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Chemical Structure| 83948-53-2 Chemical Structure| 83948-53-2

Structure of 3-(Boc-amino)propyl bromide
CAS No.: 83948-53-2

Chemical Structure| 83948-53-2

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Julianna M. Mouat ; Jonas K. Widness ; Daniel G. Enny ; Mahilet T. Meidenbauer ; Farwa Awan ; Todd D. Krauss , et al.

Abstract: Semiconductor quantum dots (QDs) offer many advantages as photocatalysts for synthetic photoredox catalysis, but no reports have explored the use of QDs with nickel catalysts for C–C bond formation. We show here that 5.7 nm CdS QDs are robust photocatalysts for photoredox-promoted cross-electrophile coupling (turnover number (TON) up to 40,000). These conditions can be utilized on a small scale (96-well plate) or adapted to flow. NMR studies show that triethanolamine (TEOA)-capped QDs are the active catalyst and that TEOA can displace native phosphonate and carboxylate ligands, demonstrating the importance of the QD surface chemistry.

Keywords: quantum dot ; nanoplatelet ; nickel ; cross-electrophile coupling ; C−C bond formation ; photochemistry

Purchased from AmBeed: ; ; ; ;

Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.

Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.

Alternative Products

Product Details of [ 83948-53-2 ]

CAS No. :83948-53-2
Formula : C8H16BrNO2
M.W : 238.12
SMILES Code : O=C(NCCCBr)OC(C)(C)C
MDL No. :MFCD02683429
InChI Key :IOKGWQZQCNXXLD-UHFFFAOYSA-N
Pubchem ID :4460490

Safety of [ 83948-53-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501

Computational Chemistry of [ 83948-53-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 0.88
Num. rotatable bonds 6
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 52.95
TPSA ?

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

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.65
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

2.05
Log Po/w (WLOGP)?

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

2.3
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.

1.96
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.1

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 1.46 mg/ml ; 0.00614 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.

-2.48
Solubility 0.782 mg/ml ; 0.00329 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

-2.9
Solubility 0.296 mg/ml ; 0.00124 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.

-6.3 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

1.0 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)

2.49

Application In Synthesis of [ 83948-53-2 ]

* 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 [ 83948-53-2 ]

[ 83948-53-2 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 34074-22-1 ]
  • [ 83948-53-2 ]
  • [ 913172-12-0 ]
  • 2
  • [ 83948-53-2 ]
  • [ 173963-91-2 ]
  • 3
  • [ 68631-52-7 ]
  • [ 83948-53-2 ]
  • [ 945489-94-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 15h; The diethyl ester of chelidamic acid (Scrimin, P.; Tecilla, P.; Tonellato, U.; Vendrame, T. J. Org. Chem. 1989, 54, 5988) (150mg) was dissolved in dry dimethylformamide (2 mL). 3-(tert-Butoxy-amino)-propyl bromide (164 mg) and potassium carbonate (130 mg) were added. The resulting mixture was stirred for 15h at 70C. The reaction was quenched with a saturated ammonium chloride aqueous solution and then washed into separatory funnel using ethyl acetate. The layers were separated, and the aqueous layer was extracted 3 times with ethyl acetate. The combined organic solutions were dried over magnesium sulfate, and concentrated in vacuo to a residue. The residue was purified by silica gel chromatography (Merck SuperVarioFlash 30g column, Si60 15-40mum), using gradient elution with a mixture of heptane (A) and ethyl acetate (B) (gradient : 60% A : 40% B up to 50% A : 50% B) to give 4-(3-tert-butoxycarbonylamino-propoxy)-pyridine-2,6-dicarboxylic acid diethyl ester (150 mg) : Cl (Method D) :m/z=397 MH+ 1H N.M.R. (400 MHz, DMSO-d6, delta in ppm) : 1,34 (t, J = 7,0 Hz, 6H) ; 1,36 (s, 9H) ; 1,86 (m, 2H) ; 3,10 (q, J = 6,5 Hz, 2H) ; 4,21 (t, J = 6,5 Hz, 2H) ; 4,37 (q, J = 7,0 Hz, 4H) ; 6,89 (m broad, 1 H) ; 7,71 (s, 2H)
  • 4
  • [ 24424-99-5 ]
  • [ 656-35-9 ]
  • [ 821-48-7 ]
  • [ 83948-53-2 ]
  • 1-(3-aminopropyl)-4-(2,4-difluorophenyl)-piperidine-4-carbonitrile dihydrochloride [ No CAS ]
  • 5
  • [ 6374-91-0 ]
  • [ 83948-53-2 ]
  • [ 1354973-83-3 ]
YieldReaction ConditionsOperation in experiment
62% General procedure: 5,7-dibromoisatin 2 (1 g, 3.28 mmol) was taken up in anhydrous DMF (30 mL) and cooled on ice with stirring. Solid K2CO3 (544 mg, 3.94 mmol) was added in one portion, and the dark colored suspension was brought to room temperature and stirred for a further 1 h. 1-Bromo-3-chloropropane (620 mg, 3.94 mmol, 0.387 mL) was added slowly with constant stirring and the reaction mixture was stirred at 80 C for 4-8 h, until the 5,7-dibromoisatin starting material had been consumed (TLC). The reaction mixture was poured into HCl (0.5 M, 50 mL) and extracted with ethyl acetate (3 × 50 mL). The ethyl acetate layer was washed with brine and dried over MgSO4. The solvent was removed, and the crude product was purified by silica gel column chromatography (CH2Cl2 as eluent) to give pure 3 (0.93 g, 74%) as orange red crystals.
  • 6
  • [ 1080-12-2 ]
  • [ 83948-53-2 ]
  • tert-butyl (3-(2-methoxy-4-(3-oxobut-1-en-1-yl)phenoxy)propyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
9% With potassium carbonate; In acetone; at 65℃; for 3h;Microwave irradiation; A mixture of 4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one (2) (101.6 mg, 0.311 mmol), 3-(boc-amino) propyl bromide (137 mg, 0.575 mmol), K2CO3 (105.2 mg, 0.76 mmol), and acetone (30 mL), was placed in an opened microwave reactor. The mixture under stirring was irradiated at 200 W for 3 h, at a final temperature of 65 C. The solid was removed by filtration with a sintered glass Buchner funnel under reduced pressure. The yellow solution was purified by semi-flash chromatography (SiO2; n-hexane:diethyl ether: several proportions). The fractions that eluted with n-hexane: diethyl ether 7.5:2.5 were gathered and after solvent evaporation a recrystallization from diethyl ether: petroleum ether(4:1) was performed providing a yellow solid of tert-butyl (3-(2-methoxy-4-(3-oxobut-1-en-1-yl)phenoxy)propyl)carbamate(8, 16.6 mg, 9%). mp 108-110 C (diethyl ether: petroleum ether). Purity 96%. IR(KBr)mmaxcm-1 3377, 1686, 1669, 1644, 1621, 1595, 1518, 1273,1260, 1225, 1167, 1138, 1033, 975. 1H NMR (CDCl3, 300 MHz) d: 7.46 (1H,d, J= 16.2 Hz, H-3), 7.11 (1H,d, J= 8.2 Hz, H-60), 7.07(1H,s, H-20), 6.86 (1H, d, J= 8.2 Hz, H-50), 6.61 (1H, d, J= 16.2 Hz,H-2), 5.50 (1H,brs, H-100) 4.14 (2H, t, J= 5 Hz, H-70), 3.92 (3H, s, 30-OCH3), 3.38 (2H, d, J= 5 Hz, H-90), 2.38 (3H, s, H-100), 2.04 (2H,t, J= 5 Hz, H-80), 1.46 (9H,s, H-110); 13C NMR (75.47 MHz, CDCl3) d: 198.4 (C-1), 156.1 (C-100), 150.5 (C-40), 149.5 (C-30), 143.5(C-3), 127.6 (C-10), 125.3 (C-2), 122.9 (C-60), 112.2 (C-50), 109.7(C-20), 79.0 (C-110), 68.2 (C-70), 55.8 (30-OCH3), 38.9 (C-90), 30.9(C-80), 28.5 (C-120), 27.4 (C-100). EI-MS (70e V) m/z (rel. intensity,%): 349 (M+, 96), 308 (32), 261 (38), 253 (52). HRMS- ESI (+) m/z: Anal. Calc. for C19H27NO5[MH]+ 350.19675, found 350.19620
  • 7
  • [ 1025718-84-6 ]
  • [ 83948-53-2 ]
  • tert-butyl 3-(3-bromo-5-(trifluoromethyl)phenoxy)propylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 120℃; for 6.0h; [00347] Synthesis of tert-butyl 3-(3-bromo-5-(trifluoromethyl)phenoxy)propylcarbamate (10): 3-Bromo-5-(trifluoromethyl)phenol (2 g, 8.4 mmol) was dissolved in 35 mL of DMF. tert-Butyl 3-bromopropylcarbamate (2.03 g, 8.4 mmol), K2CO3 (3.49 g, 25.2 mmol) and KI (2.7 g, 16.8 mmol) were added. The reaction was stirred at 120 C for 6 h. After cooling to room temperature, the mixture was poured into 35 mL of H20 and extracted with EtO Ac (50 mL X 3). The combined organic solvents were dried over anhydrous Na2S04, concentrated and purified by silica gel chromatography (40-80% EtO Ac/petroleum ether) to give 1.5 g of tert-butyl 3-(3-bromo-5-(trifluoromethyl)phenoxy)propylcarbamate (10). Yield: 45%. LCMS: m/z 344.1 [M-55]+; tR = 2.35 min.
  • 8
  • [ 1025718-84-6 ]
  • [ 83948-53-2 ]
  • tert-butyl 3-(4'-(4,4-difluoropiperidine-1-carbonyl)-5-(trifluoromethyl)biphenyl-3-yloxy)propylcarbamate [ No CAS ]
 

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Technical Information

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