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US 2006/0142580 A1Published application
N-phenyl-2-pyrimidine-amine derivatives
AssigneeNovartis AG
InventorsOlivier Loiseleur, Daniel Kaufmann, Stephan Abel, Hans Burger, Mark Meisenbach, Beat Schmitz, Gottfried Sedelmeier
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Abstract
The present invention relates to novel amides and a process for preparing these amides.
Claims20
A compound of formula I
- wherein
- one of the radicals R1, R2, R3, R4 and R5 is
- a) a radical selected from the group consisting of lower alkyl, amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- lower alkoxy-carbonyl;
- and lower alkyl which is substituted by amino, mono- or di-lower alkylamino or lower alkanoylamino, or
- b) an unsubstituted or substituted radical selected from the group consisting of benzylamino;
- benzoylamino;
- pyrrolidinyl;
- piperidyl;
- piperazinyl;
- piperazinyl-carbonyl;
- morpholinyl;
- thiomorpholinyl;
- and lower alkyl substituted by benzylamino, benzoylamino, halogene, pyrrolidinyl, piperidyl, piperazinyl, e.g. 4-methyl-piperazinyl-, thiomorpholinyl, or morpholinyl, the substituents of said substituted radical being selected from the group consisting of cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen, and
- and the other four radicals are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- or
- R1 and R2, R2 and R3, R3 and R4, or R4 and R5 together are a substituted or unsubstituted alkylene radical having 4 carbon atoms, the substituents preferably being selected from cyano, unsubstituted or hydroxy-, amino- or 4-methyl-piperazinyl-substituted lower alkyl, such as especially methyl, trifluoromethyl, free, etherified or esterified hydroxy, free, alkylated or acylated amino and free or esterified carboxy;
- and the other three radicals are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- and one of the radicals R6, R7 and R8 is halogen NH2, NO2, NHC(O)CF3, NHC(O)CH3, or NHC(NH)NH2, and the other two radicals are hydrogen, lower alkyl, lower fluorinated alkyl, benzyl or phenyl;
- or a salt or crystal form thereof.
55 more elements
Process for the preparation of a compound of formula I
- wherein
- one of the radicals R1, R2, R3, R4 and R5 is
- a) a radical selected from the group consisting of lower alkyl, amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- lower alkoxy-carbonyl;
- and lower alkyl which is substituted by amino, mono- or di-lower alkylamino or lower alkanoylamino, or
- b) an unsubstituted or substituted radical selected from the group consisting of benzylamino;
- benzoylamino;
- pyrrolidinyl;
- piperidyl;
- piperazinyl;
- piperazinyl-carbonyl;
- morpholinyl;
- thiomorpholinyl;
- and lower alkyl substituted by benzylamino, benzoylamino, halogen, pyrrolidinyl, piperidyl, piperazinyl, e.g. 4-methyl-piperazinyl-, thiomorpholinyl, or morpholinyl, the substituents of said substituted radical being selected from the group consisting of cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen, and
- and the other four radicals are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- or
- R1 and R2, R2 and R3, R3 and R4, or R4 and R5 together are a substituted or unsubstituted alkylene radical having 4 carbon atoms, the substituents preferably being selected from cyano, unsubstituted or hydroxy-, amino- or 4-methyl-piperazinyl-substituted lower alkyl, such as especially methyl, trifluoromethyl, free, etherified or esterified hydroxy, free, alkylated or acylated amino and free or esterified carboxy;
- and the other three radicals are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- and one of the radicals R6, R7 and R8 is halogen, NH2, NO2, NHC(O)CF3, NHC(O)CH3, NHC(NH)NH2, and the other two radicals are hydrogen, lower alkyl, fluorinated lower alkyl benzyl or phenyl;
- or a salt or crystal form thereof,
- wherein a compound of formula II
- is reacted with an amine of formula III
- A) wherein R9=methyl, ethyl or aryl:
- in the presence of
- 1) a Lewis acid selected from Al(lower alkyl)3, AlCl3, EtAlCl2, MeAlCl2, Me2AlCl, Et2AlCl or the corresponding sesquichlorides,
- 2) an organic solvent, and optionally
- 3) a base,
- and the resulting product is hydrolyzed;
- or
- B) wherein R9=hydrogen:
- in the presence of
- 1) thionylchloride,
- 2) an organic solvent, and optionally
- 3) a base.
69 more elements
A process for the preparation of compounds of formula I
- wherein
- the radicals R1, R2, R4 and R5 are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- or
- R1 and R2 or R4 and R5 together are a substituted or unsubstituted alkylene radical having 4 carbon atoms, the substituents preferably being selected from cyano, unsubstituted or hydroxy-, amino- or 4-methyl-piperazinyl-substituted lower alkyl, such as especially methyl, trifluoromethyl, free, etherified or esterified hydroxy, free, alkylated or acylated amino and free or esterified carboxy;
- and the other three radicals are independently hydrogen, cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- trifluoromethyl;
- free, etherified or esterified hydroxy;
- lower alkoxy;
- lower alkanoyloxy;
- free, alkylated or acylated amino;
- mono- or di-lower alkylamino;
- lower alkanoylamino;
- benzoylamino;
- free or esterified carboxy;
- lower alkoxycarbonyl and halogen;
- and R3 is a lower alkyl substituted by benzylamino, benzoylamino, pyrrolidinyl, piperidyl, piperazinyl, optionally substituted by radicals being selected from the group consisting of cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl;
- and one of the radicals R6, R7 and R8 is halogen, NH2, NO2, NHC(O)CF3, NHC(O)CH3, NHC(NH)NH2, and the other two radicals are hydrogen, lower alkyl, fluorinated lower alkyl, benzyl or phenyl,
- or a salt or crystal form thereof,
- wherein a compound of formula V
- is reacted with a compound of formula R14—H,
- wherein,
- R13 is a lower alkyl substituted by a halogen, and
- R14 is benzylamino, benzoylamino, pyrrolidinyl, piperidyl, piperazinyl, optionally substituted by radicals being selected from the group consisting of cyano;
- lower alkyl;
- hydroxy- or amino-substituted lower alkyl,
- or a salt thereof.
39 more elements
A process for the preparation of compounds of formula IV or a pharmaceutically acceptable salt or crystal form thereof, from compounds of formula I.
A pharmaceutical composition comprising,
- a) one or more pharmaceutically acceptable excipients, and
- b) at least one pharmaceutically active compound of formula IV, and
- c) between 0.00001% and 5% by weight of at least one compound of formula I.
Dependencies are inferred from the claim text.