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[ CAS No. 4246-51-9 ] {[proInfo.proName]}

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Chemical Structure| 4246-51-9
Chemical Structure| 4246-51-9
Structure of 4246-51-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 4246-51-9 ]

CAS No. :4246-51-9 MDL No. :MFCD00059850
Formula : C10H24N2O3 Boiling Point : -
Linear Structure Formula :- InChI Key :JCEZOHLWDIONSP-UHFFFAOYSA-N
M.W : 220.31 Pubchem ID :20239
Synonyms :
PROTAC Linker 24

Calculated chemistry of [ 4246-51-9 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 12
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 58.85
TPSA : 79.73 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.62 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.71
Log Po/w (XLOGP3) : -1.38
Log Po/w (WLOGP) : -0.27
Log Po/w (MLOGP) : -0.65
Log Po/w (SILICOS-IT) : 0.83
Consensus Log Po/w : 0.25

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 1.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 0.46
Solubility : 629.0 mg/ml ; 2.85 mol/l
Class : Highly soluble
Log S (Ali) : 0.21
Solubility : 354.0 mg/ml ; 1.61 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -2.44
Solubility : 0.802 mg/ml ; 0.00364 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 2.52

Safety of [ 4246-51-9 ]

Signal Word:Danger Class:8
Precautionary Statements:P234-P273-P280-P301+P330+P331-P303+P361+P353-P305+P351+P338 UN#:2735
Hazard Statements:H314-H290-H412 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 4246-51-9 ]

* 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.

  • Upstream synthesis route of [ 4246-51-9 ]
  • Downstream synthetic route of [ 4246-51-9 ]

[ 4246-51-9 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 10143-54-1 ]
  • [ 22397-31-5 ]
  • [ 4246-51-9 ]
  • [ 112-33-4 ]
Reference: [1] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4; 7
[2] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4-5; 7
  • 2
  • [ 10143-54-1 ]
  • [ 22397-31-5 ]
  • [ 4246-51-9 ]
  • [ 112-33-4 ]
Reference: [1] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 3-4; 6
[2] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4; 7
[3] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4; 7
  • 3
  • [ 10143-54-1 ]
  • [ 22397-31-5 ]
  • [ 4246-51-9 ]
  • [ 112-33-4 ]
Reference: [1] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4; 6
[2] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 4-5; 7
  • 4
  • [ 10143-54-1 ]
  • [ 22397-31-5 ]
  • [ 4246-51-9 ]
  • [ 112-33-4 ]
  • [ 111-46-6 ]
Reference: [1] Patent: EP1512675, 2005, A1, . Location in patent: Page/Page column 3; 6
  • 5
  • [ 22397-31-5 ]
  • [ 4246-51-9 ]
Reference: [1] Zhurnal Obshchei Khimii, 1954, vol. 24, p. 319,327; engl. Ausg. S. 325, 333
[2] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1967, p. 1752 - 1754[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1967, p. 1829 - 1832
  • 6
  • [ 929-75-9 ]
  • [ 1073123-93-9 ]
  • [ 4246-51-9 ]
  • [ 1073123-92-8 ]
Reference: [1] European Journal of Organic Chemistry, 2008, # 25, p. 4329 - 4333
  • 7
  • [ 4246-51-9 ]
  • [ 24424-99-5 ]
  • [ 194920-62-2 ]
YieldReaction ConditionsOperation in experiment
88% at 0 - 20℃; for 3 h; To a solution ofamine S8 (20 mL, 91.2 mmol) in CH2Cl2(100 mL) was added a solution of Boc2O (1.99 g, 9.12 mmol) in CH2Cl2(55 mL + 5 mL rinse) dropwise via addition funnel at 0 °C. After the additionwas complete, the reaction mixture was allowed to warm to RT and after 3 h, itwas quenched with H2O (100 mL). Thetwo layers were separated and the organic phase was washed with H2O (3 x 50 mL) andbrine (50 mL), dried (MgSO4), filtered, and concentrated in vacuo to give 2.571 g (88percent) of S9 as a colorless liquid.TLC: Rf = 0.14 (10percent MeOH, 0.5percent NH4OHin CH2Cl2)1H-NMR (CDCl3, 400 MHz): δ 5.10 (br s,1H), 3.51–3.64 (m, 12H), 3.61 (s, 4H), 3.21 (m, 2H), 2.79 (t, J = 6.7 Hz, 1H), 1.77–1.68 (m, 4H), 1.42(s, 9H) ppm
85% at 20℃; for 12 h; A solution of di-tert-butyl dicarbonate (Boc2O, 2.75 mmol) in dried DCM (2 mL) was added slowly, drop to drop, to a solution of 4,7,10-trioxatridecane-1,13-diamine (VIII, 6.8 mmol) in DCM (20 mL).
The reaction mixture was maintained at rt for 12 h, and then was diluted with water and extracted three times with DCM.
The organic layer was dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure and thus the mono-blocked derivative H2N-PEG-NH-Boc (IX, 85percent) was produced. 4.6.1 Compound IX Syrup; δH (CDCl3, 400MHz): 5.13 (m, 1H, NH PEG-Boc group), 3.64–3.49 (m, 12H, 6 CH2 PEG group), 3.20 (m, 2H, 1 CH2 PEG group), 2.80 (m, 2H, 1 CH2 PEG group), 1.76–1.69 (m, 4H, 2 CH2 PEG group), 1.41 (s, 9H, 3 CH3 Boc group); δC (CDCl3, 100MHz): 156.2 (CO-Boc), 79.0 (CO-Boc), 70.6, 70.3, 70.2, 69.6 (6C, CH2 PEG group), 39.7, 38.5, 32.9, 29.7 (4C, CH2 PEG group), 28.6 (3 CH3 Boc group).
82% With triethylamine In dichloromethane at 20℃; Cooling with ice To a solution of 3,3'-((oxybis(ethane-2,l-diyl))bis(oxy))bis(propan-1-amine) (10 g, 45 mmol) and triethylamine (4.6 g, 45 mmol) in DCM (150 mL) was added solution of (Boc)20 (5.0 g, 23 mmol) in DCM (100 mL) cooled in an ice-bath and was stirred at rt overnight. The solution was concentrated to dryness and purified by flash column chromatography to give the title compound (5.976 g, 82.00percent yield) as a slight yellow oil. MS (ESI): mass calcd. for ci5H32N2O5, 320.42; m/z found, 321.2 [M+H]+.
72.2% With sodium chloride In tetrahydrofuran; methanol Part C
Preparation of N-(3-(2-(2-(3-Aminopropoxy)ethoxy)ethoxy)propyl)(tert-butoxy)formamide
A 1 L 3-neck round bottom flask was fitted with a 500 mL addition funnel with nitrogen line, a thermometer, and a mechanical stirrer.
The flask was charged with 4,7,10-trioxa-1,13-tridecanediamine (72.5 g, 0.329 mol), anhydrous THF (250 mL), and anhydrous MeOH (100 mL).
The addition funnel was charged with a solution of di-tert-butyl dicarbonate (22.4 g, 0.103 mol) in anhydrous THF (100 mL).
The contents of the addition funnel were added to the flask with rapid stirring at ambient temperatures over 30 min, causing a slight rise in temperature from 21° C. to 32° C.
The reaction was stirred an additional 3 h at ambient temperatures and the solvents were removed under reduced pressure.
The resulting thick syrup was taken up in sat. NaCl (1500 mL) and extracted with ether (5*1000 mL).
The combined ether extracts were dried (MgSO4) and concentrated to give a colorless oil (29.8 g).
A 5.00 g sample of this oil was purified by flash chromatography on silica gel (DCM:MeOH:TEA, 20:15:0.75) to give the title compound as a colorless oil (4.00 g, 72.2percent).
1H NMR (CDCl3): 5.13 (s, 1H), 3.63-3.47 (m, 12H), 3.17 (q, J=6.2 Hz, 2H), 2.75 (t, J=6.7 Hz, 2H), 1.75-1.64 (m, 4H), 1.39 (s, 9H), 1.36 (s, 2H); MS: m/e 321.2 [M+H].
72.2% With sodium chloride In tetrahydrofuran; methanol Part C
Preparation of N-(3-(2-(2-(3-Aminopropoxy)ethoxy)ethoxy)propyl)(tert-butoxy)formamide
A 1 L 3-neck round bottom flask was fitted with a 500 mL addition funnel with nitrogen line, a thermometer, and a mechanical stirrer.
The flask was charged with 4,7,10-trioxa-1,13-tridecanediamine (72.5 g, 0.329 mol), anhydrous THF (250 mL), and anhydrous MeOH (100 mL).
The addition funnel was charged with a solution of di-tert-butyl dicarbonate (22.4 g, 0.103 mol) in anhydrous THF (100 mL).
The contents of the addition funnel were added to the flask with rapid stirring at ambient temperatures over 30 min, causing a slight rise in temperature from 21° C. to 32° C.
The reaction was stirred an additional 3 h at ambient temperatures and the solvents were removed under reduced pressure.
The resulting thick syrup was taken up in sat. NaCl (1500 mL) and extracted with ether (5*1000 mL).
The combined ether extracts were dried (MgSO4) and concentrated to give a colorless oil (29.8 g).
A 5.00 g sample of this oil was purified by flash chromatography on silica gel (DCM:MeOH:TEA, 20:15:0.75) to give the title compound as a colorless oil (4.00 g, 72.2percent).
1H NMR (CDCl3): 5.13 (s, 1H), 3.63-3.47 (m, 12H), 3.17 (q, J=6.2 Hz, 2H), 2.75 (t, J=6.7 Hz, 2H), 1.75-1.64 (m, 4H), 1.39 (s, 9H), 1.36 (s, 2H); MS: m/e 321.2 [M+H]
72.2% With sodium chloride In tetrahydrofuran; methanol Part C
Preparation of N-(3-(2-(2-(3-Aminopropoxy)ethoxy)ethoxy)propyl)(tert-butoxy)formamide
A 1 L 3-neck round bottom flask was fitted with a 500 mL addition funnel with nitrogen line, a thermometer, and a mechanical stirrer.
The flask was charged with 4,7,10-trioxa-1,13-tridecanediamine (72.5 g, 0.329 mol), anhydrous THF (250 mL), and anhydrous MeOH (100 mL).
The addition funnel was charged with a solution of di-tert-butyl dicarbonate (22.4 g, 0.103 mol) in anhydrous THF (100 mL).
The contents of the addition funnel were added to the flask with rapid stirring at ambient temperatures over 30 min, causing a slight rise in temperature from 21° C. to 32° C.
The reaction was stirred an additional 3 h at ambient temperatures and the solvents were removed under reduced pressure.
The resulting thick syrup was taken up in sat. NaCl (1500 mL) and extracted with ether (5*1000 mL).
The combined ether extracts were dried (MgSO4) and concentrated to give a colorless oil (29.8 g).
A 5.00 g sample of this oil was purified by flash chromatography on silica gel (DCM:MeOH:TEA, 20:15:0.75) to give the title compound as a colorless oil (4.00 g, 72.2percent).
1H NMR (CDCl3): 5.13 (s, 1H), 3.63-3.47 (m, 12H), 3.17 (q, J=6.2 Hz, 2H), 2.75 (t, J=6.7 Hz, 2H), 1.75-1.64 (m, 4H), 1.39 (s, 9H), 1.36 (s, 2H); MS: m/e 321.2 [M+H].
49% at 20℃; for 12 h; A solution of 4,7,10-trioxa-1,13-tridecanediamine (7.5g, 34.1mmol) in CHCl3 (100mL) was treated with BOC-anhydride (3.7g, 16.9mL). The mixture was stirred at room temperature for 12h. The solvent was removed, and the resulting yellow oil was purified by silica gel flash chromatography to produce the oil 5.5g of tert-butyl (3-(2-(2-(3-aminopropoxy)ethoxy)ethoxy)propyl)carbamate (4), Yield: 49percent. 1H NMR (CDCl3, 400MHz): δ 5.1 (s, 1H), 3.58–3.50 (m, 12H), 3.21 (d, J=6.9Hz, 2H), 2.79 (t, J=8Hz, 2H), 1.75–1.69 (m, 4H), 1.59 (s, 2H), 1.42 (s, 9H). 13C NMR (CDCl3, 100MHz): δ 155.0, 69.2, 68.9, 66.7, 48.0, 37.6, 30.4, 28.6, 27.3.
16% With triethylamine In chloroform at 0℃; for 0.666667 h; Preparation of compound 69: To a solution of 4,7, 10-trioxa-l, 13-tridecanediamine (2.2 g, 10 mmol) in CHC13 (100 mL) at 0 °C was added Boc20 (2.18 g, 10 mmol) and Et3N (1.4 mL, 10 mmol). The reaction was stirred at 0 °C for 40 min. The reaction was concentrated to give crude product. The crude product was purified by column chromatography using 2-6percent EtOH in CH2C12 to give purified product as slight yellow oil (516 mg, 16percent). Note: the mono- protected amine must be freshly prepared. It undergoes gradual disproportionation upon storage. Analytical data matched that described in /. Am. Chem. Soc. 2003, 125, 2416- 2425.

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  • 8
  • [ 4246-51-9 ]
  • [ 24424-99-5 ]
  • [ 320635-20-9 ]
  • [ 194920-62-2 ]
Reference: [1] Organic Letters, 2015, vol. 17, # 3, p. 422 - 425
[2] Patent: US2008/221343, 2008, A1, . Location in patent: Page/Page column 9
  • 9
  • [ 4246-51-9 ]
  • [ 1538-75-6 ]
  • [ 194920-62-2 ]
Reference: [1] Patent: WO2008/75192, 2008, A2, . Location in patent: Page/Page column 61-62
  • 10
  • [ 4246-51-9 ]
  • [ 6627-89-0 ]
  • [ 194920-62-2 ]
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