Structure of 123387-53-1
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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.
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| CAS No. : | 123387-53-1 |
| Formula : | C14H19NO2 |
| M.W : | 233.31 |
| SMILES Code : | O=C(N1CCCC2=C1C=CC=C2)OC(C)(C)C |
| English Name : | tert-Butyl 3,4-dihydroquinoline-1(2H)-carboxylate |
| MDL No. : | MFCD19684135 |
| InChI Key : | GVSRWAIRQCMAHG-UHFFFAOYSA-N |
| Pubchem ID : | 10633398 |
| Num. heavy atoms | 17 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.5 |
| Num. rotatable bonds | 3 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 72.18 |
| TPSA ? Topological Polar Surface Area: Calculated from |
29.54 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.11 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.06 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.99 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.8 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.43 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.88 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
| Solubility | 0.123 mg/ml ; 0.000528 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-3.35 |
| Solubility | 0.105 mg/ml ; 0.00045 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.47 |
| Solubility | 0.0791 mg/ml ; 0.000339 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.55 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.36 |
* 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 |
|---|---|---|
| at 165℃; | ||
| Multi-step reaction with 2 steps 1: 28 percent / benzene / 18 h / 165 °C 2: 96 percent / toluene / 24 h / 165 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 33% 2: 28% | In benzene at 165℃; for 18h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | In toluene at 165℃; for 24h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | With tert.-butylhydroperoxide; sodium hydrogencarbonate In decane; 1,2-dichloro-ethane at 40℃; for 16h; | |
| 75% | With tert.-butylhydroperoxide; Rh2(cap)4; sodium hydrogencarbonate In 1,2-dichloro-ethane at 40℃; for 16h; | tert-butyl 4-oxo-3,4-dihydroquixnoline-1(2H)-carboxylate To a 50 mL round bottom flask charged with tert-butyl3,4-dihydroquinoline-1(2II)- carboxylate (I 9,4.28 mmol), dirhodium tetracaprolactamate (140 mg, 0.21 mmol) and sodium bicarbonate (179 mg2.l4 mmol) was added anhydrous DCE (16 mL). tert-butyl hydrogen peroxide (4.28 mL,21.4 mmol) was added and the reaction placed on a pre-heated hot plate (40 'C), fitted with a septum and an empty balloon and mixed for 12 h. The following day more catalyst and tert-butyl hydrogen peroxide were added (0.005 and 5 equiv, respectively) and the reaction was allowed to mix for an additional 4 h. The reaction was cooled to ambient temperature then filtered through a short plug of silica gel eluting with DCM (125 mL). The solution was concentrated and then purified by silica gel chromatography to afford tert-butyl4- oxo-3,4-dihydroquinoline-l(2ll)-carboxylate (785 mg, 75o/o) as a colorless oil. LCMS m/2248 [M+H]+. |
| 73% | With tert.-butylhydroperoxide; C56H53ClN3P2Ru(1+)*F6P(1-) In benzene at 25℃; for 18h; Inert atmosphere; Schlenk technique; |
| 49% | With potassium permanganate; magnesium sulfate In water; acetone for 48h; | |
| 48% | With glucose dehydrogenase; D-glucose; cytochrome P450 enzyme CYP102A1 R47L/Y51F/I263A/E267V/I401P mutant; C21H25N7O17P3(3-)*2H(1+)*Na(1+) In aq. phosphate buffer; ethanol at 20℃; for 36h; Enzymatic reaction; | |
| With potassium permanganate In acetone at 25℃; for 36h; | ||
| 71 % | With Ethyl 2-mercaptopropionate; 4CzIPN; water In acetonitrile at 20℃; Irradiation; Schlenk technique; Inert atmosphere; Sealed tube; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 100℃; for 24h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 81 percent / tetrabutylammonium bromide; aq. NaOH / CH2Cl2 / 18 h / Heating 2: 33 percent / benzene / 18 h / 165 °C | ||
| Multi-step reaction with 3 steps 1: 81 percent / tetrabutylammonium bromide; aq. NaOH / CH2Cl2 / 18 h / Heating 2: 28 percent / benzene / 18 h / 165 °C 3: 96 percent / toluene / 24 h / 165 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine In tetrahydrofuran at 80℃; for 16h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | In benzene for 12h; Reflux; | |
| In benzene for 12h; Reflux; | Bis(2,2,2-trichloroethyl) 1-{1-(t-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-2(1H)-yl}hydrazine-1,2-dicarboxylate (41l) 40l (0.233 g, 1.0 mmol) was dissolved in benzene (3.3 mL), 23e (0.457 g, 1.2 mmol) was added, and stirred at reflux for 12 h. After cooled to room temperature, the solvent was removed under reduced pressure. Purification by column chromatography (n-hexane : EtOAc = 10 : 1 v /v) gave 41l (0.358 g, 58%) as colorless crystals. 1HNMR (400 MHz, CDCl3) δ 1.12~1.40 (m, 2H), 1.80~2.10 (br, 1H), 2.20 (s, 3H), 2.40~2.80 (m, 2H),4.30~5.00 (m, 4H), 6.30~6.65 (br, 1H), 6.95~7.30 (br, 5H). 13CNMR (100 MHz, CDCl3) δ 23.00, 25.60,29.61, 67.50~69.00 (br), 74.84, 75.57, 125.34, 126.20, 126.90, 127.07, 133.00~137.30 (br),137.50~139.00 (br), 151.00~153.00 (br), 171.81. IR (KBr) 3290, 2979, 1775, 1734, 752, 717 cm-1.FABMS (NBA) m/z: 613.8 (C20H2435Cl537ClN3O6: [M+H]+), 611.8 (C20H2435Cl6N3O6: [M+H]+), 557.8,513.8, 232.1, 176.0, 132.0 (100%). HR-MS calcd. for C20H2435Cl6N3O6 ([M+H]+) 611.9796, found.611.9784. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | Stage #1: tert-butyl 1,2,3,4-tetrahydroquinoline-1-carboxylate With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -78℃; for 3h; Stage #2: With 1,2-Diiodoethane In diethyl ether at -78 - 20℃; for 19h; | tert-Butyl 8-iodo-3,4-dihydroquinoline-l(2H)-carboxylate A similar procedure to that described in Peter Beak, Won-Koo Lee Tetrahedron Letters 1989, 30, 1197-1200 was used: sec- Butyllithium (0.51 mL, 0.71 mmol) was added to a -78 °C solution of tert- vXy 3,4- dihydroquinoline-l(2H)-carboxylate (139 mg, 0.59 mmol) and Ν,Ν,Ν',Ν'- tetramethylethylenediamine (TMEDA, 0.2 mL, 1.33 mmol) in diethyl ether (1.2 mL). After 3 h, a solution of 1 ,2-diiodoethane (201 mg, 0.71 mL) in 1 mL diethyl ether was added by cannula and the reaction was allowed to warm to room temperature. After 19 h, the mixture was partitioned between 20 mL 0 and 20 mL diethyl ether. The aqueous layer was further extracted with 20 mL diethyl ether and the combined ether solution was dried (Na2S04), filtered and evaporated. Purification of the residue by flash chromatography on silica gel using a Combiflash unit by Teledyne Isco (0% ethyl acetate/hexanes 40%) gave the title compound (154 mg, 73%). |
| 66% | Stage #1: tert-butyl 1,2,3,4-tetrahydroquinoline-1-carboxylate With tert.-butyl lithium Stage #2: With iodine | |
| 58% | Stage #1: tert-butyl 1,2,3,4-tetrahydroquinoline-1-carboxylate With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether; hexane at -78℃; for 1h; Stage #2: With iodine In diethyl ether; hexane at -78℃; for 0.75h; | General procedure: To a solution of N-tert-butyl 2-methylindoline-1-carboxylate (4.00 g, 17.1 mmol) and tetramethylethylenediamine (4.34 mL, 29.1 mmol) in Et2O (82 mL) was added 1.03 M sec-BuLi in hexane (34.3mL, 34.3 mmol) at -78 °C and the mixture was stirred for 1 h at the same temperature. To the mixture was added a solution of iodine (6.09 g, 24.0 mmol) in Et2O (46 mL) dropwise at -78 °C and stirred for 45 min at the same temperature. The mixture was warm up to room temperature and stirred overnight. The mixture was extracted with Et2O and the extract was washed with sat. NH4Cl and sat. Na2S2O3. After drying the extract over MgSO4, the filtrate was concentrated under reduced pressure to leave a residue, which was purified by column chromatography over silica gel with n-hexane-EtOAc(14:1) to give S1 (4.61 g, 75%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: sec.-butyllithium; N,N,N,N,-tetramethylethylenediamine / diethyl ether / 3 h / -78 °C 1.2: 19 h / -78 - 20 °C 2.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C | ||
| Multi-step reaction with 2 steps 1.1: sec.-butyllithium; N,N,N,N,-tetramethylethylenediamine / hexane; diethyl ether / 1 h / -78 °C 1.2: 0.75 h / -78 °C 2.1: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C | ||
| Multi-step reaction with 2 steps 1: tert.-butyl lithium 2: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | In tetrahydrofuran at 60℃; for 20h; Schlenk technique; | |
| 89% | With dmap In dichloromethane at 20℃; for 16h; | |
| 84% | Stage #1: 1,2,3,4-tetrahydroquinoline With sodium hydride In tetrahydrofuran; mineral oil for 1.5h; Inert atmosphere; Reflux; Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran; mineral oil for 48h; Reflux; Inert atmosphere; |
| 70% | Stage #1: 1,2,3,4-tetrahydroquinoline With sodium hydride Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran for 24h; Reflux; | |
| 14% | With triethylamine In tetrahydrofuran at 20 - 32℃; for 4h; | |
| 13% | With dmap; triethylamine In acetonitrile at 20 - 55℃; | tert-Butyl 3,4-dihydroquinoline-l(2H)-carboxylate Di-tert-butyl dicarbonate (1.181 g, 5.4 mmol) was added to a solution of 1,2,3, 4-tetrahydroquino line (626 mg, 4.7 mmol), triethylamine (1.3 mL, 9.3 mmol) and DMAP (112 mg, 0.19 mmol) in CH3CN (15 mL). The reaction was stirred for 1.5 h at room temperature and then was heated overnight at 55 °C. The solution was allowed to cool to room temperature and then was evaporated. The residue was partitioned between 25 mL ethyl acetate and 25 mL 1 M HCl. The ethyl acetate solution was further washed with 1 M HCl (2 x 25 mL) and 25 mL brine and then was dried (Na2S04), filtered and evaporated. Purification of the residue by flash chromatography on silica gel using a Combiflash unit by Teledyne Isco (0% ethyl acetate/hexanes -> 40%) gave the title compound (139 mg, 13%). |
| With triethylamine In dichloromethane for 10h; Reflux; | ||
| With triethylamine In dichloromethane at 40℃; for 24h; Inert atmosphere; Glovebox; | ||
| With dmap; triethylamine In dichloromethane at 0 - 20℃; | ||
| With dmap In dichloromethane at 0 - 20℃; for 24h; | ||
| 83 % | With dmap; triethylamine In methanol at 0 - 20℃; Inert atmosphere; | |
| 46 % | With dmap In dichloromethane at 0 - 20℃; | |
| With dmap In tetrahydrofuran at 20℃; Inert atmosphere; Glovebox; Schlenk technique; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With glucose dehydrogenase; D-glucose; cytochrome P450 enzyme CYP102A1 R47L/Y51F/I263A/E267V/I401P mutant; C21H25N7O17P3(3-)*2H(1+)*Na(1+) In aq. phosphate buffer; ethanol at 20℃; for 16h; Enzymatic reaction; | |
| Multi-step reaction with 2 steps 1: potassium permanganate / acetone / 36 h / 25 °C 2: sodium tetrahydroborate / methanol / 0.5 h / 25 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 363 mg | Stage #1: tert-butyl 1,2,3,4-tetrahydroquinoline-1-carboxylate With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -78℃; for 2h; Inert atmosphere; Stage #2: dibutyl ditelluride In diethyl ether at 20℃; Inert atmosphere; Stage #3: With trifluoroacetic acid In diethyl ether; dichloromethane for 0.5h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 320 mg | Stage #1: tert-butyl 1,2,3,4-tetrahydroquinoline-1-carboxylate With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -78℃; for 2h; Inert atmosphere; Stage #2: di-n-hexadecyl ditelluride In diethyl ether at 20℃; Inert atmosphere; Stage #3: With trifluoroacetic acid In diethyl ether; dichloromethane for 0.5h; Inert atmosphere; |

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