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[ CAS No. 1202759-91-8 ] {[proInfo.proName]}

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Chemical Structure| 1202759-91-8
Chemical Structure| 1202759-91-8
Structure of 1202759-91-8 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1202759-91-8 ]

CAS No. :1202759-91-8 MDL No. :MFCD29921609
Formula : C19H20FN5O2 Boiling Point : -
Linear Structure Formula :- InChI Key :IMAYPFGCCLDSEQ-UHFFFAOYSA-N
M.W : 369.39 Pubchem ID :59174534
Synonyms :

Calculated chemistry of [ 1202759-91-8 ]

Physicochemical Properties

Num. heavy atoms : 27
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.16
Num. rotatable bonds : 8
Num. H-bond acceptors : 5.0
Num. H-bond donors : 3.0
Molar Refractivity : 102.67
TPSA : 94.32 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.28 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.75
Log Po/w (XLOGP3) : 3.2
Log Po/w (WLOGP) : 4.14
Log Po/w (MLOGP) : 2.04
Log Po/w (SILICOS-IT) : 2.41
Consensus Log Po/w : 2.91

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.11
Solubility : 0.0286 mg/ml ; 0.0000773 mol/l
Class : Moderately soluble
Log S (Ali) : -4.85
Solubility : 0.00519 mg/ml ; 0.000014 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.33
Solubility : 0.0000171 mg/ml ; 0.0000000462 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.2

Safety of [ 1202759-91-8 ]

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 [ 1202759-91-8 ]

* 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 [ 1202759-91-8 ]
  • Downstream synthetic route of [ 1202759-91-8 ]

[ 1202759-91-8 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 1202759-90-7 ]
  • [ 1202759-91-8 ]
YieldReaction ConditionsOperation in experiment
0.94 g With trifluoroacetic acid In dichloromethane at 0℃; for 0.75 h; In a 25 mL, 3-neck RBF equipped with a magnetic stirrer, and thermo pocket was sequentially charged with tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate (1.2 g) in DCM (10 mL). Trifluoroacetic acid (6.0 mL) was added drop wise into the reaction mixture at 0° C. The reaction mixture was stirred at 0° C. for 45 minutes. The reaction was monitored by TLC using ethyl acetate:hexane (7:3) as mobile phase. After completion, the reaction mixture was quenched in water and neutralized with sodium bicarbonate. The mixture was extracted into DCM. The organic layer was washed with brine, dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. to give 0.94 g of N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine which was used without further purification.
309 mg With trifluoroacetic acid In dichloromethane at 20℃; for 4 h; To a solution of tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate (550 mg, 1.17 mmol) in DCM (20 mL) was added TFA (2 mL).
Stirred for 30 min at rt for 4 h; removed solvent via rotary evaporation and partitioned oil with cold (0° C.) saturated sodium bicarbonate (10 mL) and EtOAc (10 mL), agitated and separated layers.
Organic phase was dried over sodium sulfate and the solvent was removed via rotary evaporation to give a dark oil.
Flash chromatography using 20percent-100percent Heptane/EtOAc gradient using combiflash system gave 309 mg of a light pink solid. LC/MS (RT=2.78/(M+1)) 370.2.
Reference: [1] Patent: US2014/179720, 2014, A1, . Location in patent: Paragraph 0380; 0382
[2] Patent: US2015/174128, 2015, A1, . Location in patent: Paragraph 0716
[3] Patent: WO2009/158571, 2009, A1, . Location in patent: Page/Page column 190; 192
  • 2
  • [ 1202759-89-4 ]
  • [ 33311-29-4 ]
  • [ 1202759-91-8 ]
  • [ 1202759-90-7 ]
YieldReaction ConditionsOperation in experiment
0.55 g With acetic acid In tert-Amyl alcohol for 4 h; Reflux tert-Butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (800 mg, 2.37 mmoL) and 4-(2-methoxyethoxy)aniline (576 mg, 2.84 mmoL) were suspended in tert-amyl alcohol (14 mL) and acetic acid (5 drops).
Heated to reflux for 4 h.
After cooling, solvent was removed via rotary evaporation.
The dark oil was partitioned between water/brine and THF (10 mL each), agitated, and separated layers and dried organic phase over sodium sulfate.
The solvent was removed via rotary evaporation to afford a purple solid, 0.55 g. LC/MS (RT=2.997/(M+1)) 470.2.
Additional 150 mg of product minus the (BOC) protecting group crystallized from the aqueous layer
Reference: [1] Patent: US2015/174128, 2015, A1, . Location in patent: Paragraph 0715
  • 3
  • [ 1202759-89-4 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
[2] Patent: US2015/174128, 2015, A1,
[3] Patent: US2015/174128, 2015, A1,
[4] Patent: WO2009/158571, 2009, A1,
  • 4
  • [ 68621-88-5 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2015/174128, 2015, A1,
[2] Patent: US2015/174128, 2015, A1,
[3] Patent: US2015/174128, 2015, A1,
[4] Patent: WO2009/158571, 2009, A1,
  • 5
  • [ 33311-29-4 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
[2] Patent: US2015/174128, 2015, A1,
  • 6
  • [ 99-09-2 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
  • 7
  • [ 18437-64-4 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
  • 8
  • [ 528882-15-7 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
  • 9
  • [ 528882-16-8 ]
  • [ 1202759-91-8 ]
Reference: [1] Patent: US2014/179720, 2014, A1,
  • 10
  • [ 1202759-91-8 ]
  • [ 814-68-6 ]
  • [ 1202757-89-8 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: at -10℃;
Stage #2: With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 0.166667 h;
A solution of 6 (309 mg, 0.84 mmol) in THF (10 mL) was cooled in a water/ice- MeOH bath (-10 0C). To this was added 7 (71 μL, 0.88 mmoL), stirred for 10 min, then added Hunig's base (145uL, 0.88mmoL), and stirred for 10 min. Partitioned between water/brine (10 <n="194"/>niL), agitated and separated the layers. Dried organic phase over sodium sulfate. The solvent was removed via rotary evaporation and triturated with diethyl ether to afford after filtration 285 mg (80percent) of an off-white solid. LC/MS (RT = 2.79/(M + H)) 424.2.
0.28 g at -30℃; In a 50 mL 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube and thermo pocket was charged N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine (0.40 g) in dry DCM (10 mL) and was cooled to −30° C. An acryloyl chloride solution in DCM (0.107 g in 5.0 mL DCM) was added slowly and the reaction mixture was stirred at −30° C. for approx. 40 minutes. The reaction was monitored on TLC using chloroform:methanol (9.6:0.4) as mobile phase. The reaction mixture was poured into water (100 mL) and basified using sodium bicarbonate. The reaction mixture was extracted with MDC (2×25 mL) and the combined organic layer was washed with 50 mL brine solution. The organic layer was dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. Obtained solid was purified by triturating with diethyl ether (2×10 mL) and dried under vacuum to give 0.28 g N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide.
0.28 g at -30℃; for 0.666667 h; In a 50 mL 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube and thermo pocket was charged N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxyl)phenyl)pyrimidine-2,4-diamine (0.40 g) in dry DCM (10 mL) and was cooled to -30° C.
An acryloyl chloride solution in DCM (0.107 g in 5.0 mL DCM) was added slowly and the reaction mixture was stirred at -30° C. for approx. 40 minutes.
The reaction was monitored on TLC using chloroform:methanol (9.6:0.4) as mobile phase.
The reaction mixture was poured into water (100 mL) and basified using sodium bicarbonate.
The reaction mixture was extracted with MDC (2*25 mL) and the combined organic layer was washed with 50 mL brine solution.
The organic layer was dried over sodium sulfate and concentrated completely under reduce pressure at 40° C.
Obtained solid was purified by triturating with diethyl ether (2*mL) and dried under vacuum to give 0.28 g N-(3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide.
Reference: [1] Patent: WO2009/158571, 2009, A1, . Location in patent: Page/Page column 190; 192
[2] Patent: US2014/179720, 2014, A1, . Location in patent: Paragraph 0380; 0383
[3] Patent: US2015/174128, 2015, A1, . Location in patent: Paragraph 0629
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