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Structure of 3970-79-4

Chemical Structure| 3970-79-4

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Product Details of [ 3970-79-4 ]

CAS No. :3970-79-4
Formula : C8H16ClNO
M.W : 177.67
SMILES Code : [H]Cl.O1CCCC12CCNCC2
MDL No. :MFCD11042294
InChI Key :LAAJAVVOPJHOHB-UHFFFAOYSA-N
Pubchem ID :21934981

Safety of [ 3970-79-4 ]

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

Computational Chemistry of [ 3970-79-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 51.15
TPSA ?

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

21.26 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

1.31
Log Po/w (WLOGP)?

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

1.34
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.

1.22
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

2.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.17

Water Solubility

Log S (ESOL):?

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

-1.77
Solubility 3.04 mg/ml ; 0.0171 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.

-1.36
Solubility 7.81 mg/ml ; 0.0439 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

-1.85
Solubility 2.5 mg/ml ; 0.0141 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.

-6.45 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

1.0
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)

2.05

Application In Synthesis of [ 3970-79-4 ]

* 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 [ 3970-79-4 ]

[ 3970-79-4 ] Synthesis Path-Downstream   1~6

  • 1
  • cis (RS)-α-methyl-N-(6-phenyl-1-oxaspiro[2.5]oct-6-yl)-3,5-bis(trifluoromethyl)benzeneacetamide [ No CAS ]
  • [ 3970-79-4 ]
  • cis-(RS)-α-methyl-N-[4-hydroxy-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)methyl-1-phenylcyclohexyl]-3,5-bis(trifluoromethyl)benzeneacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% at 90℃; for 18.0h; A mixture of cis (RS)-alpha-methyl-N-6-phenyl-1-oxaspiro[2.5]oct-6-yl)-3,5-bis(trifluoromethyl)benzeneacetamide (Example 293, 24 mg, 0.051 mmol) and 1-oxa-8-azaspiro[4.5]decane (Description 75, 70 mg) was stirred in the absence of solvent at 90 C. for 18 hours. The mixture was cooled and purified by flash column chromatography on silica gel, eluting with CH2Cl2/MeOH/NH3(Aq.) (95:5:0.5), to give the title compound (27 mg, 87%). 1H NMR (400 MHz, CDCl3) delta 7.76 (1H, s), 7.64 (2H, s), 7.35-7.20 (5H, m), 5.61 (1H, br s), 3.80 (2H, t, J 7 Hz), 3.56 (1H, q, J 7 Hz), 2.75-2.62 (2H, m), 2.58-2.45 (2H, m), 2.36 (1H, t, J 6 Hz), 2.30 (2H, s), 2.17 (2H, t, J 6 Hz), 1.89 (2H, quin, J 7 Hz), 1.75-1.5 (7H, m), 1.42 (3H, d, J 7 Hz), and 1.50-1.30 (2H, m). m/z (ES+) 613 (M+1).
  • 2
  • [ 374794-89-5 ]
  • [ 3970-79-4 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogenchloride; In methanol; at 20℃; for 3.0h; Methanolic hydrogen chloride (3M, 20 mL) was added over 10 minutes to a stirred, cooled (0 C.) solution of 1,1-dimethylethyl 1-oxa-8-azaspiro[4,5]decane-8-carboxylate (Description 74, 3.18 g, 13.2 mmol) in methanol (10 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure to give the title compound (2.29 g, 98%). m/z (ES+) 142 (M+1).
98% With hydrogenchloride; In methanol; at 0 - 20℃; for 3.0h; Methanolic hydrogen chloride (3M, 20ML) was added over 10 minutes to a stirred, cooled (0C) solution of 1, 1-dimethylethyl l-oxa-8-azaspiro [4. 5] DECANE-8-CARBOXYLATE (from step (iv) above, 3. 18G, 13. 2MMOL) in methanol (10ML) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure to give the title compound (2. 29g, 98%). 1H NMR (400 MHz, CDC13) : 8 3. 85 (2H, t, J 7Hz), 3.27-3. 15 (4H, m), 1.98 (2H, QUIN. , J7HZ), 1. 86-1. 75 (6H, M); M/Z (ES+) 142 (M+1).
  • 3
  • [ 3970-79-4 ]
  • [ 729607-77-6 ]
  • [ 870082-50-1 ]
YieldReaction ConditionsOperation in experiment
65% With triethylamine; In tetrahydrofuran; at 20℃; for 96.0h; A suspension of the <strong>[3970-79-4]1-oxa-8-azaspiro[4.5]decane hydrochloride</strong> (0.264 g, 1.49 mmol; prepared according to the procedure by WO 0187838, 2001), triethylamine (0.21 mL, 1.5 mmol) and THF (3 mL) was stirred for 30 minutes at room temperature. The mixture was treated with Intermediate 1B (0.18 g, 0.50 mmol) and stirred at room temperature for 4 days and concentrated. The resulting residue was purified by flash chromatography eluding with 0%-20%-50% ethyl acetate/hexane to provide the desired product as a yellow oil (0.139 g, 65% yield). 1H NMR (300 MHz, CDCl3) delta: 7.46-7.43 (1H, m), 7.35-7.27 (2H, m), 5.12 (2H, s), 4.28 (2H, q, J=7.2 Hz), 3.82 (2H, t, J=6.8 Hz), 3.47 (3H, s), 3.31-3.23 (2H, m), 3.18-3.10 (2H, m), 1.97-1.87 (2H, m), 1.74-1.69 (4H, m), 1.55 (2H, br s), 1.26 (3H, t, J=7.1 Hz). LCMS (M+H) calcd for C23H30N3O5: 428.21; found: 428.32.
  • 4
  • [ 1532-97-4 ]
  • [ 3970-79-4 ]
  • 8-(isoquinolin-4-yl)-1-oxa-8-azaspiro[4.5]decane [ No CAS ]
  • 5
  • [ 3970-79-4 ]
  • isopropyl 2-(5-bromo-4-chloro-2, 6-dimethylpyridin-3-yl)-2-oxoacetate [ No CAS ]
  • isopropyl 2-(5-bromo-2,6-dimethyl-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)pyridin-3-yl)-2-oxoacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 18.0h; To a solution l-oxa-8-azaspiro[4.5]decane, HC1 (150 mg, 0.84 mmol) and DIEA (0.44 mL, 2.53 mmol) in anhydrous CH3CN (10 mL) was added isopropyl 2-(5- bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (282 mg, 0.84 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80 C) and stirred for 18 h; cooled, and concentrated. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5 - 35% EtOAc/hexanes) using an Isolera chromatography station to give isopropyl 2-(5-bromo-2,6-dimethyl-4-(l-oxa-8-azaspiro[4.5]decan-8- yl)pyridin-3-yl)-2-oxoacetate 176 mg (47%). 1H MR (500 MHz, CDC13) delta 5.09-5.04 (m, 1H), 3.73 (t, J=7.0 Hz, 2H), 3.36-3.35 (m, 4H), 2.61 (s, 3H), 2.30 (s, 3H), 1.89-1.84 (m, 2H), 1.66 (t, J=8.1 Hz, 2H), 1.56-1.51 (m, 4H), 1.30 (d, J=5.9 Hz, 6H). UPLC (M+H) = 441.2.
  • 6
  • [ 22177-92-0 ]
  • [ 3970-79-4 ]
  • 8-(6-morpholinopyrimidin-4-yl)-1-oxa-8-azaspiro[4.5]decane [ No CAS ]
 

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