Amino alcohol derivative and method for preparing the same

• US 6,335,444 B1
• Filed: 02/23/1999
• Issued: 01/01/2002
• Est. Priority Date: 12/08/1995
• Status: Expired due to Term

• Current Assignee: Seikagaku Kogyo Kabushiki Kaisha
• Original Assignee: Seikagaku Kogyo Kabushiki Kaisha
• Inventors: Inokuchi, Jinichi, Jinbo, Masayuki, Oyamada, Hidekazu
• Primary Examiner(s): Gerstl, Robert
• Application Number:
  US09/255,869
• Time in Patent Office: 1,043 Days
• Field of Search: 540/609, 544/168, 544/400, 560/29
• US Class Current: 544/168
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07C 215/18 with hydroxy groups and at least two amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 231/02 from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• CPC Class Codes: C07C 231/18 by stereospecific synthesis
• CPC Class Codes: C07C 233/36 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 211/22 by oxygen atoms
• CPC Class Codes: C07D 211/44 attached in position 4
• CPC Class Codes: C07D 295/125 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

A process for preparing a 2-acylamino alcohol derivative which comprises (A) reacting an aminopropanol derivative represented by the following formula (1):

Y—CH₂—C*H (NHP¹)—C*H(OH)—R¹   (1)

with an amine represented by R²H to synthesize an amino alcohol derivative represented by the following formula (2):

R²—CH₂—C*H(NHP¹)—C*H(OH)—R¹   (2)

(B) leaving P¹ from said amino alcohol derivative represented by formula (2) to synthesize an amino alcohol derivative represented by the following formula (3):

R²—CH₂—C*H(NH₂)—C*H(OH)—R¹   (3)

(C) reacting said amino alcohol derivative represented by formula (3) with a carboxylic acid represented by R¹¹COOH or a reactive derivative thereof to prepare a 2-acylamino alcohol derivative represented by the following formula (4):

R²—CH₂—C*H(NHCOR¹¹)—C*H(OH)—R¹   (4 )

wherein * represents an asymmetric carbon atom, and P¹, R¹, R² and R¹¹ are defined in the specification. A process for preparing alcohol derivatives having an acylamino group through several steps from amino group-protected 2-aminopropanol derivatives, and novel amino alcohols useful as intermediates in the process for preparing the alcohol derivative.

Claims

1. An amino alcohol derivative of formula (2):

2. The amino alcohol derivative according to claim 1,

wherein R¹ is an alkyl group or a cycloalkyl group, or a phenyl group which may be substituted with from 1 to 3 substituents which are the same or different and are selected from a lower alkyl group, a lower alkoxyl group, a hydroxyl group, a hydroxyl-lower-alkyl group and a nitro group.

3. An amino alcohol derivative represented by the following formula (3)

4. The amino alcohol derivative of claim 1,

wherein R¹ is an alkyl group having from 6 to 15 carbon atoms, a cyclohexyl group or a phenyl group;

P¹ is a decyl group or an amino-protecting group selected from the group consisting of a benzyloxycarbonyl group, a t-butoxycarbonyl group and an octyloxycarbonyl group; and

R² is an amino group selected from the group consisting of a morpholino group, a (lower alkyl)amino group, a (morpholino-lower alkyl)amino group, a cycloalkylamino group which may be substituted with a hydroxyl group, a piperazino group which may be substituted with a lower alkyl group and a bis(hydroxyl-lower-alkyl)amino group.

5. The amino alcohol derivative of claim 1,

wherein R¹ is a phenyl group;

P¹ is a benzyloxycarbonyl group; and

R² is a morpholino group, an N-methylpiperazino group, a diethanolamino group or a hydroxycyclohexylamino group; and

the configuration of said derivative is (1S,2S).

6. The amino alcohol derivative of claim 1,

wherein R¹ is a phenyl group;

P¹ is a benzyloxycarbonyl group; and

R² is a morpholino group, a cyclohexylamino group or a cyclopentylamino group; and

the configuration of said derivative is (1R,2R).

7. A process for preparing the amino alcohol derivative of any one of claims 1, 2, 4, 5 or 6, comprising the step of:

reacting an aminopropanol derivative represented by formula (1);

8. An amino alcohol derivative of formula (3):

9. The amino alcohol derivative of claim 8,

wherein R¹ is an alkyl group having from 6 to 15 carbon atoms, a cyclohexyl group or a phenyl group;

and

R² is a pyrrolidino group which may be substituted with a hydroxyl group or a hydroxyl-lower-alkyl group or a piperidino group which may be substituted with a hydroxyl group or a hydroxyl-lower-alkyl group.

10. An amino alcohol derivative of formula (3):

11. The amino alcohol derivative of claim 10,

wherein R¹ is an alkyl group having from 6 to 15 carbon atoms, a cyclohexyl group or a phenyl group;

and

R² is a morpholino group, a (lower alkyl) amino group, a (morpholino-lower alkyl) amino group, a cycloalkylamino group which may be substituted with a hydroxyl group, a piperazino group which may be substituted with a lower alkyl group or a bis(hydroxyl-lower-alkyl) amino group.