Process for preparing quinoline derivatives
AssigneeExelixis, Inc.
InventorsJo Ann Wilson, Sriram Naganathan, Neil G. Andersen, Matthew Pfeiffer
Life of this patent
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Abstract
A process for preparing a compound of Formula I is disclosed: wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl; R4 is (C1-C6)alkyl; and Q is CH or N; comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.
Claims28
A process for preparing a compound of Formula A:
- wherein R2 is H, F, Cl, or Br;
- comprising
- (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent at room temperature;
- and
- (b) adding
- and a tertiary amine base to the mixture of step (a).
A process for preparing a compound of Formula A
- wherein R2 is H, F, Cl, or Br;
- comprising
- (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in isopropyl acetate at room temperature;
- (b) adding
- and triethyl amine to the mixture of step (a);
- (c) quenching the resulting mixture in step (b) with concentrated aqueous sodium hydroxide;
- (d) extracting the compound of Formula A into dilute aqueous base;
- (e) acidifying the mixture with HCl;
- and
- (f) isolating the compound of Formula A by filtration.
A process for preparing a compound of Formula A-1:
- comprising
- (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in isopropyl acetate at room temperature;
- and
- (b) adding a mixture comprising 4-fluoroaniline and a triethyl amine in isopropyl acetate to the mixture of step (a).
A process for preparing a compound of Formula A-1:
- comprising
- (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in isopropyl acetate at room temperature;
- (b) adding a mixture comprising 4-fluoroaniline and a triethyl amine in isopropyl acetate to the mixture of step (a);
- (c) quenching the resulting mixture of step (b) with concentrated aqueous sodium hydroxide;
- (d) extracting the compound of Formula A-1 into dilute aqueous base;
- (e) acidifying the mixture of step (d) with HCl;
- and
- (f) isolating the compound of Formula A-1 by filtration.
A process for preparing a compound of Formula I:
- wherein:
- R1 is halo;
- R2 is halo;
- R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl;
- R4 is (C1-C6)alkyl;
- and
- Q is CH or N;
- comprising:
- (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent;
- (b) adding
- and a tertiary amine base to the mixture of step (a) to form a compound of Formula A
- (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I
Dependencies are inferred from the claim text.