120279-96-1

Basic information

• Product Name: Dorzolamide
• Synonyms: (2r,4r)-2-ethylamino-4-methyl-5,5-dioxo-5,7-dithiabicyclo[4.3.0]nona-8,10-diene-8-sulfonamide;DORZOLAMIDE;DORZOLAMIDE(SUBJECTTOPATENTFREE);4H-Thieno[2,3-b]thiopyran-2-sulfonamide, 4-(ethylamino)-5,6-dihydro-6-methyl-, 7,7-dioxide, (4S,6S)-;4H-Thieno[2,3-b]thiopyran-2-sulfonamide, 4-(ethylamino)-5,6-dihydro-6-methyl-, 7,7-dioxide, (4S-trans)-;4S,6S-Dorzolamide;(4S,6S)-4-(ethylamino)-5,6-dihydro-6-methyl-7,;Dorzalamide hydrochloride
• CAS NO: 120279-96-1
• Molecular Formula: C₁₀H₁₆N₂O₄S₃
• Molecular Weight: 324.44
• EINECS: 1533716-785-6
• Mol File: 120279-96-1.mol

Chemical Properties

• Boiling Point: 575.8 °C at 760 mmHg
• Flash Point: 302 °C
• Appearance: white to beige/
• Density: 1.53 g/cm³
• Refractive Index: 1.626
• Storage Temp.: room temp
• Solubility: DMSO: soluble5mg/mL (clear solution, warmed)
• PKA: pKa 6.35 (Uncertain);8.50 (Uncertain)
• CAS DataBase Reference: Dorzolamide(CAS DataBase Reference)
• NIST Chemistry Reference: Dorzolamide(120279-96-1)
• EPA Substance Registry System: Dorzolamide(120279-96-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• RTECS: XJ9095169
• Hazardous Substances Data: 120279-96-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Dorzolamide is used as a carbonic anhydrase inhibitor for the treatment of open-angle glaucoma and ocular hypertension. It is administered as the hydrochloride in ophthalmic solutions to lower increased intraocular pressure, helping to manage these eye conditions effectively.
Used in Chemical Synthesis:
Dorzolamide serves as an intermediate in synthesizing N-Acetyl Dorzolamide (A173640), a useful synthetic compound with potential applications in various fields.
Brand Name:
Dorzolamide is marketed under the brand name Trusopt by Merck, making it readily available for medical use in the treatment of eye conditions related to increased intraocular pressure.

InChI:InChI=1/C10H18N2O4S3/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16/h5-8,10,12H,3-4H2,1-2H3,(H2,11,15,16)/t6-,7?,8-,10?/m0/s1

Synthetic route

(4S,6S)‑4‑acetamido‑5,6‑dihydro‑6‑methyl‑4H‑thieno[2,3‑b]thiopyran‑2‑sulfonamide‑7,7‑dioxide (147200-03-1) → dorzolamide (120279-96-1)

Conditions	Yield
With zinc(II) tetrahydroborate In methanol at 90℃; for 3h; Temperature; Solvent; Green chemistry;	90%

N-ethyl-N-[(4S,6S)-6-methyl-7,7-dioxo-2-sulfamoyl-4,5,6,7-tetrahydro-7λ6-thieno[2,3-b]thiopyran-4-yl]acetamide → dorzolamide (120279-96-1)

Conditions	Yield
With hydrogenchloride; water In methanol for 72h; Heating / reflux;	66%

4-(acetylamino)-5,6-dihydro-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonamide 7,7-dioxide → dorzolamide (120279-96-1)

Conditions	Yield
With dimethylsulfide borane complex; sulfuric acid 1) THF, r.t.; Yield given. Multistep reaction;

(S)-5,6-dihydro-6-methylthieno<2,3-b>thiopyran-4-one (147086-79-1) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 2: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 3: 95 percent / pyridine / tetrahydrofuran / 48 h / 25 - 30 °C 4: 89.6 percent / H2SO4 / 20 - 25 °C 5: chlorosulfonic acid / 12 h / 50 °C 6: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 7: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 7 steps 1: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 2: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 3: H2SO4 / -5 °C 4: H2SO4 / -5 °C 5: chlorosulfonic acid / 12 h / 50 °C 6: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 7: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 6 steps 1: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 2: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 3: 1) conc. H2SO4 / 1) THF, 48 h, r.t., 2) overnight 4: chlorosulfonic acid / 12 h / 50 °C 5: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 6: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

5,6-dihydro-(R)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran (147086-80-4) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 2: 95 percent / pyridine / tetrahydrofuran / 48 h / 25 - 30 °C 3: 89.6 percent / H2SO4 / 20 - 25 °C 4: chlorosulfonic acid / 12 h / 50 °C 5: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 6: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 6 steps 1: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 2: H2SO4 / -5 °C 3: H2SO4 / -5 °C 4: chlorosulfonic acid / 12 h / 50 °C 5: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 6: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 5 steps 1: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 2: 1) conc. H2SO4 / 1) THF, 48 h, r.t., 2) overnight 3: chlorosulfonic acid / 12 h / 50 °C 4: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 5: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

(S)-3-(thien-2-ylthio)butyric acid (133359-80-5) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 8 steps 1: trifluoroacetic anhydride / toluene / 1 h / 25 °C 2: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 3: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 4: 95 percent / pyridine / tetrahydrofuran / 48 h / 25 - 30 °C 5: 89.6 percent / H2SO4 / 20 - 25 °C 6: chlorosulfonic acid / 12 h / 50 °C 7: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 8: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 8 steps 1: trifluoroacetic anhydride / toluene / 1 h / 25 °C 2: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 3: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 4: H2SO4 / -5 °C 5: H2SO4 / -5 °C 6: chlorosulfonic acid / 12 h / 50 °C 7: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 8: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 7 steps 1: trifluoroacetic anhydride / toluene / 1 h / 25 °C 2: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 3: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 4: 1) conc. H2SO4 / 1) THF, 48 h, r.t., 2) overnight 5: chlorosulfonic acid / 12 h / 50 °C 6: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 7: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

(S)-6-Methyl-6H-thieno[2,3-b]thiopyran 7,7-dioxide (147086-84-8) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: H2SO4 / -5 °C 2: chlorosulfonic acid / 12 h / 50 °C 3: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 4: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

methyl (S)-3-(thiophen-2-ylthio)butyrate (133359-79-2) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 9 steps 1: 45 g / 12 N HCl / H2O / 3 h / Heating 2: trifluoroacetic anhydride / toluene / 1 h / 25 °C 3: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 4: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 5: 95 percent / pyridine / tetrahydrofuran / 48 h / 25 - 30 °C 6: 89.6 percent / H2SO4 / 20 - 25 °C 7: chlorosulfonic acid / 12 h / 50 °C 8: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 9: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 9 steps 1: 45 g / 12 N HCl / H2O / 3 h / Heating 2: trifluoroacetic anhydride / toluene / 1 h / 25 °C 3: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 4: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 5: H2SO4 / -5 °C 6: H2SO4 / -5 °C 7: chlorosulfonic acid / 12 h / 50 °C 8: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 9: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 8 steps 1: 45 g / 12 N HCl / H2O / 3 h / Heating 2: trifluoroacetic anhydride / toluene / 1 h / 25 °C 3: LiAlH4 / tetrahydrofuran; toluene / 0 - 5 °C 4: 24 g / sodium tungstate dihydrate, 30 percent hydrogen peroxide / H2O; ethyl acetate; toluene / 1) 0 - 15 deg C, 30 min, 2) 25 deg C, 2 h 5: 1) conc. H2SO4 / 1) THF, 48 h, r.t., 2) overnight 6: chlorosulfonic acid / 12 h / 50 °C 7: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 8: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide (1034290-08-8) → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / pyridine / tetrahydrofuran / 48 h / 25 - 30 °C 2: 89.6 percent / H2SO4 / 20 - 25 °C 3: chlorosulfonic acid / 12 h / 50 °C 4: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 5: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 5 steps 1: H2SO4 / -5 °C 2: H2SO4 / -5 °C 3: chlorosulfonic acid / 12 h / 50 °C 4: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 5: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme
Multi-step reaction with 4 steps 1: 1) conc. H2SO4 / 1) THF, 48 h, r.t., 2) overnight 2: chlorosulfonic acid / 12 h / 50 °C 3: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 4: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

4-(acetylamino)-5,6-dihydro-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-2-sulfonyl chloride 7,7-dioxide → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 2: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

N-(5,6-dihydro-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-4-yl)acetamide 7,7-dioxide → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: chlorosulfonic acid / 12 h / 50 °C 2: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 3: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

5,6-dihydro-(R,S)-4-acetoxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide → dorzolamide (120279-96-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89.6 percent / H2SO4 / 20 - 25 °C 2: chlorosulfonic acid / 12 h / 50 °C 3: conc. NH4OH / tetrahydrofuran / 1 h / 0 - 5 °C 4: 1) borane-dimethyl sulfide, 2) H2SO4 / 1) THF, r.t. View Scheme

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;

docosahexaenoic acid (6217-54-5) + dorzolamide (120279-96-1) → (4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ*6*-thieno[2,3-b]thiopyran-2-sulfonic acid ((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyl)amide

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: docosahexaenoic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	95%

N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + dorzolamide (120279-96-1) → (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 trimethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h; Inert atmosphere;	95%

(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[ (2S)-2-{[ (2S)-2-{[(2S)-2-{[(2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[ (2S)-2-{[ (2S)-2-{[(2S)-2-{[(2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;

84%

(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-[(tert butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; Inert atmosphere; Stage #2: (2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-[(tert butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;

84%

BOC-glycine (4530-20-5) + dorzolamide (120279-96-1) → tert‐butyl N‐[({[(2S,4S)‐4‐(ethylamino)‐2‐methyl‐1,1‐dioxo‐2H,3H,4H‐1λ6‐thieno[2,3‐b]thiopyran‐6‐yl]sulfonyl}carbamoyl)methyl]carbamate

Conditions	Yield
Stage #1: dorzolamide With triethylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: BOC-glycine With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	82%

dorzolamide (120279-96-1) + tert-butylchlorodiphenylsilane (58479-61-1) → (2S,4S)-N-(tert-butyldiphenylsilyl)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-sulfonamide

Conditions	Yield
With dmap In dichloromethane at 0 - 30℃; for 2h;	76%
With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 3h; Inert atmosphere;	49%

2‐(2‐{[4‐(tert‐butoxy)‐4‐oxobutanoyl]oxy}‐N‐methylacetamido)acetic acid + dorzolamide (120279-96-1) → 1-tert-butyl 4-{[({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)methyl](methyl)carbamoyl}methyl butanedioate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 4h; Inert atmosphere;	74%

{[(acetyloxy)acetyl](methyl)amino}acetic acid + dorzolamide (120279-96-1) → {[({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)methy](methyl)carbamoyl}methyl acetate

Conditions	Yield
Stage #1: dorzolamide With triethylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: {[(acetyloxy)acetyl](methyl)amino}acetic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	72.7%

(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-[(tert butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-[(tert butyldiphenylsilyl)oxy]propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;

72%

dorzolamide (120279-96-1) + (S)-2-[(1,1-dimethylethyl)diphenylsilyl]oxypropanoic acid (125941-75-5) → (2S)-2-[(tert-butyldiphenylsilyl)oxy]-N-{[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}propanamide

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-[(1,1-dimethylethyl)diphenylsilyl]oxypropanoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	68%

(S)-2-(tert-butyldiphenylsilanyloxy)propionic acid (S)-1-((S)-1-carboxyethoxycarbonyl)ethyl ester + dorzolamide (120279-96-1) → (2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-(tert-butyldiphenylsilanyloxy)propionic acid (S)-1-((S)-1-carboxyethoxycarbonyl)ethyl ester With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	68%

(S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-[(S)-1-((S)-1-carboxy-ethoxycarbonyl)-ethoxycarbonyl]-ethyl ester + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-[(S)-1-((S)-1-carboxy-ethoxycarbonyl)-ethoxycarbonyl]-ethyl ester With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	65%

(S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-[(S)-1-((S)-1-carboxy-ethoxycarbonyl)-ethoxycarbonyl]-ethyl ester + dorzolamide (120279-96-1) → (S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-{(S)-1-[(S)-2-((4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ-6-thieno[2,3-b]thiopyran-2-sulfonylamino)-1-methyl-2-oxo-ethoxycarbonyl]ethoxycarbonyl}ethyl ether

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	65%

(S)-2-(tert-butyldiphenylsilanyloxy)propionic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxycarbonyl]ethoxycarbonyl}ethyl ester + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanoate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-(tert-butyldiphenylsilanyloxy)propionic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxycarbonyl]ethoxycarbonyl}ethyl ester With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	63%

(S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-carboxy-ethyl ester + dorzolamide (120279-96-1) → (S)-2-(tert-butyldiphenylsilanyloxy)propionic acid (S)-2-((4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ*6*-thieno[2,3-b]thiopyran-2-sulfonylamino)-1-methyl-2-oxoethyl ester

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-(tert-butyl-diphenyl-silanyloxy)-propionic acid (S)-1-carboxy-ethyl ester With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	60%

dorzolamide (120279-96-1) + Acetoxyacetyl chloride (13831-31-7) → {[(2S,4S)-6-{[2-(acetyloxy)acetamido]sulfonyl}-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-4-yl](ethyl)carbamoyl}methyl acetate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: Acetoxyacetyl chloride With dmap In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	59.6%

carbonochloridic acid, chloromethyl ester (22128-62-7) + dorzolamide (120279-96-1) → chloromethyl ethyl[(4S,6S)-6-methyl-7,7-dioxo-2-sulfamoyl-4,5,6,7-tetrahydro-7λ6-thieno[2,3-b]thiopyran-4-yl]carbamate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: carbonochloridic acid, chloromethyl ester In dichloromethane at 0 - 30℃; for 1h; Temperature; Inert atmosphere;	57%
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 25 - 30℃; for 0.5h; Stage #2: carbonochloridic acid, chloromethyl ester In dichloromethane at 0 - 5℃; for 1h;

2-(2-{[4-(tert-butoxy)-4-oxobutanoyl]oxy}acetamido)acetic acid + dorzolamide (120279-96-1) → 1-tert-butyl 4-{[({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)methyl]carbamoyl}methyl butanedioate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 4h; Inert atmosphere;	50%

4-{[(acetyloxy)acetyl]oxy}butanoic acid + dorzolamide (120279-96-1) → 3-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-6-sulfamoyl-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)propyl 2-(acetyloxy)acetate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	48%

[({[(acetyloxy)acetyl]oxy}acetyl)(methyl)amino]acetic acid + dorzolamide (120279-96-1) → {[({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)methyl](methyl)carbamoyl}methyl 2-(acetyloxy)acetate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 2h; Inert atmosphere;	45.1%

(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-(acetyloxy)propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy} propanoic acid + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-(acetyloxy)propanoate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-(acetyloxy)propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy}propanoyl]oxy} propanoic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 2h; Inert atmosphere;

42%

octadecanoic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxy carbonyl]ethoxycarbonyl}ethyl ester + dorzolamide (120279-96-1) → octadecanoic acid (S)-1-((S)-1-{(S)-1-[(S)-2-(4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ*6*-thieno[2,3-b]thiopyran-2-sulfonylamino)-1-methyl-2-oxoethoxycarbonyl]ethoxycarbonyl}ethoxycarbonyl)ethyl ester

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: octadecanoic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxy carbonyl]ethoxycarbonyl}ethyl ester With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	41%

acetic anhydride (108-24-7) + dorzolamide (120279-96-1) → N-ethyl-N-[(4S,6S)-6-methyl-7,7-dioxo-2-sulfamoyl-4,5,6,7-tetrahydro-7λ6-thieno[2,3-b]thiopyran-4-yl]acetamide

Conditions	Yield
Stage #1: dorzolamide With triethylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: acetic anhydride In dichloromethane at 0 - 30℃; for 1h; Inert atmosphere;	40%

(S)-2-((S)-2-{(S)-2-[(S)-2-((S)-2-acetoxypropionyloxy)propionyloxy]propionyloxy}propionyloxy)propionic acid + dorzolamide (120279-96-1) → (2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-(acetyloxy)propanoate

Conditions	Yield
Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-((S)-2-{(S)-2-[(S)-2-((S)-2-acetoxypropionyloxy)propionyloxy]propionyloxy}propionyloxy)propionic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 1h;	38%

(2S)-2-{[(2S)-2-[(4-{[(3Z)-3-[(4-{[2-(diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl]oxy}-4-oxobutanoyl)oxy]propanoyl]oxy}propanoic acid + dorzolamide (120279-96-1) → (3Z)-3-[(4-{[2-(diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl (2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl butanedioate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (2S)-2-{[(2S)-2-[(4-{[(3Z)-3-[(4-{[2-(diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl]oxy}-4-oxobutanoyl)oxy]propanoyl]oxy}propanoic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 2h;

38%

succinic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxycarbonyl]ethoxycarbonyl}ethyl ester 3-[1-[4-(2-diethylaminoethylcarbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl]-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl ester + dorzolamide (120279-96-1) → (3Z)-3-[(4-{[2-(diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl (2S)-1-{[(2S)-1-{[(2S)-1-[(1S)-1-({[(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ6-thieno[2,3-b]thiopyran-6-yl]sulfonyl}carbamoyl)ethoxy]-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl butanedioate

Conditions

Yield

Stage #1: dorzolamide With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: succinic acid (S)-1-{(S)-1-[(S)-1-((S)-1-carboxyethoxycarbonyl)ethoxycarbonyl]ethoxycarbonyl}ethyl ester 3-[1-[4-(2-diethylaminoethylcarbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl]-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl ester With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 30℃; for 2h;

38%

2-{2-[3-(butylamino)-4-phenoxy-5-sulfamoylbenzoyloxy]-N-methylacetamido}acetic acid + dorzolamide (120279-96-1) → C32H41N5O11S4

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 16h;	38%

Upstream product

• 120298-38-6 4-(acetylamino)-5,6-dihydro-(S)-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 
• 147086-80-4 5,6-dihydro-(R)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 
• 133359-80-5 (S)-3-(thien-2-ylthio)butyric acid 
• 147086-84-8 (S)-6-Methyl-6H-thieno[2,3-b]thiopyran 7,7-dioxide 
• 133359-79-2 methyl (S)-3-(thiophen-2-ylthio)butyrate 
• 1034290-08-8 5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide 
• 147086-83-7 N-(5,6-dihydro-(S)-6-methyl-4H-thieno<2,3-b>thiopyran-4-yl)acetamide 7,7-dioxide 
• 148810-82-6 5,6-dihydro-(R,S)-4-acetoxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide 
• 154716-03-7 (6S)-4-oxo-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 

Downstream Products

• 130693-82-2 dorzolamide hydrochloride 
• 120279-37-0 5,6-dihydro-4H-4-(R)-ethylamino-6-(R)-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide hydrochloride 

Relevant articles and documents

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.

Synthetic process of dorzolamide Hydrochloride intermediate

The invention discloses a synthetic process of a dorzolamide Hydrochloride intermediate. According to the invention, mild zinc borohydride is adopted as a reducing agent; raw material compounds IIa 4-acetamido-5, 6-dihydro-6-methyl-4H-thieno [2, 3-b] thiopyran-2-sulfonamide-7, 7-dioxide and IIb ((4S, 6S)-4-acetamido-5, 6-dihydro-6-methyl-4H-thieno [2, 3-b] thiopyran-2-sulfonamide-7, 7-dioxide) arereduced at the temperature of 60-120 DEG C, acetamido is reduced into ethylamino, usage of a reducing agent which is highly toxic and high in operation danger coefficient is avoided, the whole reaction is easier to control, and the whole reaction process is milder and more environmentally friendly.

PHOSPHATE-FREE PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF GLAUCOMA

The invention relates to a phosphate-free pharmaceutical composition which comprises at least one FP prostanoid receptor agonist and/or at least one prostamide receptor agonist and also citrate salts and/or citric acid.

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 obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7-dioxides and intermediates

The process for obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7-dioxides (I) wherein R1 is H or C1-5 alkyl, and R2 is C1-5 alkyl, starts from the corresponding 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-7,7-dioxides, and comprises protecting the alkylamine group, introducing a sulfonamide group and eliminating protecting group. Some compounds of formula (I) are inhibitors of the carbonic anhydrase and can be used in the treatment of elevated intraocular pressure.