 1 H). LC-MS: 633.2 [M-H]", RT 1.80 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
289 mg | In diphenylether; at 210℃; for 0.166667h;Inert atmosphere; | Step 3; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-7-methyl-2-oxo-2,5,6,7- tetrahydro-lH-benzo [b] pyrido [2,3-d] azepine-3-carboxylate Crude N-(8-chloro-l-methyl-3,4-dihydro-lH-benzo[b]azepin-5(2H)-ylidene)-l-(2,4- dimethoxyphenyl)methanamine (690 mg, 1.95 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (631 mg, 3.32 mmol) were mixed together in Pl^O (4.0 mL). With stirring, the mixture was placed into a pre-heated heat block at 210 C and heated for 10 minutes under a blanket of Argon. The reaction mixture was cooled to room temperature and was filtered directly on a silica cartridge. The product was purified by column chromatography (100% hexanes followed by EtOAc in hexanes 0 to 85% gradient) to provide the desired product (289 mg, 31%, two steps) as an off-white foam which was used directly in the next step. LC-MS 483.9 [M-H]", 485.8 [M+H]+, RT 1.53 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.13 g | In diphenylether; at 210℃; for 0.166667h;Inert atmosphere; | Step 3; 7-benzyl 3-methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-5,6- dihydro-lH-benzo [b] pyrido [2,3-d] azepine-3,7(2H)-dicarboxylate The crude benzyl 8-chloro-5-((2,4-dimethoxybenzyl)imino)-2,3,4,5-tetrahydro-lH- benzo[b]azepine-l-carboxylate (2.75 g, 5.75 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.85 g, 9.78 mmol) were mixed together in Rho12theta (12.0 mL). With stirring, the mixture was placed into a pre-heated heat block at 210 C and heated for 10 minutes under a blanket of Argon. The reaction mixture was cooled to room temperature and filtered directly on a silica cartridge. The product was purified by column chromatography (100% hexanes followed by EtOAc in hexanes 0 to 85% gradient) to give the desired product (1.13 g, 32%, two steps) as an off-white foam which was used directly in the next step.. LC-MS 603.4 [M-H]", 605.4 [M+H]+, RT 0.94 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.2% | In diphenylether; for 0.25h;Heating; | Step 1; methyl l-(2,4-dimethoxybenzyl)-10-(dimethylamino)-4-hydroxy-2-oxo- l,2,5,6,7,8-hexahydrobenzo[7,8]cycloocta[l,2-b]pyridine-3-carboxylate The previously obtained product 5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl- 5,6,7,8,9, 10-hexahydrobenzo[8]annulen-2-amine (Example 4, step 7, 0.30 g, 0.82 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.28 g, 1.47 mmol) were mixed together in PI12O (2.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 220 C and heated for 15 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-70% gradient) to provide the product as a yellow foam (0.178 g, 44% 2 steps) XH NMR (500 MHz, CHCh-d) delta ppm 1.29 - 1.44 (m, 2 H) 1.50 (dd, J=13.4, 1 1.2 Hz, 1 H) 1.84 - 2.03 (m, 3 H) 2.41 (dd, J=13.1, 7.7 Hz, 1 H) 2.86 (dd, J=13.7, 7.7 Hz, 1 H) 2.98 (s, 6 H) 3.51 (s, 3 H) 3.75 (s, 3 H) 4.00 (s, 3 H) 5.01 (d, J=15.8 Hz, 1 H) 5.17 (d, J=15.8 Hz, 1 H) 6.25 (d, J=2.4 Hz, 1 H) 6.33 (dd, J=8.5, 2.4 Hz, 1 H) 6.41 - 6.53 (m, 2 H) 6.74 (d, J=8.5 Hz, 1 H) 6.85 (d, J=8.5 Hz, 1 H) 13.71 (s, 1 H). LC-MS 491.4 [M-H]", 493.4 [M+H]+, RT 1.57 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.57 g | In diphenylether; at 230℃; for 0.166667h; | Step 3; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro- lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate To a suspension of the crude product obtained above (4.75 g, ca. 13.8 mmol) in Ph20 (20 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (4.7 g, 24.7 mmol, 1.8 eq). A short-path distillation apparatus was attached to the flask containing the reaction mixture. The reaction mixture was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature, then purified by flash column chromatography (0-25% EtOAc in CH2CI2) to afford the title compound (3.57 g, 7.60 mmol, 52%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 1.46 (td, J=13.69, 6.90 Hz, 1 H) 1.83 - 1.96 (m, 1 H) 2.01 (dq, J=13.36, 6.71 Hz, 1 H) 2.15 (td, J=12.69, 7.88 Hz, 1 H) 2.40 (dd, J=13.20, 6.27 Hz, 1 H) 2.99 (dd, J=14.19, 5.20 Hz, 1 H) 3.54 (s, 3 H) 3.75 (s, 3 H) 4.01 (s, 3 H) 5.03 (d, J=15.68 Hz, 1 H) 5.29 (d, J=15.68 Hz, 1 H) 6.26 (d, J=2.29 Hz, 1 H) 6.30 - 6.37 (m, 1 H) 6.78 (d, J=8.43 Hz, 1 H) 7.06 - 7.17 (m, 2 H) 7.17 - 7.25 (m, 1 H) 13.74 (s, 1 H). LC-MS 468.3/470.3 [M-H]", 470.3 [M+H]+, RT 1.57 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.4 g | In diphenylether; at 230℃; for 0.166667h; | Step 7; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-2,5,6,7- tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate To a suspension of the crude product obtained above (2.68 g, ca. 7.5 mmol) in Rho12theta (15 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (3.23 g, 17.0 mmol, 2.3 eq). A short-path distillation apparatus was attached to the flask containing the reaction mixture. The reaction was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature, then purified by flash column chromatography (0-25% EtOAc in CH2C12) to give the product (2.40 g, 4.96 mmol, 55%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.38 (d, J=7.09 Hz, 3 H) 1.62 - 1.75 (m, 1 H) 1.75 - 2.15 (m, 1 H) 2.18 - 2.27 (m, 1 H) 2.27 - 2.39 (m, 2 H) 3.52 (s, 3 H) 3.75 (s, 3 H) 4.02 (m, 3 H) 4.96 - 5.02 (m, 1 H) 5.39 (d, J=15.45 Hz, 1 H) 6.20 - 6.28 (m, 1 H) 6.28 - 6.38 (m, 1 H) 6.77 (d, J=8.35 Hz, 1 H) 7.06 - 7.13 (m, 1 H) 7.13 - 7.18 (m, 1 H) 7.18 - 7.25 (m, 1 H) 13.96 (br. s., 1 H). LC-MS 482.9/484.9 [M-H]", 484.8 [M+H]+, RT 1.60 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | To a solution of 2-(((tert-butyldimethylsilyl)oxy)methyl)-3-tosyl-7,8,9,10- tetrahydrocyclohepta[e]indol-6(3H)-one (650 mg, 1.3 mmol) in CH2C12 (6 mL) was added 2- ,4-dimethoxybenzylamine (0.22 mL, 1.43 mmol) and triethylamine (0.54 mL, 3.9 mmol). The mixture was cooled to 0 C. To the mixture was added a TiCl4 solution (1 M CH2C12, 0.85 mL, 0.85 mmol) dropwise via syringe over 5 min. The mixture was allowed to warm to room temperature and was stirred overnight. The excess reagent was quenched with aqueous saturated NaHC03 (3 mL). The organic phase was separated with vigorous shaking using a PTFE phase separator, dried over Na2S04, filtered, and concentrated. The residue was combined with <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (342 mg, 1.8 mmol) in Ph20 (2.6 mL). The mixture was placed in a pre-heated aluminum block at 230 C and stirred for 15 minutes. The reaction vessel was removed from the heating block and allowed to cool to room temperature. The crude reaction mixture was loaded directly onto a silica gel column, eluting with 0-60% EtOAc in hexanes to yield a yellow powder (0.52 g, 52%). LC-MS: 773.4 [M+H]+, RT 1.97 min. 1H NMR (500 MHz, acetone- 6) delta ppm 0.18 (s, 6H), 0.98 (s, 9H), 1.34 (m, 1H), 1.92 (m, 1H), 2.01 (m, 1H), 2.26 (m, 1H), 2.39 (s, 3H), 2.90 (m, 2H), 3.38 (s, 3H), 3.68 (s, 3H), 3.90 (s, 3H), 4.96 (d, J=15.6 Hz, 2H), 5.17 (m, 2H), 6.16 (d, J=8.3 Hz, 1H), 6.30 (d, J=2.3 Hz, 1H), 6.61 (d, J=8.3 Hz, 1H), 6.91 (s, 1H), 7.25 (d, J=8.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 2H), 7.94-8.00 (m, 3H), 13.79 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | To a solution of 3-tosyl-7,8,9,10-tetrahydrocyclohepta[e]indol-6(3H)-one (670 mg, 1.9 mmol) in CH2C12 (10 mL) was added 2-,4-dimethoxybenzylamine (0.32 mL, 2.1 mmol) and triethylamine (0.79 mL, 5.7 mmol). The mixture was cooled to 0 C. To the mixture was added a TiCl4 solution (1 M CH2C12, 1.24 mL, 1.24 mmol) dropwise via syringe over 5 min. The mixture was allowed to warm to room temperature and was stirred overnight. The excess reagent was quenched with aqueous saturated NaHC03 (5 mL). The organic phase was separated with vigorous shaking using a PTFE phase separator, dried over Na2S04, filtered, and concentrated. The residue was combined with <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (650 mg, 3.4 mmol) in Ph20 (3.8 mL). The mixture was placed in a pre-heated aluminum block at 220 C and stirred for 15 min. The reaction vessel was removed from the heating block and allowed to cool to room temperature. The crude reaction mixture was loaded directly onto a silica gel column, eluting with 0-100% EtOAc in hexanes to yield a yellow powder (0.58 g, 49%). LC-MS: 629.1 [M+H]+, RT 1.47 min. 1H NMR (500 MHz, acetone- 6) delta ppm 1.33 (m, 1H), 1.87-2.03 (m, 2H), 2.25 (m, 1H), 2.39 (s, 3H), 2.92 (m, 2H), 3.32 (s, 3H), 3.67 (s, 3H), 3.90 (s, 3H), 4.95 (d, J=15.6 Hz, 1H), 5.28 (d, J=15.2 Hz, 1H), 6.15 (m, 1H), 6.27 (m, 1H), 6.62 (d, J=8.2 Hz, 1H), 6.96 (m, 1H), 7.29 (d, J=8.2 Hz, 1H), 7.46 (m, 2H), 7.81 (d, J=8.6 Hz, 1H), 7.91 (d, J=3.8 Hz, 1H), 7.98 (m, 2H), 13.77 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | To a solution of tert-butyl 6-oxo-6,7,8,9-tetrahydro-3H-benzo[e]indole-3-carboxylate (0.425 g, 1.49 mmol) and 2-methylpropan-2-amine (0.475 mL, 4.5 mmol) in CH2CI2(7.5 mL) was added a solution of titanium(IV) tetrachloride (0.9 mL, 1M in CH2CI2, 0.9 mmol) dropwise at 0 C. After the addition was complete, the reaction mixture was stirred at 25 C for 16 h. The mixture was then diluted with CH2CI2(20 mL) and quenched with aqueous saturatedNaHCC"3 (20 mL). The organic phase was separated using a PTFE phase separator, dried over Na2S04, filtered, and concentrated to afford a crude residue which was added to a solution of <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.4 g, 2.1 mmol) in Ph20 (3.0 mL). The mixture was heated at 230 C for 15 minutes. The cooled reaction mixture was loaded directly onto silica gel, eluting with 0-100% EtOAc in hexanes to afford the title compound (100 mg, 22% over 2 steps).1H NMR (500 MHz, DMSO-6) delta ppm 2.68 (dd, J=8.51, 6.94 Hz, 2H) 3.06 (t, J=7.72 Hz, 2H) 3.85 (s, 3H) 6.60 - 6.66 (m, 1H) 7.33 (d, J=8.59 Hz, 1H) 7.42 - 7.47 (m, 1H) 7.80 (d, J=8.67 Hz, 1H) 11.36 (br. s, 1H) 11.42 (br. s, 1H) 13.54 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | To a solution of 3-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one (16.4 g, 80 mmol) in CH2CI2 (400 mL) was added t-butylamine (25.2 mL, 240 mmol). The mixture was cooled to 0 C. To the mixture was added a TiCl4 solution (1 M CH2CI2, 52 mL, 52 mmol) drop wise via an addition funnel over 30 min. The mixture was allowed to warm to room temperature and was stirred overnight. The excess reagent was quenched with aqueous saturated NaHC03 (50 mL). After vigorous shaking, the organic phase was separated using a PTFE phase separator, dried over Na2S04, filtered, and concentrated. The residue was combined with <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (33.4 g, 144 mmol) in PI12O (160 mL). The mixture was placed in a pre-heated aluminum block at 220 C and stirred for 15 minutes. The reaction vessel was removed from the heating block and allowed to cool to room temperature. The crude reaction mixture was loaded directly onto a silica gel column, eluting with 0-10% MeOH in CH2C12 to yield a tan powder (3.0 g, 11%). LC-MS: 331.0 [M+H]+, RT 1.16 min. 1H NMR (500 MHz, DMSO- 6) delta ppm 2.05-2.33 (4H), 2.64-2.74 (2H), 3.86 (s, 3H), 7.69 (d, J=8.3 Hz, 1H), 8.31 (dd, J=8.3, 2.6 Hz, 1H), 8.36 (d, J=2.4 Hz, 1H), 11.85 (br. s, 1H), 13.39 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41 mg | With diphenylether; at 230℃; for 0.166667h; | Step 9: Methyl 10-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,8-tetrahydro- lH-benzo[6,7]oxocino[5,4-b]pyridine-3-carboxylate 9-Chloro-N-(2,4-dimethoxybenzyl)-4,5-dihydro-lH-benzo[c]oxocin-6(3H)-imine (ca. 0.3 g, 0.8 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.35 g, 1.8 mmol) were mixed in Ph20 (5 mL). The stirred mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after initial bubbling of MeOH was observed (occurs at approx. 160 C internal reaction temperature). The reaction mixture was cooled to room temperature, loaded directly on a silica column, eluted first with hexanes to separate Ph20 and then EtOAc/hexanes gradient (0-50%) to yield the title compound (41 mg, 11% over 2 steps) as a yellow foam. LC-MS: 484.1 [M-H]+, RT 1.45 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Step 1: Methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-l,2,5,6-tetrahydrobenzo[2,3]thiepino[4,5-b]pyridine-3-carboxylate To a stirring solution of 8-bromo-3,4-dihydrobenzo[b]thiepin-5(2H)-one (Intermediate 9, Step 2, 36.2 g, 141 mmol), (2,4-dimethoxyphenyl)methanamine (25.9 g, 23.3 mL, 155 mmol), triethylamine (42.7 g, 58.7 mL, 423 mmol) in CH2C12(300 mL) at 0 C was added T1CI4(1M CH2C12, 71 mL, 71 mmol) dropwise. After the addition, the mixture was brought to room temperature and stirred overnight. The reaction was quenched with satd. NaHC03solution (3 mL) and the mixture was diluted with CH2C12(120 mL). The CH2C12layer was separated using a phase separator cartridge and the aqueous layer was extracted with CH2C12(2 x 30 mL). The combined organic phases were evaporated to dryness followed by the addition of <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (53.6 g, 282 mmol) and diphenyl ether (280 mL). The mixture was stirred at 230 C for 15 min., then cooled and chromato graphed (ethyl acetate in hexanes, 0-100 % gradient) to obtain the title compoundas a light brown solid (47.6 g, 64%). LC-MS: 532.0, 534.0 [M+H]+, RT 1.59 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Step 1: Methyl l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-9-tosyl-2,5,6,9-tetrahydro- 1H-pyrido[2',3':4,5]thiepino[3,2-f]indole-3-carboxylate o a stirring solution of Intermediate 9 (1.02 g, 2.75 mmol), (2,4-dimethoxyphenyl)methanamine (0.51 g, 0.45 mL, 3.03 mmol), triethylamine (0.83 g, 1.14 mL, 8.25 mmol) in CH2C12(6.0 mL) at 0 C was added a solution of TiCl4(1M in CH2C12,1.4 mL, 1.4 mmol) dropwise. After the addition, the mixture was brought to roomtemperature and stirred overnight. The reaction was quenched with satd. NaHC03solution (3 mL) and the mixture was diluted with CH2C12(12 mL). The CH2C12layer was separated and the aqueous layer was extracted with CH2C12(2 x 3 mL). The combined organics were evaporated to dryness followed by the addition of <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.05 g,5.5 mmol) and diphenyl ether (5.0 mL). The mixture was stirred at 230 C for 10 min, then cooled to room temperature and loaded directly onto a silica gel column. The product was chromato graphed (ethyl acetate in CH2C120-50 %) to furnish the title compound as a light brown solid (1.10 g, 62%). LC-MS: 647.2 [M+H]+, RT 1.57 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
620 mg | In diphenylether; at 190℃; for 1h; | Step 1: Methyl 10-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate The crude imine was combined with diphenyl ether (5 mL) and <strong>[1186-73-8]trimethylmethanetricarboxylate</strong> (1.07 g, 5.63 mmol). The reaction was stirred in a pre-heated 190 C bath for 1 hr. After cooling to room temperature, the mixture was purified by silica gel chromatography (5-50% EtOAc in hexanes). Trituration with acetone yielded the title compound (620 mg, 49%) as an off-white solid. 1H NMR (acetone- d6): delta 1.45 (m, 1H), 1.85-2.05 (m, 2H), 2.26 (m, 1H), 2.53 (dd, J = 13 Hz, 6 Hz, 1H), 2.96 (dd, J = 14 Hz, 6 Hz, 1H), 3.61 (s, 3H), 3.75 (s, 3H), 3.94 (s, 3H), 5.05 (d, J = 16 Hz, 1H), 5.28 (d, J = 16 Hz, 1H), 6.41 (m, 2H), 6.81 (d, J = 8.5 Hz, 1H), 7.27 (d, J = 8.5 Hz, 1H), 7.37 (m, 1H), 7.41 (dd, J = 8 Hz, 2.5 Hz, 1H), 13.83 (s, 1H) |
Tags: 1186-73-8 synthesis path| 1186-73-8 SDS| 1186-73-8 COA| 1186-73-8 purity| 1186-73-8 application| 1186-73-8 NMR| 1186-73-8 COA| 1186-73-8 structure
[ 13051-21-3 ]
3-Methoxy-2,2-dimethyl-3-oxopropanoic acid
Similarity: 0.96
[ 72657-23-9 ]
(R)-Methyl 3-hydroxy-2-methylpropanoate
Similarity: 0.96
[ 80657-57-4 ]
(S)-Methyl 3-hydroxy-2-methylpropanoate
Similarity: 0.96
[ 6279-86-3 ]
Triethyl methanetricarboxylate
Similarity: 0.92
[ 13051-21-3 ]
3-Methoxy-2,2-dimethyl-3-oxopropanoic acid
Similarity: 0.96
[ 72657-23-9 ]
(R)-Methyl 3-hydroxy-2-methylpropanoate
Similarity: 0.96
[ 80657-57-4 ]
(S)-Methyl 3-hydroxy-2-methylpropanoate
Similarity: 0.96
[ 6279-86-3 ]
Triethyl methanetricarboxylate
Similarity: 0.92
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :