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[ CAS No. 3095-95-2 ] {[proInfo.proName]}

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Chemical Structure| 3095-95-2
Chemical Structure| 3095-95-2
Structure of 3095-95-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 3095-95-2 ]

CAS No. :3095-95-2 MDL No. :MFCD00192032
Formula : C6H13O5P Boiling Point : -
Linear Structure Formula :- InChI Key :DVQMPWOLBFKUMM-UHFFFAOYSA-N
M.W : 196.14 Pubchem ID :36704
Synonyms :

Calculated chemistry of [ 3095-95-2 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.83
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 43.56
TPSA : 82.64 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) : -7.64 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.91
Log Po/w (XLOGP3) : -0.2
Log Po/w (WLOGP) : 1.34
Log Po/w (MLOGP) : -0.18
Log Po/w (SILICOS-IT) : -0.38
Consensus Log Po/w : 0.3

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -0.53
Solubility : 57.3 mg/ml ; 0.292 mol/l
Class : Very soluble
Log S (Ali) : -1.08
Solubility : 16.3 mg/ml ; 0.0833 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.75
Solubility : 35.2 mg/ml ; 0.179 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.83

Safety of [ 3095-95-2 ]

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

Application In Synthesis of [ 3095-95-2 ]

* 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 [ 3095-95-2 ]
  • Downstream synthetic route of [ 3095-95-2 ]

[ 3095-95-2 ] Synthesis Path-Upstream   1~24

  • 1
  • [ 3095-95-2 ]
  • [ 124-41-4 ]
  • [ 197015-32-0 ]
  • [ 98081-83-5 ]
Reference: [1] Journal of Organic Chemistry, 2003, vol. 68, # 15, p. 6011 - 6019
  • 2
  • [ 867-13-0 ]
  • [ 3095-95-2 ]
YieldReaction ConditionsOperation in experiment
100% With potassium hydroxide In ethanol; water at 20℃; After dissolving triethyl phosphonoacetate (1.7 g, 7.5 mmol, Sigma-Aldrich T61391) in ethanol / water (15 mL ie 14: 1) at room temperature, potassium hydroxide (424.2 mg, 7.56 mmol, ) 6597-4400) was added and stirred at room temperature. The reaction was neutralized with 1N HCl to pH 4, the ethanol was removed by distillation under reduced pressure, diluted with chloroform (20 mL), washed with water (10 mL) and saturated brine (10 mL). The separated organic layer was dried over anhydrous sodium sulfate (product number (Daejeong) 7630-4400), filtered and distilled under reduced pressure to obtain 2-(diethoxyphosphoryl)acetic acid 4 (1.48 gm, 100percent).
Reference: [1] Patent: KR2018/71069, 2018, A, . Location in patent: Paragraph 0090; 0091; 0093; 0156-0158
[2] Synthesis, 1981, # 4, p. 283 - 285
[3] Journal of Medicinal Chemistry, 1995, vol. 38, # 15, p. 2906 - 2921
[4] Organic Letters, 2010, vol. 12, # 7, p. 1460 - 1463
[5] Organic Letters, 2015, vol. 17, # 4, p. 816 - 819
[6] Journal of Fluorine Chemistry, 2005, vol. 126, # 11-12, p. 1467 - 1475
[7] Journal of Medicinal Chemistry, 1994, vol. 37, # 14, p. 2216 - 2223
[8] Australian Journal of Chemistry, 1987, vol. 40, # 9, p. 1511 - 1518
[9] Organic and Biomolecular Chemistry, 2011, vol. 9, # 8, p. 2702 - 2714
[10] Journal of Organic Chemistry, 2001, vol. 66, # 15, p. 5217 - 5231
[11] J. Gen. Chem. USSR (Engl. Transl.), 1971, vol. 41, p. 1432 - 1439[12] Zhurnal Obshchei Khimii, 1971, vol. 41, p. 1426 - 1434
[13] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1978, p. 1130 - 1134
[14] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1979, p. 308 - 313
[15] Chemistry Letters, 1988, p. 211 - 214
[16] Phosphorus and Sulfur and the Related Elements, 1983, vol. 14, p. 285 - 294
[17] Monatshefte fur Chemie, 1997, vol. 128, # 10, p. 995 - 1008
[18] Organic Letters, 2004, vol. 6, # 20, p. 3477 - 3480
[19] Journal of Organic Chemistry, 2013, vol. 78, # 11, p. 5401 - 5409
[20] Research on Chemical Intermediates, 2013, vol. 39, # 7, p. 3105 - 3110
[21] Patent: KR101653677, 2016, B1, . Location in patent: Paragraph 0090-0093
  • 3
  • [ 7396-44-3 ]
  • [ 3095-95-2 ]
Reference: [1] Organic Letters, 2010, vol. 12, # 7, p. 1460 - 1463
[2] Roczniki Chemii, 1963, vol. 37, p. 949 - 954
[3] Journal of Organic Chemistry, 1965, vol. 30, p. 4034 - 4038
  • 4
  • [ 79-11-8 ]
  • [ 122-52-1 ]
  • [ 3095-95-2 ]
YieldReaction ConditionsOperation in experiment
68% Reflux General procedure: In a flame-dried three-necked flask the appropriate aryl /alkyl halide (0.001 mol) was mixed with triethyl phosphite (0.249 g, 0.0015 mol) and stirred atreflux temperature for 6-8 hrs and protected with a CaCl2-tube, respectively. After thecompletion of reaction (monitored by TLC), the oily product was obtained. The product waspurified by column chromatography on silica gel using petroleum ether-ethylacetate (7:3) aseluent.
Reference: [1] Arkivoc, 2006, vol. 2006, # 16, p. 128 - 135
  • 5
  • [ 867-13-0 ]
  • [ 3095-95-2 ]
Reference: [1] Patent: EP1336611, 2003, A1,
  • 6
  • [ 762-04-9 ]
  • [ 79-08-3 ]
  • [ 3095-95-2 ]
Reference: [1] Patent: US4307232, 1981, A,
  • 7
  • [ 683-08-9 ]
  • [ 124-38-9 ]
  • [ 3095-95-2 ]
Reference: [1] Synthesis, 1986, # 8, p. 661 - 664
[2] Journal of Organic Chemistry, 1999, vol. 64, # 13, p. 4935 - 4938
[3] Organic letters, 2001, vol. 3, # 18, p. 2875 - 2878
  • 8
  • [ 115124-53-3 ]
  • [ 3095-95-2 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1987, vol. 35, # 10, p. 4368-4371
  • 9
  • [ 1067-74-9 ]
  • [ 3095-95-2 ]
Reference: [1] Heteroatom Chemistry, 2003, vol. 14, # 1, p. 67 - 71
  • 10
  • [ 1067-74-9 ]
  • [ 3095-95-2 ]
  • [ 40882-15-3 ]
Reference: [1] Heteroatom Chemistry, 2003, vol. 14, # 1, p. 67 - 71
  • 11
  • [ 10419-77-9 ]
  • [ 3095-95-2 ]
Reference: [1] Journal of Organometallic Chemistry, 1986, vol. 316, p. 13 - 18
  • 12
  • [ 2537-48-6 ]
  • [ 3095-95-2 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 1, p. 137 - 140
  • 13
  • [ 27784-76-5 ]
  • [ 3095-95-2 ]
Reference: [1] J. Gen. Chem. USSR (Engl. Transl.), 1971, vol. 41, p. 1470 - 1473[2] Zhurnal Obshchei Khimii, 1971, vol. 41, p. 1464 - 1469
  • 14
  • [ 124-38-9 ]
  • [ 110625-05-3 ]
  • [ 3095-95-2 ]
Reference: [1] Journal of Organometallic Chemistry, 1986, vol. 316, p. 13 - 18
  • 15
  • [ 867-13-0 ]
  • [ 3095-95-2 ]
  • [ 4408-78-0 ]
  • [ 35752-46-6 ]
Reference: [1] Phosphorus and Sulfur and the Related Elements, 1983, vol. 14, p. 285 - 294
  • 16
  • [ 924-44-7 ]
  • [ 3095-95-2 ]
  • [ 2459-05-4 ]
Reference: [1] Journal of the American Chemical Society, 2007, vol. 129, # 26, p. 8064 - 8065
  • 17
  • [ 67-56-1 ]
  • [ 3095-95-2 ]
  • [ 1067-74-9 ]
Reference: [1] Journal of Organic Chemistry, 1999, vol. 64, # 13, p. 4935 - 4938
  • 18
  • [ 3095-95-2 ]
  • [ 2043-61-0 ]
  • [ 56453-86-2 ]
Reference: [1] Journal of the American Chemical Society, 2007, vol. 129, # 26, p. 8064 - 8065
  • 19
  • [ 3095-95-2 ]
  • [ 75-65-0 ]
  • [ 27784-76-5 ]
Reference: [1] Organic Letters, 2001, vol. 3, # 23, p. 3733 - 3735
[2] Journal of Organic Chemistry, 2002, vol. 67, # 25, p. 8975 - 8982
[3] Synthesis, 1983, # 12, p. 1010 - 1012
[4] Organic and Biomolecular Chemistry, 2004, vol. 2, # 3, p. 397 - 401
  • 20
  • [ 3095-95-2 ]
  • [ 3972-25-6 ]
  • [ 27784-76-5 ]
Reference: [1] Organic Letters, 2001, vol. 3, # 23, p. 3733 - 3735
  • 21
  • [ 3095-95-2 ]
  • [ 100-39-0 ]
  • [ 7396-44-3 ]
Reference: [1] Journal of Organic Chemistry, 2013, vol. 78, # 11, p. 5401 - 5409
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 17, p. 2197 - 2202
  • 22
  • [ 3095-95-2 ]
  • [ 79-37-8 ]
  • [ 762-04-9 ]
  • [ 7396-44-3 ]
Reference: [1] Patent: US4336368, 1982, A,
  • 23
  • [ 3095-95-2 ]
  • [ 618061-76-0 ]
YieldReaction ConditionsOperation in experiment
69.8%
Stage #1: With 1,1'-carbonyldiimidazole In tetrahydrofuran at 40℃; for 0.5 h;
Stage #2: at 30 - 40℃; for 2 h;
Example 1
Diethyl [4-(3-Chloro-4-Fluoro-Phenylamino)-7-((S)-Tetrahydrofuran-3-Yloxy)-Quinazolin-6-Ylcarbamoyl]-Methyl}-Phosphonate
3.58 kg of 1,1-carbonyldiimidazole (22.16 mol) are placed in 12.8 litres of tetrahydrofuran and at 40° C. combined with 4.52 kg (22.16 mol) of diethylphosphonoacetic acid dissolved in 6.5 litres of tetrahydrofuran.
The mixture is stirred for 30 minutes at 40° C.
The resulting solution is referred to as solution A.
6.39 kg (17.05 mol) of N4-(3-chloro-4-fluoro-phenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine are placed in 26.5 litres of tetrahydrofuran and at 40° C. combined with solution A and stirred for 2 hours at 30° C. 64 litres of tert.-butylmethylether are added to the suspension and after cooling to 20° C. the precipitate is removed by centrifuging.
It is washed with a mixture of 16 litres of tetrahydrofuran and 16 litres of tert.
-butylmethylether and then with 32 litres of water and dried at 50° C.
Yield: 6.58 kg (69.8percent) of white crystals, content: HPLC 99.1 Fl percent
41.0 g
Stage #1: With 1,1'-carbonyldiimidazole In tetrahydrofuran at 40℃; for 1 h;
Stage #2: at 30℃; for 2.4 h;
To the suspension of 28.0 g of Ι, Γ-carbonyldiimidazole in 98.0 ml of THF at about 40 °C, a solution of 33.9 g of 2-(diethoxyphosphoryl)acetic acid in 50.6 ml of THF was added dropwise. The reaction mixture was stirred for 1 hour at about 40 °C and then added to the solution of 40.5 g of (5")-Λ^-(3-ΜθΓθ-4- fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine (prepared according to step b) in 168 ml of THF at about 40 °C dropwise. The reaction mixture was cooled down to about 30 °C and stirred for 2.4 h hours when 405.0 ml of MTBE was added dropwise. The reaction mixture was cooled down to about 20 °C and stirred for 1.5 hours. Crystals were filtered off, washed twice with 40.5 ml of THF/MTBE 1 : 1, once with 40.5 ml of water and dried at 50 °C/ 15 mbar for about 16 hours. 41.0 g of (5)-diethyl 2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran- 3-yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate was obtained
Reference: [1] Patent: WO2004/74263, 2004, A1, . Location in patent: Page 15
[2] Patent: US2005/85495, 2005, A1, . Location in patent: Page/Page column 6
[3] Patent: WO2015/103456, 2015, A1, . Location in patent: Paragraph 0095
  • 24
  • [ 3095-95-2 ]
  • [ 618061-76-0 ]
YieldReaction ConditionsOperation in experiment
88% With 1,1'-carbonyldiimidazole In DMF (N,N-dimethyl-formamide) at 20℃; for 4 - 5 h; 60.07 g of diethoxyphosphorylacetic acid are placed in 750 ml of N,N-dimethylformamide and at ambient temperature combined with 48.67 g of N,N'-carbonyldiimidazole. After the development of gas has ceased 90.00 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-6-amino-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline are added and the reaction mixture is stirred for about 4-5 hours at ambient temperature until the reaction is complete. The reaction mixture is then heated gently in the water bath and 750 ml of water are added twice. The thick suspension is stirred overnight and the next morning another 350 ml of water are added. The suspension is cooled in the ice bath, stirred for one hour and suction filtered. The filter cake is washed again with 240 ml of N,N-dimethylformamide/water (1:2) and 240 ml of diisopropylether and dried at 40° C. in the circulating air dryer. Yield: 117.30 g of (88 percent of theory) Rf value: 0.37 (silica gel, methylene chloride/methanol=9:1) Mass spectrum (ESI+): m/z=553, 555 [M+H]+
Reference: [1] Patent: US2005/107358, 2005, A1, . Location in patent: Page/Page column 5
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