[ CAS No. 1609394-78-6 ] {[proInfo.proName]}

Name: 1609394-78-6|4,6-Dichloro-N-methylpyridazine-3-carboxamide|98%
Brand: Ambeed
SKU: A575682
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2D 3D

Structure of 1609394-78-6 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 1609394-78-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1609394-78-6 ]

SDS Specification

Alternatived Products of [ 1609394-78-6 ]

Product Details of [ 1609394-78-6 ]

CAS No. :	1609394-78-6	MDL No. :	MFCD28667278
Formula :	C₆H₅Cl₂N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	206.03	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 1609394-78-6 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	45.05
TPSA :	54.88 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) :	-6.82 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.66
Log Po/w (XLOGP3) :	1.04
Log Po/w (WLOGP) :	1.14
Log Po/w (MLOGP) :	0.75
Log Po/w (SILICOS-IT) :	1.73
Consensus Log Po/w :	1.26

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.01
Solubility :	2.01 mg/ml ; 0.00976 mol/l
Class :	Soluble
Log S (Ali) :	-1.78
Solubility :	3.4 mg/ml ; 0.0165 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.28
Solubility :	0.109 mg/ml ; 0.000527 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.84

Safety of [ 1609394-78-6 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501	UN#:
Hazard Statements:	H315-H319-H335	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1609394-78-6 ]

* 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 [ 1609394-78-6 ]

[ 1609394-78-6 ] Synthesis Path-Downstream 1~46

1
[ 1609394-78-6 ]
3-amino-2-methoxybenzonitrile [ No CAS ]
[ 1609394-58-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With lithium hexamethyldisilazane In tetrahydrofuran at 20 - 25℃; for 2h;	22.3 Step 3[00298j To a solution of 3-amino-2-methoxybenzonitrile (180 mg, 1.213 mmol) and4,6-dichloro-N-methylpyridazine-3-carboxamide (250 mg, 1.21 mmol) in THF (6 mL)was added lithium bis(trimethylsilyl)amide (1M in THF, 3.6 mL, 3.6 mmol). The reaction was stirred at room temperature for 2 hour and then quenched with 1.5 M (aq.) HC1. The product was extracted using ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified via silica gel chromatography (EtOAc : petroleum ether) to provide6-chloro-4-((3 -cyano-2-methoxyphenyl)amino)-N-methylpyridazine-3 -carboxamide (220 mg, 57% yield). ‘H NMR (400MHz, CDC13) ö 11.04 (s, 1H), 8.26 (bs, 1H), 7.54 (dd, J8.0, 1.2 Hz, 1H), 7.50 (dd,J8.0, 1.2 Hz, 1H), 7.23 (t,J=8.0 Hz, 1H), 6.93 (s, 1H), 4.05 (s, 3H), 3.06 (d, J=4.2 Hz, 3H).

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - WO2014/74661, 2014, A1 Location in patent: Paragraph 00298

2
[ 213176-56-8 ]
[ 1609394-78-6 ]
[ 1609394-53-7 ]

Yield	Reaction Conditions	Operation in experiment
25%	With sodium hexamethyldisilazane In tetrahydrofuran at 20 - 25℃; for 1h;	21.4 Step 4[00288j To a solution of methyl 3-amino-2-(methylthio)benzoate (479 mg, 2.43 mmol) and 4,6-dichloro-N-methylpyridazine-3-carboxamide (500 mg, 2.43 mmol) in THF (20 mL) was added sodium bis(trimethylsilyl)amide (1M in THF, 6.1 mL, 6.1 mmol). The reaction was stirred at room temperature for 1 hour and then quenched with 1.5 M (aq.) HC1. The product was extracted using ethyl acetate and the combined organic layerswere washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified via silica gel chromatography (EtOAc : petroleum ether) to provide methyl 3 -((6-chloro-3 -(methylcarbamoyl)pyridazin-4-yl)amino)-2-(methylthio)benzoate (250 mg, 25% yield). ‘H NMR (400MHz, DMSO-d6) ö 11.30 (s, 1H), 9.40 (d, J4.8 Hz, 1H), 7.30 (dd, J=8.0, 1.2 Hz, 1H), 7.53 (t, J=8.0, 1H), 7.40 (dd, J7.2, 1.2 Hz, 1H), 7.28(s, 1H), 3.87 (s, 3H), 2.86 (d, J=4.8 Hz, 3H), 2.26 (s, 3H)

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - WO2014/74661, 2014, A1 Location in patent: Paragraph 00288

3
[ 1609394-78-6 ]
2-Methoxy-3-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)aniline [ No CAS ]
C₁₆H₁₃⁽²⁾H₃ClN₇O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere;	146.3 Step 3: Example 146f To a solution of Example 146d (400 mg, 1.94 mmol, 1.0 eq) and Example 146e (402 mg, 1.94 mmol, 1.0 eq) in dry THF (15 mL) was added LiHMDS (3.88 mL, 1M in THF, 3.88 mmol, 2.0 eq) dropwise at 0oC under N2 protection. The reaction mixture was stirred for 0.5 h at r.t.. Then the silica was added to the mixture and concentrated. The residue was purified by silica gel flash column chromatography, eluted with DCM/MeOH = (20/1) to afford the product Example 146f (310 mg, 42% yield) as a yellow solid. LCMS [M+1] + = 377.3.

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1 Location in patent: Paragraph 00616; 00618

4
[ 1609394-78-6 ]
2-Methoxy-3-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)aniline [ No CAS ]
C₂₀H₂₀⁽²⁾H₃N₉O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / 0 - 20 °C / Inert atmosphere 2: caesium carbonate; tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; [2'-(diphenylphosphanyl)-[1,1'-binaphthalen]-2-yl]diphenylphosphane / 1,4-dioxane / 4 h / 110 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

5
[ 593-51-1 ]
C₅HCl₃N₂O [ No CAS ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
400mg	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; dichloromethane at 0 - 20℃; for 0.5h;	146.2 Step 2: Example 146d To a solution of Example 146c (1.96 g, 28.4 mmol, 2.0 eq) and DIEA (14.7 g, 113.6 mmol, 8.0 eq) in THF (30 mL) was added a solution of Example 146b (3.0 g, crude) in DCM (20 mL) dropwise at 0oC. The reaction solution was stirred for 30 min at r.t.. The reaction solution was diluted with EtOAc (100 mL), washed with brine (50 mL*3), dried over Na2SO4 and concentrated. The residue was purified by silica gel flash column chromatography, eluted with Petroleum Ether/EtOAc = (3/1) to afford the product Example 146d (400 mg, 14% yield) as a yellow solid. LCMS [M+1] + = 206.2.

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1 Location in patent: Paragraph 00616-00617

6
[ 1830-54-2 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: triethylamine / acetonitrile / 1 h / 0 - 20 °C 2.1: triphenylphosphine / tert-butyl methyl ether / 16 h / 20 °C 2.2: 6 h / Reflux 3.1: lithium hydroxide monohydrate; water / methanol; tetrahydrofuran / 16 h / 20 °C 4.1: trichlorophosphate / 4 h / 100 °C 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

7
[ 83878-89-1 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: triphenylphosphine / tert-butyl methyl ether / 16 h / 20 °C 1.2: 6 h / Reflux 2.1: lithium hydroxide monohydrate; water / methanol; tetrahydrofuran / 16 h / 20 °C 3.1: trichlorophosphate / 4 h / 100 °C 4.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

8
[ 372118-00-8 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate; water / methanol; tetrahydrofuran / 16 h / 20 °C 2: trichlorophosphate / 4 h / 100 °C 3: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

9
[ 1442437-21-9 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trichlorophosphate / 4 h / 100 °C 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

10
[ 73027-79-9 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trichlorophosphate / 4 h / 100 °C 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: ALUMIS - WO2020/86616, 2020, A1

11
[ 1609394-78-6 ]
6-(3-(1-((tert-butyldimethylsilyl)oxy)ethyl)azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine [ No CAS ]
4-((6-(3-(1-((tert-butyldimethylsilyl)oxy)ethyl)azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)-6-chloro-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With potassium hexamethylsilazane In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0151-0153

12
[ 947248-68-2 ]
[ 1609394-78-6 ]
4-((6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)-6-chloro-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45.6%	With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 1h;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0189-0191

13
[ 4570-41-6 ]
[ 1609394-78-6 ]
4-(benzo[d]oxazol-2-ylamino)-6-(cyclopropanecarboxamido)-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hexamethylsilazane / tetrahydrofuran / 2 h / 20 °C 2: palladium [2'-(amino-κN)[1,1'-biphenyl]-2-yl-κC][[5-(diphenylphosphino)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphine-κP](methanesulfonato-κO); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 4 h / 130 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1

14
[ 4570-41-6 ]
[ 1609394-78-6 ]
4-(benzo[d]oxazol-2-ylamino)-6-chloro-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With potassium hexamethylsilazane In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0082-0083

15
[ 1609394-78-6 ]
6-chloro-N-methyl-4-((6-(2-oxo-4-phenylazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)pyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / 20 °C 2: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 2 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1

16
[ 1609394-78-6 ]
6-(cyclopropanecarboxamido)-N-methyl-4-((6-(2-oxo-4-phenylazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)pyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / 20 °C 2: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 2 h / 100 °C / Inert atmosphere 3: palladium [2'-(amino-κN)[1,1'-biphenyl]-2-yl-κC][[5-(diphenylphosphino)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphine-κP](methanesulfonato-κO); caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0) / 1,4-dioxane / 4 h / 140 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1

17
[ 1609394-78-6 ]
tert-butyl 3-((2-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy)azetidine-1-carboxylate [ No CAS ]
tert-butyl 3-((2-((6-chloro-3-(methylcarbamoyl)pyridazin-4-yl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With sodium hexamethyldisilazane In tetrahydrofuran at 70℃; for 0.166667h;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0097; 0102; 0103

18
[ 1609394-78-6 ]
6-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine [ No CAS ]
4-((6-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)-6-chloro-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With sodium hexamethyldisilazane In tetrahydrofuran at 70℃; for 2h;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0113; 0122; 0123

19
[ 1609394-78-6 ]
6-(3-methoxyazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine [ No CAS ]
6-chloro-4-((6-(3-methoxyazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With potassium hexamethylsilazane In tetrahydrofuran at 70℃; for 1h; Inert atmosphere;

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/170046, 2021, A1 Location in patent: Paragraph 0126; 0135; 0136

20
[ 73027-79-9 ]
[ 74-89-5 ]
[ 1609394-78-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 4,6-dichloro-nicotinic acid With triethylamine; trichlorophosphate at 80 - 110℃; for 2h; Stage #2: methylamine In tetrahydrofuran; dichloromethane at 0℃; for 0.416667h;	Preparation 5 Synthesis of 4,6-dichloro-N-methyl-pyridazine-3-carboxamide 4,6-dihydroxypyridazine-3-carboxylic acid (250 mg, 1.6 mmol) and TEA (225 μL, 1.61 mmol) were placed in a pressure tube, then phosphorus oxychloride (2 ml, 21.4 mmol) was added and the mixture was heated at 80°C first and then the temperature was raised to 110°C and the reaction run for 120 minutes. The heating was stopped and the reaction allowed to cool a bit. Then anhydrous DCE was added and the crude was concentrated. After two co-evaporations with DCE the residual black solid was taken up in DCM (10 ml) and methylamine (2M in THF, 0.96 ml) was added at 0°C and the mixture allowed to stir for 5 min. HPLC showed still the presence of starting material (as the methyl ester), so more methylamine was added (0.6 ml) at 0°C and the mixture stirred at 0°C. After 20 minutes at 0°C, water and more DCM were added. The phases were separated and the aqueous phase was extracted with dichlomethane (x 2). The combined organic extracts were dried over anh. MgS04, filtered and evaporated to have a dark solid that was purified by flash chromatography (Biotage, SNAP 12g) using DCM/DCM- MeOH (2%), 200 mg (60% yield) of a grey solid were obtained. HPLC-MS tr = 1.48 min (90%) ES+ 206/208 ^-NMR (400 MHz, CDC13) d ppm 3.07 (d, J = 5 Hz, 3H), 7.71 (s, 1H).

Reference： [1]Current Patent Assignee: ALMIRALL SA - WO2021/204626, 2021, A1 Location in patent: Page/Page column 45

21
[ 1609394-78-6 ]
6-chloro-4-[(2-methoxy-3-methylbenzoyl)amino]-N-methylpyridazine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: ammonium hydroxide / acetonitrile / 2.5 h / 100 °C 2.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 1 h / 0 - 20 °C