324763-51-1

Basic information

• Product Name: 3-Amino-2,2-dimethylpropionamide
• Synonyms: 2-(aminomethyl)-2-methylpropanamide;3-Amino-2,2-dimethylpropanamide;3-Amino-2,2-dimethylpropionamide;3-amino-2,2-dimethylpropionic acid amide;3-AMino-2,2-diMethylpropinaMid;Aliskiren Inter-5;ALISKIREN InterMediates/ AM4;PropanaMide, 3-aMino-2,2-diMethyl-
• CAS NO: 324763-51-1
• Molecular Formula: C₅H₁₂N₂O
• Molecular Weight: 116.16
• EINECS: 1806241-263-5
• Product Categories: Pharmaceutical intermediate;Amines;Intermediates & Fine Chemicals;Pharmaceuticals;aliskiren;Other APIs
• Mol File: 324763-51-1.mol
• Article Data: 10

Chemical Properties

• Melting Point: 74-75 °C
• Boiling Point: 271 °C
• Flash Point: 117 °C
• Appearance: /
• Density: 1.004
• Vapor Pressure: 0.00675mmHg at 25°C
• Refractive Index: 1.47
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: DMSO, Methanol
• PKA: 16.45±0.50(Predicted)
• CAS DataBase Reference: 3-Amino-2,2-dimethylpropionamide(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Amino-2,2-dimethylpropionamide(324763-51-1)
• EPA Substance Registry System: 3-Amino-2,2-dimethylpropionamide(324763-51-1)

Safety Data

• Hazardous Substances Data: 324763-51-1(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

3-Amino-2,2-dimethylpropionamide is a kind of Reagent, used in the synthesis of Aliskiren.

InChI:InChI=1/C5H12N2O/c1-5(2,3-6)4(7)8/h3,6H2,1-2H3,(H2,7,8)

Synthetic route

3-Chloropivaloyl chloride (4300-97-4) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / dichloromethane / 2.75 h / 20 °C / Cooling with ice 2: sodium methylate; ammonia / methanol / 50 h / 60 °C / Autoclave View Scheme
Multi-step reaction with 4 steps 1.1: ammonia / dichloromethane / 2.75 h / 20 °C / Cooling with ice 2.1: sodium hydroxide / methanol / 70 h / 50 - 53 °C / Sealed tube 2.2: 0.17 h / 0 - 20 °C 3.1: hydrogenchloride / 20 h / 20 °C 4.1: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

3-bromo-2,2-dimethylpropionic acid (2843-17-6) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonia / 1,4-dioxane / 16 h / 60 °C / 2250.23 Torr / Autoclave 2: hydrogenchloride / 20 h / 20 °C 3: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → acetic acid (1S,2S,4S)-2-azido-1-[(S)-2-(2-carbamoyl-2-methyl-propylcarbamoyl)-3-methyl-butyl]-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexyl ester

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 90℃; for 16h; After distillation of a part of Et3N over a period of 0.5 h further 8.5 h heating at 90 °ree;C;	100%

aminopivalinamide (324763-51-1) + (3S,5R)-5-((1S,3S)-1-azido-3-(4-methoxy-3-(methoxypropoxy)benzyl)-4-methylpentyl)-3-isopropyl-dihydrofuran-2(3H)-one (1309922-72-2) → (2S,4R,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (1607844-94-9)

Conditions	Yield
With propionic acid at 110℃; for 2h;	95%

tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate (866030-35-5) + aminopivalinamide (324763-51-1) → tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate (173338-07-3)

Conditions	Yield
With 2-Ethylhexanoic acid In n-heptane at 60℃; Reagent/catalyst; Temperature; Solvent; Time;	94%
With 2-Ethylhexanoic acid In n-heptane at 60℃; for 40h; Solvent; Reagent/catalyst;	93%
With 2-Ethylhexanoic acid In n-heptane at 70℃; for 8h; Inert atmosphere;	92%

aminopivalinamide (324763-51-1) + 1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate → C35H61N3O8

Conditions	Yield
2-Ethylhexanoic acid In tetrahydrofuran at 100℃; for 6h; Product distribution / selectivity;	93%

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide

Conditions	Yield
With propionic acid at 120℃; for 1.5h;	87%

aminopivalinamide (324763-51-1) + {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxo-furanidin-2-yl)-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid benzyl ester (1236549-00-0) → (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester (1236549-06-6)

Conditions	Yield
With 2-Ethylhexanoic acid In di-isopropyl ether at 60℃; Solvent; Reagent/catalyst;	86%
With 2-Ethylhexanoic acid In di-isopropyl ether at 60℃; Reagent/catalyst; Solvent;	86%
With 2-hydroxypyridin; triethylamine In toluene for 16h; Reflux; Inert atmosphere;	82%

aminopivalinamide (324763-51-1) + C30H49NO7 → C35H61N3O8

Conditions	Yield
With 2-Ethylhexanoic acid at 120℃; for 0.833333h;	84%

2-hydroxypyridin (142-08-5) + aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (324763-47-5)

Conditions	Yield
With triethylamine	79%

aminopivalinamide (324763-51-1) + (3S,5R)-5-[(1R,3S)-1-azido-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methylpentyl]dihydro-3-isopropyl-2(3H)-furanone → (2S,4R,5R,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy)benzyl)-8-methylnonanamide

Conditions	Yield
With triethylamine In toluene at 80 - 90℃; for 20h;	78.5%

aminopivalinamide (324763-51-1) + N-{(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide (1000047-42-6) → (2S,4S,5S)-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropyl-5-(2-nitrobenzenesulfonylamino)hexanoic acid (2-carbamoyl-2-methylpropyl)amide (1000047-43-7)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 15h;	78%

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (324763-47-5)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃;	76%
With 2-hydroxypyridin; triethylamine	59%

aminopivalinamide (324763-51-1) + N-{(1S)-2-{isopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide → (2S,4S,5S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-2-isopropyl-6-{isopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}-5-{[(2-nitrophenyl)sulfonyl]amino}hexanamide

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 2h;	73%

methyl 3-amino-2,2-dimethylpropionate (25307-82-8) → aminopivalinamide (324763-51-1)

Conditions	Yield
With ammonia In methanol at 60℃; under 3750.38 Torr; for 48h; Autoclave;	100%

2-cyano-2-methylpropanamide (7505-93-3) → aminopivalinamide (324763-51-1)

Conditions	Yield
Stage #1: 2-cyano-2-methylpropanamide With ammonia; Raney nickel In methanol at 25 - 35℃; Autoclave; Stage #2: With hydrogen In methanol at 60 - 65℃; under 5149.01 - 5884.58 Torr; for 10h;	87.5%
With ammonia; hydrogen; Raney nickle In methanol at 60 - 70℃; under 3750.38 Torr; for 10h; Autoclave;	78%
Multi-step reaction with 2 steps 1.1: LAH / tetrahydrofuran 1.2: Et3N 2.1: H2 / Pd()OH)2/C View Scheme
With ammonia; hydrogen; raney nickel In methanol at 40 - 45℃; under 2942.29 Torr; for 14h;
With ammonium hydroxide; 5% rhodium on activated aluminium oxide; hydrogen In ethanol; water under 3102.97 Torr; for 72h;

(2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester (666844-61-7) → aminopivalinamide (324763-51-1)

Conditions	Yield
With hydrogen; palladium-carbon In ethanol at 20℃; for 2h;	85%
With hydrogen; palladium hydroxide - carbon
With hydrogen; palladium 10% on activated carbon In methanol at 20℃; for 2h;

chloro-pivalic acid amide (41461-75-0) → aminopivalinamide (324763-51-1)

Conditions	Yield
With ammonia; sodium methylate In methanol at 60℃; for 50h; Autoclave;	62%
Multi-step reaction with 3 steps 1.1: sodium hydroxide / methanol / 70 h / 50 - 53 °C / Sealed tube 1.2: 0.17 h / 0 - 20 °C 2.1: hydrogenchloride / 20 h / 20 °C 3.1: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

α-(nitromethyl)isobutyronitrile (114583-17-4) → aminopivalinamide (324763-51-1)

Conditions	Yield
With methanol; Lindlar's catalyst Hydrogenation;
With nickel Hydrogenation;
With hydrogenchloride; iron

hydrogenchloride (7647-01-0) + α-(nitromethyl)isobutyronitrile (114583-17-4) + iron powder → 2-(5,5-dimethyl-hexahydro-pyrimidin-2-yl)-2-methyl-propionic acid amide (859065-87-5) + 2,2-Dimethyl-1,3-diaminopropane (7328-91-8) + 3-amino-2,2-dimethyl-propionitrile (67744-70-1) + aminopivalinamide (324763-51-1)

Conditions	Yield
at 60 - 70℃;
at 60 - 70℃;

methanol (67-56-1) + α-(nitromethyl)isobutyronitrile (114583-17-4) + palladium-CaCO3 → 2-(5,5-dimethyl-hexahydro-pyrimidin-2-yl)-2-methyl-propionic acid amide (859065-87-5) + 2,2-Dimethyl-1,3-diaminopropane (7328-91-8) + 3-amino-2,2-dimethyl-propionitrile (67744-70-1) + aminopivalinamide (324763-51-1)

Conditions	Yield
Hydrogenation;
Hydrogenation;

methanol (67-56-1) + α-(nitromethyl)isobutyronitrile (114583-17-4) + Raney nickel → 2-(5,5-dimethyl-hexahydro-pyrimidin-2-yl)-2-methyl-propionic acid amide (859065-87-5) + 2,2-Dimethyl-1,3-diaminopropane (7328-91-8) + 3-amino-2,2-dimethyl-propionitrile (67744-70-1) + aminopivalinamide (324763-51-1)

Conditions	Yield
Hydrogenation;
Hydrogenation;

α-(nitromethyl)isobutyronitrile (114583-17-4) + Raney nickel + methanolic NH3 → 2-(5,5-dimethyl-hexahydro-pyrimidin-2-yl)-2-methyl-propionic acid amide (859065-87-5) + 2,2-Dimethyl-1,3-diaminopropane (7328-91-8) + 3-amino-2,2-dimethyl-propionitrile (67744-70-1) + aminopivalinamide (324763-51-1)

Conditions	Yield
at 100℃; Hydrogenation;
at 100℃; Hydrogenation;

methyl 2,2-dimethyl-cyanoacetate (72291-30-6) → aminopivalinamide (324763-51-1)

Conditions	Yield
Stage #1: methyl 2,2-dimethyl-cyanoacetate With ammonia; hydrogen; nickel In 1-methyl-pyrrolidin-2-one; water at 80℃; under 3750.38 Torr; for 1.5h; Stage #2: With ammonia; hydrogen; nickel In 1-methyl-pyrrolidin-2-one; water at 80℃; under 150015 Torr; Product distribution / selectivity;
Stage #1: methyl 2,2-dimethyl-cyanoacetate With ammonia; hydrogen; cobalt In water; butan-1-ol at 80℃; under 3750.38 Torr; for 1.5h; Stage #2: With ammonia; hydrogen; cobalt In water; butan-1-ol at 80℃; under 48754.9 Torr; Product distribution / selectivity;
Stage #1: methyl 2,2-dimethyl-cyanoacetate With ammonia; hydrogen; cobalt In methanol; water at 80℃; under 3750.38 Torr; for 1.5h; Stage #2: With ammonia; hydrogen; cobalt In methanol; water at 80℃; under 48754.9 Torr; Product distribution / selectivity;
Stage #1: methyl 2,2-dimethyl-cyanoacetate With ammonia; hydrogen; nickel In water; butan-1-ol at 80℃; under 3750.38 Torr; for 1.5h; Stage #2: With ammonia; hydrogen; nickel In water; butan-1-ol at 80℃; under 48754.9 Torr; Product distribution / selectivity;

methyl 2,2-dimethyl-cyanoacetate (72291-30-6) → aminopivalinamide (324763-51-1) + methyl 3-amino-2,2-dimethylpropionate (25307-82-8)

Conditions	Yield
With ammonia; hydrogen; mixture of 28percent NiO, 28percent CoO, 13percent CuO, 31percent ZrO2; hydrogenated In methanol at 100℃; under 150015 Torr; Product distribution / selectivity;
With ammonia; hydrogen; mixture of 28percent NiO, 28percent CoO, 13percent CuO, 31percent ZrO2; hydrogenated In tetrahydrofuran at 100℃; under 150015 Torr; Product distribution / selectivity;

4,4-dimethylpyrazolidin-3-one (2941-18-6) → aminopivalinamide (324763-51-1)

Conditions	Yield
With hydrogen; Raney-Nickel In 2-methyl-propan-1-ol at 55 - 65℃; under 750.075 Torr; Inert atmosphere; Sealed tube;

2-cyano-2-methyl-propionic acid ethyl ester (1572-98-1) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / methanol / 12 h / 25 - 30 °C 2: hydrogen; ammonia / raney nickel / methanol / 14 h / 40 - 45 °C / 2942.29 Torr View Scheme
Multi-step reaction with 2 steps 1.1: ammonia / methanol / 25 - 35 °C 2.1: ammonia / Raney nickel / methanol / 25 - 35 °C / Autoclave 2.2: 10 h / 60 - 65 °C / 5149.01 - 5884.58 Torr View Scheme
Multi-step reaction with 2 steps 1: ammonia / methanol / 96 h / 35 °C / Sealed tube; Cooling with ice 2: hydrogen; ammonium hydroxide; 5% rhodium on activated aluminium oxide / ethanol; water / 72 h / 3102.97 Torr View Scheme

3-Hydroxy-2,2-dimethylpropanoic acid (4835-90-9) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogen bromide / water / 19 h / 100 °C 2: ammonia / 1,4-dioxane / 16 h / 60 °C / 2250.23 Torr / Autoclave 3: hydrogenchloride / 20 h / 20 °C 4: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

aminopivalic acid (19036-43-2) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 20 h / 20 °C 2: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

3-Chloropivaloyl chloride (4300-97-4) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / dichloromethane / 2.75 h / 20 °C / Cooling with ice 2: sodium methylate; ammonia / methanol / 50 h / 60 °C / Autoclave View Scheme
Multi-step reaction with 4 steps 1.1: ammonia / dichloromethane / 2.75 h / 20 °C / Cooling with ice 2.1: sodium hydroxide / methanol / 70 h / 50 - 53 °C / Sealed tube 2.2: 0.17 h / 0 - 20 °C 3.1: hydrogenchloride / 20 h / 20 °C 4.1: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

3-bromo-2,2-dimethylpropionic acid (2843-17-6) → aminopivalinamide (324763-51-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonia / 1,4-dioxane / 16 h / 60 °C / 2250.23 Torr / Autoclave 2: hydrogenchloride / 20 h / 20 °C 3: ammonia / methanol / 48 h / 60 °C / 3750.38 Torr / Autoclave View Scheme

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → acetic acid (1S,2S,4S)-2-azido-1-[(S)-2-(2-carbamoyl-2-methyl-propylcarbamoyl)-3-methyl-butyl]-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexyl ester

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 90℃; for 16h; After distillation of a part of Et3N over a period of 0.5 h further 8.5 h heating at 90 °ree;C;	100%

aminopivalinamide (324763-51-1) + (3S,5R)-5-((1S,3S)-1-azido-3-(4-methoxy-3-(methoxypropoxy)benzyl)-4-methylpentyl)-3-isopropyl-dihydrofuran-2(3H)-one (1309922-72-2) → (2S,4R,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (1607844-94-9)

Conditions	Yield
With propionic acid at 110℃; for 2h;	95%

tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate (866030-35-5) + aminopivalinamide (324763-51-1) → tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate (173338-07-3)

Conditions	Yield
With 2-Ethylhexanoic acid In n-heptane at 60℃; Reagent/catalyst; Temperature; Solvent; Time;	94%
With 2-Ethylhexanoic acid In n-heptane at 60℃; for 40h; Solvent; Reagent/catalyst;	93%
With 2-Ethylhexanoic acid In n-heptane at 70℃; for 8h; Inert atmosphere;	92%

aminopivalinamide (324763-51-1) + 1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate → C35H61N3O8

Conditions	Yield
2-Ethylhexanoic acid In tetrahydrofuran at 100℃; for 6h; Product distribution / selectivity;	93%

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide

Conditions	Yield
With propionic acid at 120℃; for 1.5h;	87%

aminopivalinamide (324763-51-1) + {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxo-furanidin-2-yl)-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid benzyl ester (1236549-00-0) → (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester (1236549-06-6)

Conditions	Yield
With 2-Ethylhexanoic acid In di-isopropyl ether at 60℃; Solvent; Reagent/catalyst;	86%
With 2-Ethylhexanoic acid In di-isopropyl ether at 60℃; Reagent/catalyst; Solvent;	86%
With 2-hydroxypyridin; triethylamine In toluene for 16h; Reflux; Inert atmosphere;	82%

aminopivalinamide (324763-51-1) + C30H49NO7 → C35H61N3O8

Conditions	Yield
With 2-Ethylhexanoic acid at 120℃; for 0.833333h;	84%

2-hydroxypyridin (142-08-5) + aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (324763-47-5)

Conditions	Yield
With triethylamine	79%

aminopivalinamide (324763-51-1) + (3S,5R)-5-[(1R,3S)-1-azido-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methylpentyl]dihydro-3-isopropyl-2(3H)-furanone → (2S,4R,5R,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy)benzyl)-8-methylnonanamide

Conditions	Yield
With triethylamine In toluene at 80 - 90℃; for 20h;	78.5%

aminopivalinamide (324763-51-1) + N-{(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide (1000047-42-6) → (2S,4S,5S)-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropyl-5-(2-nitrobenzenesulfonylamino)hexanoic acid (2-carbamoyl-2-methylpropyl)amide (1000047-43-7)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 15h;	78%

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl}-dihydro-3-(1-methylethyl)furan-2(3H)-one (324763-46-4) → (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide (324763-47-5)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃;	76%
With 2-hydroxypyridin; triethylamine	59%

aminopivalinamide (324763-51-1) + N-{(1S)-2-{isopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide → (2S,4S,5S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-2-isopropyl-6-{isopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}-5-{[(2-nitrophenyl)sulfonyl]amino}hexanamide

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 2h;	73%

aminopivalinamide (324763-51-1) + triethoxymethylbenzene (1663-61-2) → 5,5-dimethyl-2-phenyl-5,6-dihydropyrimidin-4(3H)-one

Conditions	Yield
With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere;	72%

aminopivalinamide (324763-51-1) + C29H49NO6S → (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide (173334-57-1)

Conditions	Yield
With 2-hydroxypyridin; hydrogenchloride; triethylamine In methanol at 80℃;	68%

aminopivalinamide (324763-51-1) + tert-butyl {(1S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamate (1000046-88-7) → tert-butyl {(2S,3S,5S)-5-[(3-amino-2,2-dimethyl-3-oxopropyl)carbamoyl]-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-3-hydroxy-6-methylheptan-2-yl}carbamate (1000046-90-1)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 18h;	66%
With 2-hydroxypyridin; triethylamine at 80℃; for 18h;	66%

aminopivalinamide (324763-51-1) + {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxo-furanidin-2-yl)-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid benzyl ester (1236549-00-0) → (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester (1236549-06-6) + C31H51N3O7

Conditions	Yield
With 2-hydroxypyridin In tert-butyl methyl ether at 65℃;	A 66% B n/a

tert-butyl (1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methylpentylcarbamate (953820-47-8) + aminopivalinamide (324763-51-1) → tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate (953820-48-9)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃;	65%

aminopivalinamide (324763-51-1) + (3S,5S)-5-((1S,3S)-1-azido-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-4-methylpentyl)-3-isopropyldihydrofuran-2(3H)-one (325740-70-3) → (2S,4S,5R,7S)-5-Azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide (325154-31-2)

Conditions	Yield
With 2-hydroxypyridin; triethylamine	59%

aminopivalinamide (324763-51-1) + (3S,5S)-5-{(1R,3S)-1-Benzylamino-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-3-isopropyl-dihydro-furan-2-one → (2S,4S,5R,7S)-5-Benzylamino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide (361460-41-5)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 72h;	53%

aminopivalinamide (324763-51-1) + {(S)-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]-2-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]ethyl}carbamic acid benzyl ester (1000047-28-8) → {(1S,2S,4S)-4-(2-carbamoyl-2-methylpropylcarbamoyl)-2-hydroxy-1-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-5-methylhexyl}carbamic acid benzyl ester (1000047-29-9)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 80℃; for 11h;	52%

aminopivalinamide (324763-51-1) + Triethyl orthoacetate (78-39-7) → 2,5,5-trimethyl-5,6-dihydropyrimidin-4(3H)-one

Conditions	Yield
With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere;	50%

aminopivalinamide (324763-51-1) + (2R,2'S,3S,4'S,5S)-3-isopropyl-5-(4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-2-(4-methoxy-3-(3-methoxypropoxy)-phenyl)-pyrrolidine-1-sulfonic acid 2,2,2-trichloro-ethyl ester (1200341-46-3) → (2R,3S,5S)-2,2,2-trichloroethyl 5-((1S,3S)-3-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-1-hydroxy-4-methylpentyl)-3-isopropyl-2-(4-methoxy-3-(3-methoxypropoxy)phenyl)pyrrolidine-1-sulfonate (1219468-79-7)

Conditions	Yield
With 2-hydroxypyridin; triethylamine at 85℃; Inert atmosphere;	47%
With 2-hydroxypyridin; triethylamine at 85℃; for 72h; Inert atmosphere;

aminopivalinamide (324763-51-1) + Triethyl orthopropionate (115-80-0) → 2-ethyl-5,5-dimethyl-5,6-dihydropyrimidin-4(3H)-one

Conditions	Yield
With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere;	44%

triethyl orthobutyrate (24964-76-9) + aminopivalinamide (324763-51-1) → 5,5-dimethyl-2-propyl-5,6-dihydropyrimidin-4(3H)-one

Conditions	Yield
With acetic acid In ethanol at 110℃; for 24h; Inert atmosphere;	36%

aminopivalinamide (324763-51-1) + 2-{[5-bromo-1-(2-chlorophenyl)-1H-1,2,4-triazol-3-yl]methyl}-5-(4-chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one → 3-{[1-(2-chlorophenyl)-3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,4-triazol-5-yl]amino}-2,2-dimethylpropanamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 180℃; for 5h; Microwave irradiation;	29%

aminopivalinamide (324763-51-1) → aminopivalic acid (19036-43-2)

Conditions	Yield
With sulfuric acid

Upstream product

• 41461-75-0 chloro-pivalic acid amide 
• 2843-17-6 3-bromo-2,2-dimethylpropionic acid 
• 4300-97-4 3-Chloropivaloyl chloride 
• 19036-43-2 aminopivalic acid 
• 4835-90-9 3-Hydroxy-2,2-dimethylpropanoic acid 
• 25307-82-8 methyl 3-amino-2,2-dimethylpropionate 
• 1572-98-1 2-cyano-2-methyl-propionic acid ethyl ester 
• 2941-18-6 5,5-dimethylpyrazolidin-3-one 
• 72291-30-6 methyl 2,2-dimethyl-cyanoacetate 
• 7505-93-3 2-cyano-2-methylpropanamide 
• 666844-61-7 (2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester 
• 114583-17-4 α-(nitromethyl)isobutyronitrile 
• 67-56-1 methanol 
• 7647-01-0 hydrogenchloride 

Downstream Products

• 173334-57-1 (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide 
• 1227383-70-1 (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy)benzoyl)-8-methylnonanamide 
• 1219468-79-7 (2R,3S,5S)-2,2,2-trichloroethyl 5-((1S,3S)-3-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-1-hydroxy-4-methylpentyl)-3-isopropyl-2-(4-methoxy-3-(3-methoxypropoxy)phenyl)pyrrolidine-1-sulfonate 
• 1236549-06-6 (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester 
• 173334-58-2 (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate 
• 324763-47-5 (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide 
• 1607844-94-9 (2S,4R,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide 
• 865720-45-2 benzyl (4-(2-carbamoyl-2-methylpropylcarbamoyl)-2-hydroxy-1-{2-[3-(3-methoxypropyl)-1-(2-trimethylsilanylethoxymethyl)-1H-indol-5-ylmethyl]-3-methylbutyl}5-methylhexyl)carbamate 
• 25307-82-8 methyl 3-amino-2,2-dimethylpropionate 
• 325154-32-3 (2S,4S,5R,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-7-(4-methoxy-3-(3-methoxypropoxy)benzyl)-8-methyl-2-isopropylnonanamide 
• 173338-07-3 tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate 
• 361460-41-5 (2S,4S,5R,7S)-5-Benzylamino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide 

Relevant articles and documents

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