Structure of 1170108-38-9
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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. : | 1170108-38-9 |
Formula : | C9H19ClN2O2 |
M.W : | 222.71 |
SMILES Code : | O=C(OC(C)(C)C)NCC1CNC1.[H]Cl |
MDL No. : | MFCD08752583 |
InChI Key : | FLSTVGQJEDAWCH-UHFFFAOYSA-N |
Pubchem ID : | 44118838 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.89 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 61.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.36 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.73 |
Solubility | 4.16 mg/ml ; 0.0187 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.99 |
Solubility | 2.28 mg/ml ; 0.0103 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.89 |
Solubility | 2.88 mg/ml ; 0.0129 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 |
-6.71 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) |
2.2 |
* 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 |
---|---|---|
71% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 25℃; for 2.0h;Inert atmosphere; | Example 41. Preparation of compound S10: To a solution of acid S3 (45 mg, 0.11 mmol) in anhydrous DMF (1.5 mL) was added <strong>[1170108-38-9]tert-butyl azetidin-3-ylmethylcarbamate hydrochloride</strong> (53 mg, 0.14 mmol) followed by DIPEA (0.1 mL, 0.54 mmol). The reaction mixture was cooled to 0 C and HATU (48 mg, 0.216 mmol) was added. Upon complete addition, the reaction as warmed up to 25C and stirred for 2 h under N2. The reaction was then quenched with pH 7 buffer (phosphate, 10 mL) and extracted with EtOAc (3 x 15 mL). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried over Na2S04 and concentrated. The mixture was purified by silica flash column chromatography (DCM:MeOH = 1000: 1 to 100: 1) to afford title compound S10 (45 mg, 71%) as a yellow solid. LC-HRMS, m/z 607.1433 [M+Na]+; Calcd for C32H28N207SNa+ : 607.1617. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 120℃; for 24.0h;Sealed tube; | For isopropyl alcohol / N, N-diisopropylethylamine (50mL / 25mL)4-chloropyridin-2-amine 8-1 (2.50 g, 19.5 mmol) solution inTert-butyl (azetidin-3-ylmethyl) carbamate hydrochloride 8-2 (5.60 g, 25.4 mmol) was added. The reaction mixture was heated in a sealed tube at 120 C for 24 hours.The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was distinguished between EtOAc and saturated sodium bicarbonate solution.The layers were separated; the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was washed with hexane to obtain((1- (2-aminopyridin-4-yl) azetidin-3-yl) methyl) t-butylaminoformate 8-3 (5.2 g, 96%),An off-white solid, which was used directly in the next step without further purification. |
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 120℃; for 24.0h;Sealed tube; | To a solution of 4~chloropyridin~2 -amine 8-1 (2.50 g, 19.5 mrnol) in isopropanoyNN-diisopropylethylamine (50 mL/25 mL) was added /erf-butyl(azetidin-3- ylmethyl)carbamate hydrochloride 8-2 (5.60 g. 25.4 mmol). The reaction mixture was heated at 120 C in a sealed tube for 24 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between EtOAd and saturated sodium bicarbonate solution. The layers were separated; the organic layer was dried over sodium sulphate, filtered and concentrated . Hie residue was washed with hexanes to provide /en-butyl ((l -(2-aminopyridin-4-yl)azetidm-3- yl)methyl)carbamate 8-3 (5.2 g, 96%) as an off-white solid, which was used for next step without further purification. ESHAPCI-MS m/z 279 M - S i j . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; for 12.0h; | Step A: A solution of 2-chloro-5,6-dimethyl-1H-benzo[d]imidazole (135 mg, 0.75 mmol), t-Butyl(azetidin-3-yl)methyl-carbamate:HCl (333 mg, 1.50 mmol) and DIEA (0.33 mL, 1.9 mmol) in DMSO (1.5 mL) were stirred at 100 C. for 12 hrs. The reaction was diluted with EtOAc and water. The aqueous layer was separated and extracted with EtOAc (3×). The combined organics were washed with water, brine, dried over Na2SO4, concentrated and chromatographed on silica gel (24 g) eluting with a 0-to-5% MeOH/DCM (with 1% conc. NH4OH) gradient to give 128 mg (52%) of tert-butyl ((1-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)azetidin-3-yl)methyl)carbamate as a light tan solid. MS (ESI) (M+H+) m/z=331. LCMS Ret time (UV 215/254): 0.83 min. |
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