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Structure of 635713-68-7

Chemical Structure| 635713-68-7

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Product Details of [ 635713-68-7 ]

CAS No. :635713-68-7
Formula : C12H15N3O
M.W : 217.27
SMILES Code : O=C1NC2=CC=CC=C2C2(CCNCC2)N1
MDL No. :MFCD11045505
InChI Key :CFLDCJYCZAHJCK-UHFFFAOYSA-N
Pubchem ID :49760350

Safety of [ 635713-68-7 ]

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

Computational Chemistry of [ 635713-68-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.42
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 3.0
Molar Refractivity 72.55
TPSA ?

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

53.16 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.84
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

0.41
Log Po/w (WLOGP)?

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

-0.04
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.

1.41
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

1.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.0

Water Solubility

Log S (ESOL):?

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

-1.72
Solubility 4.11 mg/ml ; 0.0189 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.

-1.09
Solubility 17.5 mg/ml ; 0.0807 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

-4.1
Solubility 0.0174 mg/ml ; 0.00008 mol/l
Class?

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

Moderately 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

No
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.

-7.33 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)

2.59

Application In Synthesis of [ 635713-68-7 ]

* 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 [ 635713-68-7 ]

[ 635713-68-7 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 635713-68-7 ]
  • [ 885609-41-6 ]
  • [ 912462-61-4 ]
YieldReaction ConditionsOperation in experiment
79% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In dichloromethane; for 12h; EXAMPLE 32; (S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro/piperidine-4,4'-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one; To a solution of (S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (50 mg, 0.133 mmol) in dichloromethane (25 mL) was added <strong>[635713-68-7]1'H-spiro[piperidine-4,4'-quinazolin]-2'(3'H)-one</strong> (31 mg, 0.14 mmol) followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (47 mg, 0.15 mmol) and triethylamine (1.0 mL). After 12 h, the reaction mixture was washed with aqueous NaHCO3 followed by 1.0 M HCl and dried (Na2SO4). The solvent was removed and the crude product was purified by flash chromatography using 7% MeOH in dichloromethane to give (S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinazoline]-2'(3'H)-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (61 mg, 79%) as a white powder. MS (ESI) 575 (M+H); Rf=2.133.
  • 2
  • [ 635713-67-6 ]
  • [ 635713-68-7 ]
YieldReaction ConditionsOperation in experiment
64% With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; water; under 3102.97 Torr; for 48h; To a solution of [1-BENZYL-2',] [3'-DIHYDRO-2'-OXOSPIRO- [PIPERIDINE-4, 4' (L'H)-] quinazoline (1.00 g) in degassed methanol (50 ml) and 6N hydrochloric acid (2.0 ml) was added 10% palladized charcoal (150 mg). The mixture was shaken on a Parr apparatus under an atmosphere of hydrogen at 60 psi overnight. LC/MS showed incomplete reaction. More 10% palladized charcoal (200 mg) was added, and the mixture was shaken for 2 more days. At that point, all starting material was consumed. The mixture was filtered and the filtrate concentrated to give 531 mg of the desired compound (64%). Mass spec.: 218. 12 (MH) [+.]
64% With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; water; under 3102.97 Torr; To a solution of 1-benzyl-2',3'-dihydro-2'-oxospiro-[piperidine-4,4'(1'H)-quinazoline (1.00 g) in degassed methanol (50 ml) and 6N hydrochloric acid (2.0 ml) was added 10% palladized charcoal (150 mg). The mixture was shaken on a Parr apparatus under an atmosphere of hydrogen at 60 psi overnight. LC/MS showed incomplete reaction. More 10% palladized charcoal (200 mg) was added, and the mixture was shaken for 2 more days. At that point, all starting material was consumed. The mixture was filtered and the filtrate concentrated to give 531 mg of the desired compound (64%). Mass spec.: 218.12 (MH)+.
  • 3
  • [ 635713-68-7 ]
  • 1',2'-dihydro-2'-oxospiro-4H-3',1-quinazolin'-4,4'-piperidin-1-carboxylic acid-(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-methoxycarbonyl-ethylester [ No CAS ]
  • 4
  • [ 635713-68-7 ]
  • [ 1158918-60-5 ]
  • [ 1158917-88-4 ]
YieldReaction ConditionsOperation in experiment
88% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h; General working method 1 (GMW1) for reacting (6-chloro-pyrimidin-4-yl)-(2,3-dihydro-indol-1-yl)-methanone with amine derivatives:0.41 mmol of an amine derivative were added to 100 mg (0.39 mmol) of (6-chloro-pyrimidin-4-yl)-(2,3-dihydro-indol-1-yl)-methanone and in the case of AA1 [A] 100 muL (0.58 mmol) DIPEA and in the case of AA1 [B] 150 muL (0.87 mmol) DIPEA in 10 mL DMF. The reaction mixture was stirred for 2 h at RT. The reaction mixture was evaporated down using the rotary evaporator and the residue was mixed with 20 mL water and stirred for 30 min at RT. The product precipitated was suction filtered, stirred with diisopropylether and isopropanol, suction filtered again and dried. Amine derivative [amount of amine Example derivative] Analytical Method Structure Yield data Example 2: GWM1 [A] 1'H-spiro[piperi- dine-4,4'-quinazo- lin]-2'(3'H)-one 90 mg (0.41 mmol) 150 mg (88% of theory)ESI-MS: m/z = 441 [M + H]+ Rf: 0.54 eluant A
  • 6
  • [ 635713-68-7 ]
  • [ 1146565-91-4 ]
  • [ 1146565-73-2 ]
YieldReaction ConditionsOperation in experiment
55% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; Example 14-methyl-6-(6-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidin-4,4'-quinazolin]-1-yl)pyrimidine-4-carbonyl)benzo[d]oxazol-2(3H)-one; 144 mg (0.500 mmol) 6-(6-chloropyrimidine-4-carbonyl)-4-methyl-3H-benzoxazol-2-one, 108 mg (0.500 mmol) <strong>[635713-68-7]1'H-spiro[piperidin-4,4'-quinazolin]-2'(3'H)-one</strong> and 0.174 mL (1.00 mmol) DIPEA were combined in 5.0 mL DMF and stirred overnight at RT. The reaction mixture was purified by preparative HPLC, the fractions containing the product were combined and the organic solvent was eliminated i.vac. The aqueous phase was neutralised by the addition of 4N aqueous NaOH solution. The product precipitated as a solid was filtered off, washed with water and dried.Yield: 130 mg (55% of theoretical)ESI-MS: m/z=471 (M+H)+ Rt (HPLC)=2.55 min (Method C)
  • 7
  • [ 635713-68-7 ]
  • [ 1146565-93-6 ]
  • [ 1146565-77-6 ]
YieldReaction ConditionsOperation in experiment
95% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h; Example 33,4-dimethyl-6-(6-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidin-4,4'-quinazolin]-1-yl)pyrimidin-4-carbonyl)benzo[d]oxazol-2(3H)-one; 87.0 mg (0.400 mmol) <strong>[635713-68-7]1'H-spiro[piperidin-4,4'-quinazolin]-2'(3'H)-one</strong>, 122 mg (0.400 mmol) 6-(6-chloropyrimidin-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one and 0.140 mL (0.800 mmol) DIPEA were combined in 3.0 mL DMF and stirred for 48 h at RT. The reaction mixture was diluted with MeOH, the precipitate was suction filtered, washed with diethyl ether and dried.Yield: 184 mg (95% of theoretical)ESI-MS: m/z=485 (M+H)+ Rt (HPLC): 1.14 min (method A)
  • 8
  • [ 635713-68-7 ]
  • [ 1374220-10-6 ]
  • 9
  • [ 635713-68-7 ]
  • [ 773886-68-3 ]
  • 10
  • [ 635713-68-7 ]
  • [ 855776-47-5 ]
  • [ 1374219-97-2 ]
  • 12
  • [ 635713-68-7 ]
  • [ 635713-07-4 ]
  • [ 74124-79-1 ]
  • [ 1384431-99-5 ]
 

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Technical Information

Categories

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