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

Different sources of media describe the Description of 1297538-32-9 differently. You can refer to the following data:
1. ODM-201 is a novel androgen receptor (AR) inhibit designed to inhibit the growth of prostate cancer cells through binding to the AR to inhibit the testosterone-induced AR nuclear translocation. It is particularly used in patients with progressive metastatic castration-resistant 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).Therefore, it has potential to overcome the resistance issue occurring upon AR-targeted therapies.
2. ODM-201 is an androgen receptor (AR) antagonist (Ki = 11 nM). It inhibits AR transactivation in U2OS osteosarcoma cells expressing human wild-type and mutant ARs (IC50s = 65, 66, 1,500, and 1,782 nM for wild-type, ARF876L, ARW741L, and ART877A, respectively). ODM-201 prevents androgen-induced AR nuclear translocation in AR-overexpressing HS-HEK293 and LNCaP cells and suppresses androgen-induced proliferation of VCaP cells (IC50 = 230 nM). In vivo, ODM-201 (50 mg/kg per day) reduces tumor growth in a VCaP castrated mouse xenograft model. It also inhibits tumor growth without increasing serum testosterone levels in a VCaP intact mouse xenograft model.

Uses

ODM-201 is a compound being used as a novel next-generation androgen receptor-directed therapy for prostate cancer.

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

• 548797-51-9 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile 
• 1297537-41-7 (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile 
• 949034-45-1 5-acetyl-1H-pyrazole-3-carboxylic acid 
• 1401584-94-8 C₆H₈N₂O₃ 
• 101667-74-7 3-chloro-4-cyanoacetophenone 
• 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 
• 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 

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