Claims
- 1. A process for the preparation of compounds of the formula VI ##STR12## in which R.sup.2 and R.sup.3, independently of one another, are hydrogen, (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, where alkyl, alkenyl and alkynyl are unsubstituted or substituted one or more times by fluorine, chlorine, bromine, COOH, oxo, NO.sub.2, NH.sub.2, NHC(O)--(C.sub.1 -C.sub.6)-alkyl, NHC(O)--(C.sub.6 -C.sub.12)-aryl, CN, OH, CHO, CH-[(C.sub.1 -C.sub.6)-alkoxy].sub.2, SO.sub.3 H, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl, (C.sub.1 -C.sub.6)-alkoxy; are (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.22)-arylalkyl, where aryl is unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2, NHC(O)--(C.sub.1 -C.sub.6)-alkyl, NHC(O)--(C.sub.6 -C.sub.12)-aryl, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl; or are P(O)[OH].sub.2, P(O)(OR.sup.23).sub.2, where R.sup.23 independently of one another is (C.sub.1 -C.sub.6)-alkyl, (C.sub.6 -C.sub.12)-aryl or (C.sub.7 -C.sub.13)-arylalkyl and where aryl is unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl or O--C(O)--(C.sub.6 -C.sub.12)-aryl, where R.sup.2 and R.sup.3 are not simultaneously hydrogen;
- R.sup.4 is a protective group for the amino function and
- R.sup.5 is (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.20)-arylalkyl, where alkyl, alkenyl, alkynyl and aryl are unsubstituted or substituted one or more times by fluorine, chlorine, bromine, oxo, NO.sub.2, NH.sub.2 or protected form, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl,
- which comprises converting a compound of the formula IV ##STR13## in which R.sup.4 and R.sup.5 have the abovementioned meaning and R.sup.6 and R.sup.7 independently of one another are H, Cl or Br, where not both radicals are simultaneously hydrogen
- a) by reaction with a base to a compound of the formula Va or Vb ##STR14## where R.sup.4 and R.sup.5 have the abovementioned meanings and for the preparation of the compound VI, a compound of the formula Va or Vb is reacted with carbon nucleophiles; or
- b) the compound of the formula VI is prepared by direct reaction of a compound of the formula IV with R.sup.2.sub.2 Cu(CN)Li.sub.2, R.sup.2 Li, R.sup.2 MgX, R.sup.2 ZnX, R.sup.2.sub.2 Zn, R.sup.2.sub.4-n TiR.sup.22.sub.n (n<4), P[O--R.sup.23 ].sub.3, where R.sup.2 has the abovementioned meaning; R.sup.22 is N--[(C.sub.1 -C.sub.6)-alkyl].sub.2, O--(C.sub.1 -C.sub.6)-alkyl, O--(C.sub.6 -C.sub.12)-aryl, where aryl is unsubstituted or substituted by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, CN, OH, COOH, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, or is a tartaric acid derivative; and, R.sup.23 is (C.sub.1 -C.sub.6)-alkyl (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.13)-arylalkyl, where aryl is unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, and X is a leaving group.
- 2. The process as claimed in claim 1, wherein R.sup.2 and R.sup.3 independently of one another are (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, where alkyl is unsubstituted or substituted one or more times by oxo, fluorine, chlorine, bromine, COOH, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.13)-arylalkyl, where aryl is unsubstituted or substituted one or more times by chlorine, bromine, CN, (C.sub.1 -C.sub.3)-alkoxy; P(O)[OH].sub.2, P(O)(OR.sup.23).sub.2, where R.sup.23 is (C.sub.1 -C.sub.6)-alkyl, (C.sub.6 -C.sub.12)-aryl or (C.sub.7 -C.sub.13)-arylalkyl, and R.sup.5 is (C.sub.1 -C.sub.4)-alkyl, (C.sub.2 -C.sub.4)-alkenyl, phenyl, benzyl.
- 3. The process of claim 2, wherein R.sup.2 and R.sup.3 are (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, benzyl, P(O)[OH].sub.2 or P(O)[O--(C.sub.1 -C.sub.6)-alkyl].sub.2, and R.sup.5 is (C.sub.1 -C.sub.4)-alkyl or benzyl.
- 4. The process as claimed in claim 2, wherein the base in the reaction of a compound of the formula IV is a tri-(C.sub.1 -C.sub.6)-alkylamine, pyridine, butyllithium, lithium diisopropylamide (LDA), sodium hydride, sodium amide, potassium tert-butoxide, sodium amide-R.sup.21 ONa, R.sup.21 being (C.sub.2 -C.sub.6)-alkyl or CH.sub.3 CH.sub.2 --O--CH.sub.2 CH.sub.2, or uncharged, peralkylated polyaminophosphazene bases.
- 5. The process of claim 4, wherein R.sup.21 is a tri-(C.sub.1 -C.sub.3)-alkylamine or pyridine.
- 6. The process as claimed in claim 1, wherein the carbon nucleophiles are selected from CH-acidic compounds of the formula VIIa, VIIb, VIII and IX ##STR15## R.sup.8, R.sup.9, R.sup.10, identically or independently of one another, are hydrogen, (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.20)-arylalkyl, wherein alkyl, alkenyl, alkynyl and aryl are unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, CN, OH, CHO, CH--[(C.sub.1 -C.sub.6)-alkoxy].sub.2, COOH, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl,
- R.sup.12, R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are identical to or independent of one another and are (C.sub.1 -C.sub.6)-alkyl, (C.sub.6 -C.sub.12)-aryl, where alkyl and aryl are unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl,
- R.sup.17 is hydrogen, (C.sub.1 -C.sub.6)-alkyl, where alkyl are unsubstituted or substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl, R.sup.18 and R.sup.19, identically to or independently of one another, are hydrogen, CN, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, where alkyl and aryl can be substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, CN, OH, COOH, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl, with the proviso that for R.sup.18 =hydrogen, R.sup.19 cannot also be hydrogen and vice vera,
- R.sup.20 is hydrogen, (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, (C.sub.6 -C.sub.12)-aryl, (C.sub.7 -C.sub.20)-arylalkyl, wherein alkyl, alkenyl, alkynyl and aryl can be substituted one or more times by fluorine, chlorine, bromine, NO.sub.2, NH.sub.2 or protected form, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkoxy, CN, OH, CHO, CH--[(C.sub.1 -C.sub.6)-alkoxy].sub.2, COOH, C(O)--O--(C.sub.1 -C.sub.6)-alkyl, C(O)--O--(C.sub.6 -C.sub.12)-aryl, C(O)--(C.sub.1 -C.sub.6)-alkyl, C(O)--(C.sub.6 -C.sub.12)-aryl, O--C(O)--(C.sub.1 -C.sub.6)-alkyl, O--C(O)--(C.sub.6 -C.sub.12)-aryl,
- or wherein the carbon nucleophiles are organometallic compounds selected from the group consisting of R.sup.2.sub.2 Cu(CN)Li.sub.2, R.sup.2 Li, R.sup.2 MgX, R.sup.2 ZnX, R.sup.2.sub.2 Zn and R.sup.2.sub.4-n TiR.sup.22.sub.n (n<4), where R.sup.2 and R.sup.22 have the abovementioned meanings and X is a leaving group.
- 7. The process as claimed in claim 1, wherein the base in the reaction of a compound of the formula IV is a tri-(C.sub.1 -C.sub.6)-alkylamine, pyridine, butyllithium, lithium diisopropylamide (LDA), sodium hydride, sodium amide, potassium tert-butoxide, sodium amide-R.sup.21 ONa, R.sup.21 being (C.sub.2 -C.sub.6)-alkyl or CH.sub.3 CH.sub.2 --)--CH.sub.2 CH.sub.2, or uncharged, peralkylated polyaminophosphazene bases.
- 8. The process of claim 7, wherein R.sup.21 is a tri-(C.sub.1 -C.sub.3)-alkylamine or pyridine.
Priority Claims (1)
Number |
Date |
Country |
Kind |
43 10 815.6 |
Apr 1993 |
DEX |
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Parent Case Info
This application was filed under 35 U.S.C. .sctn.371 and was based upon PCT International Application No. PCT/EP94/00950, filed Mar. 24, 1994.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP94/00950 |
3/24/1994 |
|
|
9/28/1995 |
9/28/1995 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO94/22879 |
10/13/1994 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5099063 |
Parsons et al. |
Mar 1992 |
|
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DEX |
WO9320086 |
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WOX |
Non-Patent Literature Citations (2)
Entry |
Schrader, T. et al. "Synthese von 1-Aminophosphon aure -Derivaten uber Acyliminophosphons aure-Ester" Synthesis 1986, (5), 372-375. |
Schrader, T. et al. "Phosphoranaloge von Aminos auren IV. Synthesen ungew ohnlicher 1-Aminophosphons auren uber Diels-Alder Reaktionen von (N-Acyliminomethyl)phosphons aurediethylestern" Synthesis 1990, (12), 1153-1156. |