US 2003/0125553 A1Published application

Process for the preparation of new antidiabetic agents

AssigneeDr. Reddy's Laboratories, Inc.

InventorsMahender Rao Siripragada, Prabhakar Chebiyyam, Rajender Kumar Potlapally, Chandra Sekhar Batchu, Ramabhadra Sarma Mamillapalli, Om Reddy Gaddam

Life of this patent

Estimating the term…

Abstract

The present invention relates to an improved process for the preparation of novel antidiabetic compounds having formula (1) where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom. 1

Claims52

Dependent claims

A process for the preparation of a compound of formula (I)

10
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating phydroxybenzaldehyde of formula (7)
11
to obtain a compound of formula (8),
12
(ii) reacting the compound of formula (8) with an alkyl haloacetate in the presence of a base at a temperature in the range of —10° C. to 60° C. to obtain a glycedic ester of formula (9)
13
where R represents lowercyl group,
(iii) opening up the epoxide group of the glycedic ester of a compound of formula (9) in the presence of a catalyst to obtain a compound of formula (10)
14
where R is as defined above,
(iv) hydrolyzing the compound of formula (10) followed by the resolution of the resultant compound to obtain the (S)-hydroxy compound of formula (11),
15
(v) alkylating the compound of formula (11) in the presence of a base to obtain a compound of formula (12)
16
where R1 represents hydrogen or lower alkyl, and R2 represents lower alkyl group,
(vi) debenzylating the compound of formula (12) to obtain a compound of formula (13)
17
where R1 and R2 are as defined above, if desired,
(vii) converting the compound of formula (13) to a compound of formula (14)
18
where X represents halogen atom and all other symbols are as defined above
(viii) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
19
to obtain a compound of formula (16)
20
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) hydrolyzing the compound of formula (16)
21
to obtain a compound of formula (1) as defined above, and if desired,
(x) resolving the compound of formula (1).

29 more elements

A process for the preparation of a compound of formula (I)

22
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating p-hydroxybenzaldehyde of formula (7)
23
to obtain a compound of formula (8),
24
(ii) reacting the compound of formula (8) with an alkyl haloacetate in the presence of a base at a temperature in the range of −10° C. to 60° C. to obtain a glycedic ester of formula (9)
25
where R represents lower alkyl group,
(iii) opening up the epoxide group of the glycedic ester of the compound of formula (9) in the presence of a catalyst to obtain a compound of formula (10)
26
where R has the meaning given above,
(iv) alkylating the compound of formula (10) in the presence of a base to obtain a compound of formula (12a)
27
where R1 represents hydrogen or lower alkyl and R2 represents lower alkyl group,
(v) debenzylating the compound of formula (12a) to produce a compound of formula (13a)
28
where R1 and R2 are as defined above, if desired,
(vi) converting the compound of formula (13a) to a compound of formula (14a)
29
where X represents halogen atom and R1 and R2 are as defined above,
(vii) reacting either the compound of formula (13a) or the compound of formula (14a) with phenoxazinyl mesylate of formula (15)
30
to obtain a compound of formula (4)
31
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(viii) hydrolyzing the compound of formula (4) to obtain the racemic compound of formula (5)
32
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) chemically resolving the compound of formula (5) to obtain a compound of formula (1) optionally through an intermediate amide of formula (6)
33
where X represents hydrogen or halogen atom and R1 is as defined above.

29 more elements

A process for the preparation of compound of formula (I)

34
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) reacting p-hydroxybenzaldehyde of formula (7)
35
with hydantoin of formula (17)
36
to obtain a compound of formula (18),
37
(ii) hydrolyzing the compound of formula (18) to obtain a compound of formula (19),
38
(iii) reducing the compound of formula (19) to obtain a compound of formula (20),
39
where R represents hydrogen or lower alkyl group,
(iv) benzylating the compound of formula (20) to obtain a compound of formula (10)
40
where R has the meaning given above,
(v) hydrolyzing the compound of formula (10) followed by resolution to obtain (S)-hydroxy compound of formula (11),
41
(vi) alkylating the compound of formula (11) in the presence of a base to obtain a compound of formula (12)
42
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(vii) debenzylating the compound of formula (12) to produce a compound of formula (13),
43
(viii) if desired, converting the compound of formula (13) to a compound of formula (14)
44
where X represents halogen atom, and R1 and R2 are as defined above,
(ix) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
45
to obtain a compound of formula (16)
46
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(x) hydrolyzing the compound of formula (16) to obtain the compound of formula (1) defined above, and if desired,
(xi) chemically resolving the compound of formula (1).

30 more elements

A process for the preparation of compound of formula (1)

47
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) reacting phydroxybenzaldehyde of formula (7)
48
with hydantoin of formula (I 7)
49
to obtain a compound of formula (18),
50
(ii) hydrolyzing the compound of formula (18) to obtain a compound of formula (19),
51
(iii) reducing the compound of formula (19) to obtain a compound of formula (20),
52
where R represents hydrogen or lower alkyl group,
(iv) benzylating the compound of formula (20) to obtain a compound of formula (10)
53
where R is as defined earlier,
(v) alkylating the compound of formula (10) in the presence of a base to obtain a compound of formula (12a)
54
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(vi) debenzylating the compound of formula (12a) to produce a compound of formula (13a)
55
where R1 and R2 are as defined above, if desired,
(vii) converting the compound of formula (13a) to a compound of formula (14a)
56
where X represents halogen atom, and R1 and R2 are as defined above,
(viii) reacting either the compound of formula (13a) or the compound of formula (14a) with phenoxazinyl mesylate of formula (15)
57
to obtain a compound of formula (4)
58
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) hydrolyzing the compound of formula (4) to obtain the racemic compound of formula (5)
59
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above, and
(x) chemically resolving the compound of formula (5) to a compound of formula (1) optionally through an intermediate amide of formula (6)
60
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above. The process as claimed in claim 32 wherein the reduction in step (iii) is carried out in a solvent selected from the group consisting of methanol, ethanol, propanol and ethylacetate.

33 more elements

A process for the preparation of a compound of formula (1)

61
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating L-tyrosine of formula (21)
62
to obtain a compound of formula (22),
63
(ii) diazotizing the compound of formula (22) in the presence of an acidic reagent and an organic solvent to produce compound of formula (11′)
64
where R′ represents hydrogen or acetyl group,
(iii) if desired, hydrolyzing the compound of formula (11′) where R′ represents acetyl group to a compound of formula (11′) where R′ represents hydrogen,
(iv) alkylating the compound of formula (11′) in the presence of a base where R′ represents hydrogen to the alkyl compound of formula (12)
65
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(v) debenzylating the compound of formula (12) to produce a compound of formula (13) where R1 and R2 are as defined above, if desired,
(vi) converting the compound of formula (13)
66
to a compound of formula (14)
67
where X represents halogen, and R1 and R2 are as defined above,
(vii) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
68
to obtain a compound of formula (16)
69
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(viii) hydrolyzing the compound of formula (16) to obtain the compound of formula (1) defined above, and if desired,
(ix) chemically resolving the compound of formula (1).
The process as claimed in claim 41, wherein the hydrolysis in step (iii) is carried out using an hydrolyzing agent selected from the group consisting of NaOH, KOH, LiOH, and Ba(OH)2.

24 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/325,176Filed 20 Dec 2002
Priority: IN 2431/MAS/9829 Oct 1998
Published: 3 Jul 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 265/38
Condensed with carbocyclic rings: [b, e]-condensed with two six-membered rings
C07C 51/09
Preparation of carboxylic acids or their salts, halides or anhydrides: from carboxylic acid esters or lactones
C07C 67/31
By modifying the acid moiety of the ester, such modification not being an introduction of an ester group: by introduction of functional groups…
C07D
Heterocyclic compounds

Family

Application09/786,599Division · filed 30 May 2001
Application09/786,599A 371 of international · filed 30 May 2001
Application10/325,176Division · filed 20 Dec 2002
US 6,531,596 B1Related patent
US 7,223,881 B2Related patent
US 2003/0125553 A1This patent

From the US filing history. Foreign family members aren’t listed.

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US 2003/0125553 A1Published application

Process for the preparation of new antidiabetic agents

AssigneeDr. Reddy's Laboratories, Inc.

InventorsMahender Rao Siripragada, Prabhakar Chebiyyam, Rajender Kumar Potlapally, Chandra Sekhar Batchu, Ramabhadra Sarma Mamillapalli, Om Reddy Gaddam

Life of this patent

Estimating the term…

Abstract

Claims52

Dependent claims

A process for the preparation of a compound of formula (I)

10
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating phydroxybenzaldehyde of formula (7)
11
to obtain a compound of formula (8),
12
(ii) reacting the compound of formula (8) with an alkyl haloacetate in the presence of a base at a temperature in the range of —10° C. to 60° C. to obtain a glycedic ester of formula (9)
13
where R represents lowercyl group,
(iii) opening up the epoxide group of the glycedic ester of a compound of formula (9) in the presence of a catalyst to obtain a compound of formula (10)
14
where R is as defined above,
(iv) hydrolyzing the compound of formula (10) followed by the resolution of the resultant compound to obtain the (S)-hydroxy compound of formula (11),
15
(v) alkylating the compound of formula (11) in the presence of a base to obtain a compound of formula (12)
16
where R1 represents hydrogen or lower alkyl, and R2 represents lower alkyl group,
(vi) debenzylating the compound of formula (12) to obtain a compound of formula (13)
17
where R1 and R2 are as defined above, if desired,
(vii) converting the compound of formula (13) to a compound of formula (14)
18
where X represents halogen atom and all other symbols are as defined above
(viii) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
19
to obtain a compound of formula (16)
20
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) hydrolyzing the compound of formula (16)
21
to obtain a compound of formula (1) as defined above, and if desired,
(x) resolving the compound of formula (1).

29 more elements

A process for the preparation of a compound of formula (I)

22
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating p-hydroxybenzaldehyde of formula (7)
23
to obtain a compound of formula (8),
24
(ii) reacting the compound of formula (8) with an alkyl haloacetate in the presence of a base at a temperature in the range of −10° C. to 60° C. to obtain a glycedic ester of formula (9)
25
where R represents lower alkyl group,
(iii) opening up the epoxide group of the glycedic ester of the compound of formula (9) in the presence of a catalyst to obtain a compound of formula (10)
26
where R has the meaning given above,
(iv) alkylating the compound of formula (10) in the presence of a base to obtain a compound of formula (12a)
27
where R1 represents hydrogen or lower alkyl and R2 represents lower alkyl group,
(v) debenzylating the compound of formula (12a) to produce a compound of formula (13a)
28
where R1 and R2 are as defined above, if desired,
(vi) converting the compound of formula (13a) to a compound of formula (14a)
29
where X represents halogen atom and R1 and R2 are as defined above,
(vii) reacting either the compound of formula (13a) or the compound of formula (14a) with phenoxazinyl mesylate of formula (15)
30
to obtain a compound of formula (4)
31
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(viii) hydrolyzing the compound of formula (4) to obtain the racemic compound of formula (5)
32
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) chemically resolving the compound of formula (5) to obtain a compound of formula (1) optionally through an intermediate amide of formula (6)
33
where X represents hydrogen or halogen atom and R1 is as defined above.

29 more elements

A process for the preparation of compound of formula (I)

34
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) reacting p-hydroxybenzaldehyde of formula (7)
35
with hydantoin of formula (17)
36
to obtain a compound of formula (18),
37
(ii) hydrolyzing the compound of formula (18) to obtain a compound of formula (19),
38
(iii) reducing the compound of formula (19) to obtain a compound of formula (20),
39
where R represents hydrogen or lower alkyl group,
(iv) benzylating the compound of formula (20) to obtain a compound of formula (10)
40
where R has the meaning given above,
(v) hydrolyzing the compound of formula (10) followed by resolution to obtain (S)-hydroxy compound of formula (11),
41
(vi) alkylating the compound of formula (11) in the presence of a base to obtain a compound of formula (12)
42
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(vii) debenzylating the compound of formula (12) to produce a compound of formula (13),
43
(viii) if desired, converting the compound of formula (13) to a compound of formula (14)
44
where X represents halogen atom, and R1 and R2 are as defined above,
(ix) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
45
to obtain a compound of formula (16)
46
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(x) hydrolyzing the compound of formula (16) to obtain the compound of formula (1) defined above, and if desired,
(xi) chemically resolving the compound of formula (1).

30 more elements

A process for the preparation of compound of formula (1)

47
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) reacting phydroxybenzaldehyde of formula (7)
48
with hydantoin of formula (I 7)
49
to obtain a compound of formula (18),
50
(ii) hydrolyzing the compound of formula (18) to obtain a compound of formula (19),
51
(iii) reducing the compound of formula (19) to obtain a compound of formula (20),
52
where R represents hydrogen or lower alkyl group,
(iv) benzylating the compound of formula (20) to obtain a compound of formula (10)
53
where R is as defined earlier,
(v) alkylating the compound of formula (10) in the presence of a base to obtain a compound of formula (12a)
54
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(vi) debenzylating the compound of formula (12a) to produce a compound of formula (13a)
55
where R1 and R2 are as defined above, if desired,
(vii) converting the compound of formula (13a) to a compound of formula (14a)
56
where X represents halogen atom, and R1 and R2 are as defined above,
(viii) reacting either the compound of formula (13a) or the compound of formula (14a) with phenoxazinyl mesylate of formula (15)
57
to obtain a compound of formula (4)
58
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(ix) hydrolyzing the compound of formula (4) to obtain the racemic compound of formula (5)
59
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above, and
(x) chemically resolving the compound of formula (5) to a compound of formula (1) optionally through an intermediate amide of formula (6)
60
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above. The process as claimed in claim 32 wherein the reduction in step (iii) is carried out in a solvent selected from the group consisting of methanol, ethanol, propanol and ethylacetate.

33 more elements

A process for the preparation of a compound of formula (1)

61
where R1 represents hydrogen or lower alkyl group and X represents hydrogen or halogen atom, which comprises:
(i) benzylating L-tyrosine of formula (21)
62
to obtain a compound of formula (22),
63
(ii) diazotizing the compound of formula (22) in the presence of an acidic reagent and an organic solvent to produce compound of formula (11′)
64
where R′ represents hydrogen or acetyl group,
(iii) if desired, hydrolyzing the compound of formula (11′) where R′ represents acetyl group to a compound of formula (11′) where R′ represents hydrogen,
(iv) alkylating the compound of formula (11′) in the presence of a base where R′ represents hydrogen to the alkyl compound of formula (12)
65
where R1 represents hydrogen or lower alkyl group, and R2 represents lower alkyl group,
(v) debenzylating the compound of formula (12) to produce a compound of formula (13) where R1 and R2 are as defined above, if desired,
(vi) converting the compound of formula (13)
66
to a compound of formula (14)
67
where X represents halogen, and R1 and R2 are as defined above,
(vii) reacting either the compound of formula (13) or the compound of formula (14) with phenoxazinyl mesylate of formula (15)
68
to obtain a compound of formula (16)
69
where X represents hydrogen or halogen atom, and R1 and R2 are as defined above,
(viii) hydrolyzing the compound of formula (16) to obtain the compound of formula (1) defined above, and if desired,
(ix) chemically resolving the compound of formula (1).
The process as claimed in claim 41, wherein the hydrolysis in step (iii) is carried out using an hydrolyzing agent selected from the group consisting of NaOH, KOH, LiOH, and Ba(OH)2.

24 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/325,176Filed 20 Dec 2002
Priority: IN 2431/MAS/9829 Oct 1998
Published: 3 Jul 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 265/38
Condensed with carbocyclic rings: [b, e]-condensed with two six-membered rings
C07C 51/09
Preparation of carboxylic acids or their salts, halides or anhydrides: from carboxylic acid esters or lactones
C07C 67/31
By modifying the acid moiety of the ester, such modification not being an introduction of an ester group: by introduction of functional groups…
C07D
Heterocyclic compounds

Family

Application09/786,599Division · filed 30 May 2001
Application09/786,599A 371 of international · filed 30 May 2001
Application10/325,176Division · filed 20 Dec 2002
US 6,531,596 B1Related patent
US 7,223,881 B2Related patent
US 2003/0125553 A1This patent

From the US filing history. Foreign family members aren’t listed.