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Chemical Structure| 1170108-38-9 Chemical Structure| 1170108-38-9

Structure of 1170108-38-9

Chemical Structure| 1170108-38-9

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Product Details of [ 1170108-38-9 ]

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

Safety of [ 1170108-38-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1170108-38-9 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

50.36 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.33
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.15
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.86
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.8

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.73
Solubility 4.16 mg/ml ; 0.0187 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.99
Solubility 2.28 mg/ml ; 0.0103 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.89
Solubility 2.88 mg/ml ; 0.0129 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.71 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.2

Application In Synthesis of [ 1170108-38-9 ]

* 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.

  • Downstream synthetic route of [ 1170108-38-9 ]

[ 1170108-38-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1170108-38-9 ]
  • [ 1548842-90-5 ]
  • [ 1548844-49-0 ]
YieldReaction ConditionsOperation 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.
  • 2
  • [ 19798-80-2 ]
  • [ 1170108-38-9 ]
  • tert-butyl ((1-(2-aminopyridin-4-yl)azetidin-3-yl)methyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation 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 .
  • 3
  • [ 1170108-38-9 ]
  • [ 39791-96-3 ]
  • tert-butyl ((1-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)azetidin-3-yl)methyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 4
  • [ 1170108-38-9 ]
  • [ 39791-96-3 ]
  • tert-butyl ((1-(1-(3-chloro-4-fluorobenzyl)-5,6-dimethyl-1H-benzo[d]imidazol-2-yl)azetidin-3-yl)methyl)carbamate [ No CAS ]
 

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