[ CAS No. 67279-24-7 ]

Name: 67279-24-7|1,4-Dichloro-5,6,7,8-tetrahydrophthalazine|97%
Brand: Ambeed
SKU: A117671
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Quality Control of [ 67279-24-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 67279-24-7 ]

Product Details of [ 67279-24-7 ]

CAS No. :	67279-24-7	MDL No. :	MFCD02940890
Formula :	C₈H₈Cl₂N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KLFNXIXNWZZRLE-UHFFFAOYSA-N
M.W :	203.07	Pubchem ID :	12622440
Synonyms :

Calculated chemistry of [ 67279-24-7 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.5
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	49.48
TPSA :	25.78 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) :	-5.3 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.36
Log Po/w (XLOGP3) :	3.15
Log Po/w (WLOGP) :	2.66
Log Po/w (MLOGP) :	2.52
Log Po/w (SILICOS-IT) :	3.56
Consensus Log Po/w :	2.85

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.45
Solubility :	0.0715 mg/ml ; 0.000352 mol/l
Class :	Soluble
Log S (Ali) :	-3.36
Solubility :	0.0884 mg/ml ; 0.000435 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.0
Solubility :	0.0204 mg/ml ; 0.0001 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.32

Safety of [ 67279-24-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 67279-24-7 ]

* 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 [ 67279-24-7 ]
Downstream synthetic route of [ 67279-24-7 ]

[ 67279-24-7 ] Synthesis Path-Upstream 1~3

1
[ 67279-23-6 ]
[ 67279-24-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	for 1 h; Reflux	The suspension of compound 40 (2.09 g, 12.6 mmol) in POCl₃(10 mL) is refluxed for 1 h, cooled down, and poured into ice. The precipitate is collected by filtration and dried in a vacuum oven to give 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine (41) (2.23 g, 87percent).HR MS (m/z, MH+) meas. 203.0139.
87.3%	for 1 h; Heating / reflux	The suspension of 2,3, 5,6,7, 8-Hexahydro-phthalazin-l,4-dione (2.09 g, 12.6 mmol) in POCl₃ (10 mL) is refluxed for Ih, cooled down, and poured into ice. The precipitate is collected by filtration and dried in a vacuum oven to give l,4-dichloro-5,6,7,8-tetrahydro- phthalazine (2) (2.23 g, 87.3percent). HRMS: m/z=203.0139 [M+l]
83.8%	for 16 h; Reflux	A mixture of 2,3,5,6,7,8-Hexahydro-phthalazine-1 ,4-dione (855 mg, 5.14 mmol) and phosphorus oxychloride (5 mL) was heated under reflux conditions for 16 h. The reaction was poured into ice, and neutralized very carefully with solid sodium carbonate. The water layer was extrated with EtOAc (x2), and the combined organic layers were dried (sodium sulphate), filtered and concentrated. The crude was purified by trituration with Et₂0 to give the expected compound 1 ,4-dichloro- 5,6,7,8-tetrahydro-phthalazine (876 mg, 83.8percent yield).HPLC- S (method 4): Rt= 4.16 min, [M+H]⁺ m/z 203.0.1H NMR (300 MHz, CDCI₃) δ 2.71 (m, 4H), 1.87 (m, 4H). General procedure B: bicycle formation from 3,4,5-trichloropyridazine

Reference： [1] Patent: US2010/41663, 2010, A1, . Location in patent: Page/Page column 42
[2] Patent: WO2008/110611, 2008, A1, . Location in patent: Page/Page column 104
[3] Patent: WO2011/80510, 2011, A1, . Location in patent: Page/Page column 71
[4] Journal of Organic Chemistry, 1955, vol. 20, p. 707,708
[5] Journal of Medicinal Chemistry, 2004, vol. 47, # 14, p. 3642 - 3657
[6] Patent: WO2006/4589, 2006, A2, . Location in patent: Page/Page column 58

2
[ 6651-36-1 ]
[ 106131-61-7 ]
[ 67279-24-7 ]

Reference： [1] Tetrahedron Letters, 1998, vol. 39, # 32, p. 5873 - 5874

3
[ 2426-02-0 ]
[ 67279-24-7 ]

Reference： [1] Patent: WO2011/80510, 2011, A1,
[2] Patent: WO2008/110611, 2008, A1,

[ 67279-24-7 ] Synthesis Path-Downstream 1~34

1
[ 67279-24-7 ]
[ 37813-95-9 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 707,708

2
[ 67279-24-7 ]
[ 37813-95-9 ]
1-iodo-5,6,7,8-tetrahydro-phthalazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 707,708

3
[ 67279-23-6 ]
[ 67279-24-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With trichlorophosphate; for 1.0h;Reflux;	The suspension of compound 40 (2.09 g, 12.6 mmol) in POCl3 (10 mL) is refluxed for 1 h, cooled down, and poured into ice. The precipitate is collected by filtration and dried in a vacuum oven to give 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine (41) (2.23 g, 87%).HR MS (m/z, MH+) meas. 203.0139.
87.3%	With trichlorophosphate; for 1.0h;Heating / reflux;	The suspension of 2,3, 5,6,7, 8-Hexahydro-phthalazin-l,4-dione (2.09 g, 12.6 mmol) in POCl3 (10 mL) is refluxed for Ih, cooled down, and poured into ice. The precipitate is collected by filtration and dried in a vacuum oven to give l,4-dichloro-5,6,7,8-tetrahydro- phthalazine (2) (2.23 g, 87.3%). HRMS: m/z=203.0139 [M+l]
83.8%	With trichlorophosphate; for 16.0h;Reflux;	A mixture of 2,3,5,6,7,8-Hexahydro-phthalazine-1 ,4-dione (855 mg, 5.14 mmol) and phosphorus oxychloride (5 mL) was heated under reflux conditions for 16 h. The reaction was poured into ice, and neutralized very carefully with solid sodium carbonate. The water layer was extrated with EtOAc (x2), and the combined organic layers were dried (sodium sulphate), filtered and concentrated. The crude was purified by trituration with Et20 to give the expected compound 1 ,4-dichloro- 5,6,7,8-tetrahydro-phthalazine (876 mg, 83.8% yield).HPLC- S (method 4): Rt= 4.16 min, [M+H]+ m/z 203.0.1H NMR (300 MHz, CDCI3) delta 2.71 (m, 4H), 1.87 (m, 4H). General procedure B: bicycle formation from 3,4,5-trichloropyridazine

	With trichlorophosphate;Heating / reflux;	A mixture of 3,4,5,6-tetrahydrophthalic anhydride (3.5 g, 23 mmol), hydrazine hydrate (2.0mL), sodium acetate (15.4 g, 188 mmol) in 100 mL of acetic acid is heated at 100 C overnight. Upon cooling, a white solid is formed and collected by filtration. The solid is washed with water and dried to give 2,3,5,6,7,8-hexahydro-phthalazine-l,4-dione. The solid is taken up in 15 mL of POCI3. The resultant mixture is heated at reflux overnight. After cooled, the excess POC13 is removed under reduced pressure. Crushed ice is added to the residue followed by careful addition of solid Na2CO3 to pH 9. The product is extracted with EtOAc twice. The combined extract is washed with brine, dried and concentrated. The residue is purified by flash silica gel column (Hexanes/EtOAc 4:1) to give l,4-dichloro-5,6,7,8-tetrahydro-phthalazine as a white solid. 'H NMR: (CDC13) 2.74 (m, 4H), 1.87 (m,4H).
	With trichlorophosphate; at 90.0℃; for 4.0h;	A solution of phosphoryl chloride (8.8 mL) and 2,3,5,6,7,8-hexahydrophthalazine-1,4-dione (3.2g, 19.28 mmol, 1eq) is stirred at 90C for 4h. The excess of phosphoryl chloride is removed under reducedpressure. The residue is dissolved in DCM (1 0 mL) then slowly added to an ice-water mixture. The pH isadjusted to 7-8 by the addition of solid NaHC03. The aqueous layer is extracted with DCM. The organiclayer is dried (Na2S04), filtered and concentrated to afford the desired product.

Reference： [1]Patent: US2010/41663,2010,A1 .Location in patent: Page/Page column 42
[2]Patent: WO2008/110611,2008,A1 .Location in patent: Page/Page column 104
[3]Patent: WO2011/80510,2011,A1 .Location in patent: Page/Page column 71
[4]Journal of Organic Chemistry,1955,vol. 20,p. 707,708
[5]Journal of Medicinal Chemistry,2004,vol. 47,p. 3642 - 3657
[6]Patent: WO2006/4589,2006,A2 .Location in patent: Page/Page column 58
[7]Patent: WO2019/7696,2019,A1 .Location in patent: Paragraph 0269

4
[ 110-91-8 ]
[ 67279-24-7 ]
[ 89937-28-0 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1077 - 1083

5
[ 67279-24-7 ]
[ 66597-78-2 ]
1,4-dihydrazino-5,6,7,8-tetrahydrophthalazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 2320 - 2324

6
[ 6651-36-1 ]
[ 106131-61-7 ]
[ 67279-24-7 ]

Reference： [1]Tetrahedron Letters,1998,vol. 39,p. 5873 - 5874

Yield	Reaction Conditions	Operation in experiment
92%		b 1,4-Dichloro-5,6,7,8-tetrahydrophthalazine The preceding dione (23 g, 0.14 mol) was dissolved in phosphorus oxychloride (200 ml) and heated at reflux overnight. The solvent was evaporated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (200 ml), stirred rapidly and saturated sodium bicarbonate solution (200 ml) added slowly. Solid sodium bicarbonate was added cautiously until effervescence ceased and the mixture then partitioned between dichloromethane and water. The organic layer was separated, dried (MgSO4) and evaporated in vacuo. The residue was triturated with diethyl ether and dried in vacuo to give the title-product (25.8 g, 92%), 1H NMR (250 MHz, CDCl3) delta1.84-1.90 (4 H, m, 2 of CH2), 2.72-2.78 (4 H, m, 2 of CH2).

8
[ 67279-24-7 ]
[ 613-94-5 ]
benzoic acid N'-(4-chloro-1,2,5,6,7,8-hexahydro-phthalazin-1-yl)-hydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1807 - 1822

9
[ 67279-24-7 ]
[ 66597-78-2 ]

Yield	Reaction Conditions	Operation in experiment
56%	With hydrazine; In tetrahydrofuran; at 60.0℃; for 5.5h;	[00132] To l,4-dichloro-5,6,7,8-tetrahydrophthalazine (406 mg, 2.0 mmol) in 2 mL THF was added hydrazine (704 uL, 704 mm, 12 mmol) and the mixture heated at 60 0C for 5.5 hours. To the mixture was added 3 mL of water and 10 mL EtOAc. The resulting suspension was filtered, washed with water (3x5 mL) and concentrated to provide Compound 29A as a pale tan powder (222 mg, 56%). LC/MS (m/z) = 199.7 (M+H)+.

Reference： [1]Patent: WO2008/130951,2008,A1 .Location in patent: Page/Page column 72
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3642 - 3657

10
[ 67279-24-7 ]
[ 66978-73-2 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1807 - 1822

11
[ 67279-24-7 ]
6-chloro-3-(5-methyl-isoxazol-3-yl)-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3642 - 3657

12
[ 67279-24-7 ]
5-methyl-isoxazole-3-carboxylic acid N'-(4-chloro-5,6,7,8-tetrahydro-phthalazin-1-yl)-hydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3642 - 3657

13
[ 67279-24-7 ]
3-phenyl-6-(pyridin-2-yl)methyloxy-7,8,9,10-tetrahydro-1,2,4-triazolo[3,4-a]phthalazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1807 - 1822

14
[ 67279-24-7 ]
3-(5-methyl-isoxazol-3-yl)-6-(pyridin-2-ylmethoxy)-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3642 - 3657

15
[ 67279-24-7 ]
[ 89937-42-8 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1077 - 1083

16
[ 67279-24-7 ]
[ 89937-35-9 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1077 - 1083

17
[ 67279-24-7 ]
[ 89937-36-0 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1077 - 1083

18
[ 67279-24-7 ]
[ 73075-03-3 ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 2320 - 2324

19
[ 67279-24-7 ]
[ 66978-72-1 ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 2320 - 2324

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 2 Synthesis of 1-chloro-4-allylthio-5,6,7,8-tetrahydrophthalazine 0.23 g(0.01 mol) of metallic sodium was dissolved in 30 ml of absolute methanol and then mixed with 0.93 ml(0.01 mol) of allylmercaptan. To this mixture was added 2.03 g(0.01 mol) of 1,4-dichloro-5,6,7,8-tetrahydrophthalazine obtained from Preparation 4. The reaction solution was refluxed for one hour and then treated according to the same manner as Example 1 to obtain the title compound as a freezing white crystal. Yield: 1.81 g (75.1%) Melting Point: 43-45 C. NMR(CDCl3, delta): 1.85-2.65(m, 2H*4, aromatic), 3.95(d, 2H, SCH2), 5.25(dd, 2H, CH2), 6.00(m, 1H, CH)
		Example 2 Synthesis of 1-chloro-4-allylthio-5,6,7,8-tetrahydrophthalazine 0.23g(0.01mol) of metallic sodium was dissolved in 30mlitre of absolute methanol and then mixed with 0.93mlitre(0.01mol) of allylmercaptan. To this mixture was added 2.03g(0.01mol) of 1,4-dichloro-5,6,7,8-tetrahydrophthalazine obtained from Preparation 4. The reaction solution was refluxed for one hour and then treated according to the same manner as Example 1 to obtain the title compound as a freezing white crystal. Yield: 1.81g (75.1%) Melting Point: 43-45C NMR(CDCl3, delta): 1.85-2.65(m, 2H*4, aromatic), 3.95(d, 2H, SCH2), 5.25(dd, 2H, CH2), 6.00(m, 1H, CH)

21
[ 67279-24-7 ]
[ 111-96-6 ]
[ 20116-64-7 ]
[ 765-38-8 ]
[ 79362-94-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In water;	The phthalazine-1,4-dione is then reacted with excess phosphorus oxychloride heated at reflux for about 2-4 hours, cooled and the product hydrolyzed by careful addition of ice and water to produce the dichloro intermediate. In an alternative procedure for preparing substituted triazolopyridazines of Formulae I and II, a 3,6-dihalo-4,5-substituted pyridazine of Formula V STR6 is reacted with the R6 amine base to prepare a 3-halo pyridazine of Formula VI STR7 The reaction is conveniently carried out in an inert organic solvent in the presence of an inorganic base, such as sodium carbonate, as a hydrogen halide acceptor. The resulting 3-halopyridazine is then reacted with a loweralkanoyl hydrazine of Formula VII STR8 to prepare the triazolo pyridazine product. In the above formulae, R3, R6, R7 and R8 have the significance set out above with respect to Formulae I-IV. The loweralkanoyl hydrazine and 3-halopyridazine are reacted in an inert organic liquid medium such as an alkylene glycol alkyl ether at a temperature of from about 100 C. to about 160 C. The product is recovered and purified by conventional procedures. This procedure is illustrated by the preparation of a preferred compound of the invention, 6-(2-methyl-1-pyrrolidinyl)-7,8-tetramethylene-1,2,4-triazolo[4,3-b]pyridazine, the compound of Example 30. One gram (0.49 mole) of <strong>[67279-24-7]3,6-dichloro-4,5-tetramethylene-pyridazine</strong>, 78.3 grams (0.738 mole) sodium carbonate, and 500 milliliters of diglyme (diethylene glycol dimethyl ether) were mixed. 46.1 Grams (0.54 mole) of 2-methylpyrrolidine was added slowly with stirring, and the mixture was heated at reflux (134.5 C.) for 72 hours, then cooled to 95 C. 400 Milliliters deionized water was added, and the mixture was cooled to about 25 C. The resulting crystals were separated by filtration, washed with water and dried under reduced pressure to yield 104.0 grams of 3-chloro-6-(2-methyl-1-pyrrolidinyl)-4,5-tetramethylene pyridazine, melting at 134-136 C.

Reference： [1]Patent: US4526890,1985,A

22
[ 67279-24-7 ]
[ 870221-86-6 ]
4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 41; Synthesis of 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine; A slurry of <strong>[67279-24-7]1,4-dichloro-5,6,7,8-tetrahydrophthalazine</strong> (1.66 g, 8.18 mmol) and 4-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (2.00 g, 6.82 mmol) in 14 mL 2-BuOH was heated in a sealed pressure vessel to 110 C. The reaction became a thick mass that eventually became a stirring suspension over about 30 min. After 4 h, the reaction was cooled to ambient temperature, and the material was partitioned between 2N NaOH and EtOAc. The aqueous layer was extracted once with EtOAc. The organic layers were dried over anhyd. sodium sulfate, filtered, and concentrated to yield a brown solid. This solid was dissolved in MeOH/MC and adsorbed onto 10 g silica gel, dried, and purified by chromatography (0-100% EtOAc/DCM) to give 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine as an off-white solid. MS m/z=460 [M+H]+. Calc'd for C24H22ClN7O: 459.9.
	With sodium t-butanolate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 150.0℃; for 6.0h;Product distribution / selectivity;	EXAMPLE 41-A; Synthesis of 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine; A resealable reaction tube was charged with <strong>[67279-24-7]1,4-dichloro-5,6,7,8-tetrahydrophthalazine</strong> (0.050 g, 0.246 mmol), 4-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (0.072 g, 0.246 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.011 g, 0.012 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (0.020 g, 0.049 mmol), and sodium tert-butoxide (0.033 g, 0.345 mmol). The vial was purged with nitrogen for several minutes, followed by addition of 0.50 mL of toluene. The vial was capped and heated to 150 C. for 16 h. The reaction mixture was allowed to cool and was filtered through a plug of Celite, rinsing with dichloromethane. The filtrate was concentrated, and the crude material was purified by reverse phase chromatography, Gilson, 5-95% acetonitrile/H2O/0.1% TFA over 14 min. The product-containing fractions were combined, brought to basic pH by addition of 2M Na2CO3 and extracted with dichloromethane. The organic portion was dried with MgSO4, filtered, and concentrated to give 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine as a light brown solid. MS m/z=460 [M+H]+. Calc'd for C24H22ClN7O: 459.93.

Reference： [1]Patent: US2007/185111,2007,A1 .Location in patent: Page/Page column 31-32
[2]Patent: US2007/185111,2007,A1 .Location in patent: Page/Page column 32

23
[ 67279-24-7 ]
[ 312693-07-5 ]
[ 1057682-44-6 ]

Yield	Reaction Conditions	Operation in experiment
30%	tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 50.0℃;	To a solution of <strong>[67279-24-7]1,4-dichloro-5,6,7,8-tetrahydro-phthalazine</strong> (compound 41, 0.50 g, 2.46 mmol) in THF (5 mL) are added 4-fluoro-benzyl zincchloride (0.5M in THF) (6.40 mL, 3.20 mmol) and palladium tetrakis triphenylphosphine (0.36 g, 0.31 mmol). The mixture is degassed and stirred at 50 C. overnight. Then the reaction mixture is cooled down to room temperature, sat. NaHCO3 and water are added and the mixture is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/heptane: 10% 40%) to give 1-chloro-4-(4-fluoro-benzyl)-5,6,7,8-tetrahydro-phthalazine (46) (0.51 g, 30%).MS (m/z, MH+) meas. 277.11.
30%	tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 50.0℃;	To a solution of l,4-dichloro-5,6,7,8-tetrahydro-phthalazine (0.50 g, 2.46 mmol) in THF (5 mL) are added 4-fluoro-benzyl zincchloride (0.5M in THF) (6.40 mL, 3.20 mmol) and palladium tetrakis triphenylphosphine (0.36 g, 0.31 mmol). The mixture is degassed and stirred at 500C overnight. Then the reaction mixture is cooled down to room temperature, <n="106"/>sat. NaHCO3 and water are added and the mixture is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/Hexane: 10% - 40%) to give l-chloro-4-(4-fluoro-benzyl)-5,6,7,8-tetrahydro-phthalazine (compound 1Of) (0.51g, 30%). m/z =277.11 [M+l]

Reference： [1]Patent: US2010/41663,2010,A1 .Location in patent: Page/Page column 43-44
[2]Patent: WO2008/110611,2008,A1 .Location in patent: Page/Page column 104-105

24
[ 67279-24-7 ]
[ 132834-58-3 ]
[ 1204978-58-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	With triethylamine; In 1-methyl-pyrrolidin-2-one; at 140.0℃; for 1.0h;microwave irradiation;	To a solution of <strong>[67279-24-7]1,4-dichloro-5,6,7,8-tetrahydro-phthalazine</strong> (compound 25, 100 mg, 0.492 mmol) in NMP (3 mL) is added 1-[5-trifluoromethyl)-pyrid-2-yl)-piperazine (114 mg, 0.492 mmol) followed by triethyl amine (218 muL, 1.57 mmol). The mixture was heated in a microwave reactor for 140 C. for 60 min. Water was added to the reaction mixture and extracted with EtOAc. The combined arganic extracts were washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (EtOAc/heptane 10% to 70%) to yield 96 mg (49%) of the title compound.1H NMR (400 MHz, CD2Cl2) delta=8.41 (s, 1H), 7.73 (dd, J=9.0 Hz, 2.5 Hz, 1H), 6.79 (d, J=9.0 Hz, 1H), 3.85 (m, 4H), 3.40 (m, 4H), 2.76-2.68 (m, 4H), 1.93 (m, 2H), 1.80 (m, 2H).HR MS (m/z, MH+) meas. 398.1359.

Reference： [1]Patent: US2010/41663,2010,A1 .Location in patent: Page/Page column 47

25
[ 2426-02-0 ]
[ 67279-24-7 ]

Reference： [1]Patent: WO2011/80510,2011,A1
[2]Patent: WO2008/110611,2008,A1
[3]Patent: WO2019/7696,2019,A1

26
[ 67279-24-7 ]
[ 90006-64-7 ]

Yield	Reaction Conditions	Operation in experiment
16%	With ammonium hydroxide; In ethanol; at 120.0℃; for 20.0h;Autoclave;	A solution of l,4-dichloro-5,6,7,8-tetrahydro-phthalazine (CAS 67279-24-7; 348 mg, 1.7 mmol) in concentrated aqueous N (5 ml) and ethanol (5 ml) was stirred at 120C in an autoclave for 20 h. The mixture was cooled to r.t. and concentrated. The crude product was purified by silica gel chromatography using a chromatography using a CE^Ck/MeOH gradient as eluent, to provide the title compound (52 mg, 16%>) as off- white solid. MS: M = 184.2 (M+H)+

Reference： [1]Patent: WO2014/72261,2014,A1 .Location in patent: Page/Page column 54

27
[ 67279-24-7 ]
[ 1057681-34-1 ]

Reference： [1]Patent: WO2008/110611,2008,A1

28
[ 67279-24-7 ]
[ 1073488-48-8 ]

Reference： [1]Patent: WO2008/130951,2008,A1

29
[ 67279-24-7 ]
[ 1073488-56-8 ]

Reference： [1]Patent: WO2008/130951,2008,A1

30
[ 67279-24-7 ]
[ 89981-21-5 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In water; at 110.0℃; for 4.0h;	A solution of <strong>[67279-24-7]1,4-dichloro-5,6,7,8-tetrahydrophthalazine</strong> (2.8g, 13.9 mmol, 1.0 eq), acetic acid(30 mL) and water (7 mL) is stirred at 110C for 4h. The reaction is cooled down to room temperature. A white precipitate is formed and filtered off then washed with water. The solid is dried on high vacuum lineto afford the desired product

Reference： [1]Patent: WO2019/7696,2019,A1 .Location in patent: Paragraph 0270

31
[ 67279-24-7 ]
4-oxo-5,6,7,8-tetrahydro-3H-phthalazine-1-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2019/7696,2019,A1

32
[ 67279-24-7 ]
4-oxo-5,6,7,8-tetrahydro-3H-phthalazine-1-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2019/7696,2019,A1

33
[ 67279-24-7 ]
ethyl 4-oxo-5,6,7,8-tetrahydro-3H-phthalazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2019/7696,2019,A1

34
[ 67279-24-7 ]
4-(hydroxymethyl)-5,6,7,8-tetrahydro-2H-phthalazin-1-one [ No CAS ]

Reference： [1]Patent: WO2019/7696,2019,A1

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[ 67279-24-7 ]

Chlorides

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[ 67279-24-7 ]

Other Aromatic Heterocycles

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P322
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P342	If experiencing respiratory symptoms:
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P378
P380	Evacuate area.
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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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.
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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.
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P413
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P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
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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. 67279-24-7 ]

Quality Control of [ 67279-24-7 ]

Related Doc. of [ 67279-24-7 ]

Product Details of [ 67279-24-7 ]

Calculated chemistry of [ 67279-24-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 67279-24-7 ]

Application In Synthesis of [ 67279-24-7 ]

[ 67279-24-7 ] Synthesis Path-Upstream 1~3

[ 67279-24-7 ] Synthesis Path-Downstream 1~34

Related Functional Groups of [ 67279-24-7 ]

Chlorides

Related Parent Nucleus of [ 67279-24-7 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 67279-24-7 ]

Related Parent Nucleus of
[ 67279-24-7 ]