1297538-32-9

Basic information

• Product Name: ODM-201
• Synonyms: ODM-201;BAY-1841788;N-[(1S)-2-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide;Darolutamide;N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide;Darolutamide (ODM-201)
• CAS NO: 1297538-32-9
• Molecular Formula: C₁₉H₁₉ClN₆O₂
• Molecular Weight: 398.84616
• EINECS: -0
• Product Categories: API
• Mol File: 1297538-32-9.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 719.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.41±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 11.10±0.10(Predicted)
• CAS DataBase Reference: ODM-201(CAS DataBase Reference)
• NIST Chemistry Reference: ODM-201(1297538-32-9)
• EPA Substance Registry System: ODM-201(1297538-32-9)

Safety Data

• Hazardous Substances Data: 1297538-32-9(Hazardous Substances Data)

Usage

Description

ODM-201 is a novel androgen receptor (AR) antagonist designed to inhibit the growth of prostate cancer cells. It works by binding to the AR and inhibiting testosterone-induced AR nuclear translocation, making it a promising next-generation therapy for prostate cancer. ODM-201 is particularly effective in patients with progressive metastatic castration-resistant prostate cancer and can overcome resistance issues that arise during AR-targeted therapies.

Uses

Used in Prostate Cancer Treatment:
ODM-201 is used as a next-generation androgen receptor-directed therapy for prostate cancer. It is effective in inhibiting the activity of some mutant ARs emerging during antiandrogen therapies, including the F876L mutation version which is resistant to enzalutamide and ARN-509 (the second-generation antiandrogens). This makes ODM-201 a potential treatment option for patients with progressive metastatic castration-resistant prostate cancer.
Used in Anticancer Applications:
ODM-201 is used as an anticancer agent in the treatment of prostate cancer. It inhibits AR transactivation in U2OS osteosarcoma cells expressing human wild-type and mutant ARs. ODM-201 also prevents androgen-induced AR nuclear translocation in AR-overexpressing HS-HEK293 and LNCaP cells and suppresses androgen-induced proliferation of VCaP cells.
Used in Preclinical Models:
ODM-201 is used in in vivo studies to evaluate its efficacy in reducing tumor growth. In a VCaP castrated mouse xenograft model, ODM-201 (50 mg/kg per day) has been shown to reduce tumor growth. Additionally, it inhibits tumor growth without increasing serum testosterone levels in a VCaP intact mouse xenograft model, demonstrating its potential as a therapeutic agent for prostate cancer treatment.

References

Moilanen, Anu Maarit, et al. "Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies." Sci Rep 5.2(2015):12007. Fizazi, Karim, et al. "ODM-201, a new generation androgen receptor inhibitor for castration-resistant prostate cancer: Preclinical and phase I data." Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of 2013. Fizazi, K, et al. "Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial." Lancet Oncology 5.9(2014):975-85.

Synthetic route

C21H21ClN6O3 → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With sodium hydroxide In ethanol; water at 20℃;	93.3%

5-(1-((tert-butyldimethylsilyl)oxy)ethyl)-N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamide → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 0℃; for 6h;	92.9%

C13H13ClN4*ClH + C6H7N2O3(1-)*Na(1+) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	87.5%

5-acetyl-N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-pyrazole-3-carboxamide (1297537-33-7) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran; methanol at 20℃;	85.9%
With sodium tetrahydroborate In ethanol at 0 - 20℃; for 3.5h;	80.2%
With sodium tetrahydroborate; ethanol In ethanol	76%
With sodium tetrahydroborate; ethanol	76%

(S)-4-(1-(2-aminopropyl) 1H-pyrazol-3-yl)-2-chlorobenzonitrile (1297537-41-7) + C6H8N2O3 (1401584-94-8) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In tetrahydrofuran at -10℃; for 2h; Inert atmosphere;	73.2%

(S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-phenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide (1297537-33-7) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
With hydrogenchloride; sodium borohydrid In ethanol; water
With sodium tetrahydroborate; ethanol at 22℃; for 4h; Large scale;	214 kg

4-bromo-2-chlorobenzonitrile (154607-01-9) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetonitrile; water / 0.5 h / Inert atmosphere; Reflux 1.2: 2.5 h / 60 - 70 °C / Inert atmosphere 2.1: hydrogenchloride / water / 2 h / 10 °C 2.2: 4 h / 0 - 5 °C 3.1: triphenylphosphine; hydrogenchloride; di-isopropyl azodicarboxylate / ethyl acetate / 10 - 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 10 - 20 °C / Inert atmosphere 5.1: sodium tetrahydroborate; ethanol / ethanol View Scheme
Multi-step reaction with 5 steps 1.1: trans-bis(triphenylphosphine)palladium dichloride; sodium carbonate / water; tetrahydrofuran / 40 °C 2.1: hydrogenchloride / ethanol / Reflux 3.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 6 h / 0 - 20 °C / Inert atmosphere 3.2: 24 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C / Inert atmosphere 5.1: sodium tetrahydroborate / tetrahydrofuran; methanol / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: bis-triphenylphosphine-palladium(II) chloride; potassium carbonate / tetrahydrofuran; water / 3 h / 40 °C / Inert atmosphere 2.1: hydrogenchloride / ethanol / 2 h / 30 °C / Inert atmosphere 3.1: triphenylphosphine / ethyl acetate / 0.5 h / Inert atmosphere 3.2: 3 h / 20 °C / Inert atmosphere 3.3: 1 h / 20 °C / Inert atmosphere 4.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / -10 °C / Inert atmosphere View Scheme

2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile (1297537-35-9) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 2 h / 10 °C 1.2: 4 h / 0 - 5 °C 2.1: triphenylphosphine; hydrogenchloride; di-isopropyl azodicarboxylate / ethyl acetate / 10 - 20 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 10 - 20 °C / Inert atmosphere 4.1: sodium tetrahydroborate; ethanol / ethanol View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / ethanol / Reflux 2.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 6 h / 0 - 20 °C / Inert atmosphere 2.2: 24 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C / Inert atmosphere 4.1: sodium tetrahydroborate / tetrahydrofuran; methanol / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water; methanol / 2 h / 10 °C 2.1: triphenylphosphine / ethyl acetate / Inert atmosphere 2.2: 10 - 20 °C / Inert atmosphere 2.3: 30 - 45 °C / Inert atmosphere 3.1: potassium tert-butylate / toluene / 1 h / 0 °C / Inert atmosphere 3.2: 2 h / 0 - 20 °C / Inert atmosphere 4.1: sodium tetrahydroborate; ethanol View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / ethanol / 2 h / 30 °C / Inert atmosphere 2.1: triphenylphosphine / ethyl acetate / 0.5 h / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 2.3: 1 h / 20 °C / Inert atmosphere 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / -10 °C / Inert atmosphere View Scheme

2-chloro-4- (1H-pyrazol-3-yl)benzonitrile (1297537-37-1) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: triphenylphosphine; hydrogenchloride; di-isopropyl azodicarboxylate / ethyl acetate / 10 - 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 10 - 20 °C / Inert atmosphere 3: sodium tetrahydroborate; ethanol / ethanol View Scheme
Multi-step reaction with 3 steps 1.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 6 h / 0 - 20 °C / Inert atmosphere 1.2: 24 h / 20 °C 2.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C / Inert atmosphere 3.1: sodium tetrahydroborate / tetrahydrofuran; methanol / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: triphenylphosphine / ethyl acetate / Inert atmosphere 1.2: 10 - 20 °C / Inert atmosphere 1.3: 30 - 45 °C / Inert atmosphere 2.1: potassium tert-butylate / toluene / 1 h / 0 °C / Inert atmosphere 2.2: 2 h / 0 - 20 °C / Inert atmosphere 3.1: sodium tetrahydroborate; ethanol View Scheme

ethyl 5-((tert-butyldimethylsilyl)oxy)-2-diazo-3-hydroxyhexanoate → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; trifluoroacetic anhydride / dichloromethane / 5 h / -10 - 30 °C 2.1: octane / 1 h / Reflux 2.2: 4 h / Reflux 3.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 5 h / 25 - 30 °C 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 6 h / 0 °C View Scheme

ethyl-5-((tert-butyldimethylsilyl)oxy)-2-diazohex-3-enoate → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: octane / 1 h / Reflux 1.2: 4 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 5 h / 25 - 30 °C 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 6 h / 0 °C View Scheme

5-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazole-3-carboxylic acid → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 5 h / 25 - 30 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 6 h / 0 °C View Scheme

(S)-4-(1-(2-aminopropyl) 1H-pyrazol-3-yl)-2-chlorobenzonitrile (1297537-41-7) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C / Inert atmosphere 2: sodium tetrahydroborate / tetrahydrofuran; methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / toluene / 1 h / 0 °C / Inert atmosphere 1.2: 2 h / 0 - 20 °C / Inert atmosphere 2.1: sodium tetrahydroborate; ethanol View Scheme

(S)-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propyl-2-yl)amino tert-butyl ester → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water; 1,4-dioxane / 3 h / 10 °C 2.1: potassium tert-butylate / toluene / 1 h / 0 °C / Inert atmosphere 2.2: 2 h / 0 - 20 °C / Inert atmosphere 3.1: sodium tetrahydroborate; ethanol View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / ethanol / 65 - 70 °C 2: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / ethanol / 65 - 70 °C 2: N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole / dichloromethane / 20 °C 3: sodium hydroxide / ethanol; water / 20 °C View Scheme

2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (548797-51-9) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: potassium carbonate / acetonitrile; water / 0.5 h / Inert atmosphere; Reflux 1.2: palladium catalyst / 2 h / 60 - 70 °C / Inert atmosphere 2.1: hydrogenchloride / water; methanol / 2 h / 10 °C 3.1: triphenylphosphine / ethyl acetate / Inert atmosphere 3.2: 10 - 20 °C / Inert atmosphere 3.3: 30 - 45 °C / Inert atmosphere 4.1: potassium tert-butylate / toluene / 1 h / 0 °C / Inert atmosphere 4.2: 2 h / 0 - 20 °C / Inert atmosphere 5.1: sodium tetrahydroborate; ethanol View Scheme

3-chloro-4-cyanoacetophenone (101667-74-7) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 16 h / 100 - 110 °C 2: acetic acid / ethanol / Reflux 3: hydrogenchloride / ethanol / 65 - 70 °C 4: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: 16 h / 100 - 110 °C 2.1: hydrazine hydrate; acetic acid / ethanol / Reflux 3.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C 3.2: 1 h 4.1: hydrogenchloride / ethanol / 65 - 70 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: 16 h / 100 - 110 °C 2.1: hydrazine hydrate; acetic acid / ethanol / Reflux 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl acetamide / 50 - 55 °C 3.2: 1 h / 20 °C 4.1: hydrogenchloride / ethanol / 65 - 70 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme

C12H11ClN2O → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid / ethanol / Reflux 2: hydrogenchloride / ethanol / 65 - 70 °C 3: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrazine hydrate; acetic acid / ethanol / Reflux 2.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C 2.2: 1 h 3.1: hydrogenchloride / ethanol / 65 - 70 °C 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrazine hydrate; acetic acid / ethanol / Reflux 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl acetamide / 50 - 55 °C 2.2: 1 h / 20 °C 3.1: hydrogenchloride / ethanol / 65 - 70 °C 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 20 °C View Scheme

C23H29ClN4O4 → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 3 h / 0 °C 3: sodium tetrahydroborate / ethanol / 3.5 h / 0 - 20 °C View Scheme

5-acetyl-1H-pyrazole-3-carboxylic acid (949034-45-1) → N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 3 h / 0 - 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 3 h / 0 °C 3: sodium tetrahydroborate / ethanol / 3.5 h / 0 - 20 °C View Scheme

succinic acid anhydride (108-30-5) + N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide (1297538-32-9) → 4-(1-(3-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl-carbamoyl)-1H-pyrazol-5-yl)ethoxy)-4-oxobutanoic acid (1403334-18-8)

Conditions	Yield
With dmap In tetrahydrofuran; ethyl acetate; N,N-dimethyl-formamide

Upstream product

• 1297537-41-7 (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile 
• 1401584-94-8 C₆H₈N₂O₃ 
• 101667-74-7 3-chloro-4-cyanoacetophenone 
• 548797-51-9 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile 
• 1297537-33-7 5-acetyl-N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-pyrazole-3-carboxamide 
• 1297537-37-1 2-chloro-4- (1H-pyrazol-3-yl)benzonitrile 
• 1297537-35-9 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile 
• 154607-01-9 4-bromo-2-chlorobenzonitrile 
• 1297537-33-7 (S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-phenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide 
• 949034-45-1 5-acetyl-1H-pyrazole-3-carboxylic acid 
• 1297537-37-1 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile 
• 1297537-39-3 2-Chloro-4-(1H-pyrazol-5-yl)benzonitrile hydrochloride 

Downstream Products

• 1297540-05-6 1-(5-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)-1H-pyrazol-3-yl)ethyl 2-(dimethylamino)acetate 
• 1403334-18-8 4-(1-(3-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl-carbamoyl)-1H-pyrazol-5-yl)ethoxy)-4-oxobutanoic acid 

Relevant articles and documents

Pyrazoleamide derivative and synthesis method and application

The present invention discloses a pyrazoleamide derivative and a synthetic method and application as an androgen receptor antagonist and the preparation of anti-prostate cancer drugs. The present invention provides a method of synthesizing a pentabasole r

Method for preparing antitumor drug darolutamide

The invention relates to a method for preparing an antitumor drug darolutamide. A one-step Suzuki reaction is carried out, and then deprotection, hydroxylamine condensation and amide condensation reactions are carried out to obtain the darolutamide. The method has the advantages of few reaction steps, high reaction yield of each step, and simplicity in operation, so the total yield of the whole route is high, and the method has good experiment operationality.

Preparation method of N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide

The invention relates to a preparation method of N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide, and in particular relates to two novel methods for preparing an intermediate (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile and a method for preparing N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-1H-pyrazol-3-carboxamide from the intermediate.