Structure of 37585-16-3
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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. : | 37585-16-3 |
Formula : | C7H8ClNO |
M.W : | 157.60 |
SMILES Code : | OCC1=CC=C(Cl)C=C1N |
MDL No. : | MFCD04037367 |
Boiling Point : | No data available |
InChI Key : | MUDGPJDWJIFUDB-UHFFFAOYSA-N |
Pubchem ID : | 4134900 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H317-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.27 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.6 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.51 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.16 |
Solubility | 1.09 mg/ml ; 0.00693 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.11 |
Solubility | 1.22 mg/ml ; 0.00776 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.47 |
Solubility | 0.533 mg/ml ; 0.00338 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) |
No |
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 |
-6.18 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 |
1.0 |
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 |
1.0 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) |
1.01 |
* 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 |
---|---|---|
97% | With iron; ammonium chloride; In ethanol; water; for 2h;Reflux; | General procedure: Iron powder (5.5 eq.) and NH4Cl (0.7 eq.) were suspended in EtOH : H2O 10 : 1 (0.05 M) and refluxedwith nitrophenyl derivative 12 (1 eq.) for 2 h. After completion (monitored by TLC analysis), thereaction mixture was filtrated on Celite and rinsed with CH2Cl2. The solvent was evaporated underreduced pressure and CH2Cl2 was added. The mixture was washed with a saturated solution ofNaHCO3. The aqueous phase was extracted four times with CH2Cl2 and the combined organic phaseswere washed with brine, dried over magnesium sulfate and filtrated. Evaporation of the solvent underreduced pressure gave the desired product 11, which was used in the next step without furtherpurification. |
77% | With hydrogen;platinum(IV) oxide; In ethanol; at 20℃; under 975.0980000000001 Torr; for 1h; | A suspension of (4-chloro-2-nitrophenyl)methanol (1 g, 5.33 mmol, ALDRICH) and platinum(IV) oxide (100 mg, 0.44 mmol) in ethanol (100 mL) was hydrogenated under 1300 mbar at room temperature for 1 hour. The resulting suspension was filtered, washed with ethanol and the filtrate concentrated to dryness to afford the crude (2-amino-4- chlorophenyl) methanol as a pale orange solid. The crude product was purified by flash <n="180"/>chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane. The solvent was evaporated to dryness to afford (2-amino-4-chlorophenyl)methanol (0.650 g, 77 %) as a pale orange solid. NMR Spectrum (DMSOdthetaV. 4.34 (d, 2H), 5.06 (t, IH), 5.20 (s, 2H), 6.51 (dd, IH), 6.64 (d,IH), 7.05 (d, IH) |
With hydrogen;5% platinum on sulfided carbon; In ethanol; for 2h; | (4-chloro-2-nitrophenyl)methanol (40.0 g, 0.21 mol) was dissolved in ethanol (700 ml_) and hydrogenated under hydrogen gas (20 psi) in the presence of 5% platinum on sulfided carbon (Pt-C/S) (5.0Og). After 2 hours the catalyst was removed by filtration through Celiteand the solvent removed under reduced pressure. This provided the desired compound (2-amino-4-chlorophenyl)methanol (32.9 g) which was used without further purification. HPLC Rt =1.70 minutes. 1H NMR (CDCI3) delta 6.96 (d, 1 H), 6.67 (m, 2H), 4.64 (s, 2H), 4.27 (bs, 2H)1 1.56 (bs, 1 H). |
32.9 g | With hydrogen; In ethanol; under 1034.32 Torr; for 2h; | 4-chloro-2-nitrophenyl)methanol (40.0 g, 0.21 mol) was dissolved in ethanol (700 mL) and hydrogenated under hydrogen gas (20 psi) in the presence of 5% platinum on sulfided carbon (Pt-C/S, 5.00g). After 2 hours the catalyst was removed by filtration through Celite and the solvent removed under reduced pressure. This provided the desired compound (2-amino-4-chlorophenyl)methanol (32.9 g) which was used without further purification. HPLC Rt =1.70 minutes. 1H NMR (CDCl3) delta 6.96 (d, 1H), 6.67 (m, 2H), 4.64 (s, 2H), 4.27 (bs, 2H), 1.56 (bs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 2h;Inert atmosphere; | 26.5 g (0.7 mol) of lithium tetrahydroaluminum and dry tetrahydrofuran (300 mL) were added dropwise to a mixture of 100 g of 2-amino-4-chlorobenzoic acid (0.58 mol) and dry tetrahydrofuran (800 mL) under nitrogen atmosphere. The solution was added dropwise, and stirred at room temperature for 2 hours, diluted with 10 mL of water, and a solution of 20 g of sodium hydroxide and 100 mL of water was added.Filtration, the filtrate was extracted with EtOAc. The concentrate was crystallized from ethyl acetate/petroleum ether.82.7 g of 2-amino-4-chloro-benzyl alcohol was obtained (yield: 90%). |
88% | With borane-THF; In tetrahydrofuran; at 0 - 30℃; for 1.66667h;Inert atmosphere; | General procedure: To a solution of 6-chloroanthranilic acid (1.5 g, 8.74 mmol) in THF (5 mL) was added dropwise 1.08 M borane-tetrahydrofuran complex in THF (24.3 mL, 26.2 mmol) at 0 C under an Ar atmosphere for 10 min. After 1.5 h with stirring at 30 C, the solution was cooled at 0 C, added aqueous THF (THF/H2O = 1:1, 60 mL) and potassium carbonate, and extracted with diethyl ether three times. The combined organic extracts were washed with brine, dried over Na2SO4, and evaporated in vacuo. The residue was crystallized from AcOEt to give 1a (1.2 g, 88%) as a white needle crystal. |
85.4% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere; | To a mixture of L1AIH4 (4.4 g, 116.6 mmol) in dry THF (116 mL) at 0C under N2 was added dropwise a solution of 2-amino-4-chlorobenzoic acid (10 g, 58.3 mmol) in dry THF (80 mL). The mixture was stirred at r.t. for 2 hr, then quenched, in sequence, by addition of H2O (4 mL), aq. NaOH (15 wt, 8 mL), and H2O (12 mL). The resulting mixture was filtered, and the filtrate was extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The residue was re -crystallized from EtOAc/PE to give (2-amino-4-chlorophenyl)methanol (7.8 g, 85.4% yield). LC-MS: m/z 158(M+H)+. |
81.6% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 8h;Inert atmosphere; | In a 500 niL round bottom flask, the stirred solution of 2-amino-4-chlorobenzoic acid (42.8 g, 250.29 mmol, Aldrich) was dissolved anhydrous THF (200 mL) and the solution was cooled in an ice-bath. Lithium aluminum hydride (11.76 g, 312.86 mmol) was added portionwise to the above solution at the ice-bath temperature under nitrogen atmosphere. The resulting mixture was stirred at rt for 8 h. On completion of reaction the reaction mixture was cooled to ice-bath temperature and quenched by sequential addition of cold water (12 mL), 15% NaOH (12 mL) and water (36 mL). The resulting slurry was stirred at rt for 30 min and filtered through a CELITE pad. The solid residue was washed with ethyl acetate (1000 mL) and combined filtrate was concentrated under reduced pressure to give (2-amino 4-chlorophenyl)methanol as an off white solid. Yield: 32g (81.6 %). LCMS (ESI, m/z): 181 (M+23)+. |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 8h; | 2-amino-4-chlorobenzoic acid(42. 8g, 0. 25mol) dissolved in 200 ml of THF anhyride to, cooled in an ice water bath. In this solution, lithium aluminum piece (11. 76g, 0. 31mol) is added. The mixture is stirred at room temperature for 8 hours. 12g of water is added, 12g of the next 15% NaOH is added. Next, 36g of the added water. The slurry is stirred at room temperature for 30 minutes. The slurry is filtered. Solid washed with ethyl acetate. Liquid are together, the solvent is evaporated. Its meleimide without purifying substance is used in the next step. | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 2h;Cooling with ice; | General procedure: To a stirred solution of anthranilic acid (15 mmol) in tetrahydrofuran (1 M, 15 mL) was slowly added Lithium aluminum hydride solution 1M in THF (30mL, 30 mmol, 2 eq.) in an ice bath. Upon completion of the addition, the ice bath was taken away, and stirring was continued for 2 hours at the room temperature. The reaction was quenched with water and a 5% solution of NaOH in water. The inorganic solid residue was filtered under vacuum, washed with ethyl acetate and the filtrate was transferred to a separatory funnel. The two layers were separated, and the product was extracted with ethyl acetate (x3). The organic phase was washed with brine (x1), dried over sodium sulfate, concentrated under reduced pressure and used in the next step without further purification. | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere; | General procedure: A solution of the LiAlH4 (1.5 equiv) in anhydrous THF (50 mL) was stirred at 0 C, while 2-amino-benzoic acid (1.0 equiv) in THF was added dropwise. Then the mixture was warmed to room temperature and stirred for 2 hours. After complete consumption of the acid, the mixture was quenched with 10 % NaOH. The resulting suspension was filtered and extracted with ethyl acetate. The combined organic collection was evaporated. The residue was purified by column chromatography to give the product S1 as a white solid or off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; hydrogen; In tetrahydrofuran; water; Petroleum ether; | Step A - 2-hydroxymethyl 5-chloroaniline* *may also be called 2-amino-4-chlorobenzyl alcohol STR20 To a 500 ml vessel equipped with a mechanical stirrer is added 220 ml of tetrahydrofuran (freshly distilled from lithium aluminum hydride). The mixture is cooled to 0, and 6 g of lithium aluminum hydride is then slowly added to the mixture. The temperature of the mixture is maintained at 0 to 20, while 17.159 g of 4-chloroanthranilic acid is slowly added in small portions to the mixture (vented to atmosphere). The mixture is then, slowly warmed to room temperature, then refluxed for 16 hrs. The mixture is then cooled to 0 in an ice bath and 6 ml. of water slowly added (causing evolation of hydrogen). From 6 to 8 ml of 20% aqueous sodium hydroxide are then added to the mixture dropwise. The mixture becomes thicker and more difficult to stir, and a solid form upon addition of 18 ml of water (at 0). 70 ml of tetrahydrofuran is added and the mixture stirred at room temperature for 2 hrs. The solids are recovered by filtration, digested in 100 ml of tetrahydrofuran and filtered again; the filtrates being retained and combined, then concentrated to obtain white solids. The solids are triturated with hot toluene and filtered.* The filtrate upon cooling and addition of petroleum ether, yields 2-hydroxymethyl-5-chloroaniline m.p. 104-105. *The remaining solids are mostly unreacted 4-chloroanthranilic acid, which is only slightly soluble in toluene. |
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