喹啉合成

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Cl N Br O Br OH N N O
O N O
1
Rx-ID: 23335695 View in Reaxys Yield Conditions & References
93 %
Example Name 1.II.1 To a solution of 7 (15 g, 0.056 mol) in acetonitrile (80 mL) and DIPEA (15.9 g, 0.123 mol), was added POCI3 (17.1 g, 0.112 mol) dropwisely at O0C. The reaction temperature was slowly raised to 1000C for 2 hours. The mixture was cooled and poured onto ice-water. After Neutralized with aq NaHCC>3, extracted with ethyl acetate, and dried over Na2SO4, the crude product was obtained by evaporating of solution to dryness (15 g, 93percent) as a brown solid. MS (m/z) (M++H): 287, 289. With N-ethyl-N,N-diisopropylamine, trichlorophosphate in acetonitrile, Time= 2h, T= 0 - 100 °C Patent; PROGENICS PHARMACEUTICALS, INC.; WO2009/155527; (2009); (A2) English; WO 2009/155527 A2 View in Reaxys
43 %
Example Name 1.II.1 Compound 6 (15 g, 0.052 mol) and potassium acetate (6.16 g, 0.063 mol) in acetic anhydride (100 mL) were stirred for 1.5 h at 1200C. The precipitate was filtered and washed with acetic acid until the filtrate was colorless and then with water. The solid was dried to give 7 (6 g, 43percent). MS (m/z) (M>H): 269, 271 With potassium acetate in acetic anhydride, Time= 1.5h, T= 120 °C Patent; PROGENICS PHARMACEUTICALS, INC.; WO2009/155527; (2009); (A2) English; WO 2009/155527 A2 View in Reaxys Example Name 1.b 29 g (101 mmol) of 5-bromo-2-(2-nitro-vinylamino)-benzoic acid (Example 1a) and 11.9 g (121 mmol) of potassium acetate in 129 ml (152 mmol) of acetic anhydride are stirred for 1.5 h at 120 0C. The precipitate is filtered off and washed with acetic acid until the filtrate is colorless, then is washed with H2O and dried in vacuo to give the title compound. ES-MS: 269, 271 (M + H)+, Br pattern; analytical HPLC: W= 2.70 min (Grad 1). With potassium acetate, acetic anhydride, Time= 1.5h, T= 120 °C Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2006/122806; (2006); (A2) English; WO 2006/122806 A2 View in Reaxys
Copyright © 2014 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
68 %
Example Title Synthesis of 4g After a suspension of 3g (10 mmol) in phosphorus oxychloride (15 mL) was added triethylamine slowly. The mixture was stirred and refluxed for 1.5 h. The phosphorus oxychloride was quenched with water carefully, then the suspension was filtered and the decolorized solid was recrystallized with ethyl acetate and petroleum ether. Yield 68percent. HPLC purity: 98.8percent. With triethylamine, trichlorophosphate, Time= 1.5h, Reflux Zhang, Wenjuan; Li, Zhi; Zhou, Meng; Wu, Feng; Hou, Xueyan; Luo, Hao; Liu, Hao; Han, Xuan; Yan, Guoyi; Ding, Zhenyu; Li, Rui; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 3; (2014); p. 799 - 807 View in Reaxys
38 %
Example Name A.3 6-Bromo-3-nitroquinolin-4-ol (Compound of step 2, 20 g, 74.3 mmol) and POCI3 (150 mL, 1613 mmol) were stirred for 45 minutes at 120 0C. The mixture was cooled to RT and poured slowly into ice-water. The precipitate was filtered, washed with ice-cold water, and dissolved in CH2CI2. The organic layer was washed with cold brine, and was dried over Na2SOzJ. The solvent was evaporated to dryness to obtain the title compound.Yield: 8 g (38 percent); 1H NMR (CDCl3, 500 MHz): δ 9.275 (s, IH), 8.611-8.615 (d, IH, J= 2Hz), 8.100- 8.118 (d, IH, J=9Hz), 8.026-8.048 (dd, IH, J= 8.5Hz, 2Hz). With trichlorophosphate, Time= 0.75h, T= 120 °C Patent; PIRAMAL LIFE SCIENCES LIMITED; KUMAR, Sanjay; VISHWAKARMA, Ram; MUNDADA, Ramswaroop; DEORE, Vijaykumar; KUMAR, Pramod; SHARMA, Somesh; WO2011/1212; (2011); (A1) English; WO 2011/001212 A1 View in Reaxys
Cl Br
O N O
N
1
N O Br OH N O
2
2.1
2.2
2.3 H E O N O
N
Br O N N H O
Br O N N H HO O O
O
O
O
Br O N N H HO O O
O
O
O
Br O N N H HO O O
Br OH
HO O
3
Cl H 2N O Br OH H
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OH Br
N
2.1
N H
O E
O
O
N O
Br OH
N O
Rx-ID: 24899778 View in Reaxys Yield Conditions & References
64 %
Example Name A.2 5-Bromo-2-(2-nitrovinylamino)benzoic acid (Compound of step 1, 25 g, 87 mmol) and potassium acetate (10.5 g, 104 mmol) in acetic anhydride (112 mL, 1185 mmol) were stirred for 3 hours at 120 0C. The precipitate was filtered, and washed with acetic acid till the filtrate was colorless. It was further washed with water and dried to obtain the title compound. Yield: 15 g (64 percent); 1H NMR (CDCl3, 500 MHz): δ 9.275 (s, IH), 8.611-8.615 (d, IH, J= 2Hz), 8.100-8.118 (d, IH, J=9Hz), 8.026-8.048 (dd, IH, J= 8.5Hz, 2Hz). With potassium acetate in acetic anhydride, Time= 3h, T= 120 °C Patent; PIRAMAL LIFE SCIENCES LIMITED; KUMAR, Sanjay; VISHWAKARMA, Ram; MUNDADA, Ramswaroop; DEORE, Vijaykumar; KUMAR, Pramod; SHARMA, Somesh; WO2011/1212; (2011); (A1) English; WO 2011/001212 A1 View in Reaxys
4
HN O N O OH
5
O N
Cl H
6
HN O
Br
O
H 2N O Br OH
H 2N O OH
OH
O N
O
H 2N O Br
N O
OH
Copyright © 2014 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.