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Structure of 214147-60-1

Chemical Structure| 214147-60-1

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Product Details of [ 214147-60-1 ]

CAS No. :214147-60-1
Formula : C12H13ClN2O2
M.W : 252.70
SMILES Code : O=C(N1C(Cl)=NC2=CC=CC=C12)OC(C)(C)C
MDL No. :MFCD21099394
Boiling Point : No data available
InChI Key :NSCSJISDXDCCGL-UHFFFAOYSA-N
Pubchem ID :23441223

Safety of [ 214147-60-1 ]

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

Computational Chemistry of [ 214147-60-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 9
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 66.95
TPSA ?

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

44.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.71
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

3.67
Log Po/w (WLOGP)?

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

3.47
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.

2.32
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

2.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.87

Water Solubility

Log S (ESOL):?

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

-3.91
Solubility 0.0309 mg/ml ; 0.000122 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.

-4.29
Solubility 0.0131 mg/ml ; 0.0000518 mol/l
Class?

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

Moderately 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

-3.61
Solubility 0.0626 mg/ml ; 0.000248 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

Yes
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

Yes
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

Yes
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.

-5.24 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)

2.3

Application In Synthesis of [ 214147-60-1 ]

* 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 [ 214147-60-1 ]

[ 214147-60-1 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 214147-60-1 ]
  • [ 283-38-5 ]
  • [ 439608-29-4 ]
  • 2
  • [ 4857-06-1 ]
  • [ 24424-99-5 ]
  • [ 214147-60-1 ]
YieldReaction ConditionsOperation in experiment
With dmap; In acetonitrile; Preparation 46 tert-Butyl 2-chloro-1H-1,3-benzimidazole-1-carboxylate 2-Chloro-1H-1,3-benzimidazole (1.07 g) was added to a solution of di-tert-butyldicarbonate (1.83 g) and 4-dimethylaminopyridine (86 mg) in acetonitrile (15 ml). The reaction mixture was stirred at room temperature for 30 minutes, after which time the solvent was removed under reduced pressure. The crude product was then purified by column chromatography on silica gel eluding with a solvent gradient of 100:0 changing to 90:10, by volume, hexane:ethyl acetate to afford tert-butyl 2-chloro-1H-1,3-benzimidazole-1-carboxylate (1.68 g) as a white solid. 1H-NMR (CDCl3) delta: 7.90 (1H, m), 7.35 (1H, m), 7.40 (2H, m), 1.80 (9H, s). MS: 253 (MH+).
With triethylamine; In isopropyl alcohol; at 20℃; for 19.0h;Product distribution / selectivity; Example 1. 4- (2- ( (2, 6-Dimethylphenyl) oxy)-1H-benzimidazol-1-yl)-N- (4- (4- methyl-l-piperazinyl) phenyl)-2-pyrimidinamine; Step A: 2-Chloro-benzoimidazole-l-carboxylic acid tert-butyl ester; Di-tert-butyldicarbonate (12.270 g, 56.221 mmol) was added to a solution of 2- chlorobenzimidazole (8. 41 g, 55.119 mmol) and triethylamine (20 mL) in isopropanol (90 mL). The reaction mixture was stirred at room temperature for 19 h and then concentrated. The resulting material was purified via column chromatography on silica gel (eluting with dichloromethane) to afford 2-chloro- benzoimidazole-1-carboxylic acid tert-butyl ester as a white solid.
  • 3
  • [ 214147-60-1 ]
  • [ 90-05-1 ]
  • [ 851597-50-7 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In isopropyl alcohol; at 150℃; for 17.0h; Step B: 2- (2-Methoxy-phenoxy)-lH-benzoimidazole; Cesium carbonate (3.965 g, 12.17 mmol) was added to a solution of 2-chloro- benzoimidazole-1-carboxylic acid tert-butyl ester (1.500 g, 5.936 mmol) and 2- methoxyphenol (5.90 g, 5.20 mL, 47.5 mmol) in isopropanol (25 mL). The mixture was heated at 150 C for 17 h and was then cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and 2.0 N sodium hydroxide solution. The aqueous phase was separated and extracted with ethyl acetate and dichloromethane. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford an off-white solid. Trituration with ethyl acetate and filtering afforded 2- (2-methoxy-phenoxy)- 1H-benzoimidazole as a white solid. MS (MH+) 240. 8 ; Calculated 240.09 for Ct4Hi2N202.
  • 4
  • [ 214147-60-1 ]
  • [ 576-26-1 ]
  • [ 851597-48-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In isopropyl alcohol; at 150℃; for 22.0h; Step B: 2-(2, 6-Dimethyl-phenoxy)-lH-benzoimidazole; Cesium carbonate (2.643 g, 8. 112 mmol) was added to a solution of 2-chloro- benzoimidazole-l-carboxylic acid tert-butyl ester (1.000 g, 3.957 mmol) and 2,6- dimethylphenol (3. 867 g, 31.66 mmol) in isopropanol (10 mL). The mixture was heated at 150 C for 22 h and then cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and 2.0 N sodium hydroxide solution. The aqueous phase was separated and extracted with ethyl acetate and dichloromethane. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford an orange-brown solid. Trituration with dichloromethane and filtering afforded 2- (2, 6-dimethyl- phenoxy)-lH-benzoimidazole as an off-white solid. MS (MH+) 239.2 ; Calculated 238.11 forCl5Hl4N2O.
YieldReaction ConditionsOperation in experiment
627 mg (99%) EXAMPLE 30 4-(1H-BENZOIMIDAZOL-2-YL)-1,4-DIAZA-BICYCLO[3.2.2]NONANE Di-tert-butyl dicarbonate (600 mg, 2.75 mmol) was added to a solution of 2-chloroimidazole (381 mg, 2.50 mmol), and sodium hydroxide (120 mg, 3.0 mmol) in tetrahydrofuran (2.5 mL) and water (2.5 mL). After 3 h at RT an additional portion of di-tert-butyl dicarbonate (100 mg, 0.46 mmol) was added and the mixture was stirred at RT for 16 h. The mixture was extracted with ethyl acetate (3*) and the combined organic layers were dried (Na2SO4), filtered and concentrated to afford 627 mg (99%) of 2-chloro-benzoimidazole-1-carboxylic acid tert-butyl ester which was used without further purification: MS (Cl) m/z 253.1 (M+1).
  • 6
  • [ 214147-60-1 ]
  • racemic-2,2'-bis(diphenylphosphino)-1,1 '-binaphthyl [ No CAS ]
  • [ 283-38-5 ]
  • [ 439608-29-4 ]
YieldReaction ConditionsOperation in experiment
104 mg (34%) With ammonium hydroxide; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In chloroform; toluene; 2-Chloro-benzoimidazole-1-carboxylic acid tert-butyl ester (333 mg, 1.32 mmol), 1,4-diazabicyclo[3.2.2]nonane (57%, 195 mg, 0.88 mmol), tris(dibenzylideneacetone)dipalladium (28 mg, 0.031 mmol), racemic-2,2'-bis(diphenylphosphino)-1,1 '-binaphthyl (58 mg, 0.093 mmol), sodium tert-butoxide (208 mg, 2.17 mmol) and toluene (1.55 mL) were added to a flame dried round bottom flask purged with nitrogen. The mixture was placed in an oil bath at 80 C. for 18 h and then cooled to RT. The mixture was filtered through a pad of celite and washed with chloroform and methanol. The filtrate was concentrated and the residue was purified by chromatography (Biotage, 12M) eluding with 8% methanol in chloroform with 20 drops of NH4OH per liter of eluent to afford 104 mg (34%) of 2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-benzoimidazole-1-carboxylic acid tert-butyl ester: MS (Cl) m/z 343.1 (M+1).
  • 7
  • [ 214147-60-1 ]
  • [ 116261-43-9 ]
  • [ 256527-06-7 ]
YieldReaction ConditionsOperation in experiment
Preparation 47 tert-Butyl 2-[(2S)-2-[(benzyloxy)carbonyl]-1-piperidinyl]-1H-1,3-benzimidazole-1-carboxylate The title compound was prepared by a similar method to Preparation 2 from tert-butyl 2-chloro-1H-i1,3-benzimidazole-1-carboxylate [see Preparation 46] and benzyl (2S)-2-piperidinecarboxylate [see J.A.C.S. (1 996), 118(7), 1629-1644]. The crude product was purified by column chromatography on silica gel eluding with a solvent gradient of 90:10 changing to 80:20, by volume, hexane:ethyl acetate, in 5% increments to afford tert-butyl 2-[(2S)-2-[(benzyloxy)carbonyl]-1-piperidinyl]-1H-1,3-benzimidazole-1-carboxylate as an oil. 1H-NMR (CDCl3) delta: 7.65 (1H, d), 7.45 (1H, d), 7.40 (2H, s), 7.25 (5H, m), 5.20 (2H, s), 4.70 (1H, m), 4.65 (1H, m), 3.60 (1H, m), 2.20 (1H, m), 2.05 (1H, m), 1.80-1.50 (13H, m). MS: 436 (MH+).
  • 8
  • [ 214147-60-1 ]
  • O-Trifluoromethanesulfonyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-4-aza-1H-indole [ No CAS ]
  • [ 253439-45-1 ]
YieldReaction ConditionsOperation in experiment
51.2 mg. (37%) With sodium hydroxide; trifluoroacetic acid; In dichloromethane; chloroform; water; Example 8 5-(Benzimidazol-2-yl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-Indole O-Trifluoromethanesulfonyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-4-aza-1H-indole (150 mg, 0.413 mmol) and 1-t-butyloxycarbonyl-2-chlorobenzimidazole (104 mg, 0.413 mmol) were converted to the title compound by the procedure of Example 7 except that after chromatography there was a mixture of protected and de-protected products. Therefore, 80 mg of the mixture was dissolved in 20 mL of dichloromethane and 1 mL of trifluoroacetic acid was added. The mixture was stirred for 2 hours and then taken up in water. The reaction was partitioned between 3 mL of 1N aqueous sodium hydroxide and 3 mL of 3:1 chloroform:isopropanol to give 51.2 mg. (37%). MS(FD) m/e 331.8 (M+).
YieldReaction ConditionsOperation in experiment
The crude product was purified by column chromatography on silica gel eluding with a solvent gradient of 100:0 changing to 90:10, by volume, hexane:ethyl acetate to afford tert-butyl 2-chloro-1H-benzimidizole-1-carboxylate as an oil. 1 H-NMR (CDCl3)delta: 7.95 (1H, m), 7.65 (1H, m), 7.35 (2H, m), 1.75 (9H, s).
  • 10
  • 3-oxospiro[isobenzofuran-1(3H),4'-piperidine] hydrochloride [ No CAS ]
  • [ 214147-60-1 ]
  • C24H25N3O4 [ No CAS ]
  • 11
  • [ 214147-60-1 ]
  • [ 7087-68-5 ]
  • tert-butyl 2-[1-(diisopropylamino)ethyl]-1H-benzo[d]imidazole-1-carboxylate [ No CAS ]
  • 12
  • [ 214147-60-1 ]
  • [ 86953-79-9 ]
  • (±)-tert-butyl 2-(tert-butyl 1,3-benzimidazol-1-carboxylate-2-yl)-pyrrolidine-1-carboxylate [ No CAS ]
  • 13
  • [ 214147-60-1 ]
  • [ 123387-52-0 ]
  • (±)-tert-butyl 2-(tert-butyl 1,3-benzimidazol-1-carboxylate-2-yl)-azepane-1-carboxylate [ No CAS ]
  • 14
  • [ 109-99-9 ]
  • [ 214147-60-1 ]
  • (±)-tert-butyl 2-(oxolan-2-yl)-1H-benzimidazole-1-carboxylate [ No CAS ]
  • 15
  • [ 4096-21-3 ]
  • [ 214147-60-1 ]
  • C22H25N3O2 [ No CAS ]
  • 16
  • [ 214147-60-1 ]
  • methyl 3-(3-amino-4-(cyclohexyl(isobutyl)amino)phenyl)butanoate [ No CAS ]
  • methyl 3-(3-((1H-benzo[d]imidazol-2-yl)amino)-4-(cyclohexyl(isobutyl)amino)phenyl)butanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% In toluene; A mixture of methyl 3-(3-amino-4-(cyclohexyl(isobutyl)amino)phenyl)butanoate (100 mg, 0.29 mmol) and tert-butyl 2-chloro-IH-benzo[d]imidazole-1-carboxylate (109 mg, 0.43 mmol) in toluene (2 mL) was stirred at 110 C overnight. The mixture was cooled to room temperature, quenched with water (5 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (7 mL), dried over Na2SO4, and concentrated. The residue was purified by preparative TLC (20% EtOAc/PE) to give methyl 3-(3-((1 H-benzo[d]imidazol-2-yl)amino)-4-(cyclohexyl(isobutyl)amino)phenyl)butanoate (60 mg, 45% yield). LCMS (M+H):mz = 463.6.
  • 17
  • [ 214147-60-1 ]
  • methyl 3-(3-amino-4-(cyclohexyl(isobutyl)amino)phenyl)butanoate [ No CAS ]
  • 3-(3-((1H-benzo[d]imidazol-2-yl)amino)-4-(cyclohexyl(isobutyl)amino)phenyl)butanoic acid [ No CAS ]
  • 18
  • [ 214147-60-1 ]
  • [ 60323-09-3 ]
  • C20H23N3O2 [ No CAS ]
  • 19
  • [ 214147-60-1 ]
  • 4-(1H-benzoimidazol-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane hydrochloride [ No CAS ]
  • 20
  • [ 214147-60-1 ]
  • 4-(1H-benzoimidazol-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane [ No CAS ]
 

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