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
• Article Data: 15

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

Chemical Properties

Pale Beige Solid

Uses

Different sources of media describe the Uses of 106092-09-5 differently. You can refer to the following data:
1. (S)-Pramipexole intermediate as dopamine autoreceptor agonist.
2. (S)-N-Despropyl Pramipexole is a (S)-Pramipexole (P700745) intermediate as dopamine autoreceptor agonist.
3. (S)-N-Despropyl Pramipexole (Pramipexole EP Impurity A; Pramipexole BP Impurity A; Pramipexole USP Related Compound A) is a (S)-Pramipexole (P700755) intermediate as dopamine autoreceptor agonist.

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 
• 1251861-19-4 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-chlorophenyl)urea 
• 1251861-14-9 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(2-methoxyphenyl)urea 
• 1251861-22-9 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-phenylurea 
• 1251861-17-2 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-fluorophenyl)urea 
• 1251861-15-0 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(4-methoxyphenyl)urea 
• 1251861-20-7 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-chlorophenyl)urea 
• 1251861-16-1 1-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(3-methoxyphenyl)urea 
• 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 

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.

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)