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[ CAS No. 1068-90-2 ] {[proInfo.proName]}

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Chemical Structure| 1068-90-2
Chemical Structure| 1068-90-2
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Product Details of [ 1068-90-2 ]

CAS No. :1068-90-2 MDL No. :MFCD00009146
Formula : C9H15NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :ISOLMABRZPQKOV-UHFFFAOYSA-N
M.W : 217.22 Pubchem ID :14041
Synonyms :
Diethyl 2-acetamidomalonate

Calculated chemistry of [ 1068-90-2 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.67
Num. rotatable bonds : 8
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 50.95
TPSA : 81.7 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) : -7.4 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.37
Log Po/w (XLOGP3) : 0.32
Log Po/w (WLOGP) : -0.38
Log Po/w (MLOGP) : -0.08
Log Po/w (SILICOS-IT) : 0.34
Consensus Log Po/w : 0.51

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.86
Solubility : 30.0 mg/ml ; 0.138 mol/l
Class : Very soluble
Log S (Ali) : -1.6
Solubility : 5.47 mg/ml ; 0.0252 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.29
Solubility : 11.2 mg/ml ; 0.0518 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 1.93

Safety of [ 1068-90-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1068-90-2 ]

* 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.

  • Upstream synthesis route of [ 1068-90-2 ]
  • Downstream synthetic route of [ 1068-90-2 ]

[ 1068-90-2 ] Synthesis Path-Upstream   1~27

  • 1
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  • [ 1068-90-2 ]
  • [ 3757-53-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6911 - 6923
  • 2
  • [ 1068-90-2 ]
  • [ 3757-53-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5118 - 5129
  • 3
  • [ 821-10-3 ]
  • [ 1068-90-2 ]
  • [ 3284-51-3 ]
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 25, p. 9068 - 9069
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5118 - 5129
  • 4
  • [ 13433-00-6 ]
  • [ 75-36-5 ]
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YieldReaction ConditionsOperation in experiment
96% With triethylamine In dichloromethane at 0 - 20℃; Diethyl 2-aminomalonate hydrochloride (1 .69 g, 8.0 mmol) and triethylamine (3.4 mL, 24 mmol, 3.0 eq.) were dissolved in dichloromethane (120 mL) at 0 °C. Then acetylchloride (0.57 mL, 8.0 mmol, 1 .0 eq.) was added under stirring and stirring was continued overnight while the mixture was allowed to warm up to r.t. The mixture was diluted with dichloromethane (100 mL) and washed with 1 M HCI (3 * 60 mL). The aqueous phase was extracted with dichloromethane (2 χ 60 mL) and the combined organic layer was dried over MgS04. After evaporation of the solvent in vacuo the product was isolated as a pure white solid. Yield: 1.68 g (96percent). 1 96 °C (lit. 97 °C) 1H NMR (300 MHz, CDCI3): δ [ppm]: 1.30 (t, 3JH,H = 7.1 Hz, 6 H, 7-CH3, 9-CH3), 2.08 (s, 3 H, 5-CH3), 4.27 (m, 4 H, 6-CH2, 8-CH2), 5.18 (d, 3JH,H = 7.1 Hz, 1 H, 2-CH), 6.67 (d, 3JH,H = 5.7 Hz, 1 H, 2-NH). 13C-NMR (75 MHz, CDCI3) δ [ppm]: 14.0 (q, C-7, C-9), 22.8 (q, C-5), 56.5 (d, C-2), 62.6 (t, C-6, C-8), 166.5 (s, C-1 , C-3), 169.9 (s, C-4). Exact mass (ESI+): C9H15N05 + Na+: calcd. 240.0842, found 240.0824.
Reference: [1] Patent: WO2013/26765, 2013, A1, . Location in patent: Page/Page column 15-16
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 5, p. 1011 - 1026
  • 5
  • [ 13433-00-6 ]
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YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 0 - 20℃; Alternatively, diethyl 2-aminomalonate hydrochloride (21 .4 g, 100 mmol) and triethylamine (56 ml_, 400 mmol, 4.0 eq.) were dissolved in dichloromethane (500 mL) and stirred with acetic anhydride (9.5 mL, 100 mmol, 1.0 eq.) at 0 °C and overnight at r.t. The mixture was washed with brine (2 χ 200 mL) and dried over MgS04. The organic phase was filtered through a short silica gel column I (6 χ 6 cm, dichloromethane). The product 1 was isolated as a white crystalline solid. Yield: 22.08 g (100percent); 99percent purity (GC). Refs.: Synthesis according to T. Seitz, J. Baudoux, H. Bekolo, D. Cahard, J.-C. Plaquevent, M.-C. Lasne, J. Rouden, Tetrahedron 2006, 62, 6155-6165. M.p. T. N. Ghosh, J. Indian Chem. Soc. 1955, 32, 17-22.
Reference: [1] Patent: WO2013/26765, 2013, A1, . Location in patent: Page/Page column 16
[2] Organic Letters, 2018, vol. 20, # 19, p. 6298 - 6301
  • 6
  • [ 6829-41-0 ]
  • [ 1068-90-2 ]
YieldReaction ConditionsOperation in experiment
90% With zinc In water The above crude product was dissolved in a mixture of 79 volume parts of acetic acid, 25 volume parts of acetic anhydride and 3.5 volume parts of carbon tetrachloride and, under stirring, 27 parts of zinc dust was added at a temperature not exceeding 45°C.
After the addition had been completed, the mixture was stirred at room temperature for 20 minutes and, then, the zinc dust was filtered off.
To the filtrate was added 10 volume parts of water, followed by stirring for 30 minutes.
The mixture was then extracted with chloroform and the extract was washed with water, dehydrated and distilled to remove the solvent.
The resultant crystalline residue was recrystallized from water to yield a total of 19.6 parts of colorless crystals of diethyl acetamidomalonate.
Yield 90.0 percent.
Reference: [1] Patent: US3941823, 1976, A,
[2] Journal of Organic Chemistry, 1985, vol. 50, # 26, p. 5598 - 5604
[3] Journal of the American Chemical Society, 1944, vol. 66, p. 350
  • 7
  • [ 108-24-7 ]
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YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 0 - 20℃; 1.1 Diethyl 2-acetamidomalonate[0138] Alternatively, diethyl 2-aminomalonate hydrochloride (21.4 g, 100 mmol) and triethylamine (56 mL, 400 mmol, 4.0 eq.) were dissolved in dichloromethane (500 mL) and stirred with acetic anhydride (9.5 mL, 100 mmol, 1.0 eq.) at 0° C. and overnight at r.t. The mixture was washed with brine (2×200 mL) and dried over MgSO4. The organic phase was filtered through a short silica gel column I (6×6 cm, dichloromethane). The product 1 was isolated as a white crystalline solid. Yield: 22.08 g (100percent); 99percent purity (GC). Alternatively, diethyl 2-aminomalonate hydrochloride (21.4 g, 100 mmol) and triethylamine (56 mL, 400 mmol, 4.0 eq.) were dissolved in dichloromethane (500 mL) and stirred with acetic anhydride (9.5 mL, 100 mmol, 1.0 eq.) at 0° C. and overnight at r.t. The mixture was washed with brine (2×200 mL) and dried over MgSO4. The organic phase was filtered through a short silica gel column I (6×6 cm, dichloromethane). The product 1 was isolated as a white crystalline solid. Yield: 22.08 g (100percent); 99percent purity (GC).
Reference: [1] Patent: US2014/170067, 2014, A1, . Location in patent: Paragraph 0138; 0139; 0140
  • 8
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YieldReaction ConditionsOperation in experiment
96% With triethylamine In dichloromethane at 0 - 20℃; 1.1 Diethyl 2-acetamidomalonate10133] Diethyl 12-aminomalonate hydrochloride (1.69 g,8.0 mmol) and triethylamine (3.4 mL, 24 mmol, 3.0 eq.) were dissolved in dichloromethane (120 mL) at 0° C. Then acetylchloride (0.57 mL, 8.0 mmol, 1.0 eq.) was added under stirring and stirring was continued overnight while the mixture was allowed to warm up to tt. The mixture was diluted with dichloromethane (100 mL) and washed with 1 M RC1 (3x60 mL). The aqueous phase was extracted with dichioromethane (2x60 mL) and the combined organic layer was dried over MgSO4. Afier evaporation of the solvent in vacuo the product was isolated as a pure white solid. Yield: 1.68 g (96percent).0 09_otito 7t10134] M.p.: 96° C. (lit. 97° C.)10135] ‘R NMR (300 MRz, CDC13): ö [ppm]: 1.30 (t, 3Hii=7.1 Rz, 6R, 7-CR3, 9-CR3), 2.08 (s, 3R, 5-CR3), 4.27 (m,4R, 6-CR2, 8-CR2), 5.18 (d, 3JHH=7.1 Rz, 1R, 2-CR), 6.67(d, Rz, 1R, 2-NR).10136] ‘3C-NMR (75 MRz, CDC13) ö [ppm]: 14.0 (q, C-7,C-9), 22.8 (q, C-5), 56.5 (d, C-2), 62.6 (t, C-6, C-8), 166.5 (s,C-i, C-3), 169.9 (s, C-4).10137] Exact mass (ESI): C9R15NO5+Na: calcd.240.0842, found 240.0824.
Reference: [1] Patent: US2014/170067, 2014, A1, . Location in patent: Paragraph 0133; 0134; 0135; 0136; 0137
  • 9
  • [ 105-53-3 ]
  • [ 123-91-1 ]
  • [ 1068-90-2 ]
YieldReaction ConditionsOperation in experiment
86% With acetic acid; sodium nitrite In water Example 5
A mixture of 1,4-dioxane, acetic acid and water, obtained from a previous reaction mixture by taking a low-boiling cut, was metered into a stirred mixture of 320.4 g (2.0 mol) of diethyl malonate and 160 g (2.3 mol) of sodium nitrite (technical grade), maintained at 35° C. 12.0 g of water were then metered in and 166 g (207. mol) of acetic acid (96percent) were added dropwise over 2 hours.
The mixture was allowed to continue reacting for 2 hours at 40° C. and was worked up as described in Example 4.
There remained 425 g of light yellow oil, which, after catalytic hydrogenation and recrystallization of the crude product, gave diethyl acetaminomalonate at a yield of 86percent of theory, based on the diethyl malonate employed, and with a purity of >99.8 FID area percent.
Reference: [1] Patent: US5861533, 1999, A,
  • 10
  • [ 6829-40-9 ]
  • [ 108-24-7 ]
  • [ 1068-90-2 ]
Reference: [1] Journal of the American Chemical Society, 1944, vol. 66, p. 350
[2] Monatshefte fuer Chemie, 1953, vol. 84, p. 595,604
[3] Journal of Organic Chemistry, 1985, vol. 50, # 26, p. 5598 - 5604
[4] Organic Letters, 2003, vol. 5, # 22, p. 4187 - 4190
  • 11
  • [ 6829-40-9 ]
  • [ 78-39-7 ]
  • [ 1068-90-2 ]
YieldReaction ConditionsOperation in experiment
87% for 2 h; Reflux In a 250 mL round bottom flask, to 4 g (18.90 mmol) of diethylaminomalonate hydrochloride 5 were added 9.43 mL (0.885 g mL−1) of triethylorthoacetate, and the reaction mixture was refluxed for 2 h (oil bath). In the meantime, the colourless solution became yellow-brown. At the end, the solution was concentrated in a rotary evaporator giving a light yellow oily product.
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 62, p. 486 - 497
  • 12
  • [ 6829-40-9 ]
  • [ 75-36-5 ]
  • [ 1068-90-2 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1931, vol. <4>49, p. 42
[2] Bulletin de la Societe Chimique de France, 1931, vol. <4> 49, p. 47
[3] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1928, vol. 186, p. 1361,1362[4] Bulletin de la Societe Chimique de France, 1928, vol. <4> 43, p. 933
[5] Chemistry of Heterocyclic Compounds, 1996, vol. 32, # 8, p. 960 - 970
[6] European Journal of Organic Chemistry, 2009, # 21, p. 3619 - 3627
  • 13
  • [ 603-67-8 ]
  • [ 108-24-7 ]
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Reference: [1] Nippon Kagaku Zasshi, 1953, vol. 74, p. 22[2] Chem.Abstr., 1954, p. 5802
[3] Nippon Kagaku Zasshi, 1953, vol. 74, p. 22[4] Chem.Abstr., 1954, p. 5802
  • 14
  • [ 64-19-7 ]
  • [ 105-53-3 ]
  • [ 1068-90-2 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2000, vol. 39, # 1, p. 10 - 15
  • 15
  • [ 91469-69-1 ]
  • [ 1068-90-2 ]
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 62, p. 486 - 497
  • 16
  • [ 6829-41-0 ]
  • [ 108-24-7 ]
  • [ 1068-90-2 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1952, p. 638
[2] Zhurnal Obshchei Khimii, 1952, vol. 22, p. 2011,2013; engl. Ausg. S. 2065
[3] Org. Synth. Coll. Vol. V. <1973>373,
  • 17
  • [ 67-56-1 ]
  • [ 74-85-1 ]
  • [ 201230-82-2 ]
  • [ 30412-43-2 ]
  • [ 74090-40-7 ]
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Reference: [1] Journal of the American Chemical Society, 1980, vol. 102, p. 4980
  • 18
  • [ 570-08-1 ]
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Reference: [1] Roczniki Chemii, 1957, vol. 31, p. 579,582[2] Chem.Abstr., 1958, p. 5298
  • 19
  • [ 570-08-1 ]
  • [ 15129-21-2 ]
  • [ 1068-90-2 ]
Reference: [1] Roczniki Chemii, 1957, vol. 31, p. 579,582[2] Chem.Abstr., 1958, p. 5298
[3] Roczniki Chemii, 1957, vol. 31, p. 579,582[4] Chem.Abstr., 1958, p. 5298
  • 20
  • [ 108-24-7 ]
  • [ 13636-61-8 ]
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Reference: [1] Annali di Chimica (Rome, Italy), 1957, vol. 47, p. 1293,1294
  • 21
  • [ 64-19-7 ]
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Reference: [1] Journal of the Chemical Society, 1948, p. 1969
  • 22
  • [ 91011-83-5 ]
  • [ 1069-38-1 ]
  • [ 55166-91-1 ]
  • [ 1068-90-2 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1995, # 2, p. 189 - 192
  • 23
  • [ 111-83-1 ]
  • [ 1068-90-2 ]
  • [ 17702-88-4 ]
Reference: [1] Journal of Organic Chemistry, 2007, vol. 72, # 14, p. 5146 - 5151
[2] Journal of the American Chemical Society, 2000, vol. 122, # 17, p. 4032 - 4038
  • 24
  • [ 112-29-8 ]
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  • [ 17702-88-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 14, p. 4775 - 4780
  • 25
  • [ 143-15-7 ]
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  • [ 35237-37-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 14, p. 4775 - 4780
  • 26
  • [ 637-59-2 ]
  • [ 1068-90-2 ]
  • [ 34993-02-7 ]
YieldReaction ConditionsOperation in experiment
83% With hydrogenchloride; ammonium hydroxide; sodium ethanolate; sodium In ethanol EXAMPLE 5
(+-)-2-Amino-5-phenylpentanoic acid
Diethyl acetamidomalonate (220 g) in 1 L of absolute ethanol was added to a stirred solution of sodium ethoxide in ethanol, prepared by dissolving sodium (24 g) in absolute ethanol (500 mL), under nitrogen.
The reaction mixture was refluxed under nitrogen for 30 minutes and then 1-bromo-3-phenylpropane (200 g) was added.
The reaction mixture was refluxed overnight, cooled to ambient temperature, the precipitate removed by filtration and the solvent removed in vacuo.
Concentrated hydrochloric acid (800 mL) was added to the residue and the reaction mixture was refluxed for 14 hours.
The cooled aqueous solution was washed with ether (2*200 mL).
The residual ether in the aqueous phase was removed by nitrogen bubbling through the solution.
The pH of the aqueous phase was adjusted to 7-8 by the addition of ammonium hydroxide.
The title compoundcompound was collected by filtration, air dried and recrystallized from ethanol-water to afford 150 g (83percent).
m.p. 255°-257° C. MS (FAB) m/e 194 (M+H)+.
Reference: [1] Patent: US5663148, 1997, A,
  • 27
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  • [ 80997-87-1 ]
Reference: [1] European Journal of Medicinal Chemistry, 1990, vol. 25, # 1, p. 35 - 44
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