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Structure of 442850-71-7

Chemical Structure| 442850-71-7

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Product Details of [ 442850-71-7 ]

CAS No. :442850-71-7
Formula : C7H13N3
M.W : 139.20
SMILES Code : NC1=CC=NN1C(C)(C)C
MDL No. :MFCD11054260
InChI Key :NDKNRZPWSLAZNF-UHFFFAOYSA-N
Pubchem ID :39869098

Safety of [ 442850-71-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 442850-71-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.57
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 42.2
TPSA ?

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

43.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.5
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

0.78
Log Po/w (WLOGP)?

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

1.23
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.

0.87
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

0.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.92

Water Solubility

Log S (ESOL):?

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

-1.5
Solubility 4.42 mg/ml ; 0.0317 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.

-1.28
Solubility 7.28 mg/ml ; 0.0523 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

-1.23
Solubility 8.14 mg/ml ; 0.0585 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.

-6.6 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)

1.54

Application In Synthesis of [ 442850-71-7 ]

* 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 [ 442850-71-7 ]

[ 442850-71-7 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 98-88-4 ]
  • [ 442850-71-7 ]
  • [ 442850-73-9 ]
  • 2
  • [ 7400-27-3 ]
  • [ 920-37-6 ]
  • [ 442850-71-7 ]
YieldReaction ConditionsOperation in experiment
Synthesis of 1-tert-butyl-1H-pyrazol-5-amine To 600 ml of ethanol were successively added 59.94 g of tert-butylhydrazine hydrochloride, 79.3 g of sodium acetate and 50 ml of 2-chloroacrylonitrile at room temperature, followed by stirring the reaction mixture at 80 C. for 12 hours. After removing the solvent in vacuo, water was added to the residue. The mixture was neutralized with sodium hydrogen carbonate, and extracted with ethyl acetate. The obtained ethyl acetate solution was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The obtained residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1-1/2) to give the title compound as a pale yellow oil.
  • 3
  • [ 4774-14-5 ]
  • [ 442850-71-7 ]
  • [ 1010086-61-9 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; (1) Synthesis of N-(1-tert-butyl-1H-pyrazol-5-yl)-6-chloropyrazin-2-amineA mixture of 60.6 g of 2,6-dichloropyrazine, 62.2 g of <strong>[442850-71-7]1-tert-butyl-1H-pyrazol-5-amine</strong> as obtained in Reference 3, 23.5 g of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, 21.0 g of tris(dibenzylideneacetone)dipalladium(0)-chloroform complex, 172.6 g of potassium phosphate and 1.17 l of 1,4-dioxane was stirred at 100 C. overnight, followed by cooling down to room temperature. An insoluble matter was filtered off using Celite and washed with ethyl acetate. The resulting ethyl acetate solution was washed with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The obtained residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=4/1-2/1) to give the title compound as a yellow solid.
  • 4
  • [ 442850-71-7 ]
  • [ 442850-79-5 ]
  • 5
  • [ 1184932-56-6 ]
  • [ 442850-71-7 ]
  • [ 1184932-57-7 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 4.0h; A mixture of 1.33 g of 1-tert-butyl 4-ethyl 4-((6-bromopyridin-2-yl)methyl)piperidine- 1,4-dicarboxylate, 650 mg of 1-tert-butyl- lH-pyrazol-5-amine (WO2007/126126, page72, Reference 1), 360 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, 322 mg of tris(dibenzylideneacetone)dipalladium(0)-chloroform complex, 1.98 g of potassium phosphate and 30 ml of 1 ,4-dioxane was stirred at 1000C for 4 hours, followed by cooling down to room temperature. An insoluble matter was filtered off using Celite and washed with ethyl acetate. The resulting ethyl acetate solution was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate = 20/1 - 3/2) to give the title compound as a pale brown oil.
  • 6
  • [ 5424-21-5 ]
  • [ 442850-71-7 ]
  • N-(1-tert-butyl-1H-pyrazol-5-yl)-2-chloro-6-methylpyrimidine-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In 1,4-dioxane; at 100℃; for 12.0h; (1) Synthesis ofN-(1-tert-butyl-1H-pyrazol-5-yl)-2-chloro-6-methylpyrimidine-4-amine A mixture of 9.70 g of 2,4-dichloro-6-methyl-pyrimidine, 4.50 g of 1-tert-butyl -1H-pyrazol-5-amine obtained in Reference Example 1, 1.79 g of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, 1.60 g of tris(dibenzylideneacetone)dipalladium(0)-chloroform complex, 13.27 g of potassium phosphate, and 100 ml of 1,4-dioxane was stirred at 100C for 12 hours, cooled to room temperature, and then diluted with ethyl acetate. An insoluble matter was filtered off using Celite and the resulting ethyl acetate solution was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate = 9/1 to 1/1) to give the title compound.
  • 7
  • [ 7400-27-3 ]
  • [ 920-37-6 ]
  • [ 1152980-49-8 ]
  • [ 442850-71-7 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; In ethanol; at 80℃; for 18.0h; tert-Butylhydrazinehydrochloride (5.99 g, 48.1 mmol) was added to EtOH (60 mL) to form a slurry. To this was added NaOAc (7.93 g, 96.7 mmol) and 2-chloroacrylonitrile (5 mL,62.6 mmol). The solution was heated to 80 C for 18 h, cooled, and the solvent removed in vacuo. The residue was slowly diluted with distilled H2O (35 mL) and partitioned between sat. aq NaHCO3 (40 mL) and EtOAc (40 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2 × 20 mL). The organic layers were combined, washed with brine (20 mL), dried (MgSO4), and the solvent removed in vacuo to afford a red oil; yield: 7.95 g (91%); bp 93-94C/0.9 Torr (yellow liquid). The product was a 5:1 mixture of the title compound 6c and its 1-tert-butyl-3-amino isomer. The crude product was used to prepare the Meldrum?s acid derivative 3c, which was purified by recrystallization (see below).
  • 8
  • 4-(4-chloro-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole [ No CAS ]
  • [ 76-05-1 ]
  • [ 442850-71-7 ]
  • N-(1-(tert-butyl)-1H-pyrazol-5-yl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
20 mg Example 132 Synthesis of N-(1-(tert-butyl)-1H-pyrazol-5-yl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine (Cpd. No. 183) Pd2(dba)3 (18 mg) and BINAP (26 mg) were mixed in anhydrous toluene. And the mixture was heated at reflux for 3-4 minutes. This mixture was transferred into a round-bottom flask containing S13 (60 mg), <strong>[442850-71-7]1-(tert-butyl)-1H-pyrazol-5-amine</strong> (84 mg), K3PO4 (130 mg), and toluene (2 mL). The mixture was heated at reflux for overnight before quenching with methanol. The reaction mixture was filtered and the mixture was purified by HPLC to yield Cpd. No. 183 as a CF3CO2H salt in 20 mg. ESI-MS calculated for C24H28N7O2 [M+H]+=446.23; Observed: 446.65.
  • 9
  • C10H9O4S(1-)*K(1+) [ No CAS ]
  • [ 442850-71-7 ]
  • C17H19N3O2S [ No CAS ]
  • 10
  • [ 442850-71-7 ]
  • 1-(tert-butyl)-N-(2-fluorophenyl)-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide [ No CAS ]
  • 11
  • [ 442850-71-7 ]
  • C15H15N3O2S [ No CAS ]
  • 12
  • [ 442850-71-7 ]
  • C15H14ClN3OS [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 442850-71-7 ]

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