106092-09-5

Basic information

• Product Name: (S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine
• Synonyms: (6S)-4,5,6,7-TETRAHYDRO-1,3-BENZOTHIAZOL-2,6-DIAMINE;(6S)-4,5,6,7-TETRAHYDRO-1,3-BENZOTHIAZOLE-2,6-DIAMINE;(s)-4,5,6,7-tetrahydro-2,6-benzothiazolediamine;(S)-4,5,6,7-TETRAHYDROBENZO[D]THIAZOLE-2,6-DIAMINE;(S)-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-2,6-DIAMINE;S-(-)-2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole;(-)-2,6-diamino-4,5,6,7-tetrahydroben thiazole;(-)-(6S)-2,6-Diamino-4,5,6-tetrahydrobenzothiazole
• CAS NO: 106092-09-5
• Molecular Formula: C₇H₁₁N₃S
• Molecular Weight: 169.25
• EINECS: 1308068-626-2
• Product Categories: intermidiate of Pramipexole;(intermediate of pramipexole);API;All Inhibitors;Inhibitors;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals;Pramipexole Dihydrochloride Monohydrate
• Mol File: 106092-09-5.mol

Chemical Properties

• Melting Point: 222-224°C
• Boiling Point: 359 °C at 760 mmHg
• Flash Point: 170.9 °C
• Appearance: Pale beige solid
• Density: 1.313 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.656
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 9.18±0.20(Predicted)
• Stability: Light Sensitive
• CAS DataBase Reference: (S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine(106092-09-5)
• EPA Substance Registry System: (S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine(106092-09-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 106092-09-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine is used as an intermediate in the synthesis of (S)-Pramipexole, a dopamine autoreceptor agonist. It plays a crucial role in the production of this medication, which is used to treat Parkinson's disease and restless legs syndrome.
Additionally, (S)-N-Despropyl Pramipexole, an impurity of (S)-Pramipexole, is also synthesized using (S)-4,5,6,7-Tetrahydro-2,6-benzothiazolediamine as an intermediate. This impurity is important for quality control and ensuring the purity of the final pharmaceutical product.

InChI:InChI=1/C7H11N3S/c8-4-1-2-5-6(3-4)11-7(9)10-5/h4H,1-3,8H2,(H2,9,10)/t4-/m0/s1

Synthetic route

(S)-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine tartrate trihydrate (873431-80-2) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Stage #1: (S)-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine tartrate trihydrate With water; pyrographite at 80℃; for 1h; Stage #2: With water; potassium hydroxide; sodium hydroxide at 10 - 20℃; for 0.5h; pH=12; Temperature;	92%
Stage #1: (S)-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine tartrate trihydrate With hydrogenchloride In water Acidic aqueous solution; Stage #2: With sodium hydroxide at 50℃; pH=<= 7; Alkaline aqueous solution;
With sodium hydroxide; water at 25 - 35℃; for 1.83333 - 1.91667h; pH=11.0 - 12.0;
Stage #1: (S)-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine tartrate trihydrate With hydrogenchloride In water carbon treatment; Stage #2: With potassium hydroxide In water at 25 - 30℃; for 1.5h;

(S)-2-acetylamino-6-amino-4,5,6,7-tetrahydrobenzothiazole → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
With hydrogenchloride; water In tetrahydrofuran at 80℃; for 12h;	90%

2,6-diamino-4,5,6,7-tetrahydro-benzthiazole (106006-83-1) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
With L-Tartaric acid In ethanol at 80℃; for 3h;	87.8%
With D-tartaric acid In water at 75℃; for 2h; Temperature;	48.4%
Stage #1: 2,6-diamino-4,5,6,7-tetrahydro-benzthiazole With L-Tartaric acid In water at 75℃; for 1h; Stage #2: With hydrogenchloride In water	27.9%

2,6-diamino-4,5,6,7-tetrahydro benzothiazole, (S)-tartarate salt (1315483-31-8) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
With hydrogenchloride; potassium hydroxide In water at 0 - 5℃; for 1 - 2h;	1.05%

2,6-diamino-4,5,6,7-tetrahydro-benzthiazole (106006-83-1) → (R)-4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-2,6-diamine (106092-11-9) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
optical resolution with chiral tartaric acid;
Purification / work up; Resolution of racemate;

N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)acetamide hydrobromide (104617-50-7) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: water; sulfuric acid / 10 h / Reflux 1.2: 1.5 h / 0 - 30 °C 2.1: water / 70 °C / Reflux; Resolution of racemate 3.1: hydrogenchloride / water / carbon treatment 3.2: 1.5 h / 25 - 30 °C View Scheme

N-(4-oxocyclohexyl)acetamide (27514-08-5) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: bromine; acetic acid / 0.75 h / 25 - 35 °C 1.2: 3 h / Reflux 2.1: water; sulfuric acid / 10 h / Reflux 2.2: 1.5 h / 0 - 30 °C 3.1: water / 70 °C / Reflux; Resolution of racemate 4.1: hydrogenchloride / water / carbon treatment 4.2: 1.5 h / 25 - 30 °C View Scheme
Multi-step reaction with 4 steps 1: bromine; acetic acid / 1 h / 60 °C 2: 1 h 3: water; hydrogen bromide / 15 h / Reflux 4: L-Tartaric acid / 75 °C View Scheme
Multi-step reaction with 4 steps 1: acetic acid; bromine / 4 h / 60 °C 2: 60 °C / Reflux 3: hydrogen bromide / Reflux 4: L-Tartaric acid / ethanol / 3 h / 80 °C View Scheme
Multi-step reaction with 3 steps 1.1: acetic acid; bromine / 3 h / 20 °C 1.2: 0.5 h / 110 - 120 °C 2.1: hydrogen bromide / water / 6 h / 100 - 105 °C 3.1: L-Tartaric acid / water / 1 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1.1: acetic acid; bromine 2.1: 120 °C 2.2: Reflux 3.1: D-tartaric acid / water / 0.33 h / 58 °C View Scheme

N-(2-amino-4,5,6,7-tetrahydrobenzo[1,2-d]thiazol-6-yl)acetamide (106006-80-8) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: water; hydrogen bromide / 15 h / Reflux 2: L-Tartaric acid / 75 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen bromide / Reflux 2: L-Tartaric acid / ethanol / 3 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen bromide / water / 6 h / 100 - 105 °C 2: L-Tartaric acid / water / 1 h / 75 °C View Scheme

2-bromo-4-acetamidocyclohexanone (687639-03-8) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1 h 2: water; hydrogen bromide / 15 h / Reflux 3: L-Tartaric acid / 75 °C View Scheme
Multi-step reaction with 3 steps 1: 60 °C / Reflux 2: hydrogen bromide / Reflux 3: L-Tartaric acid / ethanol / 3 h / 80 °C View Scheme

2-amino-6-oxo-4,5,6,7-tetrahydrobenzothiazole (113030-24-3) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: 0.5 h / 100 °C 2: Sucrose / aq. phosphate buffer; n-heptane / 16 h / 30 °C / pH 7 3: pyridine / 2 h / 0 - 20 °C 4: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 5: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 6: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

(R)-2-acetylamino-6-hydroxy-4,5,6,7-tetrahydrobenzothiazole → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 2 h / 0 - 20 °C 2: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 3: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 4: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

(R)-2-acetylamino-6-hydroxy-4,5,6,7-tetrahydrobenzothiazole, 6-tosylate → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 2: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 3: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

(S)-2-acetylamino-6-azido-4,5,6,7-tetrahydrobenzothiazole → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 2: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

cyclohexanedione monoethylene ketal (4746-97-8) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 1 h / 0 °C / Inert atmosphere 2.1: sodium acetate; N-Bromosuccinimide / tetrahydrofuran; water / 2 h / 20 °C 2.2: 20 - 80 °C 3.1: hydrogenchloride; water / tetrahydrofuran / 4 h / Reflux 4.1: 0.5 h / 100 °C 5.1: Sucrose / aq. phosphate buffer; n-heptane / 16 h / 30 °C / pH 7 6.1: pyridine / 2 h / 0 - 20 °C 7.1: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 8.1: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 9.1: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

1,4-cyclohexanedione-1-ethylene acetal 4-trimethylsilyl enol ether (144810-01-5) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium acetate; N-Bromosuccinimide / tetrahydrofuran; water / 2 h / 20 °C 1.2: 20 - 80 °C 2.1: hydrogenchloride; water / tetrahydrofuran / 4 h / Reflux 3.1: 0.5 h / 100 °C 4.1: Sucrose / aq. phosphate buffer; n-heptane / 16 h / 30 °C / pH 7 5.1: pyridine / 2 h / 0 - 20 °C 6.1: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 7.1: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 8.1: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

2-amino-6-(ethylenedioxy)-4,5,6,7-tetrahydrobenzothiazole (159015-33-5) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: hydrogenchloride; water / tetrahydrofuran / 4 h / Reflux 2: 0.5 h / 100 °C 3: Sucrose / aq. phosphate buffer; n-heptane / 16 h / 30 °C / pH 7 4: pyridine / 2 h / 0 - 20 °C 5: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 6: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 7: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

2-Acetylamino-6-oxo-4,5,6,7-tetrahydrobenzothiazole (404892-23-5) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: Sucrose / aq. phosphate buffer; n-heptane / 16 h / 30 °C / pH 7 2: pyridine / 2 h / 0 - 20 °C 3: sodium azide / N,N-dimethyl-formamide / 6 h / 20 - 70 °C / Inert atmosphere 4: polymer bonded triphenyl phosphine / tetrahydrofuran; water / 12 h / 40 °C 5: hydrogenchloride; water / tetrahydrofuran / 12 h / 80 °C View Scheme

N-(4-oxocyclohexyl)acetamide (27514-08-5) + thiourea (17356-08-0) → (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5)

Conditions	Yield
Stage #1: N-(4-oxocyclohexyl)acetamide; thiourea With bromine In water at 45 - 80℃; for 2h; Large scale; Stage #2: With hydrogen bromide In water for 3h; Reflux; Large scale;

propionic acid anhydride (123-62-6) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → (S)‑2‑amino‑6‑propionamido‑4,5,6,7‑tetrahydrobenzothiazole (106006-84-2)

Conditions	Yield
With triethylamine In tetrahydrofuran at -10℃; Temperature;	97.2%
With triethylamine In tetrahydrofuran at -5℃; for 2h;	90%
Stage #1: propionic acid anhydride; (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine With triethylamine In tetrahydrofuran at -10 - -4℃; for 1.83333h; Stage #2: With potassium carbonate In tetrahydrofuran; water for 1.33333h; Product distribution / selectivity;	89%

propyl bromide (106-94-5) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → (S)-(-)-2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole hydrobromide

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 20℃; for 72h; Product distribution / selectivity;	96%
In N,N-dimethyl acetamide at 20℃; for 72h; Product distribution / selectivity;	80%

di-tert-butyl dicarbonate (24424-99-5) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → tert-butyl (S)-(2-amino-4,5,6,7-tetrahydrobenzo[1,2-d]thiazol-6-yl)carbamate (1038555-08-6)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at -5 - 0℃; for 6h;	95%
In methanol at 0 - 25℃; for 1h;	90%
In tetrahydrofuran at 0 - 20℃; for 16h;	80.8%
In tetrahydrofuran at 0 - 20℃;

1-Chloropropane (540-54-5) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → pramipexole (104632-26-0)

Conditions	Yield
With NPs-Fe3O4(at)SiO2(at)[PrMIM]PW In acetonitrile at 50℃; Reagent/catalyst;	95%

2-Nitrobenzenesulfonyl chloride (1694-92-4) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → (S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-2-nitrobenzenesulfonamide (1046124-79-1)

Conditions	Yield
With triethylamine In tetrahydrofuran at -10 - 25℃;	94.6%
With triethylamine In tetrahydrofuran at -10 - 25℃; for 1.5h; Inert atmosphere;	94%
With triethylamine In tetrahydrofuran at -10 - 25℃; for 1h;

2-bromo-5-methoxy-benzoic acid (22921-68-2) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → C15H17N3O3S (1381803-12-8)

Conditions	Yield
With copper; potassium carbonate In ethyl methyl ether at 25 - 30℃; for 2h; Ullmann reaction; Inert atmosphere; Sonication;	92%

(S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) + ortho-chlorobenzoic acid (118-91-2) → C14H15N3O2S (1381802-38-5)

Conditions	Yield
With copper; potassium carbonate In ethyl methyl ether at 25 - 30℃; for 1.5h; Ullmann reaction; Inert atmosphere; Sonication;	90%

propyl tosylate (599-91-7) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole p-toluenesulfonic acid (943319-02-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In water; acetonitrile at 76℃; for 6h; Reagent/catalyst; Solvent; Temperature;	88.2%
In N,N-dimethyl-formamide at 20℃; for 96h;	64%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	54%

(S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) + 3-methoxyphenyl isocyanate (18908-07-1) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-methoxyphenyl)urea (1251861-16-1)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	85%

propionic acid anhydride (123-62-6) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → pramipexole (104632-26-0)

Conditions	Yield
Stage #1: propionic acid anhydride; (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine With triethylamine In tetrahydrofuran at -10 - 0℃; for 2h; Stage #2: With borane-THF at 50 - 55℃; for 1h;	85%

p-chlorphenylisocyanate (104-12-1) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-chlorophenyl)urea (1251861-21-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	84%

o-chlorophenyl isocyanate (3320-83-0) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-chlorophenyl)urea (1251861-19-4)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	84%

(S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) + m-chlorophenyl isocyanate (2909-38-8) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-chlorophenyl)urea (1251861-20-7)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	84%

o-fluorophenyl isothiocyanate (38985-64-7) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-fluorophenyl)thiourea (1262552-31-7)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	84%

4-fluorophenyl isothiocyanate (1544-68-9) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-fluorophenyl)thiourea (1262552-28-2)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	84%

1-Isocyanato-2-methoxy-benzene (700-87-8) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-methoxyphenyl)urea (1251861-14-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	83%

para-fluorophenyl isocyanate (1195-45-5) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-fluorophenyl)urea (1251861-17-2)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	83%

phenyl isothiocyanate (103-72-0) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-phenylthiourea (1262552-35-1)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	83%

4-Methoxyphenyl isothiocyanate (2284-20-0) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-methoxyphenyl)thiourea (1262552-27-1)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	83%

(S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) + 3-methoxyphenyl isothiocyanate (3125-64-2) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-methoxyphenyl)thiourea (1262552-30-6)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	83%

4-Methoxyphenyl isocyanate (5416-93-3) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-methoxyphenyl)urea (1251861-15-0)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	82%

phenyl isocyanate (103-71-9) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-phenylurea (1251861-22-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	81%

2-chlorophenylisothiocyanate (2740-81-0) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-chlorophenyl)thiourea (1262552-32-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	81%

4-Chlorophenyl isothiocyanate (2131-55-7) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-chlorophenyl)thiourea (1262552-34-0)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	81%

3-chlorophenyl-isothiocyanate (2392-68-9) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-chlorophenyl)thiourea (1262552-29-3)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	81%

propionaldehyde (123-38-6) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → pramipexole (104632-26-0)

Conditions	Yield
Stage #1: propionaldehyde; (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine With sulfuric acid In methanol at 0℃; for 1.5h; Stage #2: With sodium tetrahydroborate In methanol at 0 - 25℃; for 1.83333 - 1.91667h;	80.1%
Stage #1: propionaldehyde; (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine In methanol at 5℃; for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride In methanol at 5 - 25℃; for 0.583333h; Stage #3: With hydrogenchloride; sodium hydroxide more than 3 stages;	69%
With sodium tetrahydroborate; sulfuric acid In methanol; dichloromethane at 3 - 8℃;

2,4-dichlorophenyl isocyanate (2612-57-9) + (S)-4,5,6,7-tetrahydrobenzo[d]thiazol-2,6-diamine (106092-09-5) → 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2,4-dichlorophenyl)urea (1251861-18-3)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	78%

Upstream product

• 27514-08-5 N-(4-oxocyclohexyl)acetamide 
• 17356-08-0 thiourea 
• 404892-23-5 2-Acetylamino-6-oxo-4,5,6,7-tetrahydrobenzothiazole 
• 159015-33-5 2-amino-6-(ethylenedioxy)-4,5,6,7-tetrahydrobenzothiazole 
• 144810-01-5 1,4-cyclohexanedione-1-ethylene acetal 4-trimethylsilyl enol ether 
• 4746-97-8 cyclohexanedione monoethylene ketal 
• 113030-24-3 2-amino-6-oxo-4,5,6,7-tetrahydrobenzothiazole 
• 687639-03-8 2-bromo-4-acetamidocyclohexanone 
• 106006-80-8 N-(2-amino-4,5,6,7-tetrahydrobenzo[1,2-d]thiazol-6-yl)acetamide 
• 104617-50-7 N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)acetamide hydrobromide 
• 1315483-31-8 2,6-diamino-4,5,6,7-tetrahydro benzothiazole, (S)-tartarate salt 
• 873431-80-2 (S)-4,5,6,7-tetrahydro-benzothiazole-2,6-diamine tartrate trihydrate 
• 106006-83-1 2,6-diamino-4,5,6,7-tetrahydro-benzthiazole 

Downstream Products

• 104632-26-0 pramipexole 
• 104632-25-9 pramipexole dihydrochloride 
• 1262552-32-8 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-chlorophenyl)thiourea 
• 1262552-31-7 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-fluorophenyl)thiourea 
• 1262552-35-1 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-phenylthiourea 
• 1262552-34-0 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-chlorophenyl)thiourea 
• 1262552-27-1 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-methoxyphenyl)thiourea 
• 1262552-28-2 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-fluorophenyl)thiourea 
• 1262552-29-3 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-chlorophenyl)thiourea 
• 1262552-30-6 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-methoxyphenyl)thiourea 
• 1262552-33-9 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2,4-dichlorophenyl)thiourea 
• 106006-84-2 (S)?2?amino?6?propionamido?4,5,6,7?tetrahydrobenzothiazole 
• 1973461-14-1 C₂₀H₃₂N₆S₂ 
• 1381802-38-5 C₁₄H₁₅N₃O₂S 

Relevant articles and documents

Preparation method of high-purity pramipexole

The invention relates to the technical field of pharmacy, and provides a preparation method of high-purity pramipexole. According to the invention, raceme 2, 6-diamino 4, 5, 6, 7-tetrahydrobenzothiazole is used as an initial raw material, and pramipexole is obtained through a three-step chemical reaction, so the introduction of uncontrollable factors of drug quality is reduced, and the requirements of drug application are better met; the market price of the initial raw materials is low, so that the preparation cost of pramipexole can be greatly reduced; the solvent used in the method is green, environmentally friendly, cheap, easy to obtain and suitable for industrial production, the HPLC purity of the obtained pramipexole can reach 99.86%, and the isomer purity can reach 99.89%.

Crystallization process of diamino -4, 5, 6, 7- tetrahydrobenzothiazole

Reaction and formation, of the product, with acetone as a reaction solvent, takes place in acetone as a reaction solvent to give the product, as a raw material, with acetone as a reaction solvent to obtain the mixed rotation product, and then recrystallize the reaction solvent with water: to obtain the reaction . Example, shows that the reaction time, is greatly shortened by taking the product, as a reaction solvent by taking acetone as a reaction solvent as a raw material A; dropwise to obtain the reaction and the reaction of the reaction, solvent with water and dissolving: dropwise with acetone as a reaction solvent in step A as a reaction solvent in an existing production process by, acetone, L - taking acetone as a, reaction solvent to prepare a reaction solvent for, the whole process, to prepare a crystal, by taking acetone as, a reaction solvent to prepare a reaction solvent by taking acetone as a reaction solvent to prepare a. reaction solvent by taking acetone as a reaction solvent.

Alkali separation method of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole * L-tartrate

The invention relates to an alkali precipitation method of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole * L-tartrate, water is used as a solvent, and a mixed aqueous solution of sodium hydroxide and potassium hydroxide is dropped into an aqueous solution of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole * L-tartrate to precipitate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole. The method hasthe advantages that (1) the blazing slag residue of the obtained product can be reduced, and the quality level of the product is improved; (2) the amount of the reaction solvent water is reduced, thereby reducing the discharge amount of waste water and being beneficial to environmental protection; (3) Because the (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole is soluble in water, the loss of theproduct is reduced and the yield of the product is also improved after the amount of water is reduced.

Preparation method of pramipexole dihydrochloride and intermediate thereof

The invention discloses a preparation method of pramipexole dihydrochloride and an intermediate thereof. The invention provides a preparation of pramipexole II. The preparation method of the pramipexole II comprises the following steps: performing condensation reaction and reduction reaction on a pramipexole intermediate III, propylamine and hydrogen in an organic solvent and under the existence of a chiral catalyst, and performing one-pot method to obtain the pramipexole II. According to the preparation method provided by the invention, the route step is short, chiral resolution is not neededand the total molar yield is high; furthermore, the prepared product has high purity, can reach to the standard of raw material medicines and is suitable for industrialized production. (The formula is shown in the description).

A preparation method of pramipexole hydrochloride (by machine translation)

The invention discloses a method for preparation of pramipexole hydrochloride, comprises the following steps: 1) in the organic solvent, in order to 2, 6 - diamino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole as the raw material, to join the resolving agent, heating to reflux, cooling, filtering, basified, make the (-) - (6 s) - 2, 6 - diamino 4, 5, 6, 7 - tetrahydrobenzo and thiazole; 2) in ethanol solution, the (-) - (6 s) - 2, 6 - diamino 4, 5, 6, 7 - tetrahydrobenzo and thiazole, and c anhydride reaction, by heating to reflux, to obtain (-) - (6 s) - 2 - amino - 6 - propionyl amino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole; 3) (-) - (6 s) - 2 - amino - 6 - propionyl amino - 4, 5, 6, 7 - tetrahydrobenzo and thiazole in toluene solution in red aluminum reduction reaction, by heating to reflux, stirring, after devitrifying, make the use of pramipexole; the pramipexole into the isopropyl alcohol solution, by stirring, after devitrifying, react with hydrochloric acid, by decompression, drying, hydrochloride pramipexole. The preparation method is reaction low requirements on the equipment, the pramipexole prepared hydrochloric acid content is high, high purity, high solubility, the output is high, there is little impurity. (by machine translation)

Discovery of 4,5,6,7-Tetrahydrobenzo[1,2- d ]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coli DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coli DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coli topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and ΔtolC E. coli strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

Baker's yeast catalyzed preparation of a new enantiomerically pure synthon of (S)-pramipexole and its enantiomer (dexpramipexole) This work is dedicated to Professor Enzo Santaniello in the year of his 70th birthday

A biocatalyzed reduction of a prochiral bicyclic ketone afforded enantiomerically pure (R)-2-acetylamino-6-hydroxy-4,5,6,7-tetrahydrobenzothiazole, a synthon of the anti-Parkinson (S)-pramipexole and its (R)-isomer, which is currently under investigation for the treatment of amyotrophic lateral sclerosis (ALS).

IMPROVED PROCESS FOR THE PREPARATION OF (S)-2-AMINO-4,5,6,7-TETRAHYDRO-6 - (PROPYLAMINO) BENZOTHIAZOLE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

The present invention relates to an improved process for the preparation of of (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and its pharmaceutically acceptable salts. Specifically relates to the compound represented by the following structural formula- Ia.

Synthesis and identification of a new class of (S)-2,6-diamino-4,5,6,7- tetrahydrobenzo[d]thiazole derivatives as potent antileukemic agents

Benzothiazoles are multitarget agents with broad spectrum of biological activity. Among the antitumor agents discovered in recent years, the identification of various 2-(4-aminophenyl) benzothiazoles as potent and selective antitumor drugs against different cancer cell lines has stimulated remarkable interest. Some of the benzothiazoles are known to induce cell cycle arrest, activation of caspases and interaction with DNA molecule. Based on these interesting properties of benzothiazoles and to obtain new biologically active agents, a series of novel 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives 5(a-i) were synthesized and evaluated for their efficacy as antileukemic agents in human leukemia cells (K562 and Reh). The chemical structures of the synthesized compounds were confirmed by 1H NMR, LCMS and IR analysis. The cytotoxicity of these compounds were determined using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results showed that, these compounds mediate a significant cytotoxic response to cancer cell lines tested. We found that the compounds having electron withdrawing groups at different positions of the phenyl ring of the thiourea moiety displayed significant cytotoxic effect with IC50 value less than 60 μM. To rationalize the role of electron withdrawing group in the induction of cytotoxicity, we have chosen molecule 5g (IC 50 ～15 μM) which is having chloro substitution at ortho and para positions. Flow cytometric analysis of annexin V-FITC/propidium iodide (PI) double staining and DNA fragmentation suggest that 5g can induce apoptosis. Springer Science + Business Media, LLC 2009.

RHO KINASE INHIBITORS

Substituted amide and urea derivatives useful as inhibitors of Rho kinase are described, which inhibitors can be useful in the treatment of various disorders such as cardiovascular diseases, cancer, neurological diseases, renal diseases, bronchial asthma, erectile dysfunction and glaucoma.