公开(公告)号：EP0826065A1

公开(公告)日：1998-03-04

申请号：EP96913261.0

申请日：1996-04-29

申请人： MERCK & CO., INC.

发明人： CHARTRAIN, Michel, M. ,  CVETOVICH, Raymond ,  ROBERGE, Christopher

IPC分类号： C12P17 ,  C12P41

CPC分类号： C12P41/005 ,  C12P17/10 ,  Y10S435/875

摘要： The present invention relates to a process for converting a racemic mixture of 3,3-diethyl-4-[(4-carboxy)phenoxy]-2-azetidinone esters into the corresponding S-acid using lipase derived from Pseudomonas sp. The process provides the target acid in high enantiomeric excess.

公开(公告)号：EP1345878A1

公开(公告)日：2003-09-24

申请号：EP01991219.5

申请日：2001-12-18

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond ,  ASAI, Tomoyuki ,  NAKAJIMA, Yoshiko

IPC分类号： C07C45/00

CPC分类号： C07F3/02 ,  C07C17/12 ,  C07C45/004 ,  C07C49/80 ,  C07C25/13

摘要： The present invention is concerned with a novel process for the preparation of 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (CAS 30071-93-3). This compound is useful as an intermediate in the synthesis of therapeutic agents.

公开(公告)号：EP1192118A1

公开(公告)日：2002-04-03

申请号：EP00938226.8

申请日：2000-06-08

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond

IPC分类号： C07C45/45 ,  C07C49/78 ,  C07C49/303

CPC分类号： C07C17/12 ,  C07C45/004 ,  C07C25/13 ,  C07C49/80

摘要： The present invention is concerned with a novel process for the preparation of 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (CAS 30071-93-3). This compound is useful as an intermediate in the synthesis of therapeutic agents.

公开(公告)号：EP1615882A2

公开(公告)日：2006-01-18

申请号：EP04750027.7

申请日：2004-04-09

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond ,  CHUNG, John, Y. ,  AMATO, Joseph, S. ,  DIMICHELE, Lisa

IPC分类号： C07D207/16

CPC分类号： C07D401/04 ,  C07D207/16 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

摘要： A novel process is provided for the preparation of pyrrolidine carboxylic acids, and the useful intermediates obtained therein. These compounds are intermediates for the synthesis of melanocortin-4 receptor (MC-4R), which are useful for the treatment of disorders such as obesity, diabetes, male sexual dysfunction, and female sexual dysfunction.

公开(公告)号：EP0714400B1

公开(公告)日：1999-12-15

申请号：EP94926502.9

申请日：1994-08-15

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond ,  DEMCHAK, Richard ,  McCAULEY, James, A. ,  VARSALONA, Richard, J.

IPC分类号： C07H17/08 ,  A01N43/90

CPC分类号： C07H19/01 ,  A01N43/90

摘要： The most thermodynamically stable crystalline form of the benzoic acid salt of 4"-deoxy-4"-epi-methylamino avermectin B1a/B1b as the hemihydrate is obtained by crystallization from organic solvents containing a controlled amount of water.

公开(公告)号：EP1474426A2

公开(公告)日：2004-11-10

申请号：EP02775896.0

申请日：2002-09-20

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond ,  WENSLOW, Robert ,  WILLIAMS, John, M. ,  SIDLER, Daniel ,  CROCKER, Louis ,  TUNG, Hsien-Hsin ,  JOHNSON, Brian, K. ,  KUKURA, Joseph, II ,  DOLLING, Ulf

IPC分类号： C07D477/20

CPC分类号： C07D477/20 ,  C07D477/02

摘要： The present invention relates to a process for reducing the levels of organic solvents to pharmaceutically acceptable levels in thermally unstable crystalline carbapenem solids represented by formula (I), or a salt thereof, wherein R1 and R2 are the same or different, and are selected from H, alkyl, aryl, and heteroaryl, comprising washing a carbapenem solid containing organic solvent with an organic solvent containing water; and using vacuum and/or inert gas (hydrated or dry) at low temperature to produce a compound of formula (I) containing pharmaceutically acceptable levels of organic solvents, wherein the water content of the crystalline carbapenem solid, correcting for organic solvents, is maintained at about 13% to about 25% during the process.

公开(公告)号：EP0722454B1

公开(公告)日：1999-05-12

申请号：EP94931307.6

申请日：1994-10-04

申请人： Merck & Co., Inc.

发明人： AMATO, Joseph, S. ,  CVETOVICH, Raymond

IPC分类号： C07H19/01 ,  A01N43/90 ,  C07D493/22 ,  A61K31/365

CPC分类号： C07D493/22

摘要： There is disclosed a novel form of avermectin compounds wherein the avermectin compounds are crystallized as alcohol solvates to greatly enhance stability of the avermectin drug during long-term storage. The avermectin compounds have utility as highly potent antiparasitic, insecticidal, and anthelmintic agents and compositions for that use are also disclosed.

公开(公告)号：EP0722454A1

公开(公告)日：1996-07-24

申请号：EP94931307.0

申请日：1994-10-04

申请人： MERCK & CO. INC.

发明人： AMATO, Joseph, S. ,  CVETOVICH, Raymond

IPC分类号： A01N43 ,  A61K31 ,  A61P33 ,  C07D493 ,  C07H17

CPC分类号： C07D493/22

摘要： There is disclosed a novel form of avermectin compounds wherein the avermectin compounds are crystallized as alcohol solvates to greatly enhance stability of the avermectin drug during long-term storage. The avermectin compounds have utility as highly potent antiparasitic, insecticidal, and anthelmintic agents and compositions for that use are also disclosed.

公开(公告)号：EP1442038A2

公开(公告)日：2004-08-04

申请号：EP02768879.5

申请日：2002-09-20

申请人： Merck & Co., Inc.

发明人： BRANDS, Karel, M., J. ,  CVETOVICH, Raymond ,  CROCKER, Louis, S. ,  WARD, Michael, D. ,  MAHAJAN, Amar, J. ,  WENSLOW, Robert, M. ,  WILLIAMS, John, M. ,  SIDLER, Daniel, R. ,  FISHER, Elizabeth, S. ,  JOBSON, Ronald ,  ORELLA, Charles

IPC分类号： C07D477/20

CPC分类号： C07D477/20

摘要： A process for preparing a crystalline, carbapenem monosodium salt of formula IIa, characterized by the steps a) adding about 10 to 30 % of an organic solvent to an aqueous solution of the carbapenem, b) cooling the resulting solution to less than -5 °C, c) adjusting the pH using a solution containing an acid in an organic solvent to give the appropriate pH for crystallization, and d) crystallizing the compound by adding methanol, and a C2-5 alcohol at between -5 and -25 °C.

公开(公告)号：EP1192116A1

公开(公告)日：2002-04-03

申请号：EP00939672.2

申请日：2000-06-08

申请人： Merck & Co., Inc.

发明人： CVETOVICH, Raymond ,  TSAY, Fuh-Rong

IPC分类号： C07C17/12

CPC分类号： C07C17/12 ,  C07C25/13

摘要： The present invention is concerned with a novel process for the preparation of 3,5-bis(trifluoromethyl)bromobenzene (CAS 328-70-1). This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.