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Chemical Structure| 40876-98-0 Chemical Structure| 40876-98-0

Structure of 40876-98-0

Chemical Structure| 40876-98-0

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Product Details of [ 40876-98-0 ]

CAS No. :40876-98-0
Formula : C8H11NaO5
M.W : 210.16
SMILES Code : O=C([CH-]C(C(OCC)=O)=O)OCC.[Na+]
MDL No. :MFCD00035571

Safety of [ 40876-98-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 40876-98-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.5
Num. rotatable bonds 6
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 42.3
TPSA ?

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

75.66 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

-11.8
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

1.35
Log Po/w (WLOGP)?

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

0.43
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.

0.01
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

0.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-1.94

Water Solubility

Log S (ESOL):?

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

-1.6
Solubility 5.31 mg/ml ; 0.0253 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-2.54
Solubility 0.605 mg/ml ; 0.00288 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

-0.36
Solubility 91.7 mg/ml ; 0.437 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

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

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.

-6.62 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.

0.56

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

3.0 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)

2.58

Application In Synthesis of [ 40876-98-0 ]

* 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 [ 40876-98-0 ]

[ 40876-98-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 57297-29-7 ]
  • [ 40876-98-0 ]
  • [ 858956-25-9 ]
YieldReaction ConditionsOperation in experiment
63% A solution of sodium hydroxide (2.85 g, 71.3 mmol) in water (3 ml) was added to a stirred solution of diethyl oxaloacetate sodium salt (8.7 g, 50 mmol) in water (50 ml) and the mixture stirred for 20 minutes. Cyclopropylcarboxamidine hydrochloride salt (5.0 g, 40 mmol) was added to the solution and the mixture was heated at 70 0C overnight, then cooled to ambient temperature and acidified to pH1 by the cautious addition of concentrated hydrochloric acid. The precipitate was isolated by filtration and dried to yield 2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (4.7 g, 63percent). Characterising data for the compound are as follows: 1H nmr (400MHz, d6-DMSO) deltaH 13.30 (1H, br s), 12.97 (1H, br s), 6.59 (1H, s), 1.94 (1H, quintet), 1.04 (4H, m) ppm.
63% A solution of sodium hydroxide (2.85 g, 71.3 mmol) in water (3 ml) was added to a stirred solution of diethyl oxaloacetate sodium salt (8.7 g, 50 mmol) in water (50 ml) and the mixture stirred for 20 minutes. Cyclopropylcarboxamidine hydrochloride salt (5.0 g, 40 mmol) was added to the solution and the mixture was heated at 70 0C overnight, then cooled to ambient temperature and acidified to pH1 by the cautious addition of concentrated hydrochloric acid. The precipitate was isolated by filtration and dried to yield 2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (4.7 g, 63percent). 1H nmr (400MHz, d6-DMSO) deltaH 13.30 (1 H, br s), 12.97 (1 H, br s), 6.59 (1 H, s), 1.94 (1 H, quintet), 1.04 (4H, m) ppm.
  • 2
  • [ 57297-29-7 ]
  • [ 40876-98-0 ]
  • 2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 2 Preparation of 6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylic acid (Compound 135) Step Al : Preparation of 2-cyclopropyl-1, 6-dihydro-6-oxo-4-pyrimidinecarboxylic acid To a mixture of diethyl oxalacetate sodium salt (150 g, 714 mmol) in methanol (300 mL) and water (150 mL) warmed to 30 °C was added 50percent aqueous sodium hydroxide (56 g, 700 mmol) in water (60 mL) over 30 minutes, over which time the temperature remained at 25-30 °C and the pH at 11-12. Then the stirred mixture was heated for an additional 30 min at 35 °C. To this mixture was added <strong>[57297-29-7]cyclopropanecarboximidamide monohydrochloride</strong> (64 g, 530 mol) in portions over 15 minutes. The orange solution was heated to 50 °C over 30 minutes and held at that temperature for 3 h. The reaction mixture was cooled to 35 °C, and concentrated hydrochloric acid (ca. 70 g, 0.7 mol) was added gradually (resulting in foaming) over 30 minutes at 30-40 °C until the pH was about 1.5- 2.5. The mixture was concentrated with a rotary evaporator at 35-40 °C to remove alcohols, stirred for 3-4 h at 25 °C to complete crystallization of the product. After the mixture was cooled to 0 °C the solid was collected by filtration. The solid was washed with water (2 x 60 mL), suction-dried, and then dried in a vacuum-oven at 60 °C to afford the title compound as a beige solid (ca. 60 g). 1H NMR (DMSO-d6) otilde; 6. 58 (s, 1H), 1.95 (m, 1H), 1.0 (m, 4H).; Step A2: Another preparation of 2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidine- carboxylic acid To a mixture of diethyl oxalacetate sodium salt (210 g, 950 mmol) in methanol (500 mL) and water (400 mL) was added 50percent aqueous sodium hydroxide (80 g, 1.0 mol) in water (60 mL) over 30 minutes, over which time the temperature remained at 25-30 °C and the pH at 11-12. Then the stirred mixture was heated for an additional 30 min at 30 °C. To this mixture was added <strong>[57297-29-7]cyclopropanecarboximidamide monohydrochloride</strong> (110 g, 910 mol). The orange solution was heated to 50 °C over 30 minutes and held at that temperature for 5 h. The reaction mixture was cooled to 30 °C and concentrated to half volume at reduced pressure at 35-40 °C and concentrated hydrochloric acid (140 g, 1.4 mol) was added gradually (resulting in foaming) over 30 minutes at 25-30 °C until the pH was about 1-2. The mixture was stirred at 5 °C for 1 h to complete crystallization of the product. After the mixture was cooled to 0 °C the solid was collected by filtration. The solid was washed with water (3 x 60 mL), suction-dried, and then dried in a vacuum-oven at 70 °C to afford the title compound as a beige solid (100 g) ; m. p. 235-236 °C (dec. ). 1H NMR (DMSO-d6) 8 6.58 (s, 1H), 1.95 (m, 1H), 1.0 (m, 4H).
60 g To a mixture of diethyl oxalacetate sodium salt (150 g, 714 mmol) in methanol (300 mL) and water (150 mL) warmed to 30° C. was added 50percent aqueous sodium hydroxide (56 g, 700 mmol) in water (60 mL) over 30 minutes, over which time the temperature remained at 25-30° C. and the pH at 11-12. Then the stirred mixture was heated for an additional 30 min at 35° C. To this mixture was added <strong>[57297-29-7]cyclopropanecarboximidamide monohydrochloride</strong> (64 g, 530 mol) in portions over 15 minutes. The orange solution was heated to 50° C. over 30 minutes and held at that temperature for 3 h. The reaction mixture was cooled to 35° C., and concentrated hydrochloric acid (ca. 70 g, 0.7 mol) was added gradually (resulting in foaming) over 30 minutes at 30-40° C. until the pH was about 1.5-2.5. The mixture was concentrated with a rotary evaporator at 35-40° C. to remove alcohols, stirred for 3-4 h at 25° C. to complete crystallization of the product. After the mixture was cooled to 0° C. the solid was collected by filtration. The solid was washed with water (2*60 mL), suction-dried, and then dried in a vacuum-oven at 60° C. to afford the title compound as a beige solid (ca. 60 g). 1H NMR (DMSO-d6) delta 6.58 (s, 1H), 1.95 (m, 1H), 1.0 (m, 4H).
  • 3
  • [ 658-27-5 ]
  • [ 40876-98-0 ]
  • C12H11FN2O3 [ No CAS ]
 

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