公开(公告)号：JPH1171394A

公开(公告)日：1999-03-16

申请号：JP17487698

申请日：1998-06-22

Applicant: DEGUSSA

Inventor： TANNER HERBERT ,  DRAUZ KARLHEINZ ,  STINGL KLAUS DR ,  SATOR GERHARD DR ,  BETHGE HORST ,  MOELLER ROLAND ,  TACKE THOMAS DR ,  REHREN CLAUS DR

IPC: C07K1/36 ,  C07K5/02 ,  C07K5/068

Abstract: PROBLEM TO BE SOLVED: To obtain the subject compound useful as an intermediate or the like for producing a blood pressure regulator by posttreating a crude substance from a production process for a specific N-substituted-L-lysyl-L-proline with liquid or supercritical CO2 . SOLUTION: A crude substance from a production process for a 1-[N2-((S)- ethoxycarbonyl)-3-phenylpropyl)-N6-trifluoroacetyl]-L-lysyl-L-proline (LPE) in which the LPE is enriched and present is precharged into an extraction container C and supercritical CO2 or liquid CO2 prepared by making liquid CO2 flow from a collection container D to a pump P1 , compressing the liquid CO2 to an extraction pressure and heating the compressed liquid CO2 to an extraction temperature with a heat exchanger E1 is fed to the extraction container C to dissolve an extractible substance in the CO2 during the passage thereof through the extraction container C. The CO2 loaded with the dissolved substance is then led to a separator S and the pressure or temperature or both are changed to deposit the extracted substance. Thereby, the LPE which is an intermediate for an inhibitor of angiotensin converting enzymes effectively useful as a blood pressure regulator is obtained in a short time.

公开(公告)号：DE19536658C2

公开(公告)日：1998-02-19

申请号：DE19536658

申请日：1995-09-30

Applicant: DEGUSSA

Inventor： KOTTENHAHN MATTHIAS DR ,  STINGL KLAUS DR ,  DRAUZ KARLHEINZ PROF DR

IPC: C07B57/00 ,  C07D233/64 ,  C07D241/04 ,  C07D277/56 ,  C07D207/16 ,  C07D261/02 ,  C07D263/06 ,  C07D265/00 ,  C07D279/00 ,  C07B55/00

Abstract: PCT No. PCT/EP96/04073 Sec. 371 Date Mar. 24, 1998 Sec. 102(e) Date Mar. 24, 1998 PCT Filed Sep. 18, 1996 PCT Pub. No. WO97/12881 PCT Pub. Date Apr. 10, 1997The invention pertains to a process for the continuous production of basic cyclic optically active alpha -amino acids of general formula (I) by continuous racemate splitting via diastereomeric salt pairs with re-racemisation of the residual amino acid or amino acid derivative in the mother liquid with the aid of an optically active acid.

公开(公告)号：DE19524339A1

公开(公告)日：1997-01-09

申请号：DE19524339

申请日：1995-07-04

Applicant: DEGUSSA

Inventor： DRAUZ KARLHEINZ PROF DR ,  KOTTENHAHN MATTHIAS DR ,  STINGL KLAUS DR

IPC: A61K31/40 ,  A61K31/401 ,  A61P9/12 ,  C07D207/24 ,  C07D495/10 ,  C07D211/94

公开(公告)号：DE19524338A1

公开(公告)日：1997-01-09

申请号：DE19524338

申请日：1995-07-04

Applicant: DEGUSSA

Inventor： STINGL KLAUS DR ,  KOTTENHAHN MATTHIAS DR ,  DRAUZ KARLHEINZ PROF DR

IPC: C07C227/02 ,  C07C231/12 ,  C07C269/06 ,  C07D231/12 ,  C07C271/22 ,  C07B51/00 ,  C07D205/10 ,  C07D207/448 ,  C07D209/10 ,  C07D209/48 ,  C07D211/94 ,  C07D213/24 ,  C07D333/06 ,  C07D417/06

Abstract: Prepn. of N-substd. amino-acids of formula R3CH(NR1R2)(CH2)nCOOH (I) by oxidn. of corresp. amino-alcohol of formula (II) in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and hypochlorite soln. R1-R3, m, n are not defined. Pref. R1 = N, 1-6C alkyl or benzyl; R2 = H, 1-6C alkyl, benzyl, formyl, COR4 or CO2R5; or R1+R2 = phthaloyl, maleyl or malonyl; R3 = H, 1-6C alkyl (opt. interrupted or substd. by heteroatoms such as N, O or S which are opt. substd. by 1-6C alkyl, benzyl, formyl, COR4 or CO2R5), benzyl (opt. substd. by OH, F, Cl, Br or NO2), phenyl, naphth-2-ylmethyl, pyrid-3-ylmethyl, thienyl, acylamino(1-6C)alkyl, 1-6C alkyloxycarbonylamino(1-6C)alkyl, 6 or 7C aryloxycarbonylamino(1-6C)alkyl, imidazol-4-ylmethyl or indol-3-ylmethyl; or R1+R3 complete a 4-7 membered ring opt. contg. other heteroatoms (N,O, or S); R4 = 1-6C alkyl, phenyl, benzyl, NH2, nitrophenyl or nitrobenzyl; R5 = 1-6C alkyl, phenyl, benzyl, nitrophenyl or nitrobenzyl; and n = 0-2.

公开(公告)号：DE19832405A1

公开(公告)日：1999-02-04

申请号：DE19832405

申请日：1998-07-18

Applicant: DEGUSSA

Inventor： KOTTENHAHN MATTHIAS DR ,  MOELLER ROLAND ,  KRAFT MICHAEL ,  DRAUZ KARLHEINZ PROF DR ,  STINGL KLAUS DR

IPC: C07K1/30 ,  A61K38/00 ,  C07K5/02 ,  C07K5/068 ,  C07K5/078

Abstract: Isolation of 1-N -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetyl-L- lysyl-L-proline (I) (i.e. lisinoprilTFA ethyl ester) from an aqueous solution obtained in the production of (I), comprises extraction followed by crystallisation. The novelty is that the solvent (or solvent mixture) used for extraction of (I) is also a major component of the solvent (mixture) used for crystallisation of (I). Also claimed is (I) which exhibits reflections at 6.7241, 9.4851, 11.9034, 16.3074 and 17.8722 (2 eta ).

公开(公告)号：DE19536658A1

公开(公告)日：1997-04-10

申请号：DE19536658

申请日：1995-09-30

Applicant: DEGUSSA

Inventor： KOTTENHAHN MATTHIAS DR ,  STINGL KLAUS DR ,  DRAUZ KARLHEINZ PROF DR

IPC: C07B57/00 ,  C07D233/64 ,  C07D241/04 ,  C07D277/56 ,  C07D207/16 ,  C07D261/02 ,  C07D263/06 ,  C07D265/00 ,  C07D279/00 ,  C07B55/00

Abstract: The invention pertains to a process for the continuous production of basic cyclic optically active alpha -amino acids of general formula (I) by continuous racemate splitting via diastereomeric salt pairs with re-racemisation of the residual amino acid or amino acid derivative in the mother liquor with the aid of an optically active acid.

公开(公告)号：ES2217462T3

公开(公告)日：2004-11-01

申请号：ES98113455

申请日：1998-07-18

Applicant: DEGUSSA

Inventor： KOTTENHAHN MATTHIAS DR ,  MOLLER ROLAND ,  KRAFT MICHAEL ,  DRAUZ KARLHEINZ PROF DR ,  STINGL KLAUS DR

IPC: C07K1/30 ,  A61K38/00 ,  C07K5/02 ,  C07K5/068

Abstract: Isolation of 1-ÄN -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetylÜ-L- lysyl-L-proline (I) (i.e. lisinoprilÄTFAÜ ethyl ester) from an aqueous solution obtained in the production of (I), comprises extraction followed by crystallisation. The novelty is that the solvent (or solvent mixture) used for extraction of (I) is also a major component of the solvent (mixture) used for crystallisation of (I). Also claimed is (I) which exhibits reflections at 6.7241, 9.4851, 11.9034, 16.3074 and 17.8722 (2&thetas; ).

公开(公告)号：AT260932T

公开(公告)日：2004-03-15

申请号：AT98113455

申请日：1998-07-18

Applicant: DEGUSSA

Inventor： KOTTENHAHN MATTHIAS DR ,  MOELLER ROLAND ,  KRAFT MICHAEL ,  DRAUZ KARLHEINZ PROF DR ,  STINGL KLAUS DR

IPC: C07K1/30 ,  A61K38/00 ,  C07K5/02 ,  C07K5/068

Abstract: Isolation of 1-ÄN -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetylÜ-L- lysyl-L-proline (I) (i.e. lisinoprilÄTFAÜ ethyl ester) from an aqueous solution obtained in the production of (I), comprises extraction followed by crystallisation. The novelty is that the solvent (or solvent mixture) used for extraction of (I) is also a major component of the solvent (mixture) used for crystallisation of (I). Also claimed is (I) which exhibits reflections at 6.7241, 9.4851, 11.9034, 16.3074 and 17.8722 (2&thetas; ).

公开(公告)号：DE19827309A1

公开(公告)日：1998-12-24

申请号：DE19827309

申请日：1998-06-19

Applicant: DEGUSSA

Inventor： TANNER HERBERT DR ,  DRAUZ KARLHEINZ PROF DR ,  STINGL KLAUS DR ,  SATOR GERHARD DR ,  BETHGE HORST ,  MOELLER ROLAND ,  TACKE THOMAS DR ,  REHREN CLAUS DR

IPC: C07K1/36 ,  C07K5/02 ,  C07K5/068 ,  A61K38/05

Abstract: A method for working up lisinopril (Tfa) ethyl ester (LPE), i.e. 1-N2-((S)-ethoxycarbonyl)-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L -proline of formula (I), involves treating crude LPE from a synthesis process, as a mixture enriched in LPE, with liquid or supercritical carbon dioxide.

公开(公告)号：DE19524337C1

公开(公告)日：1997-05-07

申请号：DE19524337

申请日：1995-07-04

Applicant: DEGUSSA

Inventor： STINGL KLAUS DR ,  KOTTENHAHN MATTHIAS DR ,  DRAUZ KARLHEINZ PROF DR

IPC: C07C213/00 ,  C07C227/26 ,  C07C229/34 ,  C07C231/12 ,  C07C233/51 ,  C07C269/06 ,  C07D305/14 ,  A61K31/195 ,  C07C229/36 ,  C07C231/14 ,  C07C271/06 ,  C07C275/42 ,  C07D205/10 ,  C07D207/448 ,  C07D209/48