[ CAS No. 313340-08-8 ] {[proInfo.proName]}

Name: 313340-08-8|3,5-Dichloro-6-ethylpyrazine-2-carboxamide|97%
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SKU: A111867
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Quality Control of [ 313340-08-8 ]

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SDS Specification

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Product Details of [ 313340-08-8 ]

CAS No. :	313340-08-8	MDL No. :	MFCD27949199
Formula :	C₇H₇Cl₂N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KMIXLCQPYRNBEH-UHFFFAOYSA-N
M.W :	220.06	Pubchem ID :	84819960
Synonyms :

Calculated chemistry of [ 313340-08-8 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.29
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	49.92
TPSA :	68.87 Å²

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) :	-6.4 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.39
Log Po/w (XLOGP3) :	1.75
Log Po/w (WLOGP) :	1.44
Log Po/w (MLOGP) :	0.26
Log Po/w (SILICOS-IT) :	2.09
Consensus Log Po/w :	1.39

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.52
Solubility :	0.67 mg/ml ; 0.00305 mol/l
Class :	Soluble
Log S (Ali) :	-2.81
Solubility :	0.338 mg/ml ; 0.00154 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.27
Solubility :	0.117 mg/ml ; 0.000532 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.36

Safety of [ 313340-08-8 ]

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

Application In Synthesis of [ 313340-08-8 ]

* 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 [ 313340-08-8 ]
Downstream synthetic route of [ 313340-08-8 ]

[ 313340-08-8 ] Synthesis Path-Upstream 1~1

1
[ 313340-08-8 ]
[ 1254055-46-3 ]

Reference： [1] Patent: US2012/40968, 2012, A1, . Location in patent: Page/Page column 22

[ 313340-08-8 ] Synthesis Path-Downstream 1~88

1
[ 313340-08-8 ]
[ 1254055-46-3 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	To a mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (1.0 g) and DMF (15 mL), thionyl chloride (1 mL) was added at room temperature and stirred for 20 minutes. The reaction liquid was poured into ice-cold water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane) to give 3,5-dichloro-6-ethylpyrazine-2-carbonitrile (608 mg) as a slightly yellow oil.

Reference： [1]Patent: US2012/40968,2012,A1 .Location in patent: Page/Page column 22

2
[ 313340-08-8 ]
[ 23153-12-0 ]
[ 27489-62-9 ]
3-[3-chloro-4-(methylsulfonyl)phenyl]amino}-6-ethyl-5-[(trans-4-hydroxycyclohexyl)amino]pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (200 mg), 3-chloro-4-methylsulfonylaniline (374 mg) and NMP (1 mL) was stirred at 230 C. for 1 hour using a microwave reaction system. Thereafter, trans-4-aminocyclohexanol (524 mg) was added to the reaction liquid and stirred at 190 C. for 30 minutes using a microwave reaction system. After cooling, the reaction liquid was partitioned using ethyl acetate and water, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10:0 to 30:1) to give a crude product. This product was heated with ethanol and washed to give a light yellow solid. To the light yellow solid, ethyl acetate was added and heated, and insoluble materials were separated by filtration and the filtrate was concentrated. After the filtrate was concentrated, the residue was heated and washed with ethanol to give 3-[3-chloro-4-(methylsulfonyl)phenyl]amino}-6-ethyl-5-[(trans-4-hydroxycyclohexyl)amino]pyrazine-2-carboxamide (39 mg) as a light yellow solid.

Reference： [1]Patent: US2012/40968,2012,A1 .Location in patent: Page/Page column 28

3
[ 313340-08-8 ]
[ 1254048-03-7 ]

Reference： [1]Patent: US2012/40968,2012,A1

4
[ 313340-08-8 ]
[ 1254049-66-5 ]

Reference： [1]Patent: US2012/40968,2012,A1

5
[ 313340-08-8 ]
4-[(2S)-2,4-dimethylpiperazin-1-yl]aniline [ No CAS ]
5-chloro-3-({4-[(2S)-2,4-dimethylpiperazin-1-yl]phenyl}amino)-6-ethylpyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
560 mg	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 110℃;	Preparation Example 27 A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (420 mg), 4-[(2S)-2,4-dimethylpiperazin-1-yl]aniline (392 mg), diisopropylethylamine (665 muL), and dioxane (8.4 mL) was stirred at 110 C. overnight. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=95:5) to obtain 5-chloro-3-({4-[(2S)-2,4-dimethylpiperazin-1-yl]phenyl}amino)-6-ethylpyrazine-2-carboxamide (560 mg) as a brown solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0348

6
[ 313340-08-8 ]
[ 83220-73-9 ]
tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
795 mg		Preparation Example 29 To a mixture of tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1 g) and N,N-dimethylformamide (30 mL) was added 55% oily sodium hydride (233 mg) under ice-cooling. After stirring for 30 minutes under ice-cooling, <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (1.18 g) was added thereto, followed by further stirring for 1 hour under ice-cooling. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform) to obtain tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate (795 mg) as a pale yellow solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0350

7
[ 554-84-7 ]
[ 313340-08-8 ]
3-chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.68 g	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 80℃;	Preparation Example 1 A mixture of 3-nitrophenol (1 g), <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (1.74 g), diisopropylethylamine (2.63 mL), and dioxane (10 mL) was stirred at 80 C. overnight. To the reaction mixture was added water, and the precipitated solid was collected by filtration and then dried under reduced pressure to obtain 3-chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide (1.68 g) as a white solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0322

8
[ 313340-08-8 ]
6-ethyl-3-[1-(1-methylpiperidin-4-yl)-1H-imidazol-4-yl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

9
[ 313340-08-8 ]
tert-butyl 3-[(5-carbamoyl-3-ethyl-6-[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

10
[ 313340-08-8 ]
6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(pyrrolidin-3-yloxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

11
[ 313340-08-8 ]
6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

12
[ 313340-08-8 ]
6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

13
[ 313340-08-8 ]
6-ethyl-3-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

14
[ 313340-08-8 ]
6-ethyl-3-[2-methyl-4-(morpholin-4-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

15
[ 313340-08-8 ]
5-[3-(acryloylamino)phenoxy]-6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

16
[ 313340-08-8 ]
6-ethyl-3-({4-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)-5-(3-nitrophenoxy)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

17
[ 313340-08-8 ]
5-[3-(acryloylamino)phenoxy]-6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide monomethanesulfonate [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

18
[ 313340-08-8 ]
5-(3-aminophenoxy)-6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

19
[ 313340-08-8 ]
5-(3-aminophenoxy)-6-ethyl-3-({4-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

20
[ 313340-08-8 ]
5-(3-aminophenoxy)-6-ethyl-3-[2-methyl-4-(morpholin-4-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

21
5-methyl-6-(4-methylpiperazin-1-yl)pyridin-3-amine [ No CAS ]
[ 313340-08-8 ]
5-chloro-6-ethyl-3-[5-methyl-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
210 mg	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 150℃; for 0.5h;Microwave irradiation;	Preparation Example 210 A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (500 mg), 5-methyl-6-(4-methylpiperazin-1-yl)pyridin-3-amine (470 mg), diisopropylethylamine (800 muL), and dioxane (10 mL) was stirred in a microwave reaction device at 150 C. for 30 minutes. After leaving to be cooled, water was added thereto, and the precipitated solid was collected by filtration and then dried under reduced pressure to obtain 5-chloro-6-ethyl-3-[5-methyl-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}pyrazine-2-carboxamide (210 mg) as a yellow solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0374

22
[ 313340-08-8 ]
[ 93246-53-8 ]
5-chloro-6-ethyl-3-[3-fluoro-4-(morpholin-4-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
640 mg	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 180℃; for 1h;Microwave irradiation;	Preparation Example 256 A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (600 mg), 3-fluoro-4-(morpholin-4-yl)aniline (500 mg), diisopropylethylamine (880 muL), and N-methylpyrrolidone (2.5 mL) was reacted in a microwave reaction device at 180 C. for 1 hour. After leaving to be cooled, to the reactant was added water, and the precipitated solid was collected by filtration and then washed with ethanol to obtain 5-chloro-6-ethyl-3-[3-fluoro-4-(morpholin-4-yl)phenyl]amino}pyrazine-2-carboxamide (640 mg) as a yellow solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0382

23
[ 313340-08-8 ]
[ 141699-55-0 ]
tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
318 mg		Preparation Example 352 To a mixture of tert-butyl 3-hydroxyazetidine-1-carboxylate (420 mg) and N,N-dimethylformamide (12.5 mL) was added potassium tert-butoxide (260 mg) under ice-cooling, followed by stirring for 1 hour, and then <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (500 mg) was added thereto, followed by stirring for 1 hour. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; hexane:ethyl acetate), and then washed with a mixed solvent of hexane:diisopropyl ether to obtain tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]azetidine-1-carboxylate (318 mg) as a white solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0394

24
[ 581-00-0 ]
[ 313340-08-8 ]
5-chloro-6-ethyl-3-[2-methyl-4-(morpholin-4-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
660 mg	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 110℃;	Preparation Example 238 A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (630 mg), 2-methyl-4-(morpholin-4-yl)aniline (500 mg), diisopropylethylamine (900 muL), and N-methylpyrrolidone (5 mL) was stirred at 110 C. overnight. The reactant was left to be cooled, and then water was added thereto, followed by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=8:2?5:5) to obtain 5-chloro-6-ethyl-3-[2-methyl-4-(morpholin-4-yl)phenyl]amino}pyrazine-2-carboxamide (660 mg) as an orange solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0381

25
[ 313340-08-8 ]
5-(3-[(2E)-4-(dimethylamino)-2-butenoyl]amino}phenoxy)-6-ethyl-3-[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2014/323463,2014,A1

26
[ 537-91-7 ]
[ 313340-08-8 ]
3-chloro-6-ethyl-5-[(3-nitrophenyl)sulfanyl]pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.9 g		Preparation Example 39 To a mixture of 3-nitrophenyl disulfide (2 g) and N,N-dimethylformamide (60 mL) was added potassium carbonate (1.79 g), followed by stirring at room temperature for 2 minutes, and then <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (3.14 g) and formaldehyde sodium sulfoxylate (2.3 g), and water were added thereto, followed by stirring at room temperature for 2 hours. To the reaction mixture was added water, and the precipitated solid was collected by filtration, washed with water and diisopropyl ether, and then dried under reduced pressure to obtain 3-chloro-6-ethyl-5-[(3-nitrophenyl)sulfanyl]pyrazine-2-carboxamide (3.9 g) as a white solid.

Reference： [1]Patent: US2014/323463,2014,A1 .Location in patent: Paragraph 0360

27
[ 313340-08-8 ]
6-ethyl-3-((7-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838
[2]Patent: CN109384774,2019,A

28
[ 313340-08-8 ]
3-((3-cyclopropyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

29
[ 313340-08-8 ]
6-ethyl-3-((3-(3-ethylcyclopentyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

30
[ 313340-08-8 ]
6-ethyl-3-((3-(1-methylpiperidin-4-yl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

31
[ 313340-08-8 ]
C₃₁H₄₃N₇O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

32
[ 313340-08-8 ]
3-((3-(1-aminocyclopropane-1-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

33
[ 313340-08-8 ]
C₁₃H₁₈ClN₃O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838
[2]Patent: CN109384774,2019,A

34
[ 313340-08-8 ]
C₃₀H₄₀N₆O₇ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

35
[ 313340-08-8 ]
C₂₈H₃₈N₆O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

36
[ 313340-08-8 ]
C₂₅H₃₂N₆O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

37
[ 313340-08-8 ]
C₃₄H₄₉N₇O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

38
[ 313340-08-8 ]
C₂₇H₃₈N₆O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

39
[ 313340-08-8 ]
C₂₂H₃₀N₆O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

40
[ 313340-08-8 ]
methyl 6-ethyl-3-((2-methyl-6-oxo-1,2,3,4,12,12a-hexahydro-6H-benzo[f]pyrazino[2,1-c][1,4]oxazepin-8-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxylate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

41
[ 313340-08-8 ]
6-ethyl-3-((6-oxo-1,2,3,4,12,12a-hexahydro-6H-benzo[f]pyrazino[2,1-c][1,4]oxazepin-8-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

42
[ 313340-08-8 ]
6-ethyl-3-((2-methyl-6-oxo-1,2,3,4,12,12a-hexahydro-6H-benzo[f]pyrazino[2,1-c][1,4]oxazepin-8-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

43
[ 313340-08-8 ]
6-ethyl-3-((2-isopropyl-6-oxo-1,2,3,4,12,12a-hexahydro-6H-benzo[f]pyrazino[2,1-c][1,4]oxazepin-8-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

44
[ 67-56-1 ]
[ 313340-08-8 ]
C₈H₈Cl₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; at 70℃; for 7h;	Compound6(10 mmol) was dissolved in 2N HCl/MeOH (15 ml) solution. The mixture was stirred at 70oC for 7 h. The solution was concentrated under vacuum, diluted with saturated NaHCO3(60 ml) and then extracted with CH2Cl2(3×80 ml). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product7aslight yellowsolid in 81% yield.
1.9 g	With hydrogenchloride; In water; for 12h;Reflux;	Compound 1-4 (2.2 g, 10 mmol) was weighed into a single-necked flask, and 15 ml of a 2N hydrochloric acid methanol solution was added, and the reaction was refluxed for 12 h. After the reaction is completed, the reaction solution is concentrated under reduced pressure and purified by column chromatography. A colorless liquid product 3-1, 1.9 g was obtained.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838
[2]Patent: CN109384774,2019,A .Location in patent: Paragraph 0106-0109

45
[ 1037627-94-3 ]
[ 313340-08-8 ]
C₂₂H₂₈ClN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	General procedure: To a solution of compound6(0.4 mmol) and anappropriateaniline derivatives(0.2 mmol) in 1,4-dioxane, was added DIPEA (0.4 mmol). The mixture was stirred at 100oC for 12 h. The solution was diluted withwater, andfiltered. The residue was washed with water twice and dried to give the crude product as yellow solid in 42-74% yield.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

46
[ 1037627-94-3 ]
[ 313340-08-8 ]
6-ethyl-3-((7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

47
[ 313340-08-8 ]
C₂₂H₃₃N₃O₂ [ No CAS ]
C₂₉H₃₉ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	General procedure: To a solution of compound6(0.4 mmol) and anappropriateaniline derivatives(0.2 mmol) in 1,4-dioxane, was added DIPEA (0.4 mmol). The mixture was stirred at 100oC for 12 h. The solution was diluted withwater, andfiltered. The residue was washed with water twice and dried to give the crude product as yellow solid in 42-74% yield.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

48
[ 854679-17-7 ]
[ 313340-08-8 ]
3-((3-cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

49
[ 854679-17-7 ]
[ 313340-08-8 ]
C₂₂H₂₈ClN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	General procedure: To a solution of compound6(0.4 mmol) and anappropriateaniline derivatives(0.2 mmol) in 1,4-dioxane, was added DIPEA (0.4 mmol). The mixture was stirred at 100oC for 12 h. The solution was diluted withwater, andfiltered. The residue was washed with water twice and dried to give the crude product as yellow solid in 42-74% yield.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

50
[ 118454-24-3 ]
[ 313340-08-8 ]
C₂₂H₂₈ClN₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	General procedure: To a solution of compound6(0.4 mmol) and anappropriateaniline derivatives(0.2 mmol) in 1,4-dioxane, was added DIPEA (0.4 mmol). The mixture was stirred at 100oC for 12 h. The solution was diluted withwater, andfiltered. The residue was washed with water twice and dried to give the crude product as yellow solid in 42-74% yield.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 836 - 838

51
[ 313340-08-8 ]
C₁₄H₁₈F₂N₂ [ No CAS ]
C₂₁H₂₄ClF₂N₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
140 mg	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	Compound 22-1 (126 mg, 0.50 mmol), 22-2 (132 mg, 0.60 mmol) was weighed into a reaction flask, stirred with 1,4-dioxane, followed by N,N-diethylisopropylamine ( DIPEA) (195 mg, 1.50 mmol), warmed to 100C and stirred for 12 h. After the reaction was stopped, the reaction solution was cooled to room temperature, a small amount of water was added, and the solid was precipitated, suction filtered, and the filter cake was rinsed twice with ethanol and dried to give a solid product 22-3, 140 mg.

Reference： [1]Patent: CN109384774,2019,A .Location in patent: Paragraph 0212-0216

52
[ 313340-08-8 ]
C₁₄H₁₈F₂N₂ [ No CAS ]
C₂₆H₃₄F₂N₆O₂ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

53
[ 313340-08-8 ]
C₁₈H₂₇N₃O₂ [ No CAS ]
C₂₅H₃₃ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
125 mg	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 12h;	Weighing compounds 1-3 (165 mg, 0.52 mmol), 1-4 (137 mg, 0.62 mmol) in a reaction flask, After stirring with 1,4-dioxane, N,N-diethylisopropylamine (DIPEA) (201 mg, 1.56 mmol) was added, warmed to 100 C and stirred for 12 h. After stopping the reaction, the reaction solution was cooled to room temperature, a small amount of water was added, the solid was precipitated, suction filtration, and the filter cake was rinsed with ethanol for 2 times and dried. The yellow solid product 1-5, 125 mg was obtained.

Reference： [1]Patent: CN109384774,2019,A .Location in patent: Paragraph 0088; 0089; 0095; 0096

54
[ 313340-08-8 ]
C₂₈H₃₉N₅O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

55
[ 313340-08-8 ]
3-((3-cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

56
[ 313340-08-8 ]
C₂₈H₃₉N₅O₅ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

57
[ 313340-08-8 ]
C₂₃H₃₁N₅O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

58
[ 313340-08-8 ]
C₂₇H₃₅N₅O₄ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

59
[ 313340-08-8 ]
C₂₆H₃₄N₆O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

60
[ 313340-08-8 ]
C₂₇H₃₉N₅O₄ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

61
[ 313340-08-8 ]
C₂₆H₃₈N₆O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

62
[ 313340-08-8 ]
C₂₇H₃₆N₆O₃S [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

63
[ 313340-08-8 ]
C₂₀H₃₀N₆O₃S [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

64
[ 313340-08-8 ]
C₂₅H₃₈N₆O₃S [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

65
[ 313340-08-8 ]
C₂₄H₃₇N₇O₂S [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

66
[ 313340-08-8 ]
C₂₈H₃₉N₅O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

67
[ 313340-08-8 ]
6-ethyl-3-((7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

68
[ 313340-08-8 ]
C₃₀H₄₂N₆O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

69
[ 313340-08-8 ]
C₂₉H₃₉N₅O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

70
[ 313340-08-8 ]
C₂₈H₃₈N₆O₂ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

71
[ 313340-08-8 ]
C₂₉H₄₁N₅O₃ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

72
[ 313340-08-8 ]
C₂₈H₄₀N₆O₂ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

73
[ 313340-08-8 ]
C₃₅H₅₀N₆O₅ [ No CAS ]

Reference： [1]Patent: CN109384774,2019,A

74
[ 313340-08-8 ]
6-ethyl-5-[(1r,4r)-4-hydroxycyclohexyl]amino}-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

75
[ 313340-08-8 ]
rac-6-ethyl-5-[(1R,2R)-2-hydroxycyclohexyl]amino}-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

76
[ 313340-08-8 ]
6-ethyl-5-[(1r,4r)-4-methoxycyclohexyl]amino}-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

77
[ 313340-08-8 ]
6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}-5-[(propan-2-yl)amino]pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

78
[ 313340-08-8 ]
6-ethyl-5-(ethylamino)-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

79
[ 313340-08-8 ]
6-ethyl-5-[ethyl(methyl)amino]-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

80
2-methoxy-4-[4-(4-methylpiperazin-1-yl)-piperidin-1-yl]-phenylamine [ No CAS ]
[ 313340-08-8 ]
5-chloro-6-ethyl-3-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 110℃; for 25h;	A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (3a,503 mg, 2.29 mmol), 2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (699 mg, 2.30 mmol), DIPEA (0.78 mL, 4.56 mmol) and 1,4-dioxane (10 mL) was stirred at 110 C for 25 h. After the mixture was cooled to room temperature, saturated aqueous NaHCO3 solution was added, and the resulting slurry was extracted with CHCl3. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (CHCl3/MeOH/28% aqueous NH3=100:0:0 to90:9:1). The resulting product was washed with EtOAc, filtered and dried in vacuo at 50 C to give 9 (701 mg, 63%) as an orange solid. 1HNMR (DMSO-d6): delta 1.25 (3H, t, J=7.4 Hz), 1.43-1.59 (2H, m),1.77-1.91 (2H, m), 2.14 (3H, s), 2.20-2.72 (11H, m), 2.79 (2H, q,J=7.5 Hz), 3.64-3.75 (2H, m), 3.85 (3H, s), 6.51 (1H, dd, J=2.4, 8.8 Hz), 6.65 (1H, d, J=2.4 Hz), 7.83 (1H, d, J=1.6 Hz), 8.04 (1H, d,J=8.8 Hz), 8.12 (1H, d, J=1.6 Hz), 11.11 (1H, s); MS (ESI) m/z[M+H]+ 488.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

81
2-methoxy-4-[4-(4-methylpiperazin-1-yl)-piperidin-1-yl]-phenylamine [ No CAS ]
[ 313340-08-8 ]
6-ethyl-5-[(1r,4r)-4-hydroxycyclohexyl]amino}-3-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

82
[ 313340-08-8 ]
[ 1254058-34-8 ]
5-chloro-6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 110℃; for 19h;	A mixture of <strong>[313340-08-8]3,5-dichloro-6-ethylpyrazine-2-carboxamide</strong> (3a, 90 mg, 0.409 mmol), 3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (124 mg, 0.407 mmol), DIPEA (71 muL, 0.408 mmol) and 1,4-dioxane (3.6 mL) was stirred at 110 C for 19 h. After the mixture was cooled, water was added, and the resulting slurry was extracted with EtOAc. The organic layer was dried over Na2SO4, andconcentrated in vacuo. The residue was purified by silica gel columnchromatography (CHCl3/MeOH) to give 11 (110 mg, 55%) as an ochersolid. 1H NMR (CDCl3): delta 1.28 (3H, t, J=7.4 Hz), 1.72-1.99 (4H, m),2.29 (3H, s), 2.34-2.78 (11H, m), 2.85 (2H, q, J=7.5 Hz), 3.44-3.59(2H, m), 3.89 (3H, s), 5.38-5.57 (1H, m), 6.90 (1H, d, J=8.4 Hz),7.08-7.19 (1H, m), 7.32-7.41 (1H, m), 7.62-7.80 (1H, m), 10.66 (1H,s); MS (ESI) m/z [M+H]+ 488, 490.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1683 - 1692

83
[ 313340-08-8 ]
C₁₂H₁₇N₃O [ No CAS ]
C₁₉H₂₃ClN₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130℃; for 16h;Sealed tube;	Compound D1Sa (100 mg, 0.455 mmol), A1Sf (109 mg, 0.499 mmol) and DIPEA (117 mg, 0.909 mmol) were dissolved in 1,4-dioxane (3 mL) in a sealed tube, the reaction mixture was heated to 130 C. and stirred for 16 hours. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=30:1) to afford a pale yellow solid compound D1Sb (160 mg, yield 88%). 1H NMR (DMSO-d6, 400 MHz) delta 10.93 (s, 1H), 8.21 (s, 1H), 7.98 (s, 1H), 7.14 (d, J=2.0 Hz, 1H), 6.93-6.82 (m, 2H), 4.23 (dd, J=10.8 Hz, 2.8 Hz, 1H), 3.90 (dd, J=10.4 Hz, 9.2 Hz, 1H), 3.66 (d, J=11.6 Hz, 1H), 3.05-2.95 (m, 1H), 2.89-2.74 (m, 4H), 2.65-2.55 (m, 1H), 2.22 (s, 3H), 2.13-2.03 (m, 1H), 1.68 (dd, J=10.8 Hz, 10.8 Hz, 1H), 1.24 (t, J=7.4 Hz, 3H). MS m/z 403.2 [M+H]+, 405.2 [M+H]+.

Reference： [1]Patent: US2019/308993,2019,A1 .Location in patent: Paragraph 0275-0276

84
[ 313340-08-8 ]
C₁₂H₁₇N₃O [ No CAS ]
C₁₉H₂₃ClN₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130℃; for 16h;Sealed tube;	Compound D1Ra (100 mg, 0.455 mmol), A1Rf (109 mg, 0.499 mmol) and DIPEA (117 mg, 0.909 mmol) were dissolved in 1,4-dioxane (3 mL) in a sealed tube, the reaction mixture was heated to 130 C. and stirred for 16 hours. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=30:1) to afford D1Rb (150 mg, yield 82%) as light yellow solid. 1H NMR (DMSO-d6, 400 MHz) delta 10.93 (s, 1H), 8.21 (s, 1H), 7.98 (s, 1H), 7.14 (d, J=2.0 Hz, 1H), 6.93-6.82 (m, 2H), 4.23 (dd, J=10.8 Hz, 2.8 Hz, 1H), 3.90 (dd, J=10.4 Hz, 9.2 Hz, 1H), 3.66 (d, J=11.2 Hz, 1H), 3.05-2.95 (m, 1H), 2.89-2.74 (m, 4H), 2.65-2.55 (m, 1H), 2.22 (s, 3H), 2.13-2.03 (m, 1H), 1.68 (dd, J=10.4 Hz, 10.0 Hz, 1H), 1.24 (t, J=7.4 Hz, 3H). MS m/z 403.2 [M+H]+, 405.2 [M+H]+.

Reference： [1]Patent: US2019/308993,2019,A1 .Location in patent: Paragraph 0278-0279

85
[ 313340-08-8 ]
C₁₂H₁₇N₃O [ No CAS ]
C₂₄H₃₃N₇O₃ [ No CAS ]

Reference： [1]Patent: US2019/308993,2019,A1

86
[ 313340-08-8 ]
C₁₄H₁₉N₃O [ No CAS ]
C₂₁H₂₅ClN₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130℃; for 16h;Sealed tube;	Compound D1Sa (26 mg, 0.118 mmol), A6Rb (29 mg, 0.118 mmol) and DIPEA (46 mg, 0.357 mmol) were dissolved in 1,4-dioxane (2 mL), the reaction solution was heated to 130 C. and stirred for 16 hours in seal. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=100:1) to afford compound D4Rb (47 mg, yield 92%) as a pale yellow solid. MS m/z 429.2 [M+H]+, 430.2 [M+H]+.

Reference： [1]Patent: US2019/308993,2019,A1 .Location in patent: Paragraph 0291-0292

87
[ 313340-08-8 ]
C₁₃H₁₆F₃N₃O [ No CAS ]
C₂₀H₂₂ClF₃N₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130℃; for 16h;Sealed tube;	Compound D1Sa (23 mg, 0.105 mmol), A7Rb (30 mg, 0.104 mmol) and DIPEA (40 mg, 0.310 mmol) were dissolved in 1,4-dioxane (2 mL), the reaction solution was heated to 130 C. and stirred for 16 hours in seal. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=100:1) to afford pale yellow solid compound D3Rb (47 mg, yield 95%). MS m/z 471.2 [M+H]+, 473.2 [M+H]+.

Reference： [1]Patent: US2019/308993,2019,A1 .Location in patent: Paragraph 0288-0289

88
[ 313340-08-8 ]
C₁₁H₁₄N₂O₂ [ No CAS ]
C₁₈H₂₀ClN₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130℃; for 16h;Sealed tube;	Compound D1Sa (25 mg, 0.114 mmol), A8Sd (26 mg, 0.126 mmol) and DIPEA (29 mg, 0.228 mmol) were dissolved in 1,4-dioxane (2 mL), the reaction solution was heated to 130 C. and stirred for 16 hours in seal. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=50:1) to afford compound D2Sb (43 mg, yield 97%) as a pale yellow solid. MS m/z 390.2 [M+H]+, 392.2 [M+H]+.

Reference： [1]Patent: US2019/308993,2019,A1 .Location in patent: Paragraph 0282-0283

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P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 313340-08-8 ] {[proInfo.proName]}

Quality Control of [ 313340-08-8 ]

Related Doc. of [ 313340-08-8 ]

Product Details of [ 313340-08-8 ]

Calculated chemistry of [ 313340-08-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 313340-08-8 ]

Application In Synthesis of [ 313340-08-8 ]

[ 313340-08-8 ] Synthesis Path-Upstream 1~1

[ 313340-08-8 ] Synthesis Path-Downstream 1~88

Pharmaceutical Intermediates of [ 313340-08-8 ]

Gilteritinib Related Intermediates

Related Functional Groups of [ 313340-08-8 ]

Chlorides

Amides

Amines

Related Parent Nucleus of [ 313340-08-8 ]

Pyrazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Pharmaceutical Intermediates of
[ 313340-08-8 ]

Related Functional Groups of
[ 313340-08-8 ]

Related Parent Nucleus of
[ 313340-08-8 ]