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[ CAS No. 109-01-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 109-01-3
Chemical Structure| 109-01-3
Chemical Structure| 109-01-3
Structure of 109-01-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 109-01-3 ]

CAS No. :109-01-3 MDL No. :MFCD00005966
Formula : C5H12N2 Boiling Point : -
Linear Structure Formula :- InChI Key :PVOAHINGSUIXLS-UHFFFAOYSA-N
M.W :100.16 Pubchem ID :53167
Synonyms :

Calculated chemistry of [ 109-01-3 ]

Physicochemical Properties

Num. heavy atoms : 7
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 37.56
TPSA : 15.27 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.19 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.66
Log Po/w (XLOGP3) : -0.39
Log Po/w (WLOGP) : -1.24
Log Po/w (MLOGP) : -0.16
Log Po/w (SILICOS-IT) : 0.62
Consensus Log Po/w : 0.1

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.22
Solubility : 61.0 mg/ml ; 0.609 mol/l
Class : Very soluble
Log S (Ali) : 0.53
Solubility : 342.0 mg/ml ; 3.41 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.69
Solubility : 20.7 mg/ml ; 0.207 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.1

Safety of [ 109-01-3 ]

Signal Word:Danger Class:3,8
Precautionary Statements:P241-P242-P264-P270-P271-P272-P280-P304+P340-P305+P351+P338-P310-P330-P331-P363-P370+P378-P403+P233-P501 UN#:2924
Hazard Statements:H225-H303-H312+H332-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 109-01-3 ]

* 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 [ 109-01-3 ]

[ 109-01-3 ] Synthesis Path-Downstream   1~80

  • 1
  • [ 109-01-3 ]
  • [ 65009-00-9 ]
  • [ 90-89-1 ]
  • 2
  • [ 109-01-3 ]
  • [ 88-10-8 ]
  • [ 90-89-1 ]
  • 3
  • [ 109-01-3 ]
  • [ 37924-85-9 ]
  • 3-(4-methyl-piperazin-1-ylmethyl)-benzo[<i>d</i>]isoxazole [ No CAS ]
  • 4
  • [ 109-01-3 ]
  • [ 13745-86-3 ]
  • [ 1977-09-9 ]
  • 5
  • [ 109-01-3 ]
  • [ 50-00-0 ]
  • [ 4653-08-1 ]
  • [ 135509-63-6 ]
  • 7
  • [ 109-01-3 ]
  • [ 2112-22-3 ]
  • [ 97112-68-0 ]
  • 8
  • [ 109-01-3 ]
  • [ 84418-43-9 ]
  • [ 84418-38-2 ]
  • 9
  • [ 109-01-3 ]
  • [ 79-04-9 ]
  • [ 885-70-1 ]
  • [ 126856-99-3 ]
  • [ 28797-61-7 ]
  • 10
  • [ 109-01-3 ]
  • [ 885-70-1 ]
  • [ 148316-07-8 ]
  • 11
  • [ 109-01-3 ]
  • [ 39608-31-6 ]
  • [ 181999-17-7 ]
  • 12
  • [ 109-01-3 ]
  • [ 23681-89-2 ]
  • [ 50-00-0 ]
  • 5-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-benzofuran-6-ol [ No CAS ]
  • 13
  • [ 109-01-3 ]
  • [ 50-00-0 ]
  • [ 80096-64-6 ]
  • 6-hydroxy-5-(4-methyl-piperazin-1-ylmethyl)-chroman-4-one [ No CAS ]
  • 14
  • [ 109-01-3 ]
  • [ 81-96-9 ]
  • 3-N-(N'-methyl)piperazinobenzanthrone [ No CAS ]
  • 15
  • [ 109-01-3 ]
  • [ 10241-97-1 ]
  • (5-methyl-1H-indol-2-yl)-(4-methylpiperazin-1-yl)methanone [ No CAS ]
  • 16
  • [ 109-01-3 ]
  • [ 28899-75-4 ]
  • (7-chloro-1H-indol-2-yl)-(4-methylpiperazin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 18h; 2-Chlorophenylhydrazine hydrochloride (0.5 g) in ethanol (25 mL) was treated with [ETHYLPYRUVATE] (0.324 g) and concentrated sulfuric acid (3 drops). The mixture was stirred at ambient temperature for five min and treated with polyphosphoric acid (0.5 g). The mixture was heated at reflux temperature for 24 h whereupon additional polyphosphoric acid (0.5 g) was added and heating continued for a further 48 h. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the pH of the aqueous layer adjusted to neutrality by addition of saturated sodium hydrogen carbonate solution. The organic fraction was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified via silica gel chromatography (5-10% ethyl acetate/hexane) to give [7-CHLORO-1 H-] indole-2-carboxylic acid ethyl ester (0.227 g). This material (0.102 g) was used without further purification. The ester was treated with 1 M lithium hydroxide in ethanol (5 mL) followed by water {3 mL) and stirred at ambient temperature for 18 h. The solution was acidified with 10% hydrochloric acid, diluted with water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated to afford give 7- [CHLORO-1 H-INDOLE-2-CARBOXYLIC ACID] (0.089 g). This material (0.089 g), was treated with HATU (0.259 g), HOAT (0.093 g), N, [N-DIISOPROPYLETHYLAMINE] (0.158 mL) and N-methylpiperazine (0.05 mL) in DMF (0. [6] mL) and stirred at ambient temperature for 18 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with 1 M hydrochloric acid, saturated sodium hydrogencarbonate solution and then brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via silica gel chromatography (2-10% 2 M ammonia in [METHANOL/DICHLOROMETHANE)] to give the title compound (0.56 g).'H NMR (400 MHz, [CDCI3)] : [8] 9.17 [(BR S, 1 H),] 7.47 (d, J = 8.1 Hz, [1H),] 7.21 (dd, J = 7.6, 0.8 Hz, 1 H), 7.01 (t, J = 7.8 Hz, 1 H), 6.73 (d, J = 2.3 Hz, 1 H), 3.88 {br m, 4H), 2.45 (t, J = 5.1 Hz, 4H), 2.29 (s, 3H).
0.56 g With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 18h; 2-Chlorophenylhydrazine hydrochloride (0.5 g) in ethanol (25 mL) was treated with ethylpyruvate (0.324 g) and concentrated sulfuric acid (3 drops). The mixture was stirred at ambient temperature for five min and treated with polyphosphoric acid (0.5 g). The mixture was heated at reflux temperature for 24 h whereupon additional polyphosphoric acid (0.5 g) was added and heating continued for a further 48 h. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the pH of the aqueous layer adjusted to neutrality by addition of saturated sodium hydrogen carbonate solution. The organic fraction was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified via silica gel chromatography (5-10% ethyl acetate/hexane) to give 7-Chloro-1 H-indole-2-carboxylic acid ethyl ester (0.227 g). This material (0.102 g) was used without further purification. The ester was treated with 1 M lithium hydroxide in ethanol (5 mL) followed by water (3 mL) and stirred at ambient temperature for 18 h. The solution was acidified with 10% hydrochloric acid, diluted with water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated to afford give <strong>[28899-75-4]7-Chloro-1H-indole-2-carboxylic acid</strong> (0.089 g). This material (0.089 g), was treated with HATU (0.259 g), HOAT (0.093 g), N, N-diisopropylethylamine (0.158 mL) and N-methylpiperazine (0.05 mL) in DMF (0.6 mL) and stirred at ambient temperature for 18 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with 1 M hydrochloric acid, saturated sodium hydrogencarbonate solution and then brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via silica gel chromatography (2-10% 2 M ammonia in methanol/ dichloromethane) to give the title compound (0.56 g). 1H NMR (400 MHz, CDCl3): delta 9.17 (br s, 1H), 7.47 (d, J = 8.1 Hz, 1 H), 7.21 (dd, J = 7.6, 0.8 Hz, 1 H), 7.01 (t, J = 7.8 Hz, 1 H), 6.73 (d, J = 2.3 Hz, 1 H), 3.88 (br m, 4H), 2.45 (t, J = 5.1 Hz, 4H), 2.29 (s, 3H).
  • 17
  • [ 109-01-3 ]
  • [ 876-08-4 ]
  • [ 55314-16-4 ]
  • [ 119-32-4 ]
  • bis-(N-alloc)-methylthiopseudourea [ No CAS ]
  • [ 152459-95-5 ]
  • 18
  • [ 109-01-3 ]
  • Merrifield resin-OC(O)CH2CH2CH(OH)CH2I [ No CAS ]
  • [ 58077-68-2 ]
  • 20
  • [ 109-01-3 ]
  • [ 1735-53-1 ]
  • 4-(4-methyl-1-piperazinyl)-3-(trifluoromethyl)-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl acetamide; at 95℃; for 14h; A mixture of [4-BROMO-3- (TRIFLUOROMETHYL)-BENZONITRILE] (Yonezawa [ET AG,] Synthetic Communications (1996) 26,1575-8 ; 2.47 g, 12 [MMOL),] 1-methylpiperazine (Fluka, Buchs, Switzerland, 5.33 mL, 48 [MMOL)] and 15 mL [N, N-DIMETHYLACETAMIDE] is stirred in a tightly closed vessel for 14 hours at [95C.] After cooling, the reaction mixture is evaporated to dryness under reduced pressure and the residue is treated with a half-saturated aqueous solution of sodium carbonate and extracted with ethyl acetate. The combined extracts are dried [(NA2SO4)] and the solvent is evaporated off under reduced pressure. The crude product is purified by column chromatography on silica gel, eluent methylene chloride/methanol to give [4- (4-METHYL-1-PIPERAZINYL)-3- (TRIFLUOROMETHYL)-BENZONITRILE] as a pale yellow oil. A mixture consisting of 30 mL dioxane, 15 mL water and 11.25 mL of 2M aqueous sodium hydroxide solution is added to [4- (4-METHYL-1-PIPERAZINYL)-3- (TRIFLUOROMETHYL)-BENZONITRILE] and the reaction mixture is shaken for 16 hours at [95C.] After cooling, the mixture is evaporated. The resulting residue is treated with water, the pH adjusted [TO-5-6] with 1 M hydrochloric acid and the solvent evaporated off under reduced pressure. The residue is treated with hot methanol, the insoluble salt filtered off and the filtrate evaporated yielding the crude title compound which is used for the next step without further purification. ['H-NMR] (400 MHz, [DMSO-D6,] [8)] : 2.28 (s, 3H); 2.50-2. 58 (m, 4H); 2.94-3. 02 (m, 4H); 7.52 [(M, 1 H) ; 8.11-8. 17 (M, 2H); 13.19 (BR. , 1 H).]
  • 21
  • [ 109-01-3 ]
  • [ 27383-86-4 ]
  • [ 673487-02-0 ]
YieldReaction ConditionsOperation in experiment
2-hydroxypyridin; In toluene; at 125℃; for 4h;Sealed tube; A stirred solution of 2-aminophenol (300 mg, 2.75 [MMOL), METHYL] 2,2, 2- trimethoxyacetate (902 mg, 5.50 [MMOL),] and ytterbium [TRIFLATE] (170 mg, 0.28 [MMOL)] in [TOLUENE] (10 mL) was heated to reflux. After 5 h, the mixture was cooled, and the precipitate was collected and dried. The crude solid was suspended in toluene (5 mL), and [N-METHYLPIPERAZINE] (1.5 mL, 13.7 [MMOL)] was added followed by 2-hydroxypyridine (26 mg, 0.28 [MMOL).] The mixture was heated to 125 [°C] in a sealed tube for 4 h. The resulting yellow solution was concentrated under reduced pressure, and the residue was purified on silica gel (12 g; 2percent methanol/dichloromethane), yielding 320 mg (48percent) of the title compound. MS [(ESI)] : mass calculated for [C13H15N302,] 245.12 ; m/z found, 246.1 [[M+H] +. 1H] NMR (400 MHz, [CDC13)] : 7.83-7. 79 (m, 1 H), 7.66-7. 65 [(M,] 2H), 7.47-7. 41 (m, 2H), 4.19 (t, [J = 5.] 1 Hz, 4H), 3.88 (t, [J = 5.] 1 Hz, 4H), 2.55- 2.52 [(M,] 4H), 2.35 (s, 3H). [13C] NMR (400 MHz, [CDCI3)] : 156.1, 154.6, 149. 9, 140.1, 127.1, 125.3, 121. [3,] 111.5, 55.3, 54.6, 46.9, 45.9, 42.8.
  • 22
  • [ 109-01-3 ]
  • [ 81945-73-5 ]
  • [ 548767-63-1 ]
YieldReaction ConditionsOperation in experiment
(General Procedure 16)4-Methyl-piperazine-1-carboxylic Acid pyrazol-1-yl Ester The title compound was prepared from <strong>[81945-73-5]1-<strong>[81945-73-5]hydroxypyrazole</strong></strong> and N-methylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (water-acetonitrile-0.1% TFA) (17%, salt with TFA). 1H NMR (300 MHz; CDCl3): delta 2.36 (s, 3H), 2.50 (bt, 4H), 3.59 (bs, 2H), 3.71 (bs, 2H), 6.31 (t, 1H), 7.38 (dd, 1H), 7.40 (dd, 1H); HPLC-MS: m/z=211.0 (M+1); Rt=0.40 min.
  • 23
  • [ 109-01-3 ]
  • [ 16588-02-6 ]
  • [ 288251-82-1 ]
YieldReaction ConditionsOperation in experiment
STARTING MATERIAL SYNTHETIC EXAMPLE 8 5-amino-2-(4-methylpiperazin-1-yl)benzonitrile By the reaction and treatment in the same manner as in Starting Material Synthetic Example 4 using 2-chloro-5-nitrobenzonitrile (15 g) and methylpiperazine (9.8 g), the title compound (11.1 g) was obtained. melting point: 45-46° C.
  • 24
  • [ 109-01-3 ]
  • (3-Trifluoromethanesulfonyloxy-5,6,7,8-tetrahydro-naphthalen-1-yl)-acetic acid ethyl ester [ No CAS ]
  • tris(dibenzylideneacetoneacetone)-dipalladium(0) [ No CAS ]
  • [ 224311-51-7 ]
  • [ 425638-72-8 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; In tetrahydrofuran; e [3-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-naphthalen-1-yl]-acetic Acid Ethyl Ester To a solution of compound of step d) (0.5 g, 1.36 mmol) in dry THF (10 ml) K3PO4 (405 mg, 1.90 mmol), N-methylpiperazine (180 mul, 163 mmol), tris(dibenzylideneacetoneacetone)-dipalladium(0) (60 mg, 0.07 mmol) and 2-(di-t-butylphosphino)biphenyl (21 mg, 0.07 mmol) are added under argon. The reaction is kept under argon at 80° C. for 24 hours. After filtration DMF is removed under reduced pressure and the crude residue is purified on silica gel (methylene chloride/methanol 95/5) affording the pure compound. 1H NMR (400 MHz, CDCl3) delta 6.68 (d, 1H, J=2.44 Hz), 6.59 (d, 1H, J=2.20 Hz), 4.15 (q, 2H, J=7.34 Hz), 3.55 (s, 2H), 3.17 (t, 4H, J=5.13 Hz), 2.75 (t, 2H, J=5.87 Hz), 2.60 (t, 2H, J=6.11 Hz), 2.57 (t, 4H, J=4.90 Hz), 2.35 (s, 3H), 1.77 (m, 4H), 1.25 (t, 3H, J=7.10 Hz)
  • 25
  • [ 109-01-3 ]
  • [ 37091-73-9 ]
  • (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid cyclohexylester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy) cyclopenta [c]-pyrane-4-carboxylic acid; Example 9 A dichloromethane solution containing 400 mg of (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid described in Example 1 was cooled with ice followed by addition of 0.20 ml of 1-methylpiperazine, 2 ml of triethylamine and 301 mg of <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> and stirring for 15 hours at room temperature. The reaction mixture was then extracted with dichloromethane. After washing the organic phase with saturated aqueous sodium bicarbonate and brine, it was dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography to obtain a colorless powder from the dichloromethane-methanol elude in the form of (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid 4-methylpiperazylamide (264 mg, yield: 50percent). The physicochemical properties of this compound are described in Table 5, Compound No. 20. (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid cyclohexylester was produced in the same manner from (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid.
  • 26
  • [ 109-01-3 ]
  • [ 1005-38-5 ]
  • [ 96225-86-4 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 37 Using the method of Example 35, 4-methyl-piperazine was reacted with 4-amino-6-chloro-2-methylthio-pyrimidine to provide white solid 4-amino-6-[1-(4-methyl-piperazino)]-2-methylthiopyrimidine, m.p. 165°-167° C. The structural assignment was supported by infrared and nuclear magnetic resonance spectral analyses.
  • 27
  • [ 109-01-3 ]
  • [ 61150-75-2 ]
  • [ 61150-48-9 ]
  • [ 54435-09-5 ]
  • [ 110-16-7 ]
  • [ 61150-71-8 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; ammonium hydroxide; sodium hydroxide; sodium bis(2-methoxyethoxy)aluminum dihydride; copper;titanium tetrachloride; In ethanol; water; benzene; EXAMPLE 36 8-Chloro-3,7-dimethoxy-10-(4-methylpiperazino)dibenzo(b,f)thiepine 1,Methylpiperazine (20 ml) was added to a solution of 8-chloro-3,7-dimethoxydibenzo(b,f)thiepine-10(11H)-one (9.63 g) in benzene (80 ml). A solution of titanium tetrachloride (3.2 g) in benzene (10 ml) was added dropwise and the mixture refluxed for 25 hours and then decomposed with water. The separated compound was filtered and washed with benzene. The combined benzene solutions were dried over potassium carbonate and taken down. The residue represents a mixture of the desired base and the starting ketone. These compounds were separated by the following procedure: The residue was dissolved in a sufficient amount of benzene and the solution shaken with a solution of maleic acid (10 g) in water (200 ml). Whereas the ketone remains dissolved in the benzene layer, the desired base was separated as the solid maleate. This was filtered, suspended in water and the base again liberated by addition of ammonium hydroxide and extracted with benzene. This procedure affords 6.5 g of the crystalline base which was crystallized from a mixture of ethanol and benzene. The pure product melted at 188-190 C. The maleate was purified by crystallization of the crude salt from ethanol; m.p. 220-221 C. The required starting 8-chloro-3,7-dimethoxydibenzo(b,f)thiepine-10(11H)-one is a new compound. It can be prepared, e.g., from 4-chloro-3-methoxythiophenol (see Example 30) and <strong>[54435-09-5]2-iodo-4-methoxybenzoic acid</strong> (see K. Sindelar et al, Collection Czech. Chem. Commun. 39, 3548, 1974) by the following reaction sequence: 4-Chloro-3-methoxythiophenol (65.5 g), followed by <strong>[54435-09-5]2-iodo-4-methoxybenzoic acid</strong> (96.4 g) and copper (5.0 g), is added to a stirred solution of potassium hydroxide (56 g) in water (500 ml). The mixture is refluxed for 6 hours while stirring, filtered while hot and the filtrate acidified with hydrochloric acid. After standing overnight, the separated crude 2-(4-chloro-3-methoxyphenylthio)-4-methoxybenzoic acid is filtered and crystallized from an ethanol-benzene mixture, yielding 94.2 g of the pure compound, m.p. 215-216 C. To a stirred suspension of the acid from the preceding preparation (94.2 g) in benzene (600 ml), 55% benzene solution (213 ml) of sodium bis(2-methoxyethoxy)aluminum hydride is added dropwise at 30-40 C. (under slight cooling) during 1 hour. The mixture is stirred at room temperature for 6 hours, left overnight and decomposed by dropwise addition of 10% sodium hydroxide solution (400 ml). The benzene layer is separated, dried over sodium sulfate and evaporated, yielding crude 2-(4-chloro-3-methoxyphenylthio)-4-methoxybenzyl alcohol in nearly theoretical yield (about 90 g). A sample of this product boils at 215 C./1.5 Torr.
  • 28
  • [ 109-01-3 ]
  • tintetrachloride [ No CAS ]
  • 2-(2-chlorobenzyl)-6-nitrotoluene [ No CAS ]
  • [ 23876-13-3 ]
  • 2-(4-chlorobenzyl)-6-nitrotoluene [ No CAS ]
YieldReaction ConditionsOperation in experiment
In cyclohexane; chlorobenzene; a) 2-(2-Chlorobenzyl)-6-nitrotoluene and 2-(4-chlorobenzyl)-6-nitrotoluene A mixture of 25 g (0.15 mol) of <strong>[23876-13-3]2-methyl-3-nitrobenzyl alcohol</strong> and 25 ml (0.22 mol) of tintetrachloride in 250 ml of chlorobenzene is refluxed for 3 hours with stirring. After cooling 50 ml of N-methylpiperazine is slowly instilled. The precipitate is suctioned off and washed several times with ethyl acetate. The combined filtrates are dried on sodium sulfate and concentrated by evaporation and the temperature must not rise above 160 C. The residue (39 g) with a mixture of 33 parts of cyclohexane and 1 part of ethyl acetate is subjected twice to a pressure column chromatography. Thus 9.3 g (24%) of 2-(2-chlorobenzyl)-6-nitrotoluene, melting point 54-56 C., and 16 g (41%) of 2-(4-chlorobenzyl)-6-nitrotoluene, melting point 62-63 C. are obtained.
  • 29
  • [ 109-01-3 ]
  • [ 21563-29-1 ]
  • [ 207594-39-6 ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In pyridine; EXAMPLE L 4-(4-Methylpiperazinyl)-1,8-naphthalic anhydride 4-Methylpiperazine (0.6 g, 6.6 mmol) and DBU (1 mL) were added to <strong>[21563-29-1]4-bromo-1,8-naphthalic anhydride</strong> (1.5 g, 5.4 mmol) in pyridine (10 mL). The solution was refluxed for 8 hours, concentrated in vacuo, and the residue was triturated with water. The separated solid was filtered and dried to give 0.8 g of the title compound.
  • 30
  • [ 109-01-3 ]
  • 8-chloro-2-[3-(4-phenyl-3,6-dihydro-1 (2H)-pyridinyl)propyl]-4(3H)-quinazolinone [ No CAS ]
  • [ 3375-31-3 ]
  • [ 224311-51-7 ]
  • [ 437999-29-6 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; methanol; dichloromethane; toluene; EXAMPLE 15 A mixture of 8-chloro-2-[3-(4-phenyl-3,6-dihydro-1 (2H)-pyridinyl)propyl]-4(3H)-quinazolinone (50 mg), 1-methylpiperazine (19.8 mg), palladium (II) acetate (2.96 mg), 2-(di-t-butylphosphino)biphenyl (7.86 mg), sodium t-butoxide (23 mg) in toluene (0.4 ml and tetrahydrofuran (0.2 ml) was stirred at 80° C. under nitrogen atmosphere overnight. The mixture was cooled, diluted with water and extracted with dichloromethane twice. The combined extracts were dried over magnesium sulfate and concentrated. The residue was purified by preparative thin layer chromatography on silica gel using 10percent methanol in dichloromethane to give the 8-(4-methyl-1-piperazinyl)-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone. Mass (APCI): 444.3 (M++H)
  • 31
  • [ 109-01-3 ]
  • [ 3034-22-8 ]
  • [ 859522-44-4 ]
YieldReaction ConditionsOperation in experiment
76% With hydrogen bromide; potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h; 2-Amino-5-(4-methyl-piperazin-1-yl)-thiazole: To a solution of 2-amino-5-bromothiazol, HBr (500 mg, 1.9 mmol) in DMF (6 mL) were added potassium carbonate, anhydrous (1.0 g, 7.3 mmol) and N-methylpiperazine (215 muL, 1.9 mmol). The reaction mixture was stirred at room temperature for 2 hours and then filtered and evaporated to dryness in vacuo. Stirring of the residue with ethyl acetate (3 mL) gave beige crystals of 2-amino-5-(4-methyl-piperazin-1-yl)-thiazole. Yield: 290 mg (76percent). 1H-NMR (CD3OD): delta 6.34 (s, 1H), 2.94 (t, 4H), 2.56 (t, 4H), 2.32 (s, 3H).
  • 32
  • [ 109-01-3 ]
  • [ 454-16-0 ]
  • [ 209482-01-9 ]
YieldReaction ConditionsOperation in experiment
93% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 18h; 2-Fluoro-5-nitroanisole (1.0 mmol) and N-methyl-piperazine (1.0 mmol)It was added to a 25 ml dry eggplant-shaped flask and dissolved in 4 ml of dry dimethyl sulfoxide.Potassium carbonate (2.0 mmol) was then added, and the mixture was heated to 120 C for 18 h, and the reaction was completely converted by TLC.Add water after cooling to room temperature.It was extracted three times with ethyl acetate and the organic phases were combined.Wash the organic phase with saturated brine.It was then dried over anhydrous sodium sulfate.Concentrated under reduced pressure to obtain crude product and then purified by column chromatography(dichloromethane: methanol = 100:1 ? dichloromethane: methanol = 50:1),A yellow solid S5 was obtained (yield 93%).
69% In dimethyl sulfoxide; at 120℃; for 12h; A mixture of scheme 2 compound 1 (2.00 g, 11.68 mmol) and scheme 2 compound 2 (1.17 g, 11.68 mmol) in dry DMSO (5 mL) was heated to 120 C for 12 h. After TLC showed the starting material was consumed completely, the reaction mixture was diluted with water (20 mL) and extracted with EtOAc (5 x 50 mL). The organic layer was dried over Na2S04, filtered and concentrated to give scheme 2 compound 3 (2.00 g, 69% yield) as a brown solid which was used without further purification. *H NMR (400 MHz, CDCls): delta 7.87 (dd, J= 8.8, 2.6 Hz, 1H), 7.71 (d, J= 2.5 Hz, 1H), 6.90 (d, J= 8.8 Hz, 1H), 3.95 (s, 3H), 3.26 (d, J= 4.9 Hz, 4H), 2.61 (t, J= 4.9 Hz, 4H), 2.37 (s, 3H). MS [ESI, MH+] = 252.13.
  • 33
  • [ 109-01-3 ]
  • [ 50-00-0 ]
  • [ 27955-94-8 ]
  • [ 1086840-22-3 ]
YieldReaction ConditionsOperation in experiment
67% In ethanol; water; for 7h;Heating / reflux; ,l,l-tris(4-hydroxyphenyl)ethane (1.53 gr,5 mM), formaldehyde (1.35 gr, 45 mM) and1-methyl piperazine (2.5 ml,50 mM) in 20 ml water and 25 ml EtOH were refluxed for 3 hours. Evaporation provided a solid that by TLC and NMR contained 2 products, which was not the starting material. Formaldehyde (0.75 gr,25 mM) and 1-methyl piperazine (1.5 ml, 30 mM) were <n="37"/>added to 5 ml water and 10 ml EtOH and the reaction was refluxed for 4 hours. Evaporation and workup gave 3.3 gr light yellow- white solid, 67percent yield, mp. -63°. Soluble in ethanol, and very good solubility in water. NMR CDCl3 .(TM). 6.67(6H,s,ArH), 3.53(12H, s, CH2), 2.44(48H,br.m,ring piperazine),2.26(18H,s,N- CH3 ), 2.00(3H,s,C-CH3).
  • 34
  • [ 109-01-3 ]
  • [ 51282-49-6 ]
  • [ 835879-05-5 ]
YieldReaction ConditionsOperation in experiment
36% at 150℃; for 0.5h;Microwave irradiation; Methyl 5-chloro-2-nitrobenzoate acid (1 g, 4.50 mmol) and JV-methylpiperazine (3 niL, 27 mmol) are stirred in the microwave for 30 min at 150 0C. The reaction mixture is stirred in water (50 mL), the pH is adjusted to 5 with NH4Cl, and the mixture is washed with EtOAc. The aqueous phase is freeze-dried, the residue is stirred with THF (200 mL) and filtered. The filtrate is evaporated down and the residue is digested with MeCN. Yield: 434 mg (36 percent)
  • 35
  • [ 109-01-3 ]
  • [ 10124-78-4 ]
  • [ 10165-86-3 ]
  • [ 947756-66-3 ]
YieldReaction ConditionsOperation in experiment
With acetic acid; In trifluoroethanol; for 2h; Step A: Methyl-6-[1-(4-methylpiperazin-1-yl)-2-(2-naphthylamino)-2-oxoethyl]nicotinate. Methyl 6-formylnicotinate (50.0 mg, 0.303 mmol), acetic acid (19.0 muL, 0.333 mmol), N-methylpiperizine (40.4 muL, 0.364 mmol), and 2-napthylisocyanide (51.0 mg, 0.333 mmol) were dissolved in 100 muL of TFE. The solution was allowed to stir for 2 h then purified by reverse phase HPLC to give the desired product MS cal'd 419 (MH+), exp 419 (MH+).
  • 36
  • [ 109-01-3 ]
  • [ 5734-64-5 ]
  • [ 1070215-65-4 ]
  • 37
  • [ 109-01-3 ]
  • [ 55583-59-0 ]
  • [ 1070217-20-7 ]
  • 38
  • [ 109-01-3 ]
  • [ 499214-11-8 ]
  • [ 1055927-07-5 ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[499214-11-8]6-formyl-2-pyridinecarboxylic acid</strong> [Chemstep Product List ] (0.25g) in dichloromethane (6.8ml) was added 1-methylpiperazine (0.481 ml) and acetic acid (0.083ml). The mixture was stirred at room temperature for 15min when sodium triacetoxyborohydride (0.459g) was added and the mixture stirred overnight. The crude reaction mixture was diluted with dichloromethane (60ml) and methanol was added until a clear solution was observed. The mixture was loaded onto an aminopropyl-SPE cartridge (5g) pre-eluted with dichloromethane. The cartridge was eluted with dichloromethane and methanol and fractions containing product were combined and blown to dryness under a stream of nitrogen. The crude product was taken up in dichloromethane (2x25ml) and washed with 2M sodium hydroxide solution (25ml). The aqueous layer was acidified to pH7 using 5N hydrochloric acid and concentrated under vacuum to approximately 25ml. The solution was loaded onto an Oasis cartridge (6g) and eluted with water (one volume) and methanol. Fractions containing product were combined and dried to give the title compound (0.171g).LCMS (Method B): m/z 236 [MH+], R1 = 0.25min
  • 39
  • [ 109-01-3 ]
  • [ 88912-26-9 ]
  • [ 503555-56-4 ]
  • 40
  • [ 109-01-3 ]
  • [ 27514-08-5 ]
  • [ 1214265-81-2 ]
YieldReaction ConditionsOperation in experiment
71% Preparation 12: 4-(4-Methylpiperazin-l-yl)cyclohexanamine (cis and trans isomers); [0117] In a 100 mL flask, <strong>[27514-08-5]4-acetamidocyclohexanone</strong> (300 mg, 1.93 mmol), N-methyl piperazine (387 g, 3.866 mmol) were dissolved in dry toluene (25 mL) and added methanesulfonic acid (MSA) (50 muL) and refluxed using Dean-Stark apparatus for five hours with occasional decanting toluene from Dean-Stark apparatus 3-4 times. Then removed half of the toluene from the reaction using Dean-Stark apparatus and cooled to 500C and added 25 mL ethanol then removed the Dean-Stark apparatus and cooled to 15- 200C. NaBH4 (2.126 mmol) was then added portion wise under nitrogen atmosphere. Continued stirring the reaction for overnight, 2.0 mL of 4 N HCl was added drop wise to the reaction. The volatiles removed from the reaction under reduced pressure. The gummy solid reaction mixture was basified with 5.0 mL sat. K2CO3, diluted with another 5.0 mL water and further basified with 50% NaOH solution to pH of about 13. Then added EtOAc (50 mL) and filtered the solid product and washed with EtOAc and ether and collected N-(4-(4-methylpiperazin-l-yl)cyclohexyl)acetamide as white powder (328 mg, 71%). 1H NMR (400 MHz, DMSO-J6). ESI-MS: m/z 240 (M+H)+. N-(4-(4- methylpiperazin-l-yl)cyclohexyl)acetamide (328 mg, 1.372 mmol) was refluxed in 24% cone. HCl solution for 20 hours at 115C. The solution was evaporated under reduced pressure and the solid product obtained was dissolved and recrystallized from isopropyl alcohol to get the product as white hydrochloride salt (175 mg). ESI-MS: m/z 198 (M+H)+.
  • 41
  • [ 109-01-3 ]
  • [ 10320-42-0 ]
  • [ 943749-60-8 ]
YieldReaction ConditionsOperation in experiment
91% With triethylamine; In tetrahydrofuran; at 20℃; Intermediate 202-(4-Methyl- 1 -piperazinvD-5 -nitropyrimidine<strong>[10320-42-0]<strong>[10320-42-0]2-Chloro-5-nitropyrimidin</strong>e</strong> (2.0 g, 12.5 mmol) was added to a solution of N- methylpiperazine (1.4 rnL, 12.5 mmol) in tetrahydrofuran (50 mL) and triethylamine (3.5 mL, 25 mmol) and the reaction mixture was stirred overnight at room temperature. The mixture was poured onto EtOAc and a saturated aqueous solution of NaHCO3. The layers were separated and the aqueous layer was further extracted with EtOAc. The combined organic layer was washed with brine, dried (Na2SO4), filtered and concentrated to afford the title compound (2.55 g, 91percent) as a solid. LC-MS (ES) m/z = 224 [M+H]+.
  • 42
  • [ 109-01-3 ]
  • [ 55676-21-6 ]
  • [ 1224582-75-5 ]
  • 43
  • [ 109-01-3 ]
  • [ 138564-59-7 ]
  • [ 873895-41-1 ]
  • [ 132539-06-1 ]
  • 2-methyl-5,10-dihydro-4H-benzo[b]thieno[2,3-e][1,4]diazepin-4-one [ No CAS ]
  • 44
  • [ 109-01-3 ]
  • [ 138564-59-7 ]
  • [ 132539-06-1 ]
  • 45
  • [ 109-01-3 ]
  • [ 138564-59-7 ]
  • [ 132539-06-1 ]
  • 2-methyl-5,10-dihydro-4H-benzo[b]thieno[2,3-e][1,4]diazepin-4-one [ No CAS ]
  • 46
  • [ 109-01-3 ]
  • [ 16588-26-4 ]
  • [ 477846-54-1 ]
  • 47
  • [ 109-01-3 ]
  • [ 108-77-0 ]
  • [ 39136-63-5 ]
  • [ 100-46-9 ]
  • [ 1258212-04-2 ]
YieldReaction ConditionsOperation in experiment
3% Example 19To a solution of cyanuric chloride (230 mg, 1.25 mmol) in THF (16 mL) was added benzylamine (0.14 mL, 1.25 mmol) and DIPEA (0.20 mL, 1.25 mmol) at 0 C. The reaction mixture was let to stir at 0 C to room temperature for 2h. 3-amino-5- phenylthiazole (compound 17) (220 mg, 1.25 mmol) and DIPEA (0.20 mL, 1.25 mmol) were added to the above mixture and the resulting mixture was heated with microwave initiator at 150 C for 10 minutes. 1 -methylpiperazine (0.28 mL, 2.50 mmol) and DIPEA (0.44 mL, 2.50 mmol) were added to the mixture and the mixture was heated with microwave initiator at 60 C for 10 minutes. Saturated NaHCO3 in water was added and the mixture was extracted by ethyl acetate (3 x 50 mL). The combined organic was washed by brine, dried over sodium sulfate and concentrated. The residue was chromatographed on a silica gel column eluted with 0-5 % MeOH/DCM afforded 19 as white solid (16 mg, 3 %). 1H NMR (400 MHz, DMSO-d6) delta 12.56 (bs, 1H, NH), 9.20 (bs, 1Eta, NH), 7.75-5.96 (m, 9Eta, Ar-H), 3.71 (bs, 4Eta, 2CH2), 2.33 (s, 4Eta, 2CH2), 2.21 (s, 3Eta, CH3); ESI-MS: calcd for (C24Eta26N8S) 458, found 459 [M+H]+. HPLC: retention time: 7.89 min. purity: 97%.
  • 48
  • [ 109-01-3 ]
  • [ 39136-63-5 ]
  • [ 1258223-02-7 ]
  • [ 1258222-94-4 ]
YieldReaction ConditionsOperation in experiment
11% DIPEA (0.13 mL, 0.65 mmol) and 5-(phenyll)thiazol-2-amine (103 mg, 0.586 mmol) was added to a suspension of compound 4 (0.2g, 0.588 mmol) in THF (12 mL) . The mixture was heated at 150 0C for 10 minutes using microwave initiator. A solution of N- Methylpiperazine (70.4 mg, 0.703 mmol) and DIPEA ((0.13 mL, 0.65 mmol) in THF (5 mL) was added to the above vial at room temperature. The mixture was heated at 60 0C for 0.2 hours. After cooling to room temperature, saturated NaHCO3 in water was added to the flask and the mixture was extracted with dichloromethane (3 x25 ml) and washed by brine, dried over sodium sulfate and concentrated. The resulting crude product was purified by Teledyne- Isco flash system by using DCM/MeOH, 0 to 15% of Methanol in dichloromethane to provide compound 32 as a white solid (31 mg, 1 1%). IH NMR (400 MHz, DMSO-d6) 6 1 1.55 (brs, I H), 10.25 (brs, IH), 7.95 (s, IH,), 7.49-7.05 (m, 9H), 3.45 (m, 4H), 2.39 (m, 4H), 2.20 (s, 3H), 1.45 (m, IH), 0.85 (m, 4H) ; ESI-MS: calculated for (C27H28N80S2) 544, found 545 (MH+). HPLC: retention time: 16 min. purity: 98%.
  • 49
  • [ 109-01-3 ]
  • [ 960203-41-2 ]
  • [ 1293343-18-6 ]
  • 50
  • [ 109-01-3 ]
  • [ 25171-19-1 ]
  • [ 1357149-87-1 ]
YieldReaction ConditionsOperation in experiment
92% With N-ethyl-N,N-diisopropylamine; In ethyl acetate; at 0 - 20℃; for 1.5h; General procedure: 2,4-dichloroquinazoline (2.0 g, 10.1 mmol) and DIPEA (1.93 ml, 11.1 mmol) were dissolved in EtOAc (50 ml) after which N-methylpiperazine was slowly added at 0oC. The mixture was warmed to room temperature and stirred for 1.5 hours to effect complete conversion to the desired product. The mixture was washed with water (pH~11 with aq. NaOH) and brine and dried over Na2SO4. Removal of the organic solvent gave the title compound as 2.68 g (10.2 mmol, 100%) of a yellow oil that solidified upon standing. 1H-NMR (DMSO-delta6) delta (ppm) 8.03 (d, J= 7.8 Hz, 1H), 7.89-7.80 (m, 1H), 7.74-7.70 (m, 1H), 7.58-7.50 (m, 1H), 3.83 (t, J= 4.7 Hz, 4H), 2.51 (t, J=4.7 Hz, 4H), 2.25 (s, 3H); 13C-NMR (DMSO-delta6) delta (ppm) 164.23, 155.07, 152.54, 133.51, 126.83, 125.71, 125.51, 113.85, 54.11, 48.67, 45.30.
  • 51
  • [ 109-01-3 ]
  • [ 89292-91-1 ]
  • 52
  • [ 109-01-3 ]
  • [ 25177-85-9 ]
  • [ 1391602-40-6 ]
YieldReaction ConditionsOperation in experiment
94% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; 1 g N-Methylpiperazine were added to a mixture of 1.62 g <strong>[25177-85-9]2-indancarboxylic acid</strong>, 3.21 g [(benzotriazol-1-yloxy)-dimethylamino-methylene]-dimethyl-ammonium tetrafluoroborate (TBTU) and 1.72 ml Nu,Nu-diisopropylethylaminie (DIPEA) in 20 ml N,N-dimethylformamide. The mixture was stirred at ambient temperature overnight. The reaction mixture was filtered through a pad of aluminum oxide. The solvent was evaporated to obtain 1.22.Yield: 2.3 g 1.22 (94% of theory)
94% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; 1 g N-Methylpiperazine were added to a mixture of 1.62 g <strong>[25177-85-9]2-indancarboxylic acid</strong>, 3.21 g [(benzotriazol-1-yloxy)-dimethylamino-methylene]-dimethyl-ammonium tetrafluoroborate (TBTU) and 1.72 ml N,N-diisopropylethylaminie (DIPEA) in 20 ml N,N-dimethylformamide. The mixture was stirred at ambient temperature overnight. The reaction mixture was filtered through a pad of aluminum oxide. The solvent was evaporated to obtain I.22. [0199] Yield: 2.3 g I.22 (94% of theory)
  • 53
  • [ 109-01-3 ]
  • [ 21943-17-9 ]
  • [ 1410166-27-6 ]
YieldReaction ConditionsOperation in experiment
53% With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 140℃; for 1.0h;Inert atmosphere; Microwave irradiation; General procedure: A solution of 56 (1.50 g, 7.16 mmol), the appropriate secondary amine (8.59 mmol, 1.20 equiv) and diisopropylethylamine (1.50 mL, 8.59 mmol) in n-butanol (15 mL)was heated in a microwave reactor using variable wattage to 140 C for 1 h. The mixture was concentrated and purified by flash column chromatography on silica, eluting with 9:1 dichloromethane/methanol, to give gave 58-63.
  • 54
  • [ 109-01-3 ]
  • [ 36825-35-1 ]
  • [ 1403606-41-6 ]
  • 55
  • [ 109-01-3 ]
  • [ 1421372-94-2 ]
  • [ 1421372-76-0 ]
YieldReaction ConditionsOperation in experiment
80% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 140℃; for 1h;Sealed tube; Microwave irradiation; 1-Methylpiperazine (89 mg, 0.89 mmol), <strong>[1421372-94-2]N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine</strong> (Intermediate 129 (which may be prepared by the method described for Intermediate 87), 350 mg, 0.89 mmol) and DIPEA (0.186 mL, 1.07 mmol) were suspended in DMA (6 mL) and sealed into a microwave tube. The reaction was heated to 140C for1h in a microwave and then cooled to r.t. CH3OH was added and an orange solid precipitated from solution. The solid was collected by filtration and was washed with CH3OH and then diethyl ether. The solid was then dried to give the title compound (339 mg, 80%) as an orange solid; 1H NMR: 2.26 (3H, s), 3.06-3.11 (4H, m), 3.88 (3H, s), 3.99 (3H, s), 6.86 (1H, s), 7.13 (1H, t), 7.23-7.29 (2H, m), 7.53 (1H, d), 8.10 (1H, s), 8.32-8.38 (3H, m), 8.81 (1H, s); (signals for 4 protons were not observed and are likely to be obscured under the DMSO peak); m/z: ES+ MH+ 474.56.
  • 56
  • [ 109-01-3 ]
  • [ 7398-42-7 ]
  • methyl 2-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In methanol; at 20℃; for 3h; a) Methyl 2- { 4- r(4-methylpiperazin- 1 - vDmethyll phenyl I acetate (1-77) N-methyl piperazine (1.37 mL; 12.3 mmol; 3 eq) was added to a solution of methyl 2-[4-(bromomethyl)phenyl]acetate (1-72) (1.0 g; 4.11 mmol; 1 eq) in methanol (6 mL). The reaction mixture was stirred at room temperature for 3 hours, then, concentrated to dryness. The residue was taken up in water (20 mL) and the resulting aqueous layer was extracted with dichloromethane (3 x 20 mL). The combined organic layers were washed with saturated sodium chloride (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound, methyl 2-{4-[(4-methylpiperazin-l-yl)methyl]phenyl}acetate was obtained in 88percent yield (954 mg) as a white oil. 1H NMR (CDC13): delta (ppm) 2.35 (s, 3H), 2.52 (brs, 8H), 3.55 (s, 2H), 3.67 (s, 2H), 3.75 (s, 3H), 7.31 (m, 5H).
  • 57
  • [ 109-01-3 ]
  • [ 2604-39-9 ]
  • C10H15N5O2 [ No CAS ]
  • 58
  • [ 109-01-3 ]
  • [ 25710-18-3 ]
  • 2-chloro-3-(4-methylpiperazine-1-yl)pyrido[2,3-b]pyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; 2,3-Dichloropyrido[2,3-b]pyrazine (300.0 mg, 1.50 mmol) was dissolved in DMF (5.0 mL), and N-methyl piperazine (0.3 mL, 2.97 mmol) was slowly added thereto at 0° C. The reaction mixture was stirred at room temperature for 2 hours, and it was then poured into saturated NH4Cl aqueous solution and extracted with DCM (30.0 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and then distilled under reduced pressure. The residue was purified by column chromatography (DCM:MeOH=100:0) on amine silica. The fractions containing products were collected and evaporated to obtain pale yellow solid compound of 2-chloro-3-(4-methylpiperazin-1-yl)pyrido[2,3-b]pyrazine (265.0 mg, 67percent). [0432] LCMS ESI (+): 264 (M+1), 266 (M+3)
  • 59
  • [ 109-01-3 ]
  • [ 146137-79-3 ]
  • [ 105-56-6 ]
  • (E)-ethyl α-cyano-2-(4-methylpiperazine)-5-cyanocinnamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% In ethanol; at 78℃; for 1.75h; General procedure: Cyclic secondary amine (2.5 equiv) was treated with 2-halobenzaldehyde (1 mmol) and active methylidene compound (1 mmol) in EtOH (2 mL) or DMF (2 mL). The mixture was stirred and heated to reflux. After the reaction was completed, the mixture was cooled down to r.t. and poured into H2O (10 mL). Crude products were filtered off and purified by recrystallization in EtOH or by column chromatography on silica gel; 52?88percent yield.
  • 60
  • [ 109-01-3 ]
  • [ 56962-04-0 ]
  • 3-chloro-5-(4-methylpiperazin-1-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With palladium diacetate; lithium hexamethyldisilazane; 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane; In toluene; at 80℃;Inert atmosphere; Lithium bis(trimethylsilyl)amide (1M solution in tetrahydrofuran, 20 mL, 20 mmol) was added to a suspension of <strong>[56962-04-0]3-bromo-5-chlorophenol</strong> (1.75 g, 8.44 mmol), 1- methylpiperazine (0.84 g, 8.44 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraza-i-phospha bicyclo{3.3.3}undecane (0.04 g, 0.17 mmol) in toluene (32 mL) and the reaction mixturewas subjected to three cycles of evacuation-backfilling with argon. Palladium (II) acetate (0.050 g, 0.22 mmol) was added and the mixture was subjected again to three cycles of evacuation-backfilling with argon. The reaction mixture was heated at 80 °C overnight, then cooled to room temperature, filtered through diatomaceous earth (Celite®) and the solvent was evaporated to dryness. The residue was purified by flash chromatography (gradient from dichloromethane to dichloromethane/methanol /ammonia 40:8:1) to yield the title compound (0.99 g, 45percent).LRMS (mlz): 227, 229 (M+1, M+3).
  • 61
  • [ 109-01-3 ]
  • [ 41731-83-3 ]
  • C11H17N3O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 80℃; for 24h; A mixture of compound IE (2.2 g, 10.0 mmol), N-methylpiperazine (1.1 g, 11.0 mmol), and K2C03 (3.4 g, 24.9 mmol) in acetonitrile (70 mL) was stirred at 80 C for 24 h. The mixture was concentrated and diluted with H20 and extracted with EtOAc (3x). The combined organic layers were dried and then concentrated to give compound 1G (2.5 g, >100%) as a brown solid. 1H NMR (400 MHz, CDC13) delta 7.85 (s, 1H), 4.28 (q, J = 1.2 Hz, 2H), 3.58 (t, J = 5.6 Hz, 4H), 2.50 (t, J = 5.6 Hz, 4H), 2.33 (s, 3H), 1.32 (t, J = 1.2 Hz, 3H).
With triethylamine; In N,N-dimethyl-formamide; at 90℃; To a solution of compound 1 (432 mg, 4.6 mmol) and <strong>[41731-83-3]ethyl 2-bromothiazole-5-carboxylate</strong> (1 g, 4.2 mmol), Et3N (1.27 g, 12.6 mmol) in DMF (20 ml) was stirred at 90 C. for overnight. The solvent was evaporated oil and extracted by EA (20 mlx2), washed with water, brine, concentrated in vacuo to afford compound 2 as a yellow solid (1.2 g, crude).
  • 62
  • [ 109-01-3 ]
  • [ 1181816-12-5 ]
  • tert-butyl 6-(4-methylpiperazin-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% a3.1) tert-butyl 6-(4-methylpiperazin-l-yl)-2-azaspiro[3.3]heptane-2-carboxylate 1-Methylpiperazin (4.73 mmol, 0.47 g) and concentrated acetic acid (0.5 mL) were added to a solution of <strong>[1181816-12-5]tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate</strong> (4.73 mmol, 1.0 g) in EtOH (15 mL). It was stirred for lh and NaCNBH3 (5.68 mmol, 0.36 g) was added portionswise, and the reaction mixture was further stirred over night at rt. The mixture was poured onto cold 5percent aq. K2CO3 (15 mL) and extracted three-times with ethyl acetate (15 mL); the organic phases were combined, washed with water three-times (15 mL), dried on Na2S04, filtered and evaporated in vacuo. It was passed through a silicagel column [eluent: l .)EtOAc:MeOH 17:3 and 2.) CH2Cl2:MeOH 1 : 1]. Yield: 1.1 g (78percent). ESI-MS: [M+H+] = 296.2
  • 63
  • [ 109-01-3 ]
  • [ 10191-60-3 ]
  • [ 89292-91-1 ]
YieldReaction ConditionsOperation in experiment
80% General procedure: A solution of N-cyanocarbonimidodithioic acid dimethyl ester (17.4mmol), acetonitrile (10mL), and appropriate amine (17.4mmol) was refluxed for 2h. After cooling to room temperature, hydrazine monohydrate (25.6mmol) was added and the reaction mixture was further refluxed for additional 5h. The solvent was evaporated under reduced pressure and the resulting product recrystallized from ethyl acetate. Following general procedure B, compound 11k was isolated as a pale yellow solid. Yield 80%, mp=103-104C. 1H NMR (200MHz, DMSO-d6) delta: 10.95 (br s, 1H); 5.72 (br s, 2H); 3.16-3.11 (m, 4H); 2.34-2.29 (m, 4H); 2.17 (s, 3H)
  • 64
  • [ 109-01-3 ]
  • [ 2789-25-5 ]
  • 2-(4-methylpiperazin-1-yl)pyridine-3,4-diamine [ No CAS ]
  • 65
  • [ 109-01-3 ]
  • [ 2789-25-5 ]
  • 2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
73.2% at 50℃; for 1h;Microwave irradiation; A mixture of 1-methylpiperazine (XCVI) (20 mL) and 2-chloro-3- nitropyridin-4 -amine (LXVII) (4.0 g, 23.1 mmol, 1.0 eq) was stirred at 50°C for 1 h under microwave irradiation. The reaction mixture was diluted with water (100 mL) and filtered, the cake was washed with water (30 mL x 3), dried in vacuo to give 2-(4-methylpiperazin-1-yl)-3- nitropyridin-4-amine (XCVII) (4.0 g, 16.9 mmol, 73.2percent yield) as a yellow solid. ESIMS found for C10H15N5O2 m/z 238.1 (M+H).
73% In ethanol; for 2h;Reflux; General procedure: The suitable amine (6.3 mmol) was added into a solution of compound 5 (2.9 mmol) in absolute ethanol (10 mL) and this mixture was refluxed for 2 h. Upon completion of the reaction, the organic solvent was removed under reduced pressure, water was added to the residue and the precipitate was filtered in vacuo, washed with water and air-dried, to provide the pure aminosubstituted derivatives 13a?d.
73.2% at 50℃; for 1h;Microwave irradiation; j0702j A mixture of 1 -methylpiperazine (CII) (20 mL) and 2-chloro-3-nitropyridin- 4-amine (LXVIII) (4.0 g, 23.1 mmol, 1.0 eq) was stirred at 50°C for 1 h under microwaveirradiation. The reaction mixture was diluted with water(100 mL) and filtered, the cake was washed with water (30 mL x 3), dried in vacuo to give 2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine (CIII) (4.0 g, 16.9 mmol, 73.2percent yield) as a yellow solid. ESIMS found for C,0H,5N502 m/z 238.1 (M+H).
73.2% at 50℃; for 1h;Microwave irradiation; A mixture of 1-methylpiperazine (CXII) (20 mL) and <strong>[2789-25-5]2-chloro-3-nitropyridin-4-amine</strong> (LXXXI) (4.0 g, 23.1 mmol, 1.0 eq) was stirred at 50° C. for 1 h under microwave irradiation. The reaction mixture was diluted with water (100 mL) and filtered, the cake was washed with water (30 mL×3), dried in vacuo to give 2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine (CXIII) (4.0 g, 16.9 mmol, 73.2percent yield) as a yellow solid. ESIMS found for C10H15N5O2 m/z 238.1 (M+H).
73.2% at 50℃; for 1h;Microwave irradiation; Step 1 A mixture of 1-methylpiperazine (XCV) (20 mL) and <strong>[2789-25-5]2-chloro-3-nitropyridin-4-amine</strong> (LXVI) (4.0 g, 23.1 mmol, 1.0 eq) was stirred at 50° C. for 1 h under microwave irradiation. The reaction mixture was diluted with water (100 mL) and filtered, the cake was washed with water (30 mL*3), dried in vacuo to give 2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine (XCVI) (4.0 g, 16.9 mmol, 73.2percent yield) as a yellow solid. ESIMS found for C10H15N5O2 m/z 238.1 (M+H).

  • 66
  • [ 109-01-3 ]
  • [ 55876-84-1 ]
  • methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 4h; Methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate In a 50-mL round bottom flask with magnetic stir bar, <strong>[55876-84-1]methyl 5-(bromomethyl)pyridine-2-carboxylate</strong> (940 mg, 4.09 mmol, 1.00 equiv) and 1-methylpiperazine (449.6 mg, 4.49 mmol, 1.10 equiv) were dissolved in ACN (10 mL), to which DIEA (790.8 mg, 6.12 mmol, 1.50 equiv) was added at room temperature. The resulting solution was stirred for 4 h at room temperature. After the reaction was done, the reaction mixture was concentrated under reduced pressure. The residue was purified in a silica gel column eluting with methanol in dichloromethane (1percent to 10percent gradient) to afford methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate (500 mg, 49percent) as brown solid.
  • 67
  • [ 109-01-3 ]
  • [ 79099-07-3 ]
  • [ 53617-36-0 ]
YieldReaction ConditionsOperation in experiment
60% With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 0 - 20℃; for 16h; 1-Methylpiperazine (0.905 g, 9.03 mmol), sodium triacetoxyborohydride (1.92 g, 9.03 mmol), and acetic acid (0.497 g, 8.28 mmol) were added to a solution of 1-tert-butoxycarbonyl-4-piperidinone (1.50 g, 7.53 mmol) in dichloromethane (25.0 mL) at 0° C., and the resulting mixture was stirred at room temperature for 16 hours. The reaction liquid was cooled to 0° C. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction liquid, and the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in hydrochloric acid (1.0 N), and the resulting mixture was extracted with ethyl acetate. A 48percent aqueous solution of sodium hydroxide was added to the aqueous layer for basification, and then the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (25.0 mL), and concentrated hydrochloric acid (5.0 mL) was added, and then the resulting mixture was stirred at 40° C. for 12 hours. The reaction liquid was concentrated and exsiccated, and then the residue was dissolved in distilled water. A 48percent aqueous solution of sodium hydroxide was added for basification, and then the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. 4-(1-Methylpiperazin-4-yl)piperidine (0.826 g, 4.51 mmol, 60percent) was obtained as a white solid.
60% (Reference Example 3) Synthesis of 4-(1-methylpiperazin-4-yl)piperidine: 1-Methylpiperazine (0.905 g, 9.03 mmol), acetic acid (0.497 g, 8.28 mmol) and sodium triacetoxyborohydride (1.92 g, 9.03 mmol) were added to a solution of 1-tert-butoxycarbonyl-4-piperidinone (1.50 g, 7.53 mmol) in dichloromethane (25.0 mL) at 0°C and the reaction liquid was stirred at room temperature for 16 hours. The reaction liquid was cooled to 0°C. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction liquid, and the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in hydrochloric acid (1.0 N), and the resulting mixture was extracted with ethyl acetate. A 48percent aqueous solution of sodium hydroxide was added to the aqueous layer for basification, and then the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (25.0 mL), and concentrated hydrochloric acid (5.0 mL) was added, and then the resulting mixture was stirred at 40°C for 12 hours. The reaction liquid was concentrated under reduced pressure, and then the residue was dissolved in distilled water. A 48percent aqueous solution of sodium hydroxide was added for basification, and then the resulting mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, the filtrate was concentrated under reduced pressure, and 4-(1-methylpiperazin-4-yl)piperidine (0.826 g, 4.51 mmol, 60percent) was obtained as a white solid. 1H-NMR (400 MHz, CDCl3) delta: 1.35 (2H, dd, J=12.0, 3.6 Hz), 1.41 (2H, dd, J=12.0, 3.6 Hz), 1.85 (2H, d, J=12.8 Hz), 1.96-2.06 (2H, br), 2.28 (3H, s), 2.32 (1H, tt, J=11.6, 3.6 Hz), 3.37-3.70 (8H, m), 3.14 (2H, d, J=12.8 Hz). ESI-MS: m/z= 169 (M+H)+.
  • 68
  • [ 109-01-3 ]
  • [ 34662-32-3 ]
  • 2-amino-4-(4-methylpiperazin-1-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% A solution of <strong>[34662-32-3]4-chloro-2-nitrobenzonitrile</strong> (5.5g, 30mmol),Methylpiperazine (7.4mL, 66mmol) was dissolved in 50mL dioxane,The reaction was refluxed at 110 degrees for 16 hours.Methylene chloride was added under reduced pressure to remove dioxane extraction,The organic phase was dried over anhydrous sodium sulfate,Concentrated to give the intermediate was dissolved in 100mL of ethanol,Was added wet Pd / C (300mg) and hydrazine hydrate (5.8mL, 120mmol),The reaction system at 80 C overnight,After the organic solvent was removed under reduced pressure,Add MeOH: CH2Cl2 (1:10) to about 150mL solvent lysate,Diatomaceous earth columnMeOH: CH2Cl2 (1:10) solvent washed,The organic phase was concentrated to give a small amount of solid was washed with dichloromethane,Give the desired product (6.4g, 91%).
91% <strong>[34662-32-3]4-Chloro-2-nitrobenzonitril</strong>e (5.5 g, 30 mmol), methylpiperazine (7.4 mL, 66 mmol) was dissolved in 50 mL of dioxane and reacted at 110 C for 16 hours. After the addition of dichloromethane,The organic phase was dried over anhydrous sodium sulfate and the concentrated intermediate was dissolved in 100 mL of ethanol. Wet Pd / C (300 mg) and hydrazine hydrate (5.8 mL, 120 mmol) were added and the reaction was allowed to react at 80 C overnight. After the solvent was added, a solution of 150 mL of the product of MeOH: CH2Cl2 (1: 10) was added and the organic phase was concentrated to give a solid which was washed with a small amount of dichloromethane to give The target product (6.4 g, yield 91%).
91% To a stirred solution of <strong>[34662-32-3]4-chloro-2-nitrobenzonitrile</strong> 14 (5.5 g,30 mmol) in dioxane (100 mL) was added morpholine (7.4 mL,66 mmol). The reaction was refluxed overnight. The solution wascooled to rt and partitioned between EtOAc (150 mL) and saturatedNaHCO3 (50 mL). The separated organic layer was dried overNa2SO4, filtered and evaporated in vacuo. After the residue wasdissolved in EtOH (100 mL), Pd/C (300 mg) and hydrazine hydrate(5.8 mL, 4 equiv.) were added. The solution was stirred at rt for0.5 h, then heated to 80 C for 8 h. After cooling, the Pd/C catalystwas filtered through a celite pad andwashed with EtOH. The filtratewas concentrated under reduced pressure and the residue was purified by chromatography on silica gel to give compound 15(6.4 g, 91% yield). 1H NMR (400 MHz, DMSO-d6) delta: 7.41 (d, J = 8.8 Hz,1H), 6.57 (s, 2H), 6.13 (dd, J = 8.9, 2.2 Hz, 1H), 6.09 (d, J = 2.1 Hz, 1H),3.24-2.96 (m, 4H), 2.45-2.27 (m, 4H), 2.20 (s, 3H). 13C NMR(101 MHz, DMSO-d6) delta: 171.57, 153.90, 152.31, 130.39, 105.17, 103.40,100.55, 54.92, 47.42, 46.24 ppm. MS (ESI + APCI) m/z 235.2 [M+H]+.
  • 69
  • [ 109-01-3 ]
  • [ 118591-58-5 ]
  • [ 4076-31-7 ]
YieldReaction ConditionsOperation in experiment
77.1% With potassium carbonate; In 1,4-dioxane; at 70℃; Compound 1-3 (2.6 g, 10 mmol) was dissolved in 1,4-dioxane (50 mL), followed by addition of N-methylpiperazine 15-1 (3 g, 30 mmol), and potassium carbonate (2.76 g, 20 mmol) was added under stirring, followed by stirring the reaction overnight under conditions of 70° C. and a closed reaction system, TLC monitoring showed that the starting material 1-3 was completely reacted. The solvent was removed under reduced pressure to obtain a concentrated residue. The concentrated residue was dispensed with dichloromethane (20 mL), an appropriate amount of silica gel was added and the sample was stirred, spin-dried under reduced pressure and directly placed on a silica gel column for column chromatographic purification, with an eluent (dichloromethane:methanol=20/1-5/1) to obtain the target product 15-2 (1.45 g, 77.1percent) as a pale yellow oil, LC-MS: m/z=189[M+H]+.
  • 70
  • [ 109-01-3 ]
  • [ 17865-54-2 ]
  • cyclohexyl (N-methyl)piperazinyldimethoxysilane [ No CAS ]
YieldReaction ConditionsOperation in experiment
Under N2 protection conditions,To the reaction flask was successively added 3. 6 g of N-methylpiperazine,40ml is burning, stirring;At a temperature of 5 ° C,A solution of 16. 8 ml (2. 87 M) butyllithium-n-hexane was added dropwise,Dropping time is 20min;After the addition was completed at 5 ° C for 40 min, the reaction solution was added dropwise to the reaction solution. 9. 4 g of <strong>[17865-54-2]cyclohexyltrimethoxysilane</strong> was added dropwise and the reaction was continued for 17 hours. The reaction solution was centrifuged and filtered,The precipitate was washed twice with n-hexane and the washings were combined with the filtrate. The n-hexane solvent was distilled off using a rotary evaporator,Vacuum distillation, collecting 120_123 ° C / 30Pa fraction, weighing 6g, the nuclear magnetic resonance test, the following peaks
  • 71
  • [ 109-01-3 ]
  • [ 1072105-05-5 ]
  • [ 66521-66-2 ]
  • [ 152459-95-5 ]
YieldReaction ConditionsOperation in experiment
86% With copper(l) iodide; sodium acetate; N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere; Under nitrogen, 10 mmol of 4- (3-pyridyl) -2-aminopyrimidine (CAS: 66521-66-2)10 mmol of 4-chloromethylbenzoyl (3-bromo-4-methylphenyl) amine (CAS: 1072105-05-5), 10 mmol of N-methylpiperazine (CAS: 109-01-3 ) And 0.2 mmol of cuprous iodide,0.2 mmol of N, N'-diisopropylethylenediamine,110 mmol of sodium acetate in 20 mL of 1,4-dioxane,The reaction was carried out under heating at a temperature of 100 ° C for 4 hours.After completion of the reaction, the solvent was evaporated to dryness with a rotary evaporator and the residue was separated by column chromatography,Obtain 4.2 grams of imatinib in 86percent yield.
  • 72
  • [ 109-01-3 ]
  • [ 53617-36-0 ]
  • 73
  • [ 109-01-3 ]
  • [ 18507-89-6 ]
  • (6-(decyloxy)-7-ethoxy-4-hydroxyquinolin-3-yl)(4-methylpiperazin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% at 100℃;Inert atmosphere; General procedure: The mixture of <strong>[18507-89-6]decoquinate</strong> 1 (100mg, 0.24mmol) and morpholine (209muL, 2.4mmol) was stirred at 100°C for 12h, cooled to room temperature and diluted with dichloromethane (0.5mL). Then petroleum ester was added to the mixture. The solid was precipitated, filtrated and dried to obtain 13 (60mg, 55percent).
  • 74
  • [ 109-01-3 ]
  • [ 5334-40-7 ]
  • C9H13N5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% To a suspension of 4-nitro-3-pyrazole carboxylic acid (6 g, 38.196 mmol) and DMF (73.938 mu, 0.944 g/mL, 0.955 mmol) in DCM (48.93 mL) at 0 °C was added dropwise a solution of oxalyl chloride 2M in DCM (36 mL, 2 M, 72 mmol) and the reaction mixture was stirred at ambient temperature for 18h. The reaction mixture was concentrated in vacuo and the residue was dissolved in 20 mL of DCM and 1- methylpiperazine (6.355 mL, 0.903 g/mL, 57.294 mmol) was added slowly at 0°C. The reaction mixture was then allowed to warm to rt and stirred at rt overnight. DCM was removed in vacuo and the resulting slurry was diluted with DCM and a little MeOH. The insoluble residue was filtered off to give 5g (54 percent) of intermediate 582. (1737) The filtrate was concentrated in vacuo and purified by Normal phase flash (1738) chromatography (Irregular SiOH 40muiotaeta 40g GRACE). Mobile phase 98percent DCM, 2percent MeOH, 0.2percent NH4OH to 90percent DCM, 10percent MeOH, 1 percent NH4OH. The pure fractions were combined and the solvent was evaporated to give a further 2.7g (30 percent) of intermediate 582.
  • 75
  • [ 109-01-3 ]
  • [ 959795-70-1 ]
  • 76
  • [ 109-01-3 ]
  • [ 5814-41-5 ]
  • [ 1977-07-7 ]
YieldReaction ConditionsOperation in experiment
75% Compound 1 (105 mg, 0.5 mmol) was weighed into a 50 ml round bottom flask.N,N-dimethylaniline (36.3 mg, 0.3 mmol) was added in that order.Appropriate amount of ultra-dry phosphorus oxychloride and magnetron at 130 ° C,Under reflux with nitrogen, the mixture was stirred under reflux, and after 12 hours, excess phosphorus oxychloride was distilled off.Further, an appropriate amount of N-methylpiperazine was added to continue stirring, and after 12 hours, the reaction was terminated by TLC.Extract with ethyl acetate (3 x 70 mL), wash with water and aq.The organic layers were combined, and anhydrous Na2SO4 was added to remove water.After filtration, the residue is finally concentrated.Column chromatography (dichloromethane: methanol = 25:1) gave 110 mg of compound 1a.The yield was 75percent
  • 77
  • [ 109-01-3 ]
  • [ 51282-49-6 ]
  • [ 1092931-97-9 ]
  • 78
  • [ 109-01-3 ]
  • [ 499214-11-8 ]
  • N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-6-[(4-methyl-1-piperazinyl)methyl]-2-pyridinecarboxamide [ No CAS ]
  • 79
  • [ 109-01-3 ]
  • [ 7499-66-3 ]
  • C15H19N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
13% With cesiumhydroxide monohydrate; In dimethyl sulfoxide; at 120℃; for 20h; <strong>[7499-66-3]6-bromo-2-aminonaphthalene</strong> (500 mg, 2.25 mmol),N-methylpiperazine (270 mg, 2.7 mmol),cesium hydroxide hydrate(760 mg, 4.5 mmol)A solution of dimethyl sulfoxide (5.0 mL) was stirred at 120 ° C for 20 hours.The reaction system was then cooled to room temperature.Dilute with ice water (10 mL).The aqueous phase was extracted with dichloromethane (20 mL×2).Organic phase in turn,Washed with saturated saline,Dry over anhydrous sodium sulfate,filter,concentrate,The residue was purified by flash column chromatography ( petroleum ether / ethyl acetate = 1/3)Compound 21.1 (70 mg, yield: 13percent) was obtained as a brown solid.
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