198904-85-7

Basic information

• Product Name: tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate
• Synonyms: 2-4-(2-PYRIDINYL)PHENYLMETHYL-HYDRAZINE CARBOXYLATE-1,1-DIMETHYLETHYL ESTER;2-[[4-(2-pyridinyl)phenyl]methyl]-, 1,1-dimethylethyl ester;Hydrazinecarboxylicacid,2-[[4-(2-pyridinyl)pheny;1-BOC-2-PYRIDYLPHENYLMETHYL HYDRAZINE;1-Boc-2-[4-(2-pyridinyl)benzylidene]hydrazine;N-1-Boc-N-2-[4-(pyridin-2-yl)benzylidene]hydrazine;Hydrazinecarboxylic acid,2-[[4-(2-pyridinyl);phenyl]methyl]-,1,1-dimethylethyl ester
• CAS NO: 198904-85-7
• Molecular Formula: C₁₇H₂₁N₃O₂
• Molecular Weight: 299.37
• EINECS: 1312995-182-4
• Product Categories: API intermediates;Aromatics Compounds;Aromatics;Heterocycles
• Mol File: 198904-85-7.mol
• Article Data: 16

Chemical Properties

• Melting Point: 74-77 °C
• Appearance: white solid
• Density: 1.117 g/cm³
• Refractive Index: 1.555
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.38±0.43(Predicted)
• CAS DataBase Reference: tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate(198904-85-7)
• EPA Substance Registry System: tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate(198904-85-7)

Safety Data

• Hazardous Substances Data: 198904-85-7(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

An intermediate for the preparation of antiviral protease inhibitors.

InChI:InChI=1/C17H21N3O2/c1-17(2,3)22-16(21)20-19-12-13-7-9-14(10-8-13)15-6-4-5-11-18-15/h4-11,19H,12H2,1-3H3,(H,20,21)

Synthetic route

2-[4-(2-pyridinyl)phenyl]methylenehydrazinecarboxylic acid tert-butyl ester (198904-84-6) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
With hydrogen; sodium carbonate; triethylamine; 5%-palladium/activated carbon at 40℃; under 760.051 Torr; for 8h;	99.76%
With hydrogen; 5%-palladium/activated carbon at 5 - 58℃; under 1520.1 Torr; for 5 - 8h; Nitrogen;	99.14%
With hydrogen; palladium on carbon In methanol under 517.162 Torr; for 4h;	96.5%

2-[4-(2-pyridinyl)phenyl]methylenehydrazinecarboxylic acid tert-butyl ester (198904-84-6) → 2-(4-methylphenyl)pyridine (4467-06-5) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
With hydrogen; triethylamine; 5%-palladium/activated carbon at 40℃; under 760.051 Torr; for 5h;	A 0.69% B 99.17%
With hydrogen; sodium carbonate; 5%-palladium/activated carbon at 40℃; under 760.051 Torr; for 5h;	A 0.25% B 99.16%
With hydrogen; 5%-palladium/activated carbon In methanol at 50℃; under 760.051 Torr; for 5h;	A 2.69% B 97.11%
at 40 - 62℃; under 1520.1 Torr; for 5h; Hydrogen/nitrogen (1/2);	A 0.1% B 97.2%
With hydrogen; 5%-palladium/activated carbon at 5 - 58℃; under 1520.1 Torr; for 5 - 8h; Nitrogen gas;	A 2.11% B 94.41%

N-(tert-butoxycarbonyl)-N'-[4-(pyridin-2-yl)phenylmethylidene]hydrazine (857904-11-1) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In methanol for 4h;	98%
With hydrogen; palladium 10% on activated carbon In methanol	98%
With hydrogen; palladium on activated charcoal In methanol	89%

2-[4-(2-pyridinyl)phenyl]methylenehydrazinecarboxylic acid tert-butyl ester (198904-84-6) → N-(tert-butoxycarbonyl)-N'-[4-5 (pyridin-2-yl)phenylmethylidene]hydrazine + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
palladium-carbon In n-heptane; hydrogen	A n/a B 84%

2-(4-formylphenyl)pyridine (127406-56-8) + t-butoxycarbonylhydrazine (870-46-2) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
With borane pyridine; acetic acid In methanol at 0 - 20℃; for 2h;	78%

2-bromo-pyridine (109-04-6) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2, 2.) <1,3-bis(diphenylphosphino)propane>nickel(II) chloride, diisobutylaluminum hydride, 3.) aq. HCl 2: 93 percent / ethanol / 4 h / Heating 3: 89 percent / H2 / 10percent Pd/C / methanol View Scheme
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / toluene; ethanol; water / 150 °C / 6750.68 Torr / Sealed tube; Microwave irradiation 2: trimethylsilyl trifluoromethanesulfonate / toluene; isopropyl alcohol / 22 - 50 °C / Microwave irradiation; Sealed tube 3: palladium 10% on activated carbon; sodium formate / ethanol; water / 1.5 h / 57 °C View Scheme
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / toluene; ethanol / 20 h / 76 °C / Inert atmosphere 2: toluene; isopropyl alcohol / 2 h / 80 - 85 °C / Inert atmosphere; Large scale 3: palladium 10% on activated carbon; sodium formate / water; ethanol / 1.5 h / 57 °C View Scheme
Multi-step reaction with 3 steps 1: palladium diacetate; triphenylphosphine; potassium hydroxide / methanol; tetrahydrofuran / 24 h / 60 °C / Inert atmosphere; Schlenk technique 2: toluene; isopropyl alcohol / 16 h / 20 - 85 °C / Inert atmosphere; Schlenk technique 3: palladium 10% on activated carbon; sodium formate / ethanol; water View Scheme

2-(4-formylphenyl)pyridine (127406-56-8) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / ethanol / 4 h / Heating 2: 89 percent / H2 / 10percent Pd/C / methanol View Scheme
Multi-step reaction with 2 steps 1: toluene; isopropyl alcohol / 2 h / 80 - 85 °C / Inert atmosphere; Large scale 2: palladium 10% on activated carbon; sodium formate / water; ethanol / 1.5 h / 57 °C View Scheme
Multi-step reaction with 2 steps 1: toluene; isopropyl alcohol / 16 h / 20 - 85 °C / Inert atmosphere; Schlenk technique 2: palladium 10% on activated carbon; sodium formate / ethanol; water View Scheme

1,1-dimethoxy-1-(4-bromophenyl)methane (24856-58-4) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2, 2.) <1,3-bis(diphenylphosphino)propane>nickel(II) chloride, diisobutylaluminum hydride, 3.) aq. HCl 2: 93 percent / ethanol / 4 h / Heating 3: 89 percent / H2 / 10percent Pd/C / methanol View Scheme

4-formylphenylboronic acid, (87199-17-5) → N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / toluene; ethanol; water / 150 °C / 6750.68 Torr / Sealed tube; Microwave irradiation 2: trimethylsilyl trifluoromethanesulfonate / toluene; isopropyl alcohol / 22 - 50 °C / Microwave irradiation; Sealed tube 3: palladium 10% on activated carbon; sodium formate / ethanol; water / 1.5 h / 57 °C View Scheme
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / toluene; ethanol / 20 h / 76 °C / Inert atmosphere 2: toluene; isopropyl alcohol / 2 h / 80 - 85 °C / Inert atmosphere; Large scale 3: palladium 10% on activated carbon; sodium formate / water; ethanol / 1.5 h / 57 °C View Scheme
Multi-step reaction with 3 steps 1: palladium diacetate; triphenylphosphine; potassium hydroxide / methanol; tetrahydrofuran / 24 h / 60 °C / Inert atmosphere; Schlenk technique 2: toluene; isopropyl alcohol / 16 h / 20 - 85 °C / Inert atmosphere; Schlenk technique 3: palladium 10% on activated carbon; sodium formate / ethanol; water View Scheme

(2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane (98760-08-8) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → 1-[4-(pyridine-2-yl)phenyl]-5(S)-2,5-bis[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane (198904-86-8)

Conditions	Yield
In isopropyl alcohol for 24h; Inert atmosphere; Reflux; Large scale;	85.4%
In isopropyl alcohol Heating / reflux;	75%
In isopropyl alcohol for 16h; Heating;	69%

C20H32NO7P (1003888-91-2) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → C37H53N4O9P (1003888-92-3)

Conditions	Yield
In isopropyl alcohol at 80℃; for 15h;	78%

(2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoic Acid (853893-93-3) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → tert-butyl 2-{(2S,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}-2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 25℃; for 16h;	75%

2,2,2-Trifluoro-N-((S)-1-oxiranyl-2-phenyl-ethyl)-acetamide + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → 1-[4-(Pyridin-2-yl)-phenyl]-4(S)-hydroxy-2-(N-Boc-amino)-5(S)-trifluoroacetyl-amino-6-phenyl-2-azahexane (198905-11-2)

Conditions	Yield
In isopropyl alcohol at 80℃; for 16h;	60%

(1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester (98760-08-8, 98818-34-9, 98818-35-0, 103127-56-6, 98737-29-2) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → 1-[4-(pyridine-2-yl)phenyl]-5(S)-2,5-bis[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane (198904-86-8)

Conditions	Yield
In isopropyl alcohol at 65℃; for 16h;	57%
In isopropyl alcohol at 65 - 85℃; for 16h; Product distribution / selectivity;	35%
In isopropyl alcohol at 85℃; for 16h;	35%

N-methoxycarbonyl-L-valine (111398-44-8, 74761-42-5) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → Methyl (1S)-2-methyl-1-({2-[4-(2-pyridinyl)benzyl]hydrazino}carbonyl)propylcarbamate (857904-23-5)

Conditions	Yield
Stage #1: N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine With trifluoroacetic acid In dichloromethane at 25℃; for 1h; Stage #2: N-methoxycarbonyl-L-valine With N-ethyl-N,N-diisopropylamine; 3-[(diethoxyphosphinyl)oxy]-1,2,3-benzotriazin-4(3H)-one In tetrahydrofuran at 25℃; for 3h;	47%
Stage #1: N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine With trifluoroacetic acid In dichloromethane at 25℃; for 1h; Stage #2: N-methoxycarbonyl-L-valine With N-ethyl-N,N-diisopropylamine; 3-[(diethoxyphosphinyl)oxy]-1,2,3-benzotriazin-4(3H)-one In tetrahydrofuran at 25℃; for 3h;	47%

(1S)-1-(2-oxiranyl)-2-phenyl-N-(trifluoromethyl)ethanamine (857904-14-4) + N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → Tert-butyl 2-{(2S,3S)-2-hydroxy-4-phenyl-3-[(trifluoromethyl)amino]butyl}-2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate (857904-15-5)

Conditions	Yield
In isopropyl alcohol at 65℃; for 16h;	28%
In isopropyl alcohol at 65℃; for 16h;	28%

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) + 2(R)-3(S)-1,2-epoxy-3-phenylmethoxycarbonylamino-4-phenylbutane (137515-66-3) → tert-butyl 2-((2S,3S)-2-hydroxy-4-phenyl-3-{[(benzyloxy)carbonyl]amino}butyl)-2-(4-pyridin-2-ylbenzyl)hydrazinecarboxylate (1346891-05-1)

Conditions	Yield
In isopropyl alcohol for 18h; Heating / reflux;	7%

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) + [ring-13C6]-N-(tert-butoxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-bytane (1026616-57-8) → [ring-13C6]-1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis[(tert-butyloxy-carbonyl)-amino]-4(S)-hydroxy-6-phenyl-2-azahexane (866017-17-6)

Conditions	Yield
In isopropyl alcohol at 75℃; for 12h;

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → 1-(4-(pyridin-2-yl)benzyl)hydrazine (920757-34-2)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 50℃; for 3h;

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → C42H40N6O7

Conditions	Yield
Multi-step reaction with 3 steps 1: propan-2-ol / 24 h / 80 °C 2: HCl / dioxane / 4 h / 50 °C 3: Et3N / tetrahydrofuran / 8 h / 0 - 20 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → C46H44N6O9

Conditions	Yield
Multi-step reaction with 3 steps 1: propan-2-ol / 24 h / 80 °C 2: HCl / dioxane / 4 h / 50 °C 3: Et3N / tetrahydrofuran / 8 h / 0 - 20 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → 1-[4-(pyridin-2-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-diamino-6-phenyl-2-azahexane (437713-06-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: propan-2-ol / 24 h / 80 °C 2: HCl / dioxane / 4 h / 50 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → {2,2-dimethyl-1-[N-(4-pyridin-2-yl-benzyl)-hydrazinocarbonyl]-propyl}-carbamic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → (S)-{2,2-dimethyl-1-[N'-(4-pyridin-2-yl-benzyl)-hydrazinocarbonyl]-propyl}-carbamic acid methyl ester (857904-02-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 14.43 g / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → {(S)-1-[N'-((2S,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-N'-(4-pyridin-2-yl-benzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}-carbamic acid methyl ester (857900-54-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 14.43 g / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C 3: 25 percent / propan-2-ol / 24 h / Heating 4: HCl / tetrahydrofuran; H2O / 5 h / 50 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → {(1S,2S)-1-benzyl-2-hydroxy-3-[N'-((S)-2-methoxycarbonylamino-3,3-dimethyl-butyryl)-N-(4-pyridin-2-yl-benzyl)-hydrazino]-propyl}-carbamic acid tert-butyl ester (857904-03-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 14.43 g / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C 3: 25 percent / propan-2-ol / 24 h / Heating View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → C38H49(2)H3N6O7

Conditions

Yield

Multi-step reaction with 5 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 14.43 g / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C 3: 25 percent / propan-2-ol / 24 h / Heating 4: HCl / tetrahydrofuran; H2O / 5 h / 50 °C 5: 78 percent / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / K2HPO4 / CH2Cl2; H2O / 12 h / 20 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → atazanavir (198904-31-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: HCl / tetrahydrofuran; H2O / 3 h / 50 °C 2: 14.43 g / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 / 1.5 h / 20 °C 3: 25 percent / propan-2-ol / 24 h / Heating 4: HCl / tetrahydrofuran; H2O / 5 h / 50 °C 5: 95 percent / 1-hydroxybenzotriazole; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; ethyldiisopropylamine / CH2Cl2 View Scheme
Multi-step reaction with 3 steps 1: 69 percent / propan-2-ol / 16 h / Heating 2: 100 percent / aq. HCl / tetrahydrofuran / 4 h / 50 °C 3: 1.) O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, N-ethyldiisopropylamine / 1.) CH2Cl2, 0 deg C, 20 min, 2.) CH2Cl2, overnight View Scheme
Multi-step reaction with 3 steps 1: isopropyl alcohol / 24 h / Inert atmosphere; Reflux; Large scale 2: hydrogenchloride / tetrahydrofuran / 3 h / 22 - 55 °C / Large scale 3: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 22 - 25 °C / Large scale View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → C16(13)C6H26N4O*3ClH

Conditions	Yield
Multi-step reaction with 2 steps 1: propan-2-ol / 12 h / 75 °C 2: HCl / tetrahydrofuran; H2O / 30 h / 60 °C View Scheme

N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine (198904-85-7) → [ring-13C6]-1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxy-carbonyl)-L-tert-leycinyl]amino}-4(S)-hydroxy-6-phenyl-2-azahexane

Conditions	Yield
Multi-step reaction with 3 steps 1: propan-2-ol / 12 h / 75 °C 2: HCl / tetrahydrofuran; H2O / 30 h / 60 °C 3: 0.899 g / 1-hydroxybenzotriazole hydrate; 1-[3-(dimethylamino)-propyl]-3-ethyl-carbodiimide*HCl; diisopropylethylamine / CH2Cl2 / 17 h / 20 °C View Scheme

Upstream product

• 127406-56-8 4-(2'-pyridyl)benzaldehyde 
• 870-46-2 t-butoxycarbonylhydrazine 
• 87199-17-5 4-formylphenylboronic acid, 
• 198904-84-6 2-[4-(2-pyridinyl)phenyl]methylenehydrazinecarboxylic acid tert-butyl ester 
• 24856-58-4 1,1-dimethoxy-1-(4-bromophenyl)methane 
• 109-04-6 2-bromo-pyridine 
• 857904-11-1 N-(tert-butoxycarbonyl)-N'-[4-(pyridin-2-yl)phenylmethylidene]hydrazine 

Downstream Products

• 198904-86-8 1-[4-(pyridine-2-yl)phenyl]-5(S)-2,5-bis[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane 
• 437713-06-9 1-[4-(pyridine-2-yl)phenyl]-(5S)-2,5-diamino-(4S)-hydroxy-6-phenyl-2-azahexane 
• 229975-97-7 atazanavir sulphate 
• 198905-04-3 1-[4-(pyridine-2-yl)-phenyl]-4(S)-hydroxy-2-N-tert-butoxycarbonylamino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane 
• 857904-23-5 Methyl (1S)-2-methyl-1-({2-[4-(2-pyridinyl)benzyl]hydrazino}carbonyl)propylcarbamate 
• 1140968-73-5 C₄₇H₆₃N₅O₉ 
• 857904-15-5 Tert-butyl 2-{(2S,3S)-2-hydroxy-4-phenyl-3-[(trifluoromethyl)amino]butyl}-2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate 
• 198904-22-2 1-[4-(Pyridin-2-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis[N-(N-methoxycarbonyl-(L)-valyl)amino]-6-phenyl-2-azahexane 
• 198905-13-4 N'-[(2S,3S)-2-Hydroxy-3-((2S,3S)-2-methoxycarbonylamino-3-methyl-pentanoylamino)-4-phenyl-butyl]-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester 
• 198905-15-6 N'-[(2S,3S)-2-Hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester 
• 198904-87-9 1-[4-(pyridin-2-yl)phenyl]-4(S)-hydroxy-5(S)-2,5-diamino-6-phenyl-2-azahexane trihydrochloride 
• 198905-12-3 tert-butyl 2-((2S,3S)-2-hydroxy-4-phenyl-3-(amino)butyl)-2-(4-pyridin-2-ylbenzyl)hydrazinecarboxylate 

Relevant articles and documents

A scalable synthesis of biaryl unit of the HIV protease inhibitor atazanavir

Atazanavir is one of the most prescribed HIV-1 protease inhibitors approved by the FDA. It was the first protease inhibitor approved for once-a-day dosing to treat AIDS due to good oral bioa-vailability and favorable pharmacokinetic profile. This research aims to develop a new synthetic cost effective process for biaryl-hydrazine unit {tert-butyl 2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate} of atazanavir on a large scale. The synthesis involved palladium catalyzed Suzuki-Miyaura coupling of 2-chloropyridine and (4-cyanophenyl)boronic acid followed by DIBAL-H reduction of cyano group to aldehyde which is then treated with tert-butyl carbazate to furnish hydrazone subsequently in situ reduction with NaBH4. A large scale synthesis of biaryl-hydrazine unit of atazanavir was accomplished in three steps with 71% overall yield. We have developed a short and efficient synthesis of atazanavir key intermediate biaryl-hydrazine unit. The process does not require the usage of Grignard reagent, expensive catalyst, protection/deprotection of aldehyde moiety and catalytic hydrogenation.

Preparation method of tert-butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate

The invention discloses a preparation method of tert-butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate. The preparation method comprises the steps that 1, 4-(2-pyridyl)benzaldehyde, ethyl alcohol and tert-butyl carbazate are put into a reaction kettle, and stirring is started; 2, tert-butyl 2-2-[4-(2-pyridyl)benzal]hydrazinecarboxylate is obtained; 3, tert-butyl 2-2-[4-(2-pyridyl)benzal]hydrazinecarboxylate, ethyl alcohol and palladium carbon are put into the reaction kettle, and stirring is started; 4, a sodium formate solution is dropwise added into a solution obtained in the step 3; 5, after a reaction is completed, a finished product is obtained. The preparation method has the following advantages that the production steps are greatly reduced compared with the prior art, and meanwhile a produced by-product is single and easy to separate; absolute ethyl alcohol serving as a solvent can be recycled repeatedly, palladium carbon serving as a catalyst can be used multiple times through recycling and draining, the production cost is lowered, and the production benefit of an enterprise is improved.

Reductive alkylation of hydrazine derivatives with α-picoline-borane and its applications to the syntheses of useful compounds related to active pharmaceutical ingredients

An efficient method for the direct reductive alkylation of hydrazine derivatives with α-picoline-borane has been developed to synthesize a variety of N-alkylhydrazine derivatives. This method provided N,N-dialkylhydrazine derivatives and N-monoalkylhydrazine derivatives upon fine-tuning of the substrates and the reagent equivalency in a one-pot manner. The method was applied to the synthesis of active pharmaceutical ingredients of therapeutic drugs such as isocarboxazid.