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

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Quality Control of [ 1202759-91-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1202759-91-8 ]

SDS Specification

Alternatived Products of [ 1202759-91-8 ]

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 ] Expand+

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 Å²

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.

Downstream synthetic route of [ 1202759-91-8 ]

[ 1202759-91-8 ] Synthesis Path-Downstream 1~23

1
[ 1202759-91-8 ]
[ 814-68-6 ]
[ 1202757-89-8 ]

Yield	Reaction Conditions	Operation in experiment
80%		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 muL, 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 (80%) of an off-white solid. LC/MS (RT = 2.79/(M + H)) 424.2.
0.28 g	In dichloromethane; 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	In dichloromethane; at -30℃; for 0.666667h;	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 (225 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 (2mL) 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

2
[ 1202759-90-7 ]
[ 1202759-91-8 ]

Yield	Reaction Conditions	Operation in experiment
0.94 g	With trifluoroacetic acid; In dichloromethane; at 0℃; for 0.75h;	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 4h;	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 20%-100% Heptane/EtOAc gradient using combiflash system gave 309 mg of a light pink solid. LC/MS (RT=2.78/(M+1)) 370.2.
		To a solution of 6 (550 mg, 1.17 mmol) in DCM (20 mL) was added TFA (2 niL). Stirred for 30 min at rt for 4h; removed solvent via rotary evaporation and partitioned oil with cold (0 0C) 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 20%- 100% Heptane/EtOAc gradient using combifiash system gave 309 mg of a light pink solid. LC/MS (RT = 2.78/(M+l)) 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

3
[ 1202759-91-8 ]
[ 6148-64-7 ]
[ 1616380-83-6 ]

Yield	Reaction Conditions	Operation in experiment
0.19 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 8h;Inert atmosphere;	Into a 25 ml, three neck flask under nitrogen atmosphere, a solution of <strong>[1202759-91-8]N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine</strong> (0.15 g) in DMF (5 mL) was charged potassium 3-ethoxy-3-oxopropanoate (0.089 g), EDCI.HCl (0.117 g), HOBt (0.093 g) and TEA (0.164 g). The reaction mixture was stirred for 8 hr at room temperature. Completion of the reaction was monitored by TLC using hexane:ethyl acetate (5:5) as the mobile phase. After completion, the reaction mixture was poured into water. The product was extracted with ethyl acetate and the organic layer was washed with brine. The solvent was removed under reduced pressure at 40 C. The obtained solid was purified by triturating with diethyl ether (2×10 mL) to give 0.19 g of ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate. 1H NMR: DMSO-d6 (400 MHz): 1.182-1.234 (q, 3H, J=6.8), 3.306 (s, 3H), 3.461 (s, 2H), 3.623-3.646 (t, 2H, J=4.8), 4.010-4.033 (t, 2H, J=4.4), 4.090-4.144 (t, 2H, J=7.2), 6.775-6.797 (d, 2H, J=8.8), 7.267-7.283 (d, 2H, J=6.4), 7.511-7.533 (d, 1H, J=8), 7.575-7.591 (d, 1H, J=6.4), 7.817 (s, 1H), 8.058-8.066 (d, 1H, J=3.2), 8.963 (s, 1H), 9.375 (s, 1H), 10.162 (s, 1H).
0.19 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 8h;Inert atmosphere;	Into a 25 ml, three neck flask under nitrogen atmosphere, a solution of N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxyl)phenyl)pyrimidine-2,4-diamine (0.15 g) in DMF (5 mL) was charged potassium 3-ethoxy-3-oxopropanoate (0.089 g), EDCI.HCl (0.117 g), HOBt (0.093 g) and TEA (0.164 g). The reaction mixture was stirred for 8 hr at room temperature. Completion of the reaction was monitored by TLC using hexane:ethyl acetate (5:5) as the mobile phase. After completion, the reaction mixture was poured into water. The product was extracted with ethyl acetate and the organic layer was washed with brine. The solvent was removed under reduced pressure at 40 C. The obtained solid was purified by triturating with diethyl ether (2*10 mL) to give 0.19 g of ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate. 1H NMR: DMSO-d6 (400 MHz): 1.182-1.234 (q, 3H, J=6.8), 3.306 (s, 3H), 3.461 (s, 2H), 3.623-3.646 (t, 2H, J=4.8), 4.010-4.033 (t, 2H, J=4.4), 4.090-4.144 (t, 2H, J=7.2), 6.775-6.797 (d, 2H, J=8.8), 7.267-7.283 (d, 2H, J=6.4), 7.511-7.533 (d, 1H, J=8), 7.575-7.591 (d, 1H, J=6.4), 7.817 (s, 1H), 8.058-8.066 (d, 1H, J=3.2), 8.963 (s, 1H), 9.375 (s, 1H), 10.162 (s, 1H).

Reference： [1]Patent: US2014/179720,2014,A1 .Location in patent: Paragraph 0414; 0415
[2]Patent: US2015/174128,2015,A1 .Location in patent: Paragraph 0661

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 ]