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Chemical Structure| 929302-18-1 Chemical Structure| 929302-18-1

Structure of 929302-18-1

Chemical Structure| 929302-18-1

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Product Details of [ 929302-18-1 ]

CAS No. :929302-18-1
Formula : C12H23ClN2O2
M.W : 262.78
SMILES Code : O=C(N1CC2(CCNCC2)C1)OC(C)(C)C.[H]Cl
MDL No. :MFCD09835396
InChI Key :SZACTFROZQQOJB-UHFFFAOYSA-N
Pubchem ID :24820549

Safety of [ 929302-18-1 ]

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

Computational Chemistry of [ 929302-18-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 0
Fraction Csp3 0.92
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 77.51
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

41.57 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

1.86
Log Po/w (WLOGP)?

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

1.65
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.

1.71
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

1.31
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.3

Water Solubility

Log S (ESOL):?

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

-2.44
Solubility 0.947 mg/ml ; 0.00361 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.35
Solubility 1.16 mg/ml ; 0.00442 mol/l
Class?

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

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

-2.1
Solubility 2.07 mg/ml ; 0.00789 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

Yes
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.

-6.58 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<0.0
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)

2.74

Application In Synthesis of [ 929302-18-1 ]

* 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 [ 929302-18-1 ]

[ 929302-18-1 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 929301-99-5 ]
  • [ 929302-18-1 ]
YieldReaction ConditionsOperation in experiment
Preparation of compound 4A mixture of compound 3 (1.3 g, 4.11 mmol) and Pd(OH)2 (200 mg) in 15 mL of MeOH was stirred under 55 psi of H2 at 35 0C overnight. The mixture was filtered and the filtrate was evaporated. The residue was dissolved in DCM, dried over anhydrous Na2SO4 and concentrated. The residue was dissolved in anhydrous ether, then HCl(g)/MeOH was added dropwise until pH = 6-7. The mixture was filtered to afford compound 4 (0.95 g). 1H NMR (CD4O, HCl salt) delta: 3.72 (s, 4 H), 3.30 (t, 4 H), 1.99 (t 4 H), 1.43 (9 H).
  • 2
  • [ 929302-18-1 ]
  • [ 13091-23-1 ]
  • [ 1023299-47-9 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 60℃; for 15h;Product distribution / selectivity; Example 78; Preparation of Compound 78B; Step A; To a vial were added 4-chloro-3-nitro pyridine (2 mmol) and spirocyclic amine (2 mmol). The starting materials were dissolved in 4 ml. of dichloromethane followed by the addition of DIPEA (6 mmol). The reaction was stirred at 60° for about 15 hours, then the reaction mixture was concentrated and using preparative liquid chromatography (0-5percent methanol in ethyl acetate) to provide compound 78A. Recovered 1.6 mmol (80percent) of 274. Mass calculated for formula C17H24N4O4 348.18, observed LCMS m/z 348.20 (M+H).; Using the methods described in Steps A and B above, and using the appropriate reactants, the following intermediate compounds were made:
  • 3
  • [ 50-00-0 ]
  • [ 929302-18-1 ]
  • [ 1093066-77-3 ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[929302-18-1]2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride</strong> (100 mg, 0.381 mmol) in DCE (10 mL) was added an aqueous solution of formaldehyde (37 percent w/w, 40 muL, 0.537 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (121 mg, 0.571 mmol) was added and stirring was continued for 1 h. Water was added to the reaction mixture before being loaded onto an Isolute.(R). SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester. To a solution of 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester in DCM (5 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 1 h. The reaction mixture was loaded onto an Isolute.(R). SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a colourless oil (45 mg, 84 percent). 1H NMR (400 MHz, CDCl3): delta 1.81 (m, 4 H), 2.22 (s, 3 H), 2.28 (m, 2 H), 3.22 (bs, 4 H) and 3.38 (bs, 2 H).
To a solution of <strong>[929302-18-1]2,7-diazaspiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride</strong> (100 mg, 0.381 mmol) in DCE (10 mL) was added an aqueous solution of formaldehyde (37 percent w/w, 40 muL, 0.537 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (121 mg, 0.571 mmol) was added and stirring was continued for 1 h. The reaction mixture was added water and loaded onto an Isolute.(R). SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give 7-methyl-2,7- diazaspiro[3.5]nonane-2-carboxylic acid tert-butyl ester. To a solution of 7-methyl-2,7- <n="49"/>^diazaspiro[3.5]nonane-2-carboxylic acid fert-butyl ester in DCM (5 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 1 h. The reaction mixture was loaded onto an Isolute.(R). SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a colourless oil (45 mg, 84 percent). 1H NMR (400 MHz, CDCl3): delta 1.81 (m, 4 H), 2.22 (s, 3 H), 2.28 (m, 2 H), 3.22 (bs, 4 H) and 3.38 (bs, 2 H).
  • 4
  • [ 1193-21-1 ]
  • [ 929302-18-1 ]
  • [ 1233323-69-7 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 110℃; for 20h; Example 23Preparation of Compound 33Step A - Synthesis of Compound 23BCompound 23A (0.274 g, 1.04 mmol) was combined with 4,6- dichloropyrimidine (0.196 g, 1.31 mmol) and DIPEA (0.45 mL, 2.6 mmol) in dioxane (6 mL) and the resulting reaction was heated to 110 °C and allowed to stir at this temperature for 20 hours. The reaction mixture was cooled to room temperature, concentrated in vacuo, and the resulting residue was purified using preparative TLC to provide Compound 23B as an off-white solid.
  • 5
  • [ 929302-18-1 ]
  • [ 70258-18-3 ]
  • tert-butyl 7-((6-chloropyridin-3-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium carbonate; In acetonitrile; at 70℃; for 16h; A solution of 2,7-diazaspiro [3.5] nonane-2-carboxylic acid tert-butyl ester hydrochloride (400 mg, 1.5 mmol)And 2-chloro-5- (chloromethyl) pyridine(243 mg, 1.5 mmol) was dissolved in acetonitrile (50 mL), potassium carbonate (621 mg, 4.5 mmol) was added and reacted at 70 ° C for 16 hours.After cooling to room temperature, ethyl acetate (100 mL) and water (50 mL) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (150 mL x2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give The title compound was obtained as a yellow oil (480 mg, yield 90percent).
  • 6
  • [ 929302-18-1 ]
  • 7-((6-chloropyridin-3-yl)methyl)-2,7-diazaspiro[3.5]nonane [ No CAS ]
  • 7
  • [ 929302-18-1 ]
  • 7-((6-chloropyridin-3-yl)methyl)-2-methyl-2,7-diazaspiro[3.5]nonane [ No CAS ]
  • 8
  • [ 929302-18-1 ]
  • 5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole-6-yl)-N-(5-((2-methyl-2,7-diazaspiro[3,5]nonane-2-yl)methyl)pyridine-2-yl)pyridine-2-amine [ No CAS ]
  • 9
  • [ 929302-18-1 ]
  • [ 135380-50-6 ]
  • 10
  • [ 929302-18-1 ]
  • [ 13790-39-1 ]
  • tert-butyl 7-(6,7-dimethoxyquinazolin-4-yl)-2,7-diazaspiro[3.5]nonane-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 16h; [0513] Procedure: To a stirred solution of 4-chloro-6,7-dimethoxyquinazoline (0.2 g, 0.89 mmol) in DMF (10 mL) was added K2CO3 (0.184 g, 1.33 mmol) followed by <strong>[929302-18-1]2-(tert-butoxycarbonyl)-2,7-diazaspiro[3.5]nonan-7-ium hydrochloride</strong> (0.221 g, 0.979 mmol). Reaction mixture was stirred for 16 h at 90 °C. Progress of the reaction was monitored by TLC. Reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (2 x 50mL). The combined organic layer was washed with brine (10mL), dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure. The crude residue was purified by combiflash using ethyl acetate in hexaneto afford tert-butyl 7-(6,7- dimethoxyquinazolin-4-yl)-2,7-diazaspiro[3.5]nonane-2-carboxylate (0.3g, 81percent) as an off white solid. LC-MS (ES) m/z =415.2 [M+H]+.
 

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Technical Information

Categories

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[ 929302-18-1 ]

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