WO2016024284A4 - A process for the preparation of mirabegron and its intermediates - Google Patents
A process for the preparation of mirabegron and its intermediates Download PDFInfo
- Publication number
- WO2016024284A4 WO2016024284A4 PCT/IN2015/000313 IN2015000313W WO2016024284A4 WO 2016024284 A4 WO2016024284 A4 WO 2016024284A4 IN 2015000313 W IN2015000313 W IN 2015000313W WO 2016024284 A4 WO2016024284 A4 WO 2016024284A4
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- solvent
- carbonate
- ethyl
- Prior art date
Links
- TUAHDMSPHZSMQN-INIZCTEOSA-N Nc1ccc(CCNC[C@@H](c2ccccc2)O)cc1 Chemical compound Nc1ccc(CCNC[C@@H](c2ccccc2)O)cc1 TUAHDMSPHZSMQN-INIZCTEOSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a novel process for preparation of Mirabegron of Formula (I) using intermediates of Formula (II), (IIIa), (Illb) and (IV).
Claims
A com ound of Formula (II)
Formula (Ilia)
3. A compound of Formula (Illb) or its acid addition salt
Formula (Illb)
4. A process for preparation of compound of Formula (II), comprising
coupling of compound of Formula IV)
Formula (IV)
with compound of Fo
Formula (Ilia)
in presence of a base in a solvent.
5. The process as claimed in claim 4, wherein the base used is selected from alkali metal carbonates like sodium carbonate, potassium carbonate, lithium carbonate, alkaline earth metal carbonates like barium carbonate, calcium carbonate or alkali metal hydroxide like lithium hydroxide, sodium hydroxide and potassium hydroxide.
6. The process as claimed in claim 4, wherein the solvent used is selected from solvents like methylene dichloride, ethylene dichloride, chloroform carbon tetrachloride and a mixture thereof.
7. An alternate process for preparation of compound of Formula (II), comprising:
coupling of compound of Formula (IV);
Formula (IV)
with compound of Formula (V);
Formula (V)
Wherein R is -OH or -CI,
in the presence of an activating agent when R is -OH, or in the presence of a base when R
is -CI, in a solvent.
8. The process as claimed in claim 7, wherein the activating agent used is selected from
1- ethyl-3-(3-dimethylaminopropyl) carbodiimide, carbonyldiimidazole, Ν,Ν'- dicyclohexylcarbodiimide, polyphosphoric acid, Eaton's reagent, Boric acid,
2- chloro-l -methyl pyridinium iodide, benzotriazol-l-yl-oxy-tris(dimethylamino) phosphonium hexafluorophosphate, O-benzotriazol- lyl-N,N,N2,N2-tetramethyluronium hexafluorophosphate, Ethyl cyano(hydroxyimino)aceto-2-tri-( 1 -pyrrolidinyl) phosphonium hexafluoroposphate, l-[Bis(dimethylamino)methylene]-lH- 1,2,3 -triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate), Hydroxybenzotriazole, 1 -Hydroxy-7-azabenzotriazole , (Dimethylamino)(fluoro)-N,N-dimethylmethaniminium hexafluorophosphate, N-Ethoxycarbonyl-2-ethoxy- 1 ,2-dihydroquinoline , ( 1 -Cyano-2-ethoxy-2-oxoethylidenaminooxy) dimethylamino-morpholino carbenium hexafluorophosphate, Bis(2-oxo-3-oxazolidinyl)phosphinic chloride.
9. The process as claimed in claim 7, wherein the activating agent used is 1 -ethyl-3-(3-dimethylaminopropyl) carbodiimide.
10. The process as claimed in claim 7, wherein the base used is selected from sodium carbonate, potassium carbonate, lithium carbonate, barium carbonate, calcium carbonate and lithium hydroxide, sodium hydroxide and potassium hydroxide.
11. The process as claimed in claim 7, wherein the solvent is selected from polar protic solvent like water, n-butanol, Isopropyl alcohol, ethanol, methanol or polar aprotic solvent like dimethylformamide, dimethylsulfoxide, dioxane, dimethylacetamide, tetrahydrofuran, ethyl acetate dichlorome thane, acetone, acetonitrile, hexamethylphosphorous triamide (HMPT), 1,2-dimethoxy ethane (DME) Hexamethylphosphoramide (HMPA) and a mixture thereof.
12. A process for preparation of compound of Formula (Ilia) by esterifying compound of Formula (V) with p-nitro phenol in a solvent in presence of base.
13. A process for preparation of compound of Formula (Illb) by esterifying compound of Formula (VI) with p-nitro phenol in a solvent in presence of base.
Formula (VI)
Wherein R is either -OH or -CI.
14. The process as claimed in claim 12 or 13, wherein the solvent used for esterification is selected from methylene dichloride, ethylene dichloride, chloroform, carbon tetrachloride and a mixture thereof.
15. The process as claimed in claim 12 or 13, wherein the base used is selected from sodium carbonate, potassium carbonate, lithium carbonate, barium carbonate, calcium carbonate and lithium hydroxide.
16. A process for preparation of (lR)-2-[[2-(4-aminophenyl)ethyl] amino] - 1 -phenylethanol of Formula (IV) or its hydrochloride/dihydrochloride salt;
Formula (IV)
comprising steps of:
a) coupling of compound of Formula (VII) or tosyl protected compound of Formula
(VII)
with 4-nitrophenyl ethylamine of Formula (VIII) or its hydrochloride salt
Formula (VIII)
using triethylamine in a polar aprotic solvent, optionally in presence of a coupling agent to provide (R)-2-hydroxy-N[2-(4-nitrophenyl)ethyl]-2-phenylacetamide of Formula (IX);
Formula (IX)
b) selectively reducing the nitro group of compound of Formula (IX) to amino group using Raney nickel under hydrogen pressure in an alcoholic solvent to obtain compound of Formula (X);
Formula (X)
c) reducing carbonyl group of compound of Formula (X) in presence of sodium borohydride in combination with borontrifluoride-ethrate in a polar aprotic solvent to obtain compound of Formula (IV);
d) optionally, forming hydrochloride salt of compound of Formula (IV).
17. The process as claimed in claim 16, wherein the coupling agent used in step a) is combination of hydroxybentriazole and l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride.
18. The process as claimed in claim 16, wherein the step a) is carried out in two steps a-i) protecting compound of Formula (VII) by treatment with para-toluene sulfonyl chloride
in presence of triethylamine in dichloromethane; and a-ii) coupling of protected compound of Formula (VII) with compound of Formula (VIII) or its hydrochloride salt, in presence of triethylamine in dichloromethane to obtain the compound of Formula (IX).
19. The process as claimed in claim 16, wherein the polar aprotic solvent used in step a) and c) is selected from dimethylformamide, dichloromethane, tetrahydrofuran, ethylacetate, acetone, acetonitrile and dimethylsulfoxide and a mixture thereof.
20. The process as claimed in claim 16, wherein the alcoholic solvent used in step b) of the process is selected from C1-C4 alcohols like methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, iso-butanol but preferably methanol is used.
21. The process as claimed in claim 16, wherein steps a), b) and c) are carried out in-situ.
22. A process for preparation of Mirabegron of Formula (I)
Formula (I)
by hydrolysis of compound of Formula (II) in presence of acid or base.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2534MU2014 | 2014-08-07 | ||
| IN2534/MUM/2014 | 2014-08-07 | ||
| IN4142MU2014 | 2014-12-24 | ||
| IN4142/MUM/2014 | 2014-12-24 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2016024284A2 WO2016024284A2 (en) | 2016-02-18 |
| WO2016024284A3 WO2016024284A3 (en) | 2016-05-26 |
| WO2016024284A4 true WO2016024284A4 (en) | 2016-07-14 |
Family
ID=54705668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2015/000313 WO2016024284A2 (en) | 2014-08-07 | 2015-08-05 | A process for the preparation of mirabegron and its intermediates |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2016024284A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110117263A (en) * | 2019-06-11 | 2019-08-13 | 湖南中医药大学 | 2- amino -5- acyl group thiazole and its synthetic method |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278909B (en) * | 2016-08-12 | 2022-07-15 | 浙江华海药业股份有限公司 | Post-treatment method of mirabegron intermediate |
| CZ2017461A3 (en) | 2017-08-09 | 2019-02-20 | Saneca Pharmaceuticals A.S. | Method of preparing 4-nitrophenylethylamide of mandelic acid from 4-nitrobenzylcyanide |
| CN109456277B (en) * | 2018-10-29 | 2022-04-22 | 安徽省庆云医药股份有限公司 | Preparation method of mirabegron |
| CN109651290B (en) * | 2018-10-31 | 2022-04-01 | 安徽省庆云医药股份有限公司 | Preparation method of mirabegron |
| CN113816864B (en) * | 2020-06-18 | 2024-03-29 | 南京正大天晴制药有限公司 | Preparation method of (R) -2-hydroxy-N- [2- (4-aminophenyl) ethyl ] -2-phenethylamine |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8826035D0 (en) * | 1988-11-07 | 1988-12-14 | Ici Plc | Herbicidal compositions |
| JP3193706B2 (en) * | 1997-10-17 | 2001-07-30 | 山之内製薬株式会社 | Amide derivative or salt thereof |
| US7342117B2 (en) * | 2001-10-30 | 2008-03-11 | Astellas Pharma Inc. | α-form or β-form crystal of acetanilide derivative |
| CN103387500A (en) | 2012-05-11 | 2013-11-13 | 上海医药工业研究院 | Preparation methods for mirabegron and intermediate thereof |
| CN103193730A (en) * | 2013-04-17 | 2013-07-10 | 苏州永健生物医药有限公司 | Synthesis method of mirabegron |
| CN103232352B (en) | 2013-05-11 | 2015-12-23 | 苏州永健生物医药有限公司 | (R)-4-(2-(2-hydroxyl-2-phenylethylamine base) ethyl) anilino carboxylate |
-
2015
- 2015-08-05 WO PCT/IN2015/000313 patent/WO2016024284A2/en active Application Filing
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110117263A (en) * | 2019-06-11 | 2019-08-13 | 湖南中医药大学 | 2- amino -5- acyl group thiazole and its synthetic method |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016024284A2 (en) | 2016-02-18 |
| WO2016024284A3 (en) | 2016-05-26 |
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