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Structure of 1185885-86-2

Chemical Structure| 1185885-86-2

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Product Details of [ 1185885-86-2 ]

CAS No. :1185885-86-2
Formula : C30H40N2O2S2
M.W : 524.78
SMILES Code : O=C1N(CC(CC)CCCC)C(C2=CC=CS2)=C3C1=C(C4=CC=CS4)N(CC(CC)CCCC)C3=O
MDL No. :MFCD22200076
InChI Key :BTJNHAWTSFHBBN-UHFFFAOYSA-N
Pubchem ID :58517362

Safety of [ 1185885-86-2 ]

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

Computational Chemistry of [ 1185885-86-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 36
Num. arom. heavy atoms 18
Fraction Csp3 0.53
Num. rotatable bonds 14
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 159.22
TPSA ?

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

100.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

5.29
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

7.88
Log Po/w (WLOGP)?

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

8.44
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.

5.05
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

10.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

7.41

Water Solubility

Log S (ESOL):?

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

-7.5
Solubility 0.0000164 mg/ml ; 0.0000000313 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-9.84
Solubility 0.0000000761 mg/ml ; 0.0000000001 mol/l
Class?

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

Poorly 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

-9.71
Solubility 0.000000103 mg/ml ; 0.0000000002 mol/l
Class?

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

Poorly soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-3.91 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

2.0
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

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
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.

0.17

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<3.0
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)

5.43

Application In Synthesis of [ 1185885-86-2 ]

* 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 [ 1185885-86-2 ]

[ 1185885-86-2 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1185885-86-2 ]
  • [ 1000623-95-9 ]
YieldReaction ConditionsOperation in experiment
81% With bromine; In chloroform; at 20 - 60℃; for 1.16667h;Inert atmosphere; Schlenk technique; General procedure: L1-T (140mg, 0.27mmol) and 20mL chloroform were added to a 50mL round bottom flask equipped with a stirring barand a condenser. Bromine (90 mg, 0.56 mmol) was added dropwiseto the flask at room temperature. After stirring at room temperaturefor 10 min, the reaction mixture was heated to 60 C andstirred for an additional hour. After cooling, the reaction mixturewas poured into water (45 mL) and extracted with CH2Cl2. Thecombined organic layer was dried over anhydrous sodium sulfate,filtered and concentrated under reduced pressure. The crudeproduct was recrystallized from the solvent mixture of CH2Cl2 andmethanol to give the product L1-Br as a purple solid (156 mg, 86%).
80% With N-Bromosuccinimide; In chloroform; at 50℃; for 12h; In a 250 mL round bottom flask, compound 3 (1.0 g, 1.9 mmol) was added.50 mL of chloroform was stirred at room temperature for 10 minutes in the dark.Will dissolve N-bromosuccinimide (NBS) (746 mg, 4.2 mmol)50 mL of chloroform was slowly added dropwise to the reaction system.The reaction was refluxed at 50 C for 12 hours. After the reaction is over,The solvent was evaporated to dryness under reduced pressure. The dark purple solid was purified by column chromatography.The yield was 80%. Among them, the eluent: petroleum ether (PE) / ethyl acetate (EA) (50:1).
71% With N-Bromosuccinimide; In chloroform; at -0.16℃; for 2h; Compound 3 (1.01 g, 2.05 mmol) was charged in a 100 mLsingle-neck round-bottom flask filled with 50 mL of CHCl3.The mixture was cooled to 273 K and stirred while Nbromosuccinimide(NBS) was added in small portions. Themixture was allowed to warm to room temperature and stirredfor 2 h following complete addition of NBS. The reactionmixture was poured in water and extracted with CHCl3.Then CHCl3 was evaporated, the resulting red solid (darkred) was purified by column chromatography using CHCl3/petroleum ether as eluent. 0.95 g of 4 [31] were isolated (71%yield). 1H NMR (500 MHz, CDCl3): (ppm) = 8.30 (d,J = 3.7 Hz, 2 H), 6.62 (d, J = 3.7 Hz, 2 H), 3.99 (add,J = 2.7 Hz, 7.4 Hz, 4 H), 1.78-1.68 (m, 2 H), 1.39-1.24 (m,16 H), 0.92 (t, J = 7.5 Hz, 6 H), 0.88 (t, J = 7.0 Hz, 6 H). 13C(75 MHz, CDCl3): (ppm) = 161.1, 146.4, 132.9, 126.4, 122.4,115.7, 106.4, 46.4, 40.2, 30.7, 28.9, 23.9, 23.3, 14.2, 10.8. FTIR(KBr) nu max = 3422, 3084, 2957, 2926, 2859, 1657, 1556,1504.9, 1450, 1406, 1308, 1261, 1233, 1165, 1100, 1072,1027, 967, 833, 810, 731, 709, 635, 466, 430 cm-
71% With N-Bromosuccinimide; In chloroform; at 0℃; for 12h;Darkness; Charge a 500-ml eggplant-shape flask with the above- prepared compound (b) (3.0 g, 5.7 mmol), N-bromosuccinimide (2.5 g, 13.8 mmol), and chloroform (200 ml). Agitate the flask content for 12 hours at 0 C. under light shielding condition. After distilling the solvent away under reducedpressures, add MeOR (100 ml) to the flask. Separate the precipitate by filtration. Thus, a dark green powder (4.8 g, 71.0%) is obtained. mlz=683.1 (M+H)
70% With N-Bromosuccinimide; acetic acid; In chloroform; at 20℃; for 12h; 3.56 g of 2,5-diethylhexyl-3,6-dithiophen-2-ylpyrrolo[3,4-c]pyrrolo-1,4-dione dissolved in 150 ml chloroform (CF) was added to a 500 ml two-necked flask. 2.50 g of N-bromosuccinimide (NBS) was added, a small amount of acetic acid was added, and the mixture was stirred at room temperature for 12 hours. After the reaction was completed by confirming thin-layer chromatography (TLC), the solvent was concentrated to about 20 ml under reduced pressure, and ethanol was added and a solid precipitate was filtered through a filter. The solid thus separated was again dissolved in chloroform, and short column was carried out using silica to obtain a black powder. (Yield: 70%).
65% With N-Bromosuccinimide; acetic acid; In tetrahydrofuran; at 0℃; for 12h; the formula (5) Compound 6 (2.00g, 3.81mmol) was dissolved in 50ml of tetrahydrofuran (THF), cooled to 0 C, then added in three portions N- bromosuccinimide (NBS ) (1. 42g, 8. OOmmol), while dropping a few drops of glacial acetic acid. After 12 hours under reduced pressure the reaction solvent was distilled off, boiling range 60 C -90 C petroleum ether as eluent over a silica gel column to give 1. 69g of the formula (5) Compound 7 in a yield of 65%.
With N-Bromosuccinimide; In chloroform; at 0℃; for 1h; Examples Example 1; <n="44"/>a) A solution of 4.5 g of DPP 1 , 6.23 g of K2CO3 and 8.68 g of 1 -broiotamo-2-ethyl-hexyl in 60 ml of N-methyl-pyrrolidone (NMP) is heated to 14O0C for 6h. The mixture is washed with water and extracted with dichloromethane. The organic phase is then dried and filtered on a double layer of silica gel and Hyflo (CAS 91053-39-3; Fluka 56678) before it is concentrated. The residue is dissolved in 100 ml of chloroform, cooled down to O0C and 2 equivalents of N-bromosuccinimide are then added portion wise over a period of 1 h. After the reaction has been completed, the mixture is washed with water. The organic phase is extracted, dried and concentrated. The compound is then purified over a silica gel column to give 1.90 g of a violet powder of DPP 2.
With N-Bromosuccinimide; In chloroform; at 0℃; for 1h; A solution of 4.5 g of the 1 ,4-diketopyrrolo[3,4-c]pyrrole (DPP) derivative of the formula 1 , 6.23 g of K2CO3 and 8.68 g of 1 -bromo-2-ethyl-hexyl in 60 ml of N-methyl-pyrrolidone (NMP) is heated to 14O0C for 6h. The mixture is washed with water and extracted with <n="35"/>dichloromethane. The organic phase is then dried and filtered on a double layer of silica gel and Hyflo (CAS 91053-39-3; Fluka 56678) before it is concentrated. The residue is dissolved in 100 ml of chloroform, cooled down to 0 0C and 2 equivalents of N- bromosuccinimide are then added portion wise over a period of 1 h. After the reaction has been completed, the mixture is washed with water. The organic phase is extracted, dried and concentrated. The compound is then purified over a silica gel column to give 1.90 g of a violet powder of the DPP derivative of the formula 2.
With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 4.5h;Inert atmosphere; Darkness; General procedure: A solution of NBS (0.477 g, 2.68 mmol) in 8 mL of DMFwas slowly added to a solution of 3?,4?-di(octyloxy)-2,2?:5?,2?-terthiophene(0.675 g, 1.34 mmol) in 8 mL of DMF under argon atmosphere. The mixture wasleft with stirring for 4.5 h in dark. Then, 20 mL of water was added to thereaction mixture and the product was extracted with diethyl ether. The organicphase was consecutively washed with saturated NaHCO3 and then driedover MgSO4. The crude product was purified chromatographically on asilica gel column with hexane as an eluent, affording 0.77g of pure product(87% yield). 1HNMR(CDCl3,ppm):6.96 (d, J=4.0 Hz, 2H), 6.91 (d, J=3.8 Hz, 2H), 4.07 (t, J=6.8 Hz, 4H), 1.87-1.79(m, 4H), 1.51-1.42 (m, 4H), 1.39-1.25 (m, 16H), 0.90 (t, J=6.8Hz, 6H).

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  • 2
  • [ 1185885-86-2 ]
  • [ 1000623-95-9 ]
  • [ 1308671-90-0 ]
YieldReaction ConditionsOperation in experiment
73%; 11% With N-Bromosuccinimide; In chloroform; at 20℃; for 0.5h;Inert atmosphere; Darkness; Cmpd 1 (857.1 mg, 1.633 mmol) was solubilized in 60 mL CHCl3 previously deacidified onbasic alumina. The solution was stirred in the dark, degassed and an argon flow wasmaintained during the entire reaction. NBS (467.5 mg, 2.627 mmol, 1.6 equiv) was added inone portion. The reaction medium was evaporated, taken up in CH2Cl2, washed with water and brine, driedover Na2SO4. Bis- and mono-brominated products were separated by repetitive chromatography columns onsilica gel using at first a gradient of toluene/petroleum ether (50/50 to 100/0) as eluent, then a gradient ofCH2Cl2/petroleum ether (70/30 to 100/0). The bis-brominated product (3) was obtained as a deep purplesolid (73%, 815.1 mg) and the mono brominated (2) as a fushia-purple solid (107.0 mg, 11%).
26%; 53% With N-Bromosuccinimide; In chloroform; at 20℃; for 0.5h;Inert atmosphere; Darkness; NBS (230.5 mg, 1.295 mmol, 1.2 equiv) was added to a degassed solution of cmpd 1 (555.0mg, 1.058 mmol) in deacidified CHCl3. The reaction medium was stirred in the dark underan argon flow at rt for 30 min. The solution was evaporated and the residue was taken up inCH2Cl2, washed with water, brine and dried over Na2SO4. Purification on silica gel column chromatographyusing a gradient of CH2Cl2/toluene/petroleum ether (5/55/40, 13/50/37, 100/0/0) afforded the monobrominatedcmpd (2) in 53% as a fushia-purple solid. The bis-brominated product (3) was also isolated in26 % as a dark purple solid and 19 % of the starting material was recovered.
 

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