130693-82-2

Basic information

• Product Name: Dorzolomide hydrochloride
• Synonyms: 3-b)thiopyran-2-sulfonamide,5,6-dihydro-4-(ethylamino)-6-methyl-4h-thieno(;mk-0507;monohydrochloride,(4s-trans)-7-dioxide;(2s,4s)-2-ethylamino-4-methyl-5,5-dioxo-5,7-dithiabicyclo[4.3.0]nona-8,10-diene-8-sulfonamide hydrochloride;DORZOLAMIDE HCL;DORZOLAMIDE HYDROCHLORIDE;dorzolomide hydrochloride;DorzolomideHcl,Usp
• CAS NO: 130693-82-2
• Molecular Formula: C₁₀H₁₆N₂O₄S₃*ClH
• Molecular Weight: 360.9
• EINECS: 1308068-626-2
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Dorzolamide;Heterocycles;Sulfur & Selenium Compounds;API;Trusopt, Cosopt;Other APIs;Inhibitors
• Mol File: 130693-82-2.mol

Chemical Properties

• Melting Point: 265-2670C
• Boiling Point: 575.8 °C at 760 mmHg
• Flash Point: 302 °C
• Appearance: White off-white crystalline powder.
• Density: 1.53 g/cm³
• Vapor Pressure: 2.93E-13mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: Soluble in water, slightly soluble in methanol, very slightly soluble in anhydrous ethanol.
• Merck: 14,3426
• BRN: 5896026
• CAS DataBase Reference: Dorzolomide hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Dorzolomide hydrochloride(130693-82-2)
• EPA Substance Registry System: Dorzolomide hydrochloride(130693-82-2)

Safety Data

• WGK Germany: 3
• RTECS: XJ9095163
• Hazardous Substances Data: 130693-82-2(Hazardous Substances Data)

Usage

Uses

Used in Ophthalmology:
Dorzolomide hydrochloride is used as an antiglaucoma agent for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. It acts as a carbonic anhydrase inhibitor, which helps in lowering intraocular pressure (IOP) and has been shown to be effective throughout the day.
Used in Sports Doping:
Dorzolomide hydrochloride is used as a diuretic in sports doping to reduce weight or anabolic androgenic steroid-induced water retention, or as a masking agent. It is categorized as a carbonic anhydrase inhibitor diuretic and is intended for use in analytical forensic applications.
Used in Research and Development:
Dorzolomide hydrochloride is also used as an analytical reference standard and a general research tool for the development of new pharmaceuticals and the study of its properties and applications in various fields.
Used in Pain Management:
Dorzolomide hydrochloride is used as an analgesic, providing relief from pain in various conditions.

Originator

Merck (U.S.A.)

Manufacturing Process

Manufacturing process for Dorzolamide hydrochloride includes these steps as follows: Step A: Sulfuric Acid Ritter Procedure;Step B: Sulfonylation Procedure Step C: Chlorosulfonylation Procedure;Step D: Amidation Procedure;Step E: Reduction via Borane Generated in situ Procedure;Step F: Maleate Salt Formation Procedure;Step G: Crude Hydrochloride Salt Formation;Step H: Recrystallization Procedure.

Therapeutic Function

Antiglaucoma

Veterinary Drugs and Treatments

Dorzolamide is often used in the contralateral eye of a dog with primary glaucoma to prevent development of bilateral disease. It is also an excellent agent to consider for most secondary glaucomas in dogs and cats because it has no effect on pupil size. Like the related oral carbonic anhydrase inhibitors (dichlorphenamide or Daranide?, methazolamide or Neptazane?), dorzolamide decreases aqueous humor production by the ciliary body epithelium by altering pH and affecting the H+/Na+ active transport exchange mechanism. Oral carbonic anhydrase inhibitors cause numerous systemic side effects such as metabolic acidosis and panting, diarrhea, vomiting, anorexia and others, all of which can be avoided with topical carbonic anhydrase inhibitors.

InChI:InChI=1/C10H16N2O4S3.ClH/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16;/h5-6,8,12H,3-4H2,1-2H3,(H2,11,15,16);1H/t6-,8-;/m0./s1

Synthetic route

(4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide di-p-toluyl-L-tartate salt (1227941-29-8) → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Stage #1: (4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide di-p-toluyl-L-tartate salt With sodium hydrogencarbonate In water; ethyl acetate at 25 - 30℃; for 0.25h; Stage #2: With hydrogenchloride In ethyl acetate; isopropyl alcohol at 25 - 85℃; for 12.5h; Product distribution / selectivity;	100%
With hydrogenchloride In isopropyl alcohol at 80℃; for 0.0833333 - 0.166667h; pH=3 - 4; Product distribution / selectivity; Heating / reflux;
Stage #1: (4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide di-p-toluyl-L-tartate salt With sodium hydrogencarbonate In ethyl acetate at 20℃; Stage #2: With hydrogenchloride In methanol; isopropyl alcohol for 0.666667h;

5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonamide 7,7-dioxide maleate salt → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Stage #1: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonamide 7,7-dioxide maleate salt With hydrogenchloride; sodium hydroxide In water at 52℃; pH=7.7; Inert atmosphere; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 20 - 75℃;	99.2%
Stage #1: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonamide 7,7-dioxide maleate salt With sodium hydroxide In water at 52℃; Inert atmosphere; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 75℃;	8.1 g

dorzolamide (120279-96-1) → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
With hydrogenchloride In ethyl acetate pH=1;	95%
With hydrogenchloride In water; dimethyl sulfoxide at 5 - 10℃; for 3h; pH=1.0;

5,6-dihydro-4-(S)-ethylamino-6-(S)-methyl-4H-thieno[2,3-b]thiopyran-7,7-dioxide hydrochloride → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Stage #1: 5,6-dihydro-4-(S)-ethylamino-6-(S)-methyl-4H-thieno[2,3-b]thiopyran-7,7-dioxide hydrochloride With sulfuric acid; sulfur trioxide at 20℃; for 2 - 3h; Stage #2: With thionyl chloride for 3 - 6h; Heating / reflux; Stage #3: With hydrogenchloride; ammonia Product distribution / selectivity; more than 3 stages;	70%
Stage #1: 5,6-dihydro-4-(S)-ethylamino-6-(S)-methyl-4H-thieno[2,3-b]thiopyran-7,7-dioxide hydrochloride With sulfuric acid; sulfur trioxide at -7 - 20℃; for 22h; Stage #2: With thionyl chloride at 20 - 65℃; for 24h; Stage #3: With hydrogenchloride; ammonia Product distribution / selectivity; more than 3 stages;

Reaxys ID: 11712783 → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
With (-)-di-p-toluoyl-L-tartaric acid	22.48%

trans-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Stage #1: trans-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide; Di-p-toluoyl-L-tartaric acid In propan-1-ol Heating / reflux; Stage #2: With sodium hydrogencarbonate In water Stage #3: With hydrogenchloride In ethanol	22.48%

2C10H16N2O4S3*C11H10O7 → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Stage #1: 2C10H16N2O4S3*C11H10O7 With sodium carbonate In water; ethyl acetate Stage #2: With hydrogenchloride In ethyl acetate; isopropyl alcohol pH=1 - 2;

5,6-dihydro-6-methyl-4-oxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide → dorzolamide hydrochloride (130693-82-2)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: dihydrogen peroxide / sodium tungstate (VI) dihydrate / ethyl acetate; water / -20 °C 2.1: water; sodium tetrahydroborate; methanol / ethyl acetate / 10 - 20 °C 3.1: sulfuric acid / 0 - 30 °C 3.2: 10 °C / pH 7 - 8 4.1: sodium tetrahydroborate / tetrahydrofuran / -5 - 5 °C 4.2: 5 - 20 °C 5.1: sodium hydroxide / 20 °C / pH 7.5 - 8 6.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 7.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 7.2: 0.67 h View Scheme

4-hydroxy-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sulfuric acid / 0 - 30 °C 1.2: 10 °C / pH 7 - 8 2.1: sodium tetrahydroborate / tetrahydrofuran / -5 - 5 °C 2.2: 5 - 20 °C 3.1: sodium hydroxide / 20 °C / pH 7.5 - 8 4.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 5.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 5.2: 0.67 h View Scheme

(+/-)-(4S,6S;4R,6R)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 2.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 2.2: 0.67 h View Scheme

(+/-)-(4S,6S;4R,6R)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide maleate → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / 20 °C / pH 7.5 - 8 2.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 3.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 3.2: 0.67 h View Scheme

N-(6-methyl-7,7-dioxido-2-sulfamoyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-yl)acetamide → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / tetrahydrofuran / -5 - 5 °C 1.2: 5 - 20 °C 2.1: sodium hydroxide / 20 °C / pH 7.5 - 8 3.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 4.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 4.2: 0.67 h View Scheme

6-methyl-4-oxo-5,6-dihydro-4H-thieno[2.3-b]thiopyran-2-sulfonamide-7,7-dioxide (935289-26-2) → dorzolamide hydrochloride (130693-82-2)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: water; sodium tetrahydroborate; methanol / ethyl acetate / 10 - 20 °C 2.1: sulfuric acid / 0 - 30 °C 2.2: 10 °C / pH 7 - 8 3.1: sodium tetrahydroborate / tetrahydrofuran / -5 - 5 °C 3.2: 5 - 20 °C 4.1: sodium hydroxide / 20 °C / pH 7.5 - 8 5.1: isopropyl alcohol; acetonitrile / 1 h / 70 °C / Reflux 6.1: sodium hydrogencarbonate / ethyl acetate / 20 °C 6.2: 0.67 h View Scheme

(6S)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-4-one-2-sulfonamide (1383784-43-7) → dorzolamide hydrochloride (130693-82-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium tungstate (VI) dihydrate; oxygen / methanol; water / 6 h / 10 - 50 °C / Inert atmosphere 2.1: sodium tetrahydroborate / water; tetrahydrofuran / 2 h / 15 °C / Inert atmosphere 3.1: methanesulfonic acid / 18 h / 10 - 87 °C / Inert atmosphere 3.2: 4.5 h / 7 - 40 °C / pH 7.3 4.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 4.2: 40 °C 5.1: sodium hydroxide / water / 52 °C / Inert atmosphere 5.2: 75 °C View Scheme

(6S)-4-oxo-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide (154716-03-7) → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / water; tetrahydrofuran / 2 h / 15 °C / Inert atmosphere 2.1: methanesulfonic acid / 18 h / 10 - 87 °C / Inert atmosphere 2.2: 4.5 h / 7 - 40 °C / pH 7.3 3.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 3.2: 40 °C 4.1: sodium hydroxide / water / 52 °C / Inert atmosphere 4.2: 75 °C View Scheme

cis-(6S)-4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: methanesulfonic acid / 18 h / 10 - 87 °C / Inert atmosphere 1.2: 4.5 h / 7 - 40 °C / pH 7.3 2.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 2.2: 40 °C 3.1: sodium hydroxide / water / 52 °C / Inert atmosphere 3.2: 75 °C View Scheme

(4S,6S)‑4‑acetamido‑5,6‑dihydro‑6‑methyl‑4H‑thieno[2,3‑b]thiopyran‑2‑sulfonamide‑7,7‑dioxide (147200-03-1) → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 1.2: 40 °C 2.1: sodium hydroxide / water / 52 °C / Inert atmosphere 2.2: 75 °C View Scheme

(S)-5,6-dihydro-6-methylthieno<2,3-b>thiopyran-4-one (147086-79-1) → dorzolamide hydrochloride (130693-82-2)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: thionyl chloride; chlorosulfonic acid / 10 h / -3 - 28 °C / Inert atmosphere 2.1: ammonia / methanol; acetone / -10 °C / Inert atmosphere 3.1: sodium tungstate (VI) dihydrate; oxygen / methanol; water / 6 h / 10 - 50 °C / Inert atmosphere 4.1: sodium tetrahydroborate / water; tetrahydrofuran / 2 h / 15 °C / Inert atmosphere 5.1: methanesulfonic acid / 18 h / 10 - 87 °C / Inert atmosphere 5.2: 4.5 h / 7 - 40 °C / pH 7.3 6.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 6.2: 40 °C 7.1: sodium hydroxide / water / 52 °C / Inert atmosphere 7.2: 75 °C View Scheme

(S)-6-methyl-4-oxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonyl chloride (1083006-59-0) → dorzolamide hydrochloride (130693-82-2)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: ammonia / methanol; acetone / -10 °C / Inert atmosphere 2.1: sodium tungstate (VI) dihydrate; oxygen / methanol; water / 6 h / 10 - 50 °C / Inert atmosphere 3.1: sodium tetrahydroborate / water; tetrahydrofuran / 2 h / 15 °C / Inert atmosphere 4.1: methanesulfonic acid / 18 h / 10 - 87 °C / Inert atmosphere 4.2: 4.5 h / 7 - 40 °C / pH 7.3 5.1: borane-THF / tetrahydrofuran / 17 h / 38 °C / Inert atmosphere 5.2: 40 °C 6.1: sodium hydroxide / water / 52 °C / Inert atmosphere 6.2: 75 °C View Scheme

(6S)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide → 4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride (1417607-96-5) + dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
With hydrogenchloride In acetone at 0 - 5℃; for 2h; pH=1 - 2;	A n/a B n/a

(6S)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride → dorzolamide hydrochloride (130693-82-2)

Conditions	Yield
In methanol; water for 2h; Solvent; Reflux;	3.2 g

N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + dorzolamide hydrochloride (130693-82-2) → (E)-N'-{[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}-N,N-dimethylmethanimidamide

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 3h;	80%

1,8-octanediol bis(4-nitrophenylcarbonate) + dorzolamide hydrochloride (130693-82-2) → 8-(((((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)carbamoyl)oxy)octyl (((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)carbamate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	56%

dorzolamide hydrochloride (130693-82-2) + N,N-dimethylformamide diethyl diacetal (1188-33-6) → N'-[(4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ6-thieno[2,3-b]thiopyran-2-sulfonyl]-N,N-dimethylmethanimidamide (1034583-83-9)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;

Upstream product

• 120279-96-1 dorzolamide 
• 1227941-29-8 (4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide di-p-toluyl-L-tartate salt 
• 154802-22-9 5,6-dihydro-4-hydroxy-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide 
• 935289-26-2 6-methyl-4-oxo-5,6-dihydro-4H-thieno[2.3-b]thiopyran-2-sulfonamide-7,7-dioxide 
• 1383784-43-7 (6S)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-4-one-2-sulfonamide 
• 154716-03-7 (6S)-4-oxo-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide 
• 154802-22-9 cis-(6S)-4-hydroxy-5,6-dihydro-6-methyl-7,7-dioxo-4H-thieno[2,3-b]thiopyran-2-sulfonamide 
• 147200-03-1 (4S,6S)?4?acetamido?5,6?dihydro?6?methyl?4H?thieno[2,3?b]thiopyran?2?sulfonamide?7,7?dioxide 
• 147086-79-1 (S)-5,6-dihydro-6-methylthieno<2,3-b>thiopyran-4-one 
• 1083006-59-0 (S)-6-methyl-4-oxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonyl chloride 
• 120279-37-0 (6S)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride 

Relevant articles and documents

Method for preparing dorzolamide hydrochloride and method for purifying intermediate

The invention relates to a method for preparing dorzolamide hydrochloride and a method for purifying an intermediate. The method for preparing the dorzolamide hydrochloride comprises the following steps: carrying out crystallization treatment on an ester solution of a compound ((4S, 6R-trans)-4-ethylamino-5, 6-dihydro-6-methyl-4H-thieno [2, 3-b] thiapyran-2-sulfonamide-7, 7-dioxide) as shown in the formula D15 of an intermediate to obtain a purified compound as shown in the formula D15; and reacting the compound as shown in the formula D15 with hydrochloric acid to obtain the dorzolamide hydrochloride. The synthesis process is shortened, so that the production time is saved, the efficiency is improved, and the cost is reduced.

Chiral synthesis method of dorzolamide hydrochloride

The invention relates to a chiral synthesis method of dorzolamide hydrochloride, which comprises the following steps: (1) by taking a compound I that is (6S)-4-carbonyl-5,6-dihydro-4H-6-methyl-thieno[2,3b] thiopyran-2-sulfonamide-7,7-dioxide as an initial raw material, carrying out imidization reaction on the initial raw material and ethylamine to obtain a compound II that is (6S)-4-ethyl imino-5,6-dihydro-4H-6-methyl-thieno[2, 3b]thiopyran-2-sulfonamide-7,7-dioxide; (2) carrying out asymmetric hydrogenation reaction on the compound II obtained in the step (1), a catalyst and a chiral ligand (R)-(+)-1,1'-binaphthyl-2'-isopropoxy-2-diphenylphosphine to obtain a compound III that is dorzolamide; and (3) mixing the compound III obtained in the step (2) with hydrochloric acid, acidifying, washing and drying to obtain a compound IV, namely dorzolamide hydrochloride. The synthesis method is simple and easy to implement, high in chiral selectivity and low in cost, and the obtained dorzolamide hydrochloride is high in purity and suitable for industrial production.

PROCESS FOR THE PREPARATION OF DORAOLZMIDE HYDROCHLORIDE

The present invention discloses an improved process for the preparation of dorzolamide hydrochloride the compound of Formula I.

Process for Preparing Enantiomerically Enriched Oxamides

The present invention relates to a chiral oxamide of formula (I) useful as an intermediate in the preparation of dorzolamide, and to the preparation thereof. The invention also relates to the preparation of dorzolamide, to the hydrochloride salt thereof, and to the active ingredient contained in a drug useful in the treatment of glaucoma, by means of the intermediate of formula (I).

PROCESS FOR PREPARING ENANTIOMERICALLY ENRICHED OXAMIDES

The present invention relates to a chiral oxamide of formula (I) useful as an intermediate in the preparation of dorzolamide, and to the preparation thereof. The invention also relates to the preparation of dorzolamide, to the hydrochloride salt thereof, and to the active ingredient contained in a drug useful in the treatment of glaucoma, by means of the intermediate of formula (I).

PROCESS FOR PREPARING (4S, 6S)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO-[2,3-B]THIOPYRAN-2-SULFONAMIDE-7,7-DIOXIDE AND ITS INTERMEDIATES

Disclosed herein is an improved process for the preparation of (4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide-7,7- dioxide (Dorzolamide) and its intermediates.

PROCESS FOR PREPARING DORZOLAM IDE

There is provided a process for preparing dorzolamide and processes for preparing intermediates useful in the preparation of dorzolamide. In particular, there is provided a process for preparing an acetoamido sulfone of formula (viii) comprising oxidation of a hydroxysulfonamide of formula (vii) in the presence of an oxidizing agent selected from the group consisting of: a peracid, tert-butyl hydroperoxide, dimethyl dioxirane, selenium dioxide, m-phenanthroline di-N-oxide, nitric acid and hydrogen peroxide. There is also provided a process for preparing an acetoamidosulfone of formula (ix-a) comprising converting a hydroxysulfone of formula (viii) to the acetoamidosulfone of formula (ix-a) in the presence of acetonitrile and an acid. There is also provided a process for separating the cis- and trans-isomers of dorzolamide from a mixture of the trans-isomer of dorzolamide and the cis-isomer of dorzolamide comprising reacting the mixture of isomers with a carboxylic acid.

Method of making dorzolamide hydrochloride

Processes for the preparation of dorzolamide hydrochloride and an intermediate of Formula IV, are provided.

PROCESS FOR PREPARING 5,6-DIHYDRO-4-(S)-(ETHYLAMINO)-6-(S) METHYL-4H-THIENO[2,3b]THIOPYRAN-2-SULPHONAMIDE-7,7-DIOXIDE HCI

The present invention relates to an improved process for the preparation of 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride of formula (I) commonly known as Dorzolamide Hydrochloride useful as an agent to reduce intraoccular pressure by inhibiting carbonic anhydrase enzyme.

Process for preparing 5,6-dihydro-4-(S)-(ethylamino)-6-(S) methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide HCI

The present invention relates to an improved process for the preparation of 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride of formula (I) commonly known as Dorzolamide Hydrochloride useful as an agent to reduce intraoccular pressure by inhibiting carbonic anhydrase enzyme