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Chemical Structure| 1211443-61-6

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Product Details of [ 1211443-61-6 ]

CAS No. :1211443-61-6
Formula : C14H17ClN4O
M.W : 292.76
SMILES Code : O=C(C1=CC2=CN=C(Cl)N=C2N1C3CCCC3)N(C)C
MDL No. :MFCD20527881
InChI Key :PMDDQOHZLBZUSO-UHFFFAOYSA-N
Pubchem ID :58315432

Safety of [ 1211443-61-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H412
Precautionary Statements:P273-P280

Computational Chemistry of [ 1211443-61-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 9
Fraction Csp3 0.5
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 78.81
TPSA ?

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

51.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.98
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

2.54
Log Po/w (WLOGP)?

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

2.9
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.

2.01
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

1.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.47

Water Solubility

Log S (ESOL):?

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

-3.39
Solubility 0.119 mg/ml ; 0.000407 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.

-3.26
Solubility 0.161 mg/ml ; 0.000552 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

-3.54
Solubility 0.0846 mg/ml ; 0.000289 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

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

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

Yes
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.

-6.28 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<0.0
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)

2.26

Application In Synthesis of [ 1211443-61-6 ]

* 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 [ 1211443-61-6 ]

[ 1211443-61-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1211443-58-1 ]
  • [ 124-40-3 ]
  • [ 1211443-61-6 ]
YieldReaction ConditionsOperation in experiment
96.4% Toluene (500 mL) and 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid (lOO.Og, 0.377 moles) were charged into 2L 4N RB flask under CaCb guard tube condition, and stirred of 5-10 min to get cream colored suspension. Added N,N-dimethylformamide (10.0 mL) and stirred for 5-10 min. Charged thionyl chloride (67.2g, 0.566 moles) to the reaction mass and stir for 5-l0min. at 25-35C to get pale brown colored suspension. Reaction mass was heated to 75-80C and stirred for 3-4h. After completion of reaction (by HPLC), cooled to 0-5C to become brown colored suspension. Mixture of 2M solution of dimethylamine in THF (470.0 mL, 0.942 moles) and triethylamine (l22.0g, 1.20 moles) added dropwise to the reaction mass through addition funnel by maintaining the mass temperature at 0-10C and then stirred for 5-10 min. Reaction mass temperature was raised to 25-35 C and stirred for 1 -2h. After completion of reaction (by HPLC) solvent was distilled off under vacuum on rotavapor at 60-65 C to yield brown colored crude. The resulting crude was dispersed in DM water (1000.0 mL) and stirred for lh at 25-35C to get cream colored suspension. Product was filtered under suction with the help of DM water (500 mL). The wet product was dried in hot air oven at 60-65 C for 6h to afford the title compound. Wt. of the product l06.0g (96.4% by theory). Purity by HPLC > 99.0%.
92% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 0 - 25℃; A three-necked flask was charged with 5 (26.57 g, 100 mmol)And N, N-dimethylformamide (133 mL) were added, the mixture was cooled to 0-5 C while stirring, EDCI (23.00 g, 120 mmol) was added,A solution of dimethylamine in tetrahydrofuran (2.0 M, 75 mL, 150 mmol) was added. Triethylamine (20.24 g, 200 mmol) was added dropwise and the mixture was stirred at 20-25 C for 6-8 hours.The reaction mixture was extracted with ethyl acetate (133 mL) three times and the combined organic phases washed twice with brine (133 mL), dried over anhydrous sodium sulfate and concentrated. Compound A was isolated by column chromatography on a mixture of dichloromethane and methanol (26.93 g , 92%).
92% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 0 - 25℃; <strong>[1211443-58-1]2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid</strong> (26.57 g, 100 mmol) and N,N-dimethylformamide (133 mL) were added to a three-neck flask. stir well, then cool to 0 ~ 5 C, add EDCI (23.00g, 120mmol), A solution of dimethylamine tetrahydrofuran (2.0 M, 75 mL, 150 mmol) was added, and triethylamine (20.24 g, 200 mmol) was added dropwise, and the mixture was reacted at 20 to 25 C for 6 to 8 hours. The reaction was extracted with ethyl acetate (133 mL) three times.The organic phase was washed twice with saturated brine (133 mL).After concentration, it was beaten with isopropyl alcohol and water, and the solid was separated by filtration. drying in vacuo to gave 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (26.93 g, 92%).
79% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In ethanol; N,N-dimethyl-formamide; for 0.5h; 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (1.07g, 4.03mmol), HBTU (1.53g, 4.03mmol) and diisopropylethylamine (2mL, 12.1mmol) are dissolves in dimethylformamide (20 mL). 2 M solution of dimethylamine in ethanol (2.4mL, 4.8 mmol) is added and the mixture is stirred for 30 minutes to achieve complete conversion. The reaction mixture is diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate, water, then brine. The organic phase is dried (Na2SC^), filtered and concentrated. Purification by chromatography on silicagel(ethyl acetate :heptane) provides 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6- carboxylic acid dimethylamide (927mg,79% yield) MS(ESI) m/z 293.1 (M+H)+
78.1% Compound VII (719.1 g, 2.70 mol, 1.0 e.q.) was added to 6 L DMF in a 10 L four-necked flask.At 0 C, DIPEA (1399.2 g, 10.83 mol, 4.0 e.q.) was added at -20 C.HATU (2566.6g, 6.75mol, 2.5e.q.) was added in batches, and the reaction was stirred for 0.5 h.At 5 C, dimethylamine methanol solution (2.5 M) 1.62 L was added dropwise, and the reaction was stirred for 1 h.LC-MS showed the reaction was completed.The reaction solution was poured into 12 L of ice water, stirred, and extracted with ethyl acetate.Wash with saturated aqueous sodium carbonate solution, wash with water, wash with dilute hydrochloric acid, and dry.The solvent was distilled off under reduced pressure, petroleum ether was filtered to obtain compound VIII as a yellow solid 617.4g,The yield was 78.1%.

  • 2
  • [ 1211443-58-1 ]
  • [ 506-59-2 ]
  • [ 1211443-61-6 ]
YieldReaction ConditionsOperation in experiment
99% A stirring solution of 6-chloro-l-cyclopentyl-l,5,7-triaza-lH-indene-2-carboxylic acid (199 mg, 0.75 mmol) and triethylamine (631 L, 4.5 mmol) in DMF (4 mL) was treated with HBTU (427 mg, 1.13 mmol) in one portion. The resulting mixture was stirred at room temperature for 30 minutes. Dimethylamine hydrochloride salt (122 mg, 1.50 mmol) was added in one portion and the resulting solution was stirred at room temperature overnight. Next morning, LCMS analysis indicated clean conversion to product (m/z = 293.4). The reaction mixture was diluted with EtOAc, transferred to a separatory funnel and washed with 0.1 N HC1 aqueous and brine. The organics were dried over anhydrous MgS04, filtered and concentrated to yield the crude product. This was purified on a S1O2 column using a hexanes/EtOAc gradient eluent. The fractions containing the product were concentrated to yield 215 mg (0.74 mmol, 99 %). LC/MS - HPLC (254 nm) - Rt 2.90 min. MS (ESI) m/z 293.4 [M+ + H+].
  • 3
  • [ 3177-20-6 ]
  • [ 1211443-61-6 ]
 

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