Methods of making quinoline amides
AssigneePfizer Inc.
InventorsNorma J. Tom, David C. Whritenour
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Abstract
The present invention relates to methods of making quinoline amides of Formula I below, which are microsomal triglyceride transfer protein inhibitors and can be used as medicines. 1 The present invention also relates to compounds that are used to make quinoline amides of Formula I and methods of making these compounds.
Claims22
A method of making a compound of Formula Ia
- 96
- wherein
- each R3 is independently hydrogen or C1-C6alkyl;
- A is
- 97
- X is O or S;
- n is 0 to 6;
- each Rb is independently hydrogen, —CF3, —OC1-C6alkyl, halo, —SH, —SC1-C6alkyl, phenyl, or —C1-C6alkyl;
- B is hydrogen,
- 98
- each R is independently hydrogen or C1-C6alkyl;
- each Y is independently phenyl, substituted phenyl, pyridyl or substituted pyridyl, wherein any substituents are independently selected from —CF3, halo, —OC1-C6alkyl, or —C1-C6alkyl;
- and
- m is 0 to 5;
- the method comprising the steps of:
- a. reacting
- 99
- b. reducing
- 100
- c. reacting
- 101
- d. oxidizing
- 102
- e. coupling
- 103
- to form a compound of Formula Ia.
The compound:
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The compound:
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A method of making
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- the method comprising the step of:
- a. reacting
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A method of making
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- the method comprising the steps of:
- a. reacting
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- b. reducing
- 111
A method of making
- 112
- the method comprising the steps of:
- a. reacting
- 113
- b. reducing
- 114
- c. reacting
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A method of making
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- the method comprising the step of:
- reacting
- 117
A method of making a compound of Formula I
- 118
- wherein
- each R3 is independently hydrogen or C1-C6alkyl;
- A is
- 119
- X is O or S;
- n is 0 to 6;
- each R is independently hydrogen, —CF3, —OC1-C6alkyl, halo, —SH, —SC1-C6alkyl, phenyl, or —C1-C6alkyl;
- B is hydrogen,
- 120
- each R is independently hydrogen or C1-C6alkyl;
- each Y is independently phenyl, substituted phenyl, pyridyl or substituted pyridyl, wherein any substituents are independently selected from —CF3, halo, —OC1-C6alkyl, or —C1-C6alkyl;
- and
- m is 0 to 5;
- the method comprising the steps of:
- 1. reacting
- 121
- 2. reacting
- 122
- 3. hydrolyzing
- 123
- 4. reacting
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- with H2N—B to provide a compound of Formula I.
The compound:
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A method of making
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- the method comprising the step of:
- reacting
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A method of making a compound of Formula I
- 130
- wherein
- each R3 is inependently hydrogen or C1-C6alkyl;
- A is
- 131
- X is O or S;
- n is 0 to 6;
- each Rb is independently hydrogen, —CF3, —OC1-C6alkyl, halo, —SH, —SC1-C6alkyl, phenyl, or —C1-C6alkyl;
- B is hydrogen,
- 132
- each Y is independently phenyl, substituted phenyl, pyridyl or substituted pyridyl, wherein any substituents are independently selected from —CF3, halo, —OC1-C6alkyl, or —C1-C6alkyl;
- and
- m is 0 to 5;
- the method comprising the steps of:
- A. reacting
- 133
- B. hydrolyzing
- 134
- C. reacting
- 135
- D. hydrolyzing
- 136
- to give
- E. reacting
- 137
- with H2N—B to provide a compound of Formula I.
The compound:
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- wherein R3 is hydrogen or C1-C6alkyl.
A method of making
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- wherein R3 is hydrogen or C1-C6alkyl,
- the method comprising the steps of:
- 140
A method of resolving phenyl-(2-pyridyl)-methylamine to obtain (S)-phenyl-(2-pyridyl)-methylamine, (S)-(+)-α-methoxyphenylacetic acid salt, the method comprising the steps of:
- a. reacting phenyl-(2-pyridyl)-methylamine with (S)-(+)-α-methoxyphenylacetic acid in isopropanol, which results in a precipitate being formed;
- and
- b. isolating the precipitate, which is (S)-phenyl-(2-pyridyl)-methylamine, (S)-(+)-α-methoxyphenylacetic acid salt.
Dependencies are inferred from the claim text.