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[ CAS No. 51940-64-8 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 51940-64-8
Chemical Structure| 51940-64-8
Chemical Structure| 51940-64-8
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Product Details of [ 51940-64-8 ]

CAS No. :51940-64-8 MDL No. :MFCD09910281
Formula : C7H6Cl2N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :SRJBDGLSCPDXBL-UHFFFAOYSA-N
M.W : 221.04 Pubchem ID :104020
Synonyms :

Calculated chemistry of [ 51940-64-8 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.29
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 48.14
TPSA : 52.08 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.99 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.18
Log Po/w (XLOGP3) : 2.34
Log Po/w (WLOGP) : 1.96
Log Po/w (MLOGP) : 1.07
Log Po/w (SILICOS-IT) : 2.35
Consensus Log Po/w : 1.98

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.83
Solubility : 0.328 mg/ml ; 0.00149 mol/l
Class : Soluble
Log S (Ali) : -3.07
Solubility : 0.187 mg/ml ; 0.000845 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.37
Solubility : 0.0936 mg/ml ; 0.000424 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.89

Safety of [ 51940-64-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 51940-64-8 ]

* 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 [ 51940-64-8 ]
  • Downstream synthetic route of [ 51940-64-8 ]

[ 51940-64-8 ] Synthesis Path-Upstream   1~18

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Reference: [1] Journal of Organic Chemistry, 1955, vol. 20, p. 829,833,835
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  • [ 71406-78-5 ]
Reference: [1] Patent: WO2013/12915, 2013, A1, . Location in patent: Paragraph 00667-00669
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  • [ 71406-78-5 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1954, vol. 588, p. 45,56
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  • [ 15400-54-1 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1954, vol. 588, p. 45,56
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  • [ 28485-17-8 ]
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YieldReaction ConditionsOperation in experiment
100% for 2 h; Heating / reflux 4-(3-fluorophenethylamino)-2-(1H-pyrazol-4-yl)-N-(pyridin-2-ylmethyl)pyrimidine-5-carboxamide
A mixture of 5-carbeoxyuracil (3.01 g, 16.34 mmol), POCl3 (27 mL) and N,N-diethylaniline (4.5 mL) was stirred and refluxed for 2 h until 5-carbeoxyuracil was completely consumed.
The mixture was cooled to r.t. and poured into ice-water (50 mL) and extracted with ether (2*100 mL).
The ether solution was washed with saturated sodium bicarbonate, followed by brine.
After concentration, the desired product was obtained as a brownish liquid in quantitative yield (3.6 g). LRMS (M+H+) m/z 221.0.
75% for 0.5 h; Heating / reflux Step i.
Ethyl 2,4-dichloropyrimidine-5-carboxylate
Under an N2 atmosphere, a mixture of 5-carbethoxyuracil (1.0 g, 5.4 mmol) and POCl3 (10 mL) was heated at reflux for 30 minutes.
The solution was concentrated under reduced pressure to remove the excess of POCl3, and the residue was poured into ice (20 g). CH2Cl2 (100 mL) was added, and the mixture was basified to pH 9 using saturated aqueous NaHCO3 solution.
The organic portion was dried over MgSO4 and concentrated to obtain ethyl 2,4-dichloropyrimidine-5-carboxylate as a yellow oil (900 mg, 75percent).
70%
Stage #1: at 180℃; for 1 h; Inert atmosphere
Stage #2: With sodium hydrogencarbonate In water
Ethyl 2,4-dichloropyrimidine-5-carboxylate
Ethyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (5.0 g, 27.15 mmol) was added to phenyl phosphorodichloridate (32.4 ml, 217.21 mmol) under nitrogen.
The resulting suspension was stirred at 180° C. for 1 hour.
The reaction mixture was poured into ice/water (500 mL) and adjusted to pH 7 with saturated NaHCO3.
The mixture was extracted with EtOAc (3*100 mL).
The organic layers were combined and washed with water (2*100 mL), dried over Na2SO4, filtered and evaporated to afford crude product.
The crude product was purified by flash silica chromatography, elution gradient 0 to 10percent EtOAc in isohexane.
Pure fractions were evaporated to dryness to afford ethyl 2,4-dichloropyrimidine-5-carboxylate (4.22 g, 70percent) as a colourless oil which crystallized on standing.
1H NMR (400.13 MHz, DMSO-d6) δ 1.33 (3H, t), 4.37 (2H, q), 9.15 (1H, s)
68% at 110℃; for 3.16 h; Cooling with ice To a 100 ml three-necked flask was added ethyl uracil-5-carboxylate (2.2 g, 11.95 mmol)N, N-dimethylaniline (2 g, 16.50 mmol).Under ice bath, phosphorus oxychloride (9.2 g, 60 mmol) was gradually added and stirred continuously.After the addition of 10 minutes, gradually heating 110 ° C, and insulation 3h reaction.The reaction solution was slowly poured into an ice-water mixture (100 ml) and quenched and kept at a temperature below 5 ° C. And extracted twice with ethyl acetate (200 ml).The organic phases were combined, washed with saturated brine, dried and concentrated to give the crude product.The crude product was purified by column chromatography to give 1.8 g of solid in 68percent yield.
37% With <i>N</i>,<i>N</i>-dimethyl-aniline; trichlorophosphate In benzene at 90℃; for 8 h; Inert atmosphere Step 2. A mixture of ethyl 2,4-dioxo-l,2,3,4-tetrahydropyrimidine-5-carboxylate obtained in step 1 (8.5 g, 46.2 mmol, 1.0 eq), N,N-dimethylbenzenamine (1.12 g, 9.24 mmol, 0.2 eq), POCl3 (21.25 g, 138.6 mmol, 3.0 eq) in benzene (300 mL) was stirred at 9O 0C under a nitrogen atmosphere for 8 h. The reaction mixture was allowed to cool to room temperature and throw into ice (300 g). The mixture was extracted by EtOAc (2x300 mL). The combined organic phases were washed (brine), dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel chromatography (PE/EtOAc=500:l to 15:1 as eluent) to afford ethyl 2,4- dichloropyrimidine-5-carboxylate (3.83 g, 37percent) as white solid. LC-MS (m/z) =220.9 [M+H]+.

Reference: [1] Patent: US2009/198057, 2009, A1, . Location in patent: Page/Page column 18
[2] Patent: US2006/160817, 2006, A1, . Location in patent: Page/Page column 83-84
[3] Patent: US2009/264401, 2009, A1, . Location in patent: Page/Page column 47
[4] Patent: CN104650045, 2017, B, . Location in patent: Paragraph 0058-0060
[5] Patent: WO2011/19405, 2011, A1, . Location in patent: Page/Page column 119
[6] Justus Liebigs Annalen der Chemie, 1954, vol. 588, p. 45,56
[7] Journal of Organic Chemistry, 1955, vol. 20, p. 829,833,835
[8] Patent: US2015/266828, 2015, A1, . Location in patent: Paragraph 0367
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YieldReaction ConditionsOperation in experiment
99% at 20℃; for 0.166667 h; 11.2: 2,4-Dichloropyrimidine-5-carboxylic acid ethyl ester
Compound 11.1 (13.5 g, 64 mmol) is dissolved in THF (100 ml).
Ethanol (15 ml) is added and the mixture is stirred at ambient temperature for 10 min.
The solvents are evaporated and an oil is recovered and hydrolyzed with a saturated K2CO3 solution and extracted with AcOEt (3*250 ml).
The organic phase is washed with an NaCl solution (100 ml) and dried over Na2SO4.
After filtering and evaporating, an orange oil is recovered (14 g, yd: 99percent).
1H NMR, d6-DMSO (300 MHz): 9.16 (s, 1H), 4.37 (q, 2H, J=7.11 Hz), 1.34 (t, 3H, J=7.11 Hz).
99% at 20℃; for 0.166667 h; Inert atmosphere 9.2: 2,4-Dichloropyrimidine-5-carboxylic Acid Ethyl Ester; In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 13.5 g (64.0 mmol) of above compound are dissolved in 100 ml of anhydrous THF. 15 ml of absolute ethanol are added and the mixture is stirred for 10 min at ambient temperature. The mixture is diluted with a saturated aqueous solution of K2CO3 (100 ml) and extracted with ethyl acetate (4.x.100 ml). The organic phases are combined and then washed with 150 ml of a saturated aqueous solution of NaCl. After separation, the organic phase is dried over MgSO4 and filtered, and the solvent is evaporated off under reduced pressure, so as to obtain 14.0 g (63.3 mmol) of compound in the form of an orange oil. Yield=99percent. 1H NMR DMSO d6 (300 MHz): 1.34 (t, J=7.1 Hz, 3H); 4.37 (q, J=7.1 Hz, 2H); 9.16 (s, 1H).
Reference: [1] Patent: US2010/222319, 2010, A1, . Location in patent: Page/Page column 18
[2] Patent: US2011/251194, 2011, A1, . Location in patent: Page/Page column 22
[3] Patent: WO2014/85225, 2014, A1, . Location in patent: Page/Page column 53; 54
[4] Patent: WO2015/157127, 2015, A1, . Location in patent: Page/Page column 293
[5] ChemMedChem, 2017, vol. 12, # 3, p. 207 - 213
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YieldReaction ConditionsOperation in experiment
85% at 105℃; Ester 1.3 (22g, 120 mmol) was dissolved in phosphorous oxychloride(60 mL, 600 mmol) and the mixture treated with N,N-diethylaniline (27 mL, 167 mmol) and the mixture heated to 1050C until the reaction was determined to be complete by HPLC. It was then cooled to rt and slowly added to 1 L of crushed ice resulting in the formation of a beige precipitate which was collected by filtration and dried under vacuum affording the desired dichloride (1.4) as a light yellow powder (22.5g, 85percent). 1H NMR (DMSOd6, 400 MHz): δ 9.13 (s, IH), 4.37 (q, 2H), 1.32 (t, 3H).
85% at 105℃; Ester 1.3 (22g, 120 mmol) was dissolved in phosphorous oxychloride (60 niL, 600 mmol) and the mixture treated with N,N-diethylaniline (27 mL, 167 mmol) and the mixture heated to 1050C until the reaction was determined to be complete by HPLC. It was then cooled to it and slowly added to 1 L of crushed ice resulting in the formation of a beige precipitate which was collected by filtration and dried under vacuum affording the desired dichloride (1.4) as a light yellow powder (22.5g, 85percent). 1H NMR (DMSOd6, 400 MHz): δ 9.13 (s, IH), 4.37 (q, 2H), 1.32 (t, 3H).
81% for 2 h; Reflux N,N-Diethylaniline (1.5 mL, 9.45 mmol) was added to a suspension of 5-carbethoxyuracil, i (1.00 g, 5.43 mmol), in phosphorus (V) oxychloride (10 mL). The mixture was heated under reflux for 2 h, cooled to room temperature and reduced in vacuo. The resulting syrupy residue was transferred carefully onto stirred ice / water (50 mL). After 1 h, the resulting beige solid was collected by filtration, washed with water (10 mL) and air-dried to give compound ii (0.97 g, 4.41 mmol, 81 percent) as a light beige powder. *Η NMR (300MHz, CDCL): δ 9.04 (1H, s), 4.46 (2H, q, / 7.2), 1.43 (3H, t, J 7.2); [M+H]+ mJz = 221.0.
Reference: [1] Patent: WO2009/131687, 2009, A2, . Location in patent: Page/Page column 101
[2] Patent: WO2010/129802, 2010, A1, . Location in patent: Page/Page column 73-74
[3] Patent: WO2013/91011, 2013, A1, . Location in patent: Page/Page column 66; 74
[4] Indian Journal of Heterocyclic Chemistry, 2010, vol. 20, # 2, p. 133 - 136
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YieldReaction ConditionsOperation in experiment
69% at 105℃; To a mixture of ethyl 2,4-dioxohexahydropyrimidine-5-carboxylate 2 (46.3 g, 0.251 mol) in 126 mL of POC was added N, N-diethylaniline (52.4 g, 0.351 mol). The mixture was stirred at 105 °C overnight. This mixture was cooled to r.t. and poured into ice, filtered to afford pale yellow solid. The solid was dissolved in 100 mL of DCM and dried over Na2S04, filtered and evaporated to afford 41.6 g of 69 as a yellow solid (69percent). Ή NMR (300 MHz, CDC13) δ ppm 9.01 (s, 1 H), 4.47 (q, J= 7.2 Hz, 2H), 1.41 (t, J= 7.2 Hz, 3H).
Reference: [1] Patent: WO2013/43232, 2013, A2, . Location in patent: Paragraph 00569
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Reference: [1] Patent: WO2015/19037, 2015, A1, . Location in patent: Page/Page column 66
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Reference: [1] Patent: US2003/32647, 2003, A1,
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Reference: [1] Patent: WO2011/19405, 2011, A1,
[2] Indian Journal of Heterocyclic Chemistry, 2010, vol. 20, # 2, p. 133 - 136
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Reference: [1] Patent: US2011/251194, 2011, A1,
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Reference: [1] Patent: WO2013/43232, 2013, A2,
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Reference: [1] Patent: WO2014/58747, 2014, A1, . Location in patent: Page/Page column 191
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Reference: [1] Patent: CN104650045, 2017, B,
[2] Patent: CN104650045, 2017, B,
[3] Patent: CN104650045, 2017, B,
[4] Patent: CN104710411, 2017, B,
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Reference: [1] Patent: CN104650045, 2017, B,
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  • [ 1240597-30-1 ]
  • [ 71406-78-5 ]
Reference: [1] Patent: WO2013/12915, 2013, A1, . Location in patent: Paragraph 00667-00669
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Reference: [1] Tetrahedron Letters, 2016, vol. 57, # 3, p. 449 - 451
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