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Structure of 59702-07-7

Chemical Structure| 59702-07-7

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Product Details of [ 59702-07-7 ]

CAS No. :59702-07-7
Formula : C5H10N2O
M.W : 114.15
SMILES Code : O=C1N(C)CCNC1
MDL No. :MFCD00102572
InChI Key :KJCIMSSFGUGTGA-UHFFFAOYSA-N
Pubchem ID :4399042

Safety of [ 59702-07-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 59702-07-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 37.76
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

32.34 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.35
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.9
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-1.71
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.78
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.36

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

0.02
Solubility 119.0 mg/ml ; 1.05 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.7
Solubility 577.0 mg/ml ; 5.05 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.6
Solubility 28.9 mg/ml ; 0.254 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.64 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.21

Application In Synthesis of [ 59702-07-7 ]

* 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.

  • Downstream synthetic route of [ 59702-07-7 ]

[ 59702-07-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 3159-04-4 ]
  • [ 59702-07-7 ]
  • [ 69478-48-4 ]
  • 2
  • [ 3158-91-6 ]
  • [ 59702-07-7 ]
  • [ 69478-49-5 ]
  • 3
  • [ 98105-79-4 ]
  • [ 59702-07-7 ]
  • [ 98106-36-6 ]
YieldReaction ConditionsOperation in experiment
1-tert-Butoxycabonyl-4-methyl-3-oxopiperazine (3.87 g) was dissolved in trifluoroacetic acid (80 ml), and the mixture stirred at ambient temperature for 2 hours. Solvent was evaporated to give 1-methyl-2-oxopiperazine as a trifluoroacetate salt, with some excess trifluoroacetic acid. MS (CI): 114 (MH+). NMR (CDCl3) delta: 3.11 (s,3H); 3.62 (t,2H); 3.72 (t,2H); 4.05 (s,2H).
(2) A solution of N-[2-(N-t-butoxycarbonyl-N-methylamino)ethyl]glycine methyl ester (1.06 g) in trifluoroacetic acid (15 ml) was stirred at 0° C. for 1 hour. After evaporation of the solvent in vacuo, the residue was dissolved in 6N ammonia in methanol (20 ml). The solution was stirred at ambient temperature for 30 minutes, and concentrated in vacuo to give 1-methyl-2piperazinone (490 mg) as an oil. Rf: 0.28 (chloroform:methanol, 10:1, V/V)
  • 5
  • C19H22BrF3N2O2S [ No CAS ]
  • [ 59702-07-7 ]
  • C24H31F3N4O3S [ No CAS ]
  • 6
  • (1R,3R)-3-Bromo-1-(4-chloro-phenoxy)-9-piperidin-4-ylmethyl-1,2,3,9-tetrahydro-carbazol-4-one [ No CAS ]
  • [ 59702-07-7 ]
  • (1R,3S)-1-(4-Chloro-phenoxy)-3-(4-methyl-3-oxo-piperazin-1-yl)-9-piperidin-4-ylmethyl-1,2,3,9-tetrahydro-carbazol-4-one [ No CAS ]
  • 7
  • [ 832696-36-3 ]
  • [ 59702-07-7 ]
  • 1-methyl-1<i>H</i>-indole-2-carboxylic acid (4-{4-amino-7-[3-(4-methyl-3-oxo-piperazin-1-yl)-propenyl]-thieno[3,2-<i>c</i>]pyridin-3-yl}-2-methoxy-phenyl)-amide [ No CAS ]
  • 8
  • [ 87-13-8 ]
  • [ 59702-07-7 ]
  • [ 1068150-01-5 ]
YieldReaction ConditionsOperation in experiment
In toluene; at 100℃; A mixture of <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (183 g, 1.6 mol) and diethyl ethoxymethylenemalonate (346 g, 1.6 mol) in toluene (12 L) was heated at 100 °C overnight. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous THF (8 L), brought to reflux under an atmosphere of nitrogen, and treated with a solution of lithium bis (trimethylsilyl)amide in THF (1 M, 1.05 eq). The reaction mixture was allowed to cool to room temperature and concentrated under vacuum. The residue was partitioned between methylene chloride and dilute aqueous HCI. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with ethyl acetate, cooled to -20 °C, and the solid precipitated was filtered to provide the title compound. 1H NMR (400 MHz, DMSO-d6) 8 8.50 (s, 1H), 7.33 (s, 1H), 4.18 (q, J = 7.1 Hz, 2H), 4.11 (t, J = 5.5 Hz, 2H), 3.59 (t, J = 5.5 Hz, 2H), 2.92 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H). ES MS M+l = 239
  • 9
  • [ 870006-58-9 ]
  • [ 59702-07-7 ]
  • [ 870006-59-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In ethanol; at 100℃; A mixture of 4,5-dibromo-2-(4-fluorobenzyl)pyridazin-3(2H)-one (0.8 g, 2.21 mmol), 1- <strong>[59702-07-7]methylpiperazin-2-one</strong> (0.33,2.87 mmol; see Example 7, Step 3), and diisopropylethyl-amine (0.34 g, 3.32 mmol) in absolute ethanol (3 mL) was heated in a sealed tube in an oil bath at 100 °C overnight. The mixture was concentrated under vacuum. The residue was partitioned between ethyl acetate and brine. The organic extract was dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with hexanes and ethyl acetate gradient to give titled material. 1H NMR (400 MHz, CDCI3) No. 7.50 (s, 1H), 7.44 (dd, J = 8.6,5.4 Hz, 2H), 7.00 (t, J = 8.7 Hz, 2H), 5.27 (s, 2H), 4.00 (s, 2H), 3.71 (t, J = 5.6 Hz, 2H), 3.51 (t, J = 5.6 Hz, 2H), 3.03 (s, 3H). ES MS M+l = 395.2, 397.2
  • 10
  • [ 869901-94-0 ]
  • [ 59702-07-7 ]
  • 2-(4-fluorobenzyl)-10-hydroxy-8-methyl-4-(4-methyl-3-oxopiperazin-1-yl)-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
at 100℃; A mixture of 10-(benzyloxy)-4-bromo-2-(4-fluorobenzyl)-8-methyl-7,8- dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione (0.10 g, 0.19 mmol; Example 160, Step 1) and <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (2 mL) was heated in a sealed tube in an oil bath at 100 °C overnight. The benzyl protecting group was also cleaved in the process. The reaction mixture was subjected to reverse phase preparative HPLC purification. Collection and lyophilization of appropriate fractions provided the title compound. 1H NMR (400 MHz, DMSO-d6) No. 7.33 (dd, J = 8.6,5.7 Hz, 2H), 7.14 (t, J = 9.0 Hz, 2H), 5.08 (s, 2H), 4.49 (br s, 2H), 3.68 (m, 2H), 3.30 (m, 2H), 2.99 (s, 3H), 2.83 (s, 3H). ES MS M+l = 455
  • 11
  • [ 760995-54-8 ]
  • [ 59702-07-7 ]
  • [ 940941-06-0 ]
  • 12
  • [ 156478-71-6 ]
  • [ 59702-07-7 ]
  • C16H28N4O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In dichloromethane; at 20℃; for 16h; A mixture [OF N-BOC-4-PIPERAZINE-ACETIC] acid hydrochloride dihydrate (0.4g, 1.26 mmol), N- methyl-2-piperazinone (0.194g, [1.] [7MMOL),] DMAP [(L.] [OG,] 8.2 mmol) and EDC (0.4g, 2. [1MMOL)] in dichloromethane (60 ml) was stirred under a nitrogen atmosphere for 16h. The reaction mixture was washed with a [L.] OM aq. citric acid solution (2 x 50ml), sat. sodium bicarbonate solution, the organics separated, dried and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica eluting with 10- 20percent MEOH/EtOAc to give 66 (0.3g) as a solid foam. MS-ESI: 341 [(M++H).] [1H NMR (DMSOD6)] 1.50 (s, 9H), 2.48 (m, 4H), 2.97 (s, 3H), 3.22-3. 56 (m, 8H), 3.78 3.90 (2t, 2H), 4.09 4.29 (2s, 2H).
  • 13
  • [ 87-13-8 ]
  • [ 59702-07-7 ]
  • [ 701208-31-3 ]
YieldReaction ConditionsOperation in experiment
Step 4: Ethyl 8-hydroxy-2-methyl-l-oxo-l,2,3,4-tetrahydropyrrolo[l,2-alpha]-pyrazine-7-carboxylate; -A mixture of l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (183 g, 1.6mol) and diethyl ethoxymethylenemalonate (346 g, 1.6 mol) in toluene (12 L) was heated at 100 0C overnight. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous THF (8 L), brought to reflux under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (I M, 1.05 eq). The reaction mixture was allowed to cool to room temperature and concentrated under vacuum. The residue was partitioned between methylene chloride and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with ethyl acetate, cooled to -20 0C, and the solid precipitated was filtered to provide the title compound. lH NMR (400 MHz,DMSO-d6) delta 8.50 (s, IH), 7.33 (s, IH), 4.18 (q, J= 7.1 Hz, 2H), 4.11 (t, J= 5.5 Hz, 2H), 3.59 (t, J= 5.5Hz, 2H), 2.92 (s, 3H), 1.24 (t, J= 7.1 Hz, 3H). ES MS M+l = 239.
A mixture of l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (183 g, 1-6mol) and diethyl ethoxymethylenemalonate (346 g, 1.6 mol) in toluene (12 L) was heated at 100 °C ovemight. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous THF (8 L), brought to reflux under an atmosphere of nitrogen, and treated with a solution of lithium bis (trimethylsilyl) amide in THF (1 M, 1.05 eq). The reaction mixture was allowed to cool to rt and concentrated under vacuum. The residue was partitioned between methylene chloride and dilute aqueous HC1. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with ethyl acetate, cooled to-20 °C, and the solid precipitated was filtered to provide the title compound. 1H NMR (400 MHz, DMSO-d6) S 8.50 (s, 1H), 7.33 (s, 1H), 4.18 (q, J = 7.1 Hz, 2H), 4.11 (t, J = 5.5 Hz, 2H), 3.59 (t, J = 5.5 Hz, 2H), 2.92 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H). ES MS M+1 = 239
  • 14
  • N-[5-chloro-7-(3-isopropoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine [ No CAS ]
  • [ 59702-07-7 ]
  • 4-{3-[(4-[5-chloro-7-(3-isopropoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-1-methylpiperazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With triethylamine; In 2-methoxy-ethanol; at 80 - 100℃; for 19h; A mixture of N [5-chloro-7- (3-isopropoxyprop-1-yn-1-yl)-1, 3-benzodioxol-4-yl]-7- (3- chloropropoxy) -6-methoxyquinazolin-4-amine (0.22g, 0. 43mmol), triethylamine (0. 29ml, 2.13mmol), <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (0.24g, 2. 13mmol) in 2-methoxyethanol (3ml) was heated to 80 C for 12 hours and then at 100 C for 7 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 2-8 percent methanol in dichloromethane to give the product as an light orange solid (0.129g, 51percent). NMR Spectrum: (DMSOd6) 1. 18 (d, 6H), 1.98 (m, 2H), 2.52 (t, 2H under DMSO), 2.72 (t, 2H), 2.88 (s, 3H), 3.04 (s, 2H), 3.34 (t, 2H under H20), 3.83 (m, 1H), 3.97 (s, 3H), 4.22 (t, 2H), 4.42 (s, 2H), 6.17 (s, 2H), 7.15 (s, 1H), 7.21 (s, 1H), 7.83 (s, 1H), 8.34 (s, 1H), 9.52 (s, 1H). Mass Spectrum: M+H+ 596 and M+ll 594
  • 15
  • [ 643086-35-5 ]
  • [ 59702-07-7 ]
  • 4-{3-[(4-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-1-methylpiperazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 2-methoxy-ethanol; at 80 - 100℃; A solution of N [5-bromo-7- (3-methoxybut-1-yn-1-yl)-1, 3-benzodioxol-4-yl]-7- (3- chloropropoxy) -6-methoxyquinazolin-4-amine (0.12g, 0. 22mmol), <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (0.125g, l. lmmol) and triethylamine (0. 15ml, l. lmmol) in 2-methoxyethanol (2ml) was heated to 80 C overnight followed by heating to 100 C for a further 24 hours. The solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. Flash chromatography on silica eluting with increasingly polar solutions of methanol (0-8percent) in dichloromethane followed by trituration with diethyl ether gave the product as a racemate and in the form of a cream coloured solid (0.052g). NMR Spectrum : (d6DMSO) 1.43 (d, 3H), 1.96-1. 99 (m, 2H), 2.50-2. 55 (m, 2H), 2.64-2. 69 (m, 2H), 2.82 (s, 3H), 3.01 (s, 2H), 3.25-3. 29 (m, 2H), 3.36 (s, 3H), 3.94 (s, 3H), 4.16-4. 21 (m, 2H), 4.40 (q, 1H), 6.16 (s, 2H), 7.19 (s, 1H), 7.29 (s, 1H), 7.84 (s, 1H), 8.32 (s, 1H), 9.50 (s, 1H). Mass Spectrum : M+HF 626/628.
  • 16
  • N-[5-bromo-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine [ No CAS ]
  • [ 59702-07-7 ]
  • 4-{3-[(4-[5-bromo-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-1-methylpiperazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 2-methoxy-ethanol; at 80 - 100℃; A solution of N [5-bromo-7- (3-methoxyprop-1-yn-1-yl)-1, 3-benzodioxol-4-yl]-7- (3- chloropropoxy) -6-methoxyquinazolin-4-amine (0.14g, 0. 26mmol), <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (0. 15g, 1. 3mmol) and triethylamine (0. 18ml, 1. 3mmol) in 2-methoxy ethanol (2ml) was heated at 80 C overnight and then further heated at 100 C for 24 hours. The solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. Flash chromatography on silica eluting with increasingly polar solutions of methanol (0-8percent) in dichloromethane followed by trituration with diethyl ether gave the product as a cream coloured solid (0. 042g). NMR Spectrum: (d6DMSO) 1.93-2. 03 (m, 2H), 2.50-2. 57 (m, 2H), 2.63-2. 70 (m, 2H), 2.82 (s, 3H), 3.01 (s, 2H), 3.25-3. 29 (m, 2H), 3.35 (s, 3H), 3.94 (s, 3H), 4.16-4. 22 (m, 2H), 4.37 (s, 2H), 6.16 (s, 2H), 7.19 (s, 1H), 7.30 (s, 1H), 7.84 (s, 1H), 8.32 (s, 1H), 9.50 (s, 1H). Mass Spectrum: M+H+ 612/614.
  • 17
  • [ 643086-87-7 ]
  • [ 59702-07-7 ]
  • 4-(3-{4-[5-chloro-7-(3-methoxy-prop-1-ynyl)-benzo[1,3]dioxol-4-ylamino]-5-isopropoxy-quinazolin-7-yloxy}-propoxy)-1-methyl-piperazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; sodium iodide; In 2-methoxy-ethanol; at 110℃; for 24h; A mixture N [5-chloro-7- (3-methoxyprop-1-yn-1-yl)-1, 3-benzodioxol-4-yl]-7- (3- chloropropoxy) -5-isopropoxyquinazolin-4-amine (0.320 g, as a 1: 1.3 wt.: wt. mixture with triphenylphosphine) and <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (0.280 g) was dissolved in 2- methoxyethanol (7 ml), then sodium iodide (0.040 g) was added and the reaction mixture was then heated at 110°C with stirring for 24 hours. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (70 ml) and washed with water: brine (1: 1) then water then brine and dried over magnesium sulfate before filtration and evaporation of solvents under reduced pressure. The residues so resulting were then purified by column chromatography on silica using increasingly polar mixtures of methanol in dichloromethane as eluent. There was thus obtained 4- (3- {4- [5-chloro-7- (3-methoxy-prop-1-ynyl)- benzo [1, 3] dioxol-4-ylamino]-5-isopropoxy-quinazolin-7-yloxy}-propoxy)-1-methyl- piperazin-2-one (0.086 g) as a white foam; NMR Spectrum: (CDC13) 1.53 (d, 6H), 2.02 (quin, 2H), 2.61 (t, 2H), 2.72 (t, 2H), 2.96 (s, 3H), 3.18 (s, 2H), 3.33 (t, 2H), 3.45 (s, 3H), 4.15 (t, 2H), 4.35 (s, 2H), 4.83 (sept, 1H), 6.10 (s, 2H), 6.49 (d, 1H), 6.82 (d, 1H), 7.05 (s, 1H), 8.51 (s, 1H), 9.41 (s, 1H); Mass Spectrum: M+H+ 596/598.
  • 18
  • [ 851726-65-3 ]
  • [ 59702-07-7 ]
YieldReaction ConditionsOperation in experiment
Step 3: l-methylpiperazin-2-one; A mixture of 4-benzyloxycarbonyl-l-methyl-3,4-dihydropyrazin-2(lH)-one (510 g, 2.1 mol) and 10% Pt/C (40 g) in ethanol (12 L) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. Pearlmans catalyst (50 g; 20% Pd(OH)2 on C) was added and stirred under an atmosphere of hydrogen gas for additional 24 hours. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide l-methylpiperazin-2-one. lH NMR (400 MHz, CDCI3) delta 3.52 (s, 2H), 3.32 (t, J= 5.7 Hz, 2H) 3.09 (t, J= 5.7 Hz, 2H), 2.97 (s, 3H).
A mixture of 4-benzyloxycarbonyl-l-methyl-3, 4-dihydropyrazin-2 (1H)-one (510 g, 2. 1mol) and 10% Pt/C (40 g) in ethanol (12 L) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. Pearlmans catalyst (50 g; 20% Pd (OH) 2 on C) was added and stirred under an atmosphere of hydrogen gas for additional 24 hours. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide l-methylpiperazin-2-one. 1H NMR (400 MHz, CDC13) 8 3.52 (s, 2H), 3.32 (t, J = 5.7 Hz, 2H) 3.09 (t, J = 5.7 Hz, 2H), 2.97 (s, 3H).
A mixture of 4-benzyloxycarbonyl-1-methyl-3,4-dihydropyrazin-2(1Fn-one (510 g, 2.1mol) and 10% Pt/C (40 g) in ethanol (12 L) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. Pearlman's catalyst (50 g; 20% Pd (OH)2 C) was added and stirred under an atmosphere of hydrogen gas for additional 24 hours. The product mixture was filtered through a pad of Celite, and then concentrated under vacuum to provide 1-methylpiperazin-2-one. ¹H NMR (400 MHz, CDCI3) 8 3.52 (s, 2H), 3.32 (t, J = 5.7 Hz, 2H) 3.09 (t, J = 5.7 Hz, 2H), 2.97 (s, 3H).
  • 19
  • 4-methoxy-7-piperidin-1-yl-benzothiazol-2-yl-amine [ No CAS ]
  • [ 59702-07-7 ]
  • [ 546093-49-6 ]
YieldReaction ConditionsOperation in experiment
84% EXAMPLE 18 4-Methyl-3-oxo-piperazine-1-carboxylic Acid (4-methoxy-7-piperidin-1-yl-benzothiazol-2-yl)-amide Using 4-methoxy-7-piperidin-1-yl-benzothiazol-2-ylamine and 4-methyl-3-oxo-piperazine, the title compound was prepared as yellow solid in 84percent yield. MS: m/e=404(M+H+).
  • 20
  • [ 410544-56-8 ]
  • [ 59702-07-7 ]
  • [ 410545-06-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; In 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; EXAMPLE 160 N-(4-fluorobenzyl)-8-hydroxy-5-(4-methyl-3-oxopiperazin-1-yl)-1,6-naphthyridine-7-carboxamide A solution of 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.20 g, 0.53 mmol), <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (0.21 g, 1.86 mmol) and diisopropylethylamine (0.19 mL, 1.06 mmol) in DMPU (2.0 mL) were heated at 135C for 26 hr. Diisopropylethylamine (0.19 mL, 1.06 mmol) was added and the reaction heated at 135C for a further 24 hr. The reaction was cooled to room temperature, neutralized by the addition of TFA and purified by reverse phase HPLC. (Vydak C18, Gradient elution with Water: Acetonitrile 95:5 to 5:95 with 0.1percent TFA at 30 mL/min over 15 mins). Lyophilization of the pure fractions afforded the title compound as an off white solid. 1H NMR (CDCl3, 400 MHz) delta 12.95 (1H, s), 9.18 (1H, dd, J=1.6 and 4.4 Hz), 8.43 (1H, dd, J=1.7 and 8.4 Hz), 8.21 (1H, m), 7.63(1H, dd, J=4.3 and 8.4 Hz), 7.40(2H, m), 7.05(2H, t, J=8.7 Hz), 4.65 (2H, d, J=6.4 Hz), 4.01 (2H, s), 3.61 (2H, t, J=5.7 Hz), 3.34(2H, t, J=5.7 Hz), 2.95 (3H, s) ppm. FAB MS calcd for C21H20FN5O3 410 (MH+), found 410.
  • 21
  • [ 369-34-6 ]
  • [ 7087-68-5 ]
  • [ 59702-07-7 ]
  • 3-fluoro-4-(4-methyl-3-oxopiperazin-1-yl)nitrobenzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 2-Methylpentane; ethyl acetate; acetonitrile; N,N-Diisopropylethylamine (11.5 ml) and 1-methyl-2-oxopiperazine (4.12 g) were added to a solution of 3,4-difluoronitrobenzene (1.82 ml) in acetonitrile (100 ml), and the mixture heated to reflux for 16 hours. Solvent was evaporated, and the residue chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 100percent ethyl acetate in iso-hexane. Relevant fractions were combined and evaporated to give 3-fluoro-4-(4-methyl-3-oxopiperazin-1-yl)nitrobenzene (3.37 g). MS (CI): 254 (MH+). NMR (DMSO-D6) delta: 3.06 (s,3H); 3.53 (t,2H); 3.67 (t,2H); 3.97 (s,2H): 6.90 (t,1H); 7.95 (dd,1H); 8.02 (m,1H).
  • 22
  • [ 110-85-0 ]
  • [ 59702-07-7 ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydroxide; In acetone; This piperazine was dissolved in 70 ml of a 50percent aqueous acetone solution containing 2.2 g of sodium hydroxide, and the resulting solution was reacted at room temperature for 3 hours. Thereafter, the solvent was removed by distillation under reduced pressure, and the residue was charged into acetone to deposit insolubles. The insolubles were separated by filtration, and the acetone was removed from the filtrate by distillation under reduced pressure. Subsequently, the residue was subjected to reduced pressure distillation to obtain 5.2 g of 1-methyl-2-oxo-piperazine, b.p. 104° C/4 mmHg, yield 91percent.
  • 23
  • [ 344778-59-2 ]
  • [ 59702-07-7 ]
  • [ 344778-72-9 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 14 3-(2-Fluorophenyl)-5-(1-methyl-2-oxopiperazin-4-yl)-[1,2,3]triazolo[1,5-a]quinazoline Prepared from 1-methylpiperazin-2(1H)-one as described for Example 1, step c (0.033 g, 73percent). deltaH (360 MHz; DMSO) 2.91 (3H, s), 3.61 (2H, dd, J=6 and 6), 3.96 (2H, dd, J=6 and 6), 4.24 (2H, s), 7.35-7.40 (2H, m), 7.44-7.46 (1H, m), 7.78 (1H, dd, J=7 and 7), 8.06-8.12 (2H, m), 8.23 (1H, d, J=7), 8.59 (1H, d, J=7); m/z (ES+) 377 (M+H+).
  • 24
  • [ 916733-13-6 ]
  • [ 59702-07-7 ]
  • C25H35N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 100℃; for 2h; EXAMPLE 202; 4-{7-[2-(4-Methyl-3-oxo-piperazin-1-yl)-ethoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; To a solution of 4-[7-(-hydroxy-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.5 mmol), prepared as described in Example 169a, in anhydrous DCM, was added Et3N (1 mmol) and methanesulfonyl chloride (1 mmol) and the mixture was stirred at rt for 2 h. It was then washed with water (3.x.), dried over anhydrous MgSO4, filtered and concentrated in vacuo to obtain crude 4-[7-(3-methanesulfonyloxy-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester. This (0.1 mmol) was dissolved in anhydrous DMSO together with 1-methyl-piperazin-2-one (0.2 mmol) and the mixture was stirred at 100° C. for 2 h and then diluted with water and extracted with DCM. The DCM extract was washed with water (3.x.), dried over anhydrous MgSO4, filtered and concentrated in vacuo. To this was added 3M HCl/MeOH (1 mL) and the mixture was stirred at rt for 2 h and then concentrated in vacuo and the residue was dissolved in a 1:1 mixture of DCM:MeOH, neutralized with excess Et3N and treated with (4-pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride (0.11 mmol), as prepared by the method outlined in Example 74a. The mixture was stirred at rt overnight and then concentrated in vacuo and partitioned between water and DCM. DCM layer was drawn off, washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by Preparative TLC (silica gel; DCM:MeOH, 95:5) followed by a further purification by Preparative HPLC to obtain 5.6 mg (6percent) of the title compound. 1H-NMR (300 MHz, CD3OD): 9.10 (s, 1H), 8.44 (d, 1H), 7.59-7.31 (m, 6H), 4.62 (t, 2H), 4.37 (m, 2H), 4.04-3.93 (m, 4H), 3.78-3.54 (m, 8H), 3.21 (m, 2H), 3.03 (s, 3H), 2.30-2.18 (m, 5H), 2.11-1.91 (m, 4H). LC/MS (ESI): 558.3 (MH)+.
  • 25
  • [ 109384-27-2 ]
  • [ 59702-07-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In dichloromethane; water; Reference Example 46] 1-Methylpiperazin-2-one [Show Image] An aqueous 1 N sodium hydroxide solution was added to a suspension of 1-methylpiperazin-2-one hydrochloride (19.6 g) of Reference Example 21-(3) in dichloromethane, and the resultant mixture was partitioned. Further, sodium chloride was added to the aqueous layer to saturate the layer, and then the aqueous layer was extracted with dichloromethane. The organic layers were combined and dried over anhydrous sodium sulfate. After separation by filtration, the solvent was evaporated under reduced pressure, and the title compound (5.90 g) was obtained as an oily product. ESI-MSm/z: 115(M+H)+.
  • 26
  • [ 944058-89-3 ]
  • [ 59702-07-7 ]
  • 1-methyl-4-[4-(methylsulfonylmethyl)-6-morpholin-4-yl-pyrimidin-2-yl]piperazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In N,N-dimethyl acetamide; at 160℃; for 0.166667h;Microwave irradiation; Example 95: l-Methyl-4-[4-(methylsuIfonylmethyl)-6-morpholin-4-yl-pyrimidin-2-yl]piperazin-2- oneA mixture of 2-chloro-4-(methylsulfonylmethyl)-6-morpholin-4-yl-pyrimidine (200 mg), l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (157 mg) and sodium carbonate (146 mg) in DMA (4 mL) was heated in a microwave reactor at 16O0C for 10 minutes. The reaction mixture was loaded onto a SCX-2 column and product removed with 7N ammonia in methanol. The solution was evaporated to dryness and chromatographed on silica, eluting with 0 - 2.5percent methanol in DCM, to give the desired material (179 mg) as a white solid. Mass Spectrum; MH+ 370NMR Spectrum: 1H NMR (DMSOd6) 52.89 (3H, s), 3.13 (3H, s), 3.38 (2H, t), 3.55 - 3.56 (4H, m), 3.67 - 3.68 (4H, m), 3.93 (2H, t), 4.19 (2H, s), 4.28 (2H, s), 6.28 (IH, s)
  • 27
  • [ 713138-81-9 ]
  • [ 59702-07-7 ]
  • 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-methyl-3-oxo-piperazin-1-yl-carbonyl)-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
8.7% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; EXAMPLE 20 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(4-methyl-3-oxo-piperazin-1-yl-carbonyl)-benzamide Prepared analogously to Example 19c from 2-chloro-4-[N-(5-chloro-benzimidazol-2-yl-methyl)-carbamoyl]-benzoic acid, TBTU, diisopropylethylamine and N-methyl-piperazinone in N,N-dimethylformamide. Yield: 8.7percent
  • 28
  • [ 59702-07-7 ]
  • [ 287714-35-6 ]
  • [ 1035271-42-1 ]
YieldReaction ConditionsOperation in experiment
57% In dichloromethane; at 20 - 25℃; for 4h; A solution of <strong>[59702-07-7]1-<strong>[59702-07-7]methylpiperazin-2-one</strong></strong> (198 mg, 1.74 mmol) in dichloromethane (4.00 mL) was added to a stirred solution of methyl 2-chloropyrimidine-5-carboxylate (300 mg, 1.74 mmol) in dichloromethane (4.70 mL) at 25° C. The resulting solution was stirred at room temperature for 4 h under nitrogen. The reaction mixture was concentrated and dissolved in ethyl acetate (25 ml) and NaOH (50 ml, 1M aqueous solution). The organic layer was washed with ethyl acetate (25 ml). The organic layers were combined and washed with brine (50 ml), dried using MgSO4, filtered and evaporated to dryness to afford methyl 2-(4-methyl-3-oxopiperazin-1-yl)pyrimidine-5-carboxylate (246 mg, 57percent) as a cream solid. 1H NMR (399.9 MHz, DMSO-d6) delta 2.91 (3H, s), 3.44 (2H, t), 3.83 (3H, s), 4.09 (2H, t), 4.35 (2H, s), 8.86 (2H, s). MS: m/z 501 (2MH+)
  • 29
  • [ 1123515-92-3 ]
  • [ 59702-07-7 ]
  • [ 1123514-43-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 1h; 4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzoic acid 54 (0.022 mmol), HATU (0.027 mmol) and l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (0.022 mmol) are dissolved in dry DMF (0.5 mL) at rt. Diisopropylethylamine (0.06 mmol) is added to the solution. The reaction mixture is stirred for 1 h at rt. HPLC purification affords 4-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzoyl)- l-<strong>[59702-07-7]methylpiperazin-2-one</strong> Gl as a TFA salt. 1H NMR (400MHz, J6-DMSO) delta 10.1 (s, IH), 8.87 (s, 2H), 7.90 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.4Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 51.2 Hz, IH), 4.1 (s, 2H), 2.87 (s, 3H), 2.55 (m, 4H). MS (m/z) (M+l)+: 454.2.
  • 30
  • [ 1002970-32-2 ]
  • [ 59702-07-7 ]
  • [ 1135439-58-5 ]
  • 31
  • 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline dihydrochloride [ No CAS ]
  • [ 79-04-9 ]
  • [ 59702-07-7 ]
  • 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[1-(4-methyl-3-oxopiperazin-1-yl)acetyl]piperidin-3-yloxy}quinazoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 65: 4- afluoroanilino)-7-methoxy-6-[1-(4-methyl-3-oxopiperazin-1- yl) acetyl] piperidin-3-yloxy} quinazoline; Chloroacetyl chloride (47mul) was added to a solution of 4- (3-Chloro-2-fluoroanilino)- 7-methoxy-6- (piperidin-3-yloxy) quinazoline dihydrochloride (250mg) and diisopropylethylamine (373, u1) in methylene chloride (10ml) and the mixture was stirred at room temperature for 1 hour. 1-Methyl-piperazin-2-one (195mg) was added, and the solution stirred for 1 hour before being washed with saturated aqueous sodium bicarbonate (10ml) and purified by flash column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5) to give a foam. This foam was dissolved in methylene chloride (5ml) and crystallised by the addition of isohexane (50ml) to give the title compound (177mg) ; 1H NMR Spectrum: (DMSO d6, 100°C) 1.57 (m, 1H), 1.91 (m, 2H), 2.08 (m, 1H), 2.67-2. 85 (m, 5H), 3. 08 (s, 2H), 3.18 (m, 3H), 3.32 (d, J=15Hz, 1H), 3.47-3. 60 (m, 2H), 3.71-3. 83 (m, 2H, ), 3.95 (s, 3H), 4.57 (m, 1H), 7.27 (m, 2H), 7.42 (m, 1H), 7.60 (m, 1H), 7.89 (s, 1H), 8. 40 (s, 1H), 9.23 (br s, 1H); Mass Spectrum: (M+H) + 557.
  • 32
  • [ 4746-97-8 ]
  • [ 59702-07-7 ]
  • [ 1046452-61-2 ]
YieldReaction ConditionsOperation in experiment
26.18 g Sodium triacetoxyborohydride are added at 5° C. to a solution of 10.0 g 4-methyl-3-oxo-piperazine, 13.51 g 1,4-dioxa-spiro[4,5]decan-8-one, 5.65 ml acetic acid and 200 ml dichloromethane. After 23 hours stirring at ambient temperature 100 ml dichloromethane and 100 ml 4N sodium hydroxide solution are added. The phases are separated and the organic phase is evaporated down. The residue is purified by chromatography.Mass spectrum (ESI+): m/z=255 [M+H]+
  • 33
  • [ 1202410-75-0 ]
  • [ 59702-07-7 ]
  • [ 1202409-70-8 ]
YieldReaction ConditionsOperation in experiment
Example 1786-(3-fluorophenyl)-N-{(1S,3R)-3-[(4-methyl-3-oxopiperazin-1 -yl)carbonyl] cyclopenty^nicotinamide To a solution of (1 R, 3S)-3-([6-(3-fluorophenyl)pyridine-3-yl]carbonyl}amino) cyclyopentanecarboxylic acid (Example 1 1 b, 49.3 mg, 0.15 mmol) and triethylamine (68.2 mg, 0.675 mmol) in dimethylformamide (1.3 mL) was added HBTU (65.2 mg, 0.172 mmol) and the solution was stirred at room temperature for 1 hour. 1-Methylpiperazin-2-one (29.4 mg, 0.195 mmol) was added and the solution was stirred at room temperature overnight. The dimethylformamide was removed by evapouration in vacuo and the residue was partitioned <n="129"/>between water (7 mL) and ethyl acetate (7 ml_). The organic layer was separated and evaporated to give a red-brown gum which was purified by HPLC Method (B) to give 23.2 mg of the title compound (LCMS Method (A), RT 2.83 min, 100percent area ES m/z [M+] 424.19).
  • 34
  • [ 1240300-07-5 ]
  • [ 59702-07-7 ]
  • [ 1240300-21-3 ]
YieldReaction ConditionsOperation in experiment
68.5% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 110℃; for 1h; Preparation of l-methyl-4-[2-(4-{l-[3-(trifluoromethyl)[l,2,4]triazolo[4,3- b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one; DIPEA (15.27 mL, 87.69 mmol) was added to 2-(4-{l-[3-(trifluoromethyl)[l,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (14.19 g, 29.23 mmol) and l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (CAS 59702-07-7, 3.67 g, 32.15 mmol) in DMA (70 mL). The resulting solution was stirred at 1100C for 1 hour. The reaction mixture was cooled to room temperature, absorbed onto silica, evaporated to dryness and then purified by flash silica chromatography, elution gradient 0 to 3percent MeOH in DCM. Pure fractions were evaporated and the resulting gum was scratched with ether until solid. The solid was stirred in ether (100 mL) for 4 hours then collected by filtration and dried to give l-methyl-4-[2-(4-{l-[3-(trifluoromethyl)[l,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4- yl}phenoxy)ethyl]piperazin-2-one (10.08 g, 68.5percent) as a solid.IH NMR (399.9 MHz, CDC13) delta 1.76 (2H, m), 2.00 (2H, m), 2.75 - 2.87 (5H, m), 2.95(3H, s), 3.11 (2H, m), 3.28 (2H, s), 3.34 (2H, t), 4.09 (2H, t), 4.37 (2H, m), 6.86 (2H, d),7.11 - 7.14 (3H, m), 7.92 (IH, d); m/z = 504 [M+H]+.
68.5% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 110℃; for 1h; Preparation of l-methyl-4-r2-(4-{l-r3-(trifluoromethyl)ri,2,41triazolor4,3- blpyridazin-6-yllpiperidin-4-yl}phenoxy)ethyllpiperazin-2-oneDIPEA (15.27 niL, 87.69 mmol) was added to 2-(4-{l-[3-(trifluoromethyl)[l,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (14.19 g, 29.23 mmol) and 1 -<strong>[59702-07-7]methylpiperazin-2-one</strong> (CAS 59702-07-7, 3.67 g, 32.15 mmol) in DMA (70 mL). The resulting solution was stirred at 1100C for 1 hour. The reaction mixture was cooled to room temperature, absorbed onto silica, evaporated to dryness and then purified by flash silica chromatography, elution gradient 0 to 3percent MeOH in DCM. Pure fractions were evaporated and the resulting gum was scratched with ether until solid. The solid was stirred in ether (100 mL) for 4 hours then collected by filtration and dried to give l-methyl-4-[2-(4-{l-[3- (trifTuoromethyl)[ 1 ,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4- yl}phenoxy)ethyl]piperazin-2-one (10.08 g, 68.5percent) as a solid.IH NMR (399.9 MHz, CDC13) delta 1.76 (2H, m), 2.00 (2H, m), 2.75 - 2.87 (5H, m), 2.95 (3H, s), 3.11 (2H, m), 3.28 (2H, s), 3.34 (2H, t), 4.09 (2H, t), 4.37 (2H, m), 6.86 (2H, d), 7.11 - 7.14 (3H, m), 7.92 (IH, d); m/z = 504 [M+H]+.
  • 35
  • [ 873065-80-6 ]
  • [ 59702-07-7 ]
  • C23H30ClN3O6S [ No CAS ]
 

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Technical Information

Categories

Related Functional Groups of
[ 59702-07-7 ]

Amides

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[ 59702-07-7 ]

Piperazines

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