The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Dauming Hsieh - One of the best experts on this subject based on the ideXlab platform.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
Zhongmin Xu - One of the best experts on this subject based on the ideXlab platform.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
Jinkun Huang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of pyrido fused quinazolinone derivatives via copper catalyzed domino reaction
ChemInform, 2016Co-Authors: Meilin Liu, Miaomiao Shu, Chaochao Yao, Guodong Yin, Dunjia Wang, Jinkun HuangAbstract:The copper-catalyzed reaction of isatins (I) with 2-bromopyridines (II) leads to a variety of pyrido-fused quinazolinones (III).
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synthesis of pyrido fused quinazolinone derivatives via copper catalyzed domino reaction
Organic Letters, 2016Co-Authors: Meilin Liu, Miaomiao Shu, Chaochao Yao, Guodong Yin, Dunjia Wang, Jinkun HuangAbstract:A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C–N/C–C bond cleavage and two C–N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed.
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Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction
2016Co-Authors: Meilin Liu, Miaomiao Shu, Chaochao Yao, Guodong Yin, Dunjia Wang, Jinkun HuangAbstract:A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C–N/C–C bond cleavage and two C–N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed
Philip Deshong - One of the best experts on this subject based on the ideXlab platform.
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synthesis of the cd ring of the anticancer agent streptonigrin studies of aryl aryl coupling methodologies
Tetrahedron, 2006Co-Authors: William T Mcelroy, Philip DeshongAbstract:A series of functionalized 4-Bromopyridines, representing the C-ring of the anticancer agent streptonigrin have been prepared and their abilities to undergo Pd-catalyzed cross-coupling with streptonigrin D-ring siloxanes were evaluated. The coupling reaction was generally tolerant to the preparation of hindered CD biaryls; however, the electronic effects of both partners play a pivotal role in the success of the coupling process. Analogs of the CD biaryl were prepared by coupling of aryl siloxane derivatives (D-ring component) with highly functionalized 4-Bromopyridines (C-ring); however, the CD biaryl of the natural product could not be prepared in high yield by siloxane coupling due to the facile formation of reduced pyridine under the coupling conditions. Alternatively, the fully functionalized CD biaryl of streptonigrin was prepared using a Suzuki coupling of appropriately functionalized C-ring bromide and D-ring aryl boronic acid. The described approach is highly convergent and readily amenable to the synthesis of analogs.
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siloxane based cross coupling of bromopyridine derivatives studies for the synthesis of streptonigrin and lavendamycin
Organic Letters, 2003Co-Authors: William T Mcelroy, Philip DeshongAbstract:Highly functionalized 4-Bromopyridines were prepared and found to undergo fluoride-promoted, Pd-catalyzed cross-coupling with aryltrialkoxysilanes to give sterically demanding biaryls. The 3-nitro-4-Bromopyridine derivative coupled in good yield with TBAT (tetrabutylammonium triphenyldifluorosilicate) to provide a biaryl adduct that serves as a model system for the total synthesis of the antitumor antibiotics streptonigrin and lavendamycin.
Bharat P. Patel - One of the best experts on this subject based on the ideXlab platform.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
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process research and development for an efficient synthesis of the hiv protease inhibitor bms 232632
Organic Process Research & Development, 2002Co-Authors: Zhongmin Xu, Michael J Humora, Fernando Quiroz, Thomas P. Kissick, Bharat P. Patel, Janak Singh, Bin Zheng, Mark D. Schwinden, Lin Dong, Dauming HsiehAbstract:Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.
