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Chemical Structure| 171879-99-5

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4-Chloro-6-methyl-7-azaindole

CAS No.: 171879-99-5

4.5 *For Research Use Only !

Cat. No.: A313989 Purity: 98%

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Product Details of [ 171879-99-5 ]

CAS No. :171879-99-5
Formula : C8H7ClN2
M.W : 166.61
SMILES Code : CC1=CC(Cl)=C2C(NC=C2)=N1
MDL No. :MFCD09880146
InChI Key :KPYXZCLJFKCACT-UHFFFAOYSA-N
Pubchem ID :24729584

Safety of [ 171879-99-5 ]

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

Calculated chemistry of [ 171879-99-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 46.07
TPSA ?

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

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.81
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

2.34
Log Po/w (WLOGP)?

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

2.52
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.

1.9
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

3.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.34

Water Solubility

Log S (ESOL):?

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

-2.95
Solubility 0.186 mg/ml ; 0.00112 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.

-2.58
Solubility 0.437 mg/ml ; 0.00262 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

-3.91
Solubility 0.0207 mg/ml ; 0.000124 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

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.

-5.65 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)

1.39

Application In Synthesis [ 171879-99-5 ]

* 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 [ 171879-99-5 ]

[ 171879-99-5 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 171879-99-5 ]
  • [ 1415925-19-7 ]
  • 2
  • [ 171879-99-5 ]
  • [ 1415928-52-7 ]
YieldReaction ConditionsOperation in experiment
55% With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 4.0h; To a 0 C suspension of <strong>[171879-99-5]4-chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine</strong> (1.7 g, 10mmol) in N,N-dimethylformamide (20 mL) was added potassium hydroxide (1.14 g, 20.3 mmol), followed by iodine (2.54 g, 10.0 mmol). The reaction mixture was allowed to warm to room temperature and stir for 4 hours, whereupon it was diluted with water and filtered, to afford the product as a white solid. Yield: 1.6 g, 5.5 mmol, 55%. H NMR (400 MHz, CD3OD) oe 7.47 (s, 1 H), 7.04 (s, 1 H), 2.54 (s, 3H).
With N-iodo-succinimide; In dichloromethane; at 0 - 20℃; for 18.0h; D124-chloro-3-iodo-6-methyl-lH-pyrrolo[2,To a stirred solution of 4-chloro-6-methyl-lH-pyrrolo[2,3-b]pyridine (4.06 g, 24.37 mmol) in DCM (80 mL) at 0 C, was added NIS (6.22 g, 27.6 mmol). The reaction mixture was then warmed to RT and stirred for 18 hours. The reaction mixture was then filtered (washed with excess DCM) to give the title compound (4.01 g). LCMS (A): m/z (M+H)+ 293, C8H6C1IN2 requires 292 (acidic).
  • 3
  • [ 171879-99-5 ]
  • [ 1415928-53-8 ]
  • 4
  • [ 171879-99-5 ]
  • [ 1415928-54-9 ]
  • 5
  • [ 171879-99-5 ]
  • 4-chloro-3-iodo-6-methyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
  • 6
  • [ 171879-99-5 ]
  • [ 69385-30-4 ]
  • N-[(2,6-difluorophenyl)methyl]-6-methyl-1H-pyrrolo[2,3-b]pyridin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With toluene-4-sulfonic acid; In water; acetonitrile; at 20 - 150℃; for 4.0h;Inert atmosphere; Microwave irradiation; To a solution of 4-chloro-6-methyl-lH-pyrrolo[2,3-]pyridine (0.5 g, 3 mmol) in MeCN (15 mL) was added 2,6-difluorobenzylamine (2 eq) and pTSA.H20 (2 eq) under N2 at room temperature. The reaction mixture was heated at 150 C in a CEM microwave reactor for 4 hours. The mixture was diluted with sat. aq. NaHC03 (20 mL) solution and EtOAc (20 mL). The organic layer was separated, washed with brine, dried over MgSC^ and concentrated in vacuo. The residue was purified via flash chromatography using MeOH and DCM as eluent to give the product (0.521 g, 1.90 mmol, 63%) as yellow solid. 1H NMR (399 MHz, DMSO-d6) delta 10.96 (s, 1H), 7.43 (tt, 1H), 7.20 - 7.08 (m, 2H), 6.95 (d, 1H), 6.77 (t, 1H), 6.53 (d, 1H), 6.15 (s, 1H), 4.44 (d, 2H), 2.35 (s, 3H).
  • 7
  • [ 171879-99-5 ]
  • 5-methoxy-4-[3-(pyrrolidin-1-yl)propoxy]pyridin-2-amine [ No CAS ]
  • N-(5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)pyridin-2-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
9.5% With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 4.0h; Into a 50-mL round-bottom flask, was placed 4-chloro-6-methyl-lH- pyrrolo[2,3-b]pyridine (150 mg, 0.90 mmol, 1 equiv), 5-methoxy-4-[3-(pyrrolidin-l- yl)propoxy]pyridin-2-amine (228 mg, 0.91 mmol, 1 equiv), CS2CO3 (884 mg, 2.71 mmol, 3.00 equiv), Pd2(dba)3-CHC13 (50 mg), X-phos (50 mg), 1,4-dioxane (10 mL). The resulting solution was stirred for 4 h at 100 C. The crude product was purified by Flash-Prep-HPLC A 1 : 1. This resulted in 35.9 mg (9.5%) of N-(5-methoxy-4-(3-(pyrrolidin-l-yl)propoxy)pyridin- 2-yl)-6-methyl-lH-pyrrolo[2,3-b]pyridin-4-amine as a light yellow solid.
  • 8
  • [ 824-51-1 ]
  • [ 171879-99-5 ]
  • 9
  • [ 178268-96-7 ]
  • [ 171879-99-5 ]
YieldReaction ConditionsOperation in experiment
42% With methanesulfonyl chloride; In N,N-dimethyl-formamide; at 75℃; A suspension of 6-methyl-1 H-pyrrolo[2,3-b]pyridine 7-oxide (100mg, 0.68mmol) in anhydrous DMF (3ml) was treated with methanesulfonyl chloride (0.13ml, 1.7mmol) and heated at 75C overnight. After cooling to room temperature it was neutralised with 6N NaOH, resulting suspension filtered, and washed with water. The aqueous was extracted with ethyl acetate and the organic extracts were combined, washed with saturated sodium bicarbonate, brine, dried (Na2S04) and concentrated in vacuo. The crude product was dissolved in DCM / MeOH, preadsorbed onto HMN and purified by FCC eluting with a gradient from 0-30% EtOAc / DCM to afford the title compound as a white solid (50mg, 42%) LCMS (Method 3): Rt 1.14 min, m/z 167.1 [MH+].
  • 10
  • [ 171879-99-5 ]
  • [ 1423078-56-1 ]
  • 3-(6-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-b]pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With methanesulfonic acid(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); In ethanol; water; at 140℃; for 0.5h;Microwave irradiation; A mixture of 4-chloro-6-methyl-1 H-pyrrolo[2,3-b]pyridine (47mg, 0.291 mmol), 3-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyrazolo[1 ,5-b]pyridazine (107mg, 0.436mmol), X Phos Pd G3 (19.6mg, 0.023mmol) and potassium phosphate (124mg, 0.582mmol) in degassed ethanol (3.0ml_) and water (1.5ml_) was heated at 140C for 30 mins in the microwave. After cooling it was partitioned between ethyl acetate and water and the organic layer was separated, washed with brine, dried (Na2S04) and concentrated in vacuo. The crude product was purified by MDAP (Basic) to afford the title compound as a glass (27mg, 37%) LCMS (Method 1): Rt 2.12 min, m/z 249.8 [MH+]. 1 H NMR (400 MHz, d6-DMSO): 2.59 (3H, s), 6.56 (1 H, d, J=3.5 Hz), 7.19 (1 H, s), 7.34 (1 H, dd, J=4.4, 9.1 Hz), 7.43 (1 H, d, J=3.5 Hz), 8.48 (1 H, dd, J=1.8, 9.2 Hz), 8.56- 8.58 (2H, m), 11.59 (1 H, s)
  • 11
  • [ 55052-28-3 ]
  • [ 171879-99-5 ]
  • 12
  • [ 74420-03-4 ]
  • [ 171879-99-5 ]
  • 13
  • [ 1171896-08-4 ]
  • [ 171879-99-5 ]
YieldReaction ConditionsOperation in experiment
35% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; dimethyl zinc(II); In tetrahydrofuran; toluene; at 70℃; for 16.0h;Inert atmosphere; A solution of dimethylzinc in toluene (4 mL, 4 mmol, 1 M) was slowly added dropwise under nitrogen. (6-Bromo-4-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)(phenyl)methanone (1.7 g, 5 mmol) And [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (365 mg, 0.5 mmol) in tetrahydrofuran (20 mL). The reaction solution was reacted at 70 C for 16 hours under a nitrogen atmosphere. (25mL * 2) After the reaction solution was cooled and extracted with saturated sodium bicarbonate solution (10 mL) was quenched with ethyl acetate, the organic phases were combined, dried and concentrated to give a crude product. The crude product was separated by column (ethyl acetate: petroleum ether = 1:1). 4-Chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine (290 mg, yield 35%).
  • 14
  • [ 171879-99-5 ]
  • N-(4-(2,4-difluorophenoxy)-3-(6-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)ethanesulfonamide [ No CAS ]
  • 15
  • [ 171879-99-5 ]
  • 4-(2-(2,4-difluorophenoxy)-5-(ethylsulfonylamino)phenyl)-6-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine 7-oxide [ No CAS ]
  • 16
  • [ 171879-99-5 ]
  • N-[4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanesulfonamide [ No CAS ]
  • N-(4-(2,4-difluorophenoxy)-3-(6-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)ethanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 0.5h;Inert atmosphere; N-(4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene Ethyl sulfonamide (395 mg, 0.9 mmol), 4-Chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.6 mmol), tetrakistriphenylphosphine palladium (69 mg, 0.06 mmol) and potassium carbonate (414 mg, 3 mmol) Ethanol/toluene/water (v/v/v = 9:3:1, 10 mL). The reaction solution was subjected to microwave reaction at 120 C for 0.5 hour under a nitrogen atmosphere. The reaction solution was evaporated to dryness, and the crude material was purified (yield: ethyl ether: 1:1) N-(4-(2,4-difluorophenoxy)-3-(6-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)ethanesulfonamide (190 mg) , yield 71%).
 

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