[ CAS No. 1178884-53-1 ]

Name: 1178884-53-1|4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one|95%
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SKU: A296532
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Quality Control of [ 1178884-53-1 ]

COA NMR CNMR HPLC LC-MS

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Alternatived Products of [ 1178884-53-1 ]

Product Details of [ 1178884-53-1 ]

CAS No. :	1178884-53-1	MDL No. :	MFCD21364605
Formula :	C₅H₄BrClN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	223.46 g/mol	Pubchem ID :	59216474
Synonyms :

Calculated chemistry of of [ 1178884-53-1 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	42.47
TPSA :	34.89 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) :	-6.65 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.82
Log Po/w (XLOGP3) :	1.42
Log Po/w (WLOGP) :	1.2
Log Po/w (MLOGP) :	1.58
Log Po/w (SILICOS-IT) :	1.81
Consensus Log Po/w :	1.57

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.56
Solubility :	0.61 mg/ml ; 0.00273 mol/l
Class :	Soluble
Log S (Ali) :	-1.76
Solubility :	3.91 mg/ml ; 0.0175 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.6
Solubility :	0.565 mg/ml ; 0.00253 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.9

Safety of [ 1178884-53-1 ]

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 [ 1178884-53-1 ]

* 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 [ 1178884-53-1 ]
Downstream synthetic route of [ 1178884-53-1 ]

[ 1178884-53-1 ] Synthesis Path-Upstream 1~1

1
[ 74-88-4 ]
[ 1178884-53-1 ]

Yield	Reaction Conditions	Operation in experiment
79%	With caesium carbonate In N,N-dimethyl-formamide for 3.33333 h;	Step 3: To a solution of 4-bromo-6-chloropyridazin-3(2H)-one (1.0 equiv.) and Cs₂CO₃(1.2 equiv.) in DMF (0.07 M) was added iodomethane (1.5 equiv.) drop-wise over 20 min. The resulting mixture was stirred for 3 h. The reaction mixture was then diluted with ammonium chloride, then extracted with ethyl acetate, dried over MgSO₄and concentrated in vacuo to yield as a brown solid. The oil was further purified via silica gel column chromatography eluting with 100percent heptanes to 80percent ethyl acetate:heptanes to yield 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one as an off-white solid in 79percent yield. LCMS (m/z) (M+H)=222.9/224.9, Rt=0.54 min. ¹H NMR (400 MHz, ) δ ppm 3.77-3.86 (m, 3H) 7.56-7.69 (m, 1H).
68%	Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.166667 h; Inert atmosphere Stage #2: at 20℃; for 1.5 h;	A 250-mL single-necked round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 4-bromo-6-chloropyridazin-3(2H)-one (1.00 g, 4.77 mmol) and DMF (15 mL). Sodium hydride (60percent by weight in oil, 229 mg, 5.73 mmol) was added in one portion. After stirring at room temperature for 10 minutes, iodomethane (1.02 g, 7.16 mmol) was added and the reaction stirred at room temperature for 1.5 h. The reaction was then quenched with aqueous saturated sodium bicarbonate (10 mL) and the resulting solution poured into water (150 mL). The mixture was then extracted with ethyl acetate (250 mL). The organic layer was dried over sodium sulfate. The drying agent was then removed by filtration, and the filtrate was concentrated under reduced pressure to residue. Purification by column chromatography afforded 103e in a 68percent yield (722 mg) as a white solid: mp 107- 108 °C; ^]H NMR (300 MHz, CDC1₃) δ 7.62 (s, 1H), 3.81 (s, 3H).
68%	Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.166667 h; Stage #2: at 20℃; for 1.5 h;	A 250-mL single-necked round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 4-bromo-6-chloropyridazin-3(2H)-one (1.00 g, 4.77 mmol) and DMF (15 mL). Sodium hydride (60percent by weight in oil, 229 mg, 5.73 mmol) was added in one portion. After stirring at room temperature for 10 minutes, iodomethane (1.02 g, 7.16 mmol) was added and the reaction stirred at room temperature for 1.5 h. The reaction was then quenched with aqueous saturated sodium bicarbonate (10 mL) and the resulting solution poured into water (150 mL). The mixture was then extracted with ethyl acetate (250 mL). The organic layer was dried over sodium sulfate. The drying agent was then removed by filtration, and the filtrate was concentrated under reduced pressure to residue. Purification by column chromatography afforded 103a in a 68percent yield (722 mg) as a white solid: mp 107- 108 °C; ^]H NMR (300 MHz, CDC1₃) δ 7.62 (s, 1H), 3.81 (s, 3H).

Reference： [1] Patent: US2014/275003, 2014, A1, . Location in patent: Paragraph 0215; 0218
[2] Patent: WO2011/140488, 2011, A1, . Location in patent: Page/Page column 128
[3] Patent: WO2012/30990, 2012, A1, . Location in patent: Page/Page column 65
[4] Patent: WO2009/98144, 2009, A1, . Location in patent: Page/Page column 68-69
[5] Patent: US2010/222325, 2010, A1, . Location in patent: Page/Page column 93

[ 1178884-53-1 ] Synthesis Path-Downstream 1~16

1
[ 1178884-53-1 ]
[ 89088-56-2 ]
[ 1346672-99-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In tetrahydrofuran; 1,4-dioxane at 100℃; for 6h; Inert atmosphere;	119.119b In a 3-neck RBF was placed 119a (500mg, 3.2mmol), 4-bromo-6-chloro-2- methylpyridazin-3(2H)-one (725mg, 3.2mmol), cesium carbonate (2.3g, 7.0mmol), and Xantphos (160mg, 8.5mol ). The flask was evacuated and filled with nitrogen 3X. Dioxane (20ml) was added and the mixture degassed for 25min with bubbling nitrogen.Tris(dibenzylideneacetone)dipalladium(0) (150mg, 5mol ) was then added and the reaction heated to 100°C for 6hrs. The reaction was cooled and diluted with EtOAc (125mL) and saturated aqueous NaHC03 (50mL), the layers were separated and extracted EtOAc(2xl00mL). The organics were washed with brine 3X, dried over Na2S04, filtered, and concentrated under reduced pressure. The residue was purified by chromatography: ISCO 40g silica, EtOAc/hexanes, to give 119b.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC; ROCHE HOLDING AG - WO2011/140488, 2011, A1 Location in patent: Page/Page column 168

2
[ 1178884-53-1 ]
[ 1227210-33-4 ]
[ 1346672-51-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With lithium hexamethyldisilazane In tetrahydrofuran; 1,4-dioxane at 0℃; for 2h; Inert atmosphere; Reflux;	103.103f A 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 4-bromo-6-chloro-2-methylpyridazin- 3(2H)-one 103e (1.90 g, 8.53 mmol), lOle (1.18 g, 7.75 mmol) and 1,4-dioxane (40 mL). The flask was purged with nitrogen and cooled to 0 °C. A 1 M solution of lithium hexamethyldisilazide in THF (39 mL, 39.0 mmol) was added. After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (381 mg, 0.659 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (355 mg, 0.388 mmol) were added, and the reaction mixture was heated at reflux for 2 h. After this time, the mixture was cooled to room temperature and diluted with water (10 mL). The pH of the solution was adjusted to 7.6 with 2 N hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica to afford a 76% yield (1.74 g) of 103f as an off-white solid: mp 184-186 °C; ]H NMR (300 MHz, DMSO-i¾) δ 9.62 (s, 1H), 7.72 (s, 1H), 6.00 (s, 1H), 4.04 (t, 2H, / = 5.1 Hz), 3.65 (s, 3H), 3.53 (s, 2H), 2.82 (t, 2H, / = 5.1 Hz), 2.37 (s, 3H); MS (ESI+) m/z 295.1 (M+H).
76%	Stage #1: 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one; 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl-amine With lithium hexamethyldisilazane In tetrahydrofuran; 1,4-dioxane at 0℃; for 0.5h; Inert atmosphere; Stage #2: With 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran; 1,4-dioxane for 2h; Reflux; Stage #3: With hydrogenchloride In tetrahydrofuran; 1,4-dioxane	106f A 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 103a (1.90 g, 8.53 mmol), 1011 (1.18 g, 7.75 mmol) and 1,4-dioxane (40 mL). The flask was purged with nitrogen and cooled to 0 °C. A I M solution of lithium hexamethyldisilazide in THF (39 mL, 39.0 mmol) was added. After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (381 mg, 0.659 mmol) and tris(dibenzylideneacetone)dipalladium(0) (355 mg, 0.388 mmol) were added, and the reaction mixture was heated at reflux for 2 h. After this time, the mixture was cooled to room temperature and diluted with water (10 mL). The pH of the solution was adjusted to 7.6 with 2 N hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica to afford a 76% yield (1.74 g) of 106f as an off-white solid: mp 184-186 °C; ]H NMR (300 MHz, DMSO-d6) δ 9.62 (s, 1H), 7.72 (s, 1H), 6.00 (s, 1H), 4.04 (t, 2H, / = 5.1 Hz), 3.65 (s, 3H), 3.53 (s, 2H), 2.82 (t, 2H, / = 5.1 Hz), 2.37 (s, 3H); MS (ESI+) m/z 295.1 (M+H).
76%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; lithium hexamethyldisilazane In tetrahydrofuran; 1,4-dioxane for 2h; Inert atmosphere; Reflux;	133a Example 133a 6-Chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one 133a Example 133a 6-Chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one 133a A 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1.90 g, 8.53 mmol): 113e (1.18 g, 7.75 mmol) and 1,4-dioxane (40 mL). The flask was purged with nitrogen and cooled to 0 °C. A 1 M solution of lithium hexamethyldisilazide in THF (39 mL, 39.0 mmol) was added. After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (381 mg, 0.659 mmol) and tris(dibenzylidene-acetone)dipalladium(0) (355 mg, 0.388 mmol) were added, and the reaction mixture was heated at reflux for 2 h. After this time, the mixture was cooled to room temperature and diluted with water (10 mL). The pH of the solution was adjusted to 7.6 with 2 N hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 * 40 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica to afford a 76% yield (1.74 g) of 133a as an off-white solid: mp 184-186 °C; 1H NMR (300 MHz, DMSO-d6) δ 9.62 (s, 1H), 7.72 (s, 1H), 6.00 (s, 1H), 4.04 (t, 2H, J= 5.1 Hz), 3.65 (s, 3H), 3.53 (s, 2H), 2.82 (t, 2H, J= 5.1 Hz), 2.37 (s, 3H); MS (ESI+) m/z 295.1 (M+H).

69%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 18h; Sealed tube;	I-18 Preparation of 1-18 A solution of 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine (342 mg, 2.25 mmo 1), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (527 mg, 2.36 mmol), cesium carbonate (2.2 g, 6.74 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (195 mg, 0.34 mmol) in dioxane (15 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (154 mg, 0.17 mmol) was added and the resulting solution was heated in a sealed tube at 110 °C for 18 h. The mixture was cooled to room temperature and filtered through celite. The cake was washed with dichloromethane. The combined filtrate and washes were diluted with 3M HCl and separated. The DCM layer was back extracted with aqueous HCl and discarded. The combined aqueous HCl extracts were made basic with 3M NaOH. The resulting aqueous phase was extracted 2 times with DCM. The combined DCM extracts were concentrated in vacuo and the resulting solid was triturated with ethyl ether, filtered, and dried to give 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3 (2H)-one (455 mg, 69%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.35 (s, 3 H) 2.81 (t, J5.48 Hz, 2 H) 3.51 (s, 2 H) 3.63 (s, 3 H) 4.03 (t, J=5.48 Hz, 2 H) 5.98 (s, 1 H) 7.71 (s, 1 H) 9.60 (s, 1 H).
60%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 2h; Inert atmosphere;	153.a 6-Chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one 153a Example 153a 6-Chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one 153a A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (30 mL), 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine 128b (1.70 g, 11.2 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.68 g, 12.0 mmol), and cesium carbonate (7.30 g, 22.4 mmol). After bubbling nitrogen through the suspension for 30 minutes, Xantphos (0.59 g, 1.02 mmol) and tris(dibenzylideneacetone)dipalladium(0) (467 mg, 0.51 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at 90° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 153a (1.9 g, 60%) as a brown solid. LCMS: [M+H]+ 295.1
57%	With caesium carbonate In 1,4-dioxane at 90℃; for 18h; Inert atmosphere;	59 A solution of 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine (55.7 mg, 0.37 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (81.8 mg, 0.37 mmol) cesium carbonate (417 mg, 1.28 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (31.8 mg, 0.05 mmol) in dioxane (6 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (25.1 mg, 0.03 mmol) was added and the resulting solution was heated at 90° C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane (50 mL) and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2*25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 24 g, 2% to 7% methanol in dichloromethane) to give 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one (61 mg, 57%) as a light yellow solid.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC; ROCHE HOLDING AG - WO2011/140488, 2011, A1 Location in patent: Page/Page column 128; 129
[2]Current Patent Assignee: GILEAD SCIENCES INC - WO2012/30990, 2012, A1 Location in patent: Page/Page column 72-73
[3]Current Patent Assignee: ROCHE HOLDING AG - EP2773638, 2015, B1 Location in patent: Paragraph 0432; 0433; 0434
[4]Current Patent Assignee: ROCHE HOLDING AG - WO2013/24078, 2013, A1 Location in patent: Page/Page column 95
[5]Current Patent Assignee: ROCHE HOLDING AG - US2013/116246, 2013, A1 Location in patent: Paragraph 0533
[6]Current Patent Assignee: ROCHE HOLDING AG - US2012/40949, 2012, A1 Location in patent: Page/Page column 121

3
[ 1178884-53-1 ]
[ 1227210-33-4 ]
[ 1346669-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane; tetrahydrofuran / 2 h / 0 °C / Inert atmosphere; Reflux 2: sodium carbonate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide; 1,4-dioxane; water / 14 h / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC; ROCHE HOLDING AG - WO2011/140488, 2011, A1

4
[ 1178884-53-1 ]
[ 69816-38-2 ]
[ 1360055-12-4 ]

Reference： [1]Patent: US2012/40949,2012,A1

5
[ 1178884-53-1 ]
[ 35196-11-3 ]
[ 1360055-04-4 ]

Reference： [1]Patent: US2012/40949,2012,A1

6
[ 1178884-53-1 ]
[ 1197333-44-0 ]
[ 1360056-89-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In 1,4-dioxane Inert atmosphere;	I-41.3 Step 3 6-Chloro-2-methyl-4-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-2H-pyridazin-3-one: 5-((4-Methylpiperazin-1-yl)methyl)pyridin-2-amine (3.2 g, 15.5 mmol, Eq:1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (3.64 g, 16.3 mmol, Eq:1.05), xantphos (1.35 g, 2.33 mmol, Eq: 0.15) tris(dibenzylideneacetone)dipalladium (0) (1.07 g, 1.16 mmol, Eq: 0.075) and cesium carbonate (15.2 g, 46.5 mmol, Eq: 3.00) were added to a sealed tube under nitrogen. Dioxane (103 ml) was added and the solution was degassed with nitrogen. The tube was capped and heated at 110° C. overnight. The reaction mixture was filtered through celite and the cake was washed with DCM. 1M HCl was added to and the layers were separated. The aqueous layer was basified with 2M NaOH and extracted several times with DCM. Most of the solvent was evaporated and the residue was triturated with ether. The solid that formed was filtered and dried to give 2.75 g (50.8%) of product which was used without further purification.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2012/40949, 2012, A1 Location in patent: Page/Page column 107

7
[ 1178884-53-1 ]
[ 35100-92-6 ]
[ 1227210-61-8 ]

Yield	Reaction Conditions	Operation in experiment
45%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 18h;Inert atmosphere;	Step 1 1,5-Dimethyl-1H-pyrazol-3-amine (400 mg, 3.6 mmol, Eq: 1.00) and 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (965 mg, 4.32 mmol, Eq: 1.20) were combined with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (312 mg, 540 mumol, Eq: 0.15), cesium carbonate (3.52 g, 10.8 mmol, Eq: 3) and tris(dibenzylideneacetone)dipalladium(0) (165 mg, 180 mumol, Eq: 0.05) in dioxane (10.0 ml). The solution was degassed with Ar. The reaction mixture heated at 100 C. for 18 h. The mixture was cooled to room temperature. The solution was diluted with 100 ml DCM. The organic layer was washed with water. The organic layer was dried over MgSO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one (408 mg, 45%). LC/MS-ESI observed [M+H]+ 235.

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 96

8
[ 571189-49-6 ]
[ 1178884-53-1 ]
[ 1346676-35-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere;	A solution of 5-(4-methylpiperazin-1-yl)pyridin-2-amine (172 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol) cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (77.7 mg, 0.13 mmol) in dioxane (10 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) was added and the resulting solution was heated at 90 C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2*25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was triturated with methanol and dichloromethane and filtered, washed with ether and dried to give 6-chloro-4-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-2-methyl-2H-pyridazin-3-one (223 mg, 74%) as a yellow solid.

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 115

9
[ 1178884-53-1 ]
[ 69816-38-2 ]
[ 1360056-16-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere;	Example 11 To a solution of <strong>[69816-38-2]5-(trifluoromethyl)pyrazin-2-amine</strong> (146 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol), cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine (77.7 mg, 0.13 mmol) in dioxane (10.0 ml) was added tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) and the reaction mixture purged with argon (3) before being warmed to 90 C. for 18 hr. The mixture was cooled, diluted with dichloromethane and water (50 mL) and the layers separated. The aqueous phase was extracted with methylene chloride (225 mL). The organic phases were combined and dried over MgSO4. The mixture was filtered and evaporated and the residue purified via automated flash chromatography (Analogix, SF15-24 g column, 1%-10% methanol/dichloromethane gradient) to give 6-chloro-2-methyl-4-(5-trifluoromethyl-pyrazin-2-ylamino)-2H-pyridazin-3-one (197 mg, 72%) as a yellow solid: LC/MS m/e calculated for C10H7ClF3N5O [M]+305.03, observed 305.9

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 65

10
[ 1178884-53-1 ]
[ 35196-11-3 ]
[ 1360055-99-7 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃;	6-Chloro-4-(5-methanesulfonyl-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1 g, 4.48 mmol, Eq: 1.00), <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> (771 mg, 4.48 mmol, Eq: 1), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (388 mg, 671 μmol, Eq: 0.15) and cesium carbonate (5.1 g, 15.7 mmol, Eq: 3.5) were suspended in dioxane (80.0 ml). Finally tris (dibenzylideneacetone)dipalladium(0) (307 mg, 336 μmol, Eq: 0.075) was added. The reaction mixture was heated to 90 C. over night. Reaction mixture was filtered over celite; washed with dioxane; concentrated. Crude material was triturated with dichloromethane and precipitate was collected by filtration to afford an off-white solid (70 mg, 222 μmol) 1H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3H) 3.69 (s, 3H) 7.73 (d, J=8.69 Hz, 1H) 8.16 (dd, J=1.00 Hz, 1H) 8.42 (s, 1H) 8.83 (d, J=2.27 Hz, 1H)
5.05 g		In a round-bottom flask under argon was placed 1.14 g 95% sodium hydride in oil dispersion and 90 mL of tetrahydrofuran (Aldrich, anhydrous, no inhibitor). The mixture was cooled in an ice bath and 3.10 g <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> was added one portion. The cooling bath was removed and the mixture stirred at room temperature. After 15 minutes the mixture was cooled in an ice bath and 4.103 g of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one was added in one portion. The cooling bath was removed and the mixture stirred at room temperature. After 90 minutes, the mixture was cooled in an ice bath and quenched by the dropwise addition of 90 mL of 0.5 M hydrochloric acid (gas evolution at first few drops, color change from red brown to light tan, 15 minute addition). The cooling bath was removed, the mixture stirred for an additional 15 minutes and the solid collected by suction filtration, washing with water, then ether. The solid was air dried overnight to afford the desired product (5.05 g) as a light yellow solid. H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3 H) 3.69 (s, 3 H) 7.73 (d, J=8.69 Hz, 1 H) 8.16(dd, J=1.00 Hz, 1 H) 8.42 (s, 1 H) 8.83 (d, J=2.27 Hz, 1 H).

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 52-53
[2]Patent: WO2013/24078,2013,A1 .Location in patent: Page/Page column 66; 67

11
[ 1178884-53-1 ]
[ 1198408-35-3 ]
[ 1360056-60-5 ]

Yield	Reaction Conditions	Operation in experiment
84%		Method B A 12L three neck flask equipped with mechanical stirrer, N2 bubbler, and thermometer was charged with tert-butyl 4-(6-aminopyridin-3-yl)piperidine-l-carboxylate (381 g, 1.37 mol), followed by THF (2.35 kg, 2.67 1). The reaction mixture was stirred until the reagent went into solution. Sodium tert-pentoxide, 2.5M in THF (577 ml, 1.44 mol) was added to the solution dropwise. The temperature went from 22C to 25C. The reaction mixture stirred for 30 min. A solution of 4-bromo-6-chloro-2-methyl-2H-pyridazin-3-one (322 g, 1.44 mol) in THF (1.17 kg, 1.33 1) for a total volume of 1640 mL was prepared. 820 mL of the 4-bromo-6-chloro-2-methyl- 2H-pyridazin-3-one solution (0.5 eq.) was slowly added over 30 min to the tert-butyl 4-(6- aminopyridin-3-yl)piperidine-l-carboxylate; keeping the temperature of the reaction below 30 C by adding some ice to the water bath. The reaction mixture was stirred for 30 minutes more. Sodium tert-pentoxide, 2.5M in THF (275 ml, 687 mmol) was added to the reaction mixture, then the mixture was stirred for an additional 20 min. 410 mL more of the 4-bromo-6-chloro-2- methyl-2H-pyridazin-3-one solution (0.25 eq.) was slowly added, keeping the temperature below 30 C, then the reaction mixture was stirred for 20 min. Sodium tert-pentoxide, 2.5M in THF (137 ml, 343 mmol) was added to the reaction mixture, and then the mixture was stirred for an additional 20 min. The final 410 mL of the 4-bromo-6-chloro-2-methyl-2H-pyridazin-3-one solution (0.25 eq.) were added, keeping the temperature below 30 C, then the reaction mixture was stirred for another 20 min. Sodium tert-pentoxide, 2.5M in THF (137 ml, 343 mmol) was added to the reaction mixture, and then the red mixture was stirred for an additional hour and 20 min. A 600 ml of a solution of citric acid prepared by dissolving citric acid(264 g, 1.37 mol) in water (1.14 kg, 1.14 1) (-20% solution) was slowly added to the reaction, maintaining the temperature below 30C, bringing the pH of the reaction to 4.6. The reaction mixture turned to yellow suspension. Water (800 ml) was added. The mixture was heated to 50 C and was stirred for 2 hours. The reaction mixture was cooled to room temperature overnight, giving a nice, yellow suspension amenable to stirring. The suspension was transferred into a 20 L Buchi flask and concentrated under vacuum at 40 C to remove about 3.2 L of solvent. The slurry was stirred at room temperature for 3 hours, then the solids were filtered using table top funnel and washed with water. The off-white solids were dried by suction for 1 hour. The solid was dried in a vacuum oven at 60C/26 in Hg with N2 bleed to a constant weight to give 488 g (84%) of the desired product. *H NMR (300 MHz, DMSO-i) delta ppm 1.42 (s, 9 H) 1.50 (dd, 7=12.65, 3.59 Hz, 2 H) 1.74 (d, 7=11.33 Hz, 2 H) 2.58 - 2.96 (m, 3 H) 3.68 (s, 3 H) 4.07 (d, 7=12.09 Hz, 2 H) 7.48 (d, 7=8.69 Hz, 1 H) 7.67 (dd, 7=8.50, 2.45 Hz, 1 H) 8.27 (d, 7=2.27 Hz, 1 H) 8.33 (s, 1 H) 9.62 (s, 1 H).
82%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere;Product distribution / selectivity;	Step 3 4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (509 mg, 2.28 mmol, Eq: 1.00), <strong>[1198408-35-3]tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate</strong> (632 mg, 2.28 mmol, Eq: 1.00), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (198 mg, 342 mumol, Eq: 0.15) and cesium carbonate (2.6 g, 7.98 mmol, Eq: 3.5) were suspended in dioxane (20 ml) under argon. Finally tris(dibenzylideneacetone)dipalladium(0) (156 mg, 171 mumol, Eq: 0.075) was added. The reaction mixture was heated to 90 C. for 18 h. The reaction mixture was filtered over celite; washed with dioxane, and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 20% to 50% EtOAc/Hex gradient) to give tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (782 mg, 82%). LC/MS-ESI observed [M+H]+ 420.
76.4%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃;Inert atmosphere;	4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (3.59 g, 16.0 mmol, Eq: 1.00), <strong>[1198408-35-3]tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate</strong> (4.45 g, 16.0 mmol, Eq: 1.00), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (696 mg, 1.2 mmol, Eq: 0.075) and cesium carbonate (18.3 g, 56.2 mmol, Eq: 3.5) were suspended in dioxane (150 ml) under an argon atmosphere. Finally tris(dibenzylideneacetone)dipalladium(0) (551 mg, 602 jimol, Eq: 0.0375) was added. The reaction mixture was heated at 90 C overnight. The reaction mixture was filtered over celite, and the celite cake was washed with dioxane several times. The combined filtrate and washes were concentrated in vacuo and the resultant solid was triturated with EtOAc, washed with ether and dried in a vacuum oven overnight at 50 C to afford 4.57 g of the desired product as a white solid. The combined filtrate and washes were evaporated to dryness and dissolved in CH2Cl2 (4 ml) and the crude material was purified by flash chromatography (silica gel, 120 g Analogix column, 20% to 50% EtOAc in hexanes over 20 mm) to afford and additional 582 mg. Total yield (5.15 g, 12.3 mmol, 76.4 % yield). (M+H)+ =420 m/e; 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.50 (s, 9 H) 1.54 - 1.69 (m, 3 H) 1.83 (d, J=13.64 Hz, 2 H) 2.67 (tt, J=12.38, 3.66 Hz, 1 H) 2.83 (t, J=13.14 Hz, 2 H) 3.82 (s, 3 H) 6.89 (d, J=8.59 Hz, 1 H) 7.51 (dd, J=8.46, 2.40 Hz, 1 H) 8.25 (d, J=2.27 Hz, 1 H) 8.27 (br. s., 1 H) 8.30 (s, 1 H).

Reference： [1]Patent: WO2014/83026,2014,A1 .Location in patent: Page/Page column 26; 49-50
[2]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 94
[3]Patent: WO2013/24078,2013,A1 .Location in patent: Page/Page column 58

12
[ 1178884-53-1 ]
[ 1018505-59-3 ]
[ 1360055-69-1 ]

Reference： [1]Patent: US2012/40949,2012,A1

13
[ 1178884-53-1 ]
[ 1018505-59-3 ]
[ 1360057-20-0 ]

Yield	Reaction Conditions	Operation in experiment
44%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 18.0h;Inert atmosphere;	A solution of <strong>[1018505-59-3]5-(4-ethylpiperazin-1-yl)pyridin-2-amine</strong> (185 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol) cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (77.7 mg, 0.13 mmol) in dioxane (10 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) was added and the resulting solution was heated at 90 C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2*25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was triturated with methanol and dichloromethane and filtered, washed with ether and dried to give 6-chloro-4-[5-(4-ethyl-piperazin-1-yl)-pyridin-2-ylamino]-2-methyl-2H-pyridazin-3-one (138 mg, 44%) as a yellow solid.

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 135

14
[ 1178884-53-1 ]
[ 1227210-33-4 ]
[ 1361386-70-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / 1,4-dioxane; tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 1.2: 2 h / Reflux 1.3: pH 7.6 2.1: sodium carbonate / N,N-dimethyl-formamide; 1,4-dioxane; water / 0.5 h / Inert atmosphere 2.2: 16 h / Reflux 2.3: 16 h / 20 °C

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2012/30990, 2012, A1

15
[ 1178884-53-1 ]
[ 1904-24-1 ]
[ 1433852-96-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; for 2.0h;Inert atmosphere; Reflux;	Example 127a 6-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one 127a A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (20 mL), <strong>[1904-24-1]5-ethyl-1H-pyrazol-3-amine</strong> (971 mg, 10.0 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.46 g, 11.0 mmol), and cesium carbonate (6.52 g, 20.0 mmol). After bubbling nitrogen through the suspension for 10 minutes, xantphos (1.74 g, 3.0 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.37 g, 1.5 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 2 h. It was then filtered immediately when the reaction mixture was still hot. The solid was washed with dioxane (3*30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel chromatography eluting with 6:1 petroleum ether/ethyl acetate to afford 127a (1.8 g, 75%) as a yellow solid. MS-ESI: [M+H]+ 239.9

Reference： [1]Patent: US2013/116246,2013,A1 .Location in patent: Paragraph 0384; 0385

16
[ 74-69-1 ]
[ 1178884-53-1 ]
6-chloro-2-methyl-4-[(2-methylpyrimidin-4-yl)amino]pyridazin-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃;Inert atmosphere;	Example 225a 6-Chloro-2-methyl-4-(2-methylpyrimidin-4-ylamino)pyridazin-3(2H)-one 225a A 100-mL single-neck round-bottomed flask equipped with a reflux condenser was charged with <strong>[74-69-1]2-methylpyrimidin-4-amine</strong> (330 mg, 3.03 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (675 mg, 3.03 mmol), Pd2(dba)3 (274 mg, 0.30 mmol), XantPhos (143 mg, 0.30 mmol), Cs2CO3 (2960 mg, 9.09 mmol), and dioxane (40 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100C for overnight. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 225a as a yellow solid (560 mg, 73%). MS-ESI: [M+H]+ 252.1

Reference： [1]Patent: EP2773638,2015,B1 .Location in patent: Paragraph 0891; 0892

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Code	Phrase
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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

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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. 1178884-53-1 ]

Quality Control of [ 1178884-53-1 ]

Related Doc. of [ 1178884-53-1 ]

Product Details of [ 1178884-53-1 ]

Calculated chemistry of of [ 1178884-53-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1178884-53-1 ]

Application In Synthesis of [ 1178884-53-1 ]

[ 1178884-53-1 ] Synthesis Path-Upstream 1~1

[ 1178884-53-1 ] Synthesis Path-Downstream 1~16

Related Functional Groups of [ 1178884-53-1 ]

Chlorides

Bromides

Amides

Related Parent Nucleus of [ 1178884-53-1 ]

Pyridazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1178884-53-1 ]

Related Parent Nucleus of
[ 1178884-53-1 ]