Structure of 6940-80-3
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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. : | 6940-80-3 |
Formula : | C10H15NO |
M.W : | 165.23 |
SMILES Code : | C[C@H](NCC1=CC=CC=C1)CO |
MDL No. : | MFCD03840382 |
InChI Key : | PJXWCRXOPLGFLX-VIFPVBQESA-N |
Pubchem ID : | 5356540 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 49.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
32.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.29 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.78 |
Solubility | 2.76 mg/ml ; 0.0167 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.56 |
Solubility | 4.58 mg/ml ; 0.0277 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.11 |
Solubility | 0.128 mg/ml ; 0.000776 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) |
No |
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 |
-6.4 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 |
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) |
1.31 |
* 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 |
---|---|---|
60% | Step 1: (S)-Alininol (17.5 g, 233 mmol), PhCHO (26 g), and MgSO4 (70 g) were taken up in DCM and stirred at 25 0C for 19 h. The solution was filtered and concentrated which furnished a yellow solid. The residue was taken up in MeOH and cooled to O 0C. Sodium borohydride (11 g, 288 mmol) was added in portions to the solution at 0 0C (gas evolution). After the addition, the solution was stirred at 25 0C for 18 h. The solution was concentrated, and the residue was quenched carefully with 3 M HCI (aq.) (gas evolution/exotherm). The aqueous acidic layer was extracted with Et2O (4 X 200 ml_). The aqueous layer was cooled to 0 0C and made basic via addition of NaOH pellets (pH = 11 -12). The aqueous layer was extracted with DCM. The combined DCM layers were dried (MgSO4). Filtration and concentration gave 23.2 g (60percent) of the amino-alcohol as a white solid. | |
Preparation 11; Sodium triacetoxyborohydride (36.7 g) was added portion wisely to a mixture of (2S)-2-amino-1-propanol (10.0 g) and benzaldehyde (13.53 ml) in a mixture of dichloromethane (140 ml) and acetic acid (8.38 ml) at 0° C. and the whole was stirred at room temperature overnight. The mixture was washed successively with 2N sodium hydroxide and brine, and dried over sodium sulfate. The solution was evaporated under reduced pressure and the resulting residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (30:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2S)-2-benzylamino-1-propanol (15.96 g). IR (KBr): 2843, 1496, 1454, 1377, 1340, 1065 cm-1 NMR (CDCl3, delta): 1.10 (3H, d, J=6.4 Hz), 2.77-2.93 (1H, m), 3.28 (1H, dd, J=10.6 and 6.9 Hz), 3.61 (1H, dd, J=10.6 and 4.0 Hz), 3.75, 3.87 (2H, ABq, J=13 Hz), 7.21-7.34 (5H, m) MASS (API-ES): 166 (M+H)+ | ||
With hydrogen;5% Pd(II)/C(eggshell); In ethanol; at 20℃; for 8h; | [Preparation 6]: Synthesis of Compound 6(1) Optically-Active Compound of 2-benzylaminopropan-1-olTo a solution of (S)-(+)-2-aminopropan-1-ol (50.0 g) and benzaldehyde (74 ml) in ethanol (500 ml) was added 5percent palladium carbon (5.0 g), and the mixture was hydrogenated at room temperature under ordinary pressure for 8 hours. The reaction mixture was filtered through Celite, and concentrated under reduced pressure to give the titled compound (111.2 g).1H-NMR (DMSO-D6) delta: 7.34-7.27 (4H, m), 7.23-7.18 (1H, m), 4.53-4.47 (1H, m), 3.76 (1H, d, J=13.5 Hz), 3.66 (1H, d, J=13.5 Hz), 3.29-3.24 (2H, m), 2.65-2.55 (1H, m), 1.99 (1H, br s), 0.93 (3H, d, J=6.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine; In dichloromethane; at 0 - 20℃; | Step-5: N-Benzyl-2-chloro-N-((S)-2-hydroxy-1-methyl-ethyl)-acetamide To a solution of (S)-2-Benzylamino-propan-1-ol (4.1 g, 0.025 mol) in DCM was added triethylamine (3.8 ml, 0.028 mol) and chloroacetyl chloride (1.97 ml, 0.025 mol) at 0° C. The solution was stirred for 2 h at room temperature. The reaction mixture was concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to afford 560 mg (95percent) of N-Benzyl-2-chloro-N-((S)-2-hydroxy-1-methyl-ethyl)-acetamide. LC/MS [M+H]+: 242.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 19.8333h; | (2) Optically-Active Compound of [benzyl-(2-hydroxy-1-methylethyl)-amino]acetic acid tert-butyl esterTo a mixture of an optically-active compound of 2-benzylaminopropan-1-ol (111.2 g), potassium carbonate (111.6 g) and N,N-dimethylformamide (556 ml) cooled to 0° C. was added dropwise bromoacetic acid tert-butyl ester (109 ml) over 20 minutes, and the mixture was stirred at room temperature for 19.5 hours. The mixture was acidified by the addition of 2M aqueous hydrochloric acid solution and 6M aqueous hydrochloric acid solution to pH 2, and washed with toluene (1000 ml). The separated organic layer was extracted with 0.1M aqueous hydrochloric acid solution (300 ml). The combined aqueous layer was adjusted to pH 10 by 4M aqueous sodium hydroxide solution, and extracted with ethyl acetate (700 ml). The organic layer was sequentially washed with water (900 ml) and saturated aqueous sodium chloride solution (500 ml). The separated aqueous layer was extracted with ethyl acetate (400 ml) again. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the titled compound (160.0 g).1H-NMR (DMSO-D6) delta: 7.37-7.26 (4H, m), 7.24-7.19 (1H, m), 4.26 (1H, dd, J=6.9, 3.9 Hz), 3.76 (1H, d, J=14.1 Hz), 3.68 (1H, d, J=13.9 Hz), 3.45-3.39 (1H, m), 3.29-3.20 (1H, m), 3.24 (1H, d, J=17.2 Hz), 3.13 (1H, d, J=17.0 Hz), 2.84-2.74 (1H, m), 1.37 (9H, s), 0.96 (3H, d, J=6.8 Hz). | |
With potassium carbonate; In water; toluene; at 65℃; for 21h;Inert atmosphere; | S-BAPO [1] (35.0 g, 212 mmol) was added to water (175 mL) at room temperature under nitrogen atmosphere. To the resulting suspension were added toluene (53 mL) and potassium carbonate (32.2 g, 233 mmol) at room temperature. To the resulting solution was added dropwise TBBA (434.4 g, 223 mmol) at room temperature, and then the used dropping funnel was washed with toluene (17 mL) and the washings were added to the reaction mixture. The reaction mixture was stirred at 65°C for 21 hours, and then cooled to room temperature. After toluene (105 mL) was added to the reaction mixture and then the mixture was stirred, the organic layer was separated out. The organic layer was washed with water (175 mL), aqueous layer was removed, and then the solvent was removed out of the organic layer in vacuo. Toluene (105 mL) was added to the residue and the toluene solution was concentrated. The operation was repeated two more times to give a toluene solution of S-BBMO [2] (74.0 g, 212 mmol in theory). The given toluene solution of S-BBMO was used in the next step, assuming that the yield was 100 percent. A crude product of S-BBMO which was prepared by the same process was evaporated to dryness and then measured about NMR and MS. 1H-NMR (DMSO-d 6) delta: 7.36-7.13 (5H, m), 4.26 (1H, dd, J = 6.8, 3.9 Hz), 3.72 (2H, dd, J = 14.2, 6.8 Hz), 3.47-3.38 (1H, m), 3.30-3.08 (3H, m), 2.79 (1H, sext, J = 6.8 Hz), 1.35 (9H, s), 0.96 (3H, d, J = 6.8 Hz). MS: m/z = 280 [M+H] + | |
With potassium carbonate; In water; toluene; at 65℃; for 21h;Inert atmosphere; | 5-HAPO [1] (35.0 g, 212 mmol) was added to water (175 mE) at room temperature under nitrogen atmosphere. To the resulting suspension were added toluene (53 mE) and potassium carbonate (32.2 g, 233 mmol) at room temperature. To the resulting solution was added dropwise THEA (434.4 g, 223 mmol) at room temperature, and then a dropping thnnel used was washed with toluene (17 mE) and the washings were added to the reaction mixture. The reaction mixture was stirred at 65° C. for 21 hours, and then cooled to room temperature. Afier toluene (105 mE) was added to the reaction mixture and then the mixture was stirred, the organic layer was separated out. The organic layer was washed with water (175 mE), aqueous layer was removed, and then the solvent was removed out of the organic layer in vacuo. Toluene (105 mE) was added to the residue and the toluene solution was concentrated. The operation was repeated two more times to give a toluene solution of 5-HEMO [21(74.0 g, 212 mmol in theory). The given toluene solution of 5-HEMO was used in the next step, assuming that the yield was 100percent. A crude product of 5-HEMO which was prepared by the same process was evaporated to dryness and then measured about NMR and MS. ?H-NMR (DMSO-d5) oe: 7.36-7.13 (5H, m), 4.26 (1H, dd, J=6.8, 3.9 Hz), 3.72 (2H, dd, J=14.2, 6.8 Hz), 3.47-3.38 (1H, m), 3.30-3.08 (3H, m), 2.79 (1H, sext, J=6.8 Hz), 1.35 (9H, s), 0.96 (3H, d, J=6.8 Hz).10256] MS: mlz=280 [M+H] |
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