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[ CAS No. 21091-98-5 ]

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2D
Chemical Structure| 21091-98-5
Chemical Structure| 21091-98-5
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Product Details of [ 21091-98-5 ]

CAS No. :21091-98-5MDL No. :MFCD00585638
Formula : C12H15N3O3 Boiling Point : -
Linear Structure Formula :-InChI Key :-
M.W :249.27Pubchem ID :716396
Synonyms :

Computed Properties of [ 21091-98-5 ]

TPSA : 69.4 H-Bond Acceptor Count : 4
XLogP3 : - H-Bond Donor Count : 0
SP3 : 0.42 Rotatable Bond Count : 1

Safety of [ 21091-98-5 ]

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305 P351 P338UN#:N/A
Hazard Statements:H302-H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 21091-98-5 ]

  • Upstream synthesis route of [ 21091-98-5 ]
  • Downstream synthetic route of [ 21091-98-5 ]

[ 21091-98-5 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 109-01-3 ]
  • [ 122-04-3 ]
  • [ 21091-98-5 ]
YieldReaction ConditionsOperation in experiment
92%
Stage #1: at 0℃; for 1.17 h; Inert atmosphere
Stage #2: With triethylamine In dichloromethane at 20℃; for 1.00 h;
A 100 mL 3-necked flask was equipped with a magnetic stirrer bar, nitrogen in- and outlet and septum. The setup was thoroughly dried using a heat gun and allowed to cool to room temperature under a nitrogen flow. Then, 4-nitrobenzoyl chloride (4.64 g, 25.0 mmol) was dissolved in dry dichloromethane (50 mL) and the solution was 10 minutes in an ice-water bath. N-methylpiperazine (2.58 g, 25.8 mmol, 1.03 eq) was added drop wise over a 10 minute time interval while stirring vigorously. The resulting suspension was stirred for 1 hour at 0° C., after which triethylamine (5.01 g, 50.0 mmol, 2.0 eq) was added and stirrring was continued at r.t. for 1 h. The reaction mixture was transferred into a separatory funnel and washed with demineralized water (3×50 mL). The organic layer was dried over Na2SO4, filtered over a paper filter and all volatiles were removed under reduced pressure using a rotary evaporator to give the desired product as a pale orange solid (5.77 g 23.1 mmol, 92percent).
82%
Stage #1: at 10℃; for 1.17 h;
Stage #2: With triethylamine In acetonitrile for 0.50 h;
A solution of 4-nitrobenzoyl chloride (25) (1 g, 5.39 mol) in CH3CN (50 mL) was treated with 1-methylpiperazine (26) at 10° C. over 10 min. The reaction mixture was stirred for another 1 h followed by addition of TEA (1.49 mL, 2 eq) and stirring for an additional half hour. The reaction mixture was diluted with ice-cold water (150 mL) and extracted with EtOAc (4.x.150 mL). The organic layer was dried over MgSO4 and concentrated to give 1.1 g (82percent yield) (4-methylpiperazin-1-yl)(4-nitrophenyl)methanone 27 as a yellow solid. TLC: 10percent MeOH/DCM, Rf=0.6. 1NMR (400 MHz, CDCl3) 8.28(d, J=8.5 Hz, 2H), 7.56(d, J=8.5 Hz, 2H), 3.88(br-s, 4H), 3.46(br-s, 4H), 2.40(s, 3H) ESI/MS m/z 250.0 (M+H)
0.249 g With triethylamine In dichloromethane at 20℃; This amine was required for the synthesis of 5. 4-nitrobenzoylchloride (1 mmol, 0.186 g) in anhydrous dichloromethane (5 mL) was reacted with 1-methylpiperazine (1 mmol, 0.11 mL) and triethylamine (1.5 mmol, 0.21 mL) overnight with stirring at room temperature. Workup was carried out as described in Section 6.6 to give 0.249 g of (4-methylpiperazin-1-yl) (4-nitrophenyl)methanone, yellow liquid. 1H NMR (300 MHz, CDCl3) δ 2.33 (s, 3H), 2.40 (m, 2H), 2.51 (m, 2H), 3.39 (m, 2H), 3.82 (m, 2H), 7.57 (d, J = 8.6, 2H), 8.28 (d, J = 8.6, 2H). MS(ESI) m/z [M + H+] 250.1. Reduction to give the title compound was carried out as described in Section 6.6.
Reference: [1] Patent: US2018/223077, 2018, A1. Location in patent: Paragraph 0116-0117
[2] Patent: US2008/214558, 2008, A1. Location in patent: Page/Page column 23-24
[3] Patent: WO2004/26829, 2004, A2. Location in patent: Page/Page column 94
[4] Patent: WO2004/63195, 2004, A1. Location in patent: Page 60
[5] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 9, p. 2740 - 2744
[6] Patent: WO2010/80474, 2010, A1. Location in patent: Page/Page column 133
[7] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 2917 - 2929
  • 2
  • [ 109-01-3 ]
  • [ 62-23-7 ]
  • [ 21091-98-5 ]
YieldReaction ConditionsOperation in experiment
95% With ethylene dichloride hydrochloride; benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 12.00 h; Step 1: (4-Methyl-piperazin-l-yl)-( -nitro-phenyl)-methanoneTo a solution of 4-nitro-benzoic acid (10 g, 0.0598 mol) in DMF (300 mL) 1- methyl-piperazine (7.19 g, 0.0718 mol), HOBt (10.5 g, 0.0777 mol), EDC-HCl (17.12 g, 0.0897 mol) and TEA (12.1 g, 0.1 196 mol) were added. The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x 200 mL). The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford the title compound [14 g, 95percent]; LC-MS (ESI): Calculated mass: 249.1; Observed mass: 250.0 [M+H]+ (RT: 0.10 min).
80% With 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℃; To a solution of 4-nitrobenzoicacid (1.0 g, 5.98 mmol), 1-methylpiperazine (0.599 g, 5.98 mmol) and DIPEA (2.320 g,17.95 mmol) in DMF (10 mL) was added HATU (4.55 g, 11.97 mmol). The reaction wasstirred overnight at room temperature. The mixture was quenched with water andextracted with a mix solvent of DCM and MeOH (10:1, 20 mL×3). The combinedextracts were dried over Na2SO4, filtered and concentrated. The crude was purified bycolumn chromatography on silica gel (DCM: MeOH= 20:1) to give the title compound 3a(1.2 g, 80 percent yield). LCMS: 250.1 [M+H]+.
59% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; Step: 3A-lSynthesis of (4-Methyl-piperazin-l-yl)-(4-nitro-phenyl)-methanone. Procedure:To a solution of 4-Nitro-benzoic acid (500mg, 2.9918mmol) in THF was added EDCI (856mg, 4.4865mmol), followed by HOBt (200mg, 2.9918mmol), DIPEA (1.5ml,8.9754mmol) and 1 -Methyl -piperazine (329mg, 3.291mmol) at 0°C. The resultant was stirred overnight. The reaction was monitored by the TLC (10percent methanol: chloroform).The reaction mixture was extracted with ethyl acetate and washed with water. The organic layer was concentrated and dried over Na2S04 to afford 440mg (59percent yield) of (4- Methy 1-piperazin- 1 -yl)-(4-nitro-phenyl)-methanone.
Reference: [1] Patent: WO2012/58671, 2012, A1. Location in patent: Page/Page column 79
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 9, p. 1615 - 1620
[3] Patent: WO2012/59932, 2012, A1. Location in patent: Page/Page column 120-121
[4] Patent: WO2010/71885, 2010, A1. Location in patent: Page/Page column 461
[5] Patent: US2012/277220, 2012, A1. Location in patent: Page/Page column 15
  • 3
  • [ 367-24-8 ]
  • [ 30806-83-8 ]
  • [ 21091-98-5 ]
YieldReaction ConditionsOperation in experiment
70% With triethylamine In dichloromethane at 20℃; for 3.00 h; Step 1: 4- [3-(4-Bromo-2-fluoro-phenyl)-ureido] -benzoic acid ethyl esterTo a solution of 4-bromo-2-fluoroaniline (0.5 g, 0.0026 mol) and TEA (0.38 mL, 0.0026 mol) in DCM (15 mL) was added ethyl 4-isocyanatobenzoate (0.503 g, 0.0026 mol). The reaction mixture was stirred at room temperature for 3 h. The white solid was obtained and was filtered and dried to afford the title compound [0.7 g, 70percent]; LC-MS (ESI): Calculated mass: 380.0; Observed mass: 381.0 [M+H]+ (RT: 1.78 min).
Reference: [1] Patent: WO2012/58671, 2012, A1. Location in patent: Page/Page column 81
  • 4
  • [ 109-01-3 ]
  • [ 122-04-3 ]
  • [ 21091-98-5 ]
YieldReaction ConditionsOperation in experiment
82% With triethanolamine In acetonitrile (4-(4-(3-chloro-4-fluorophenylamino)pyrimidin-2-ylamino)phenyl)(4-methyl piperazin-1-yl)methanone (Compound 1-15)
A solution of 4-nitrobenzoyl chloride (25) (1 g, 5.39 mol) in CH3CN (50 mL) was treated with 1-methylpiperazine (26) at 10° C. over 10 min.
The reaction mixture was stirred for another 1 h followed by addition of TEA (1.49 mL, 2 eq) and stirring for an additional half hour.
The reaction mixture was diluted with ice-cold water (150 mL) and extracted with EtOAc (4*150 mL).
The organic layer was dried over MgSO4 and concentrated to give 1.1 g (82percent yield) (4-methylpiperazin-1-yl)(4-nitrophenyl)methanone 27 as a yellow solid. TLC: 10percent MeOH/DCM, Rf=0.6. 1NMR (400 MHz, CDCl3) 8.28 (d, J=8.5 Hz, 2H), 7.56 (d, J=8.5 Hz, 2H), 3.88 (br-s, 4H), 3.46 (br-s, 4H), 2.40 (s, 3H) ESI/MS m/z 250.0 (M+H)
Reference: [1] Patent: US2010/29675, 2010, A1
  • 5
  • [ 109-01-3 ]
  • [ 555-16-8 ]
  • [ 21091-98-5 ]
Reference: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 17, p. 4622 - 4626[2] Angew. Chem., 2018, vol. 130, # 17, p. 4712 - 4716,5
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