7531-52-4

Basic information

• Product Name: L-Prolinamide
• Synonyms: PROLINE-NH2;PROLINAMIDE;(S)-PYRROLIDINE-2-CARBOXYLIC ACID AMIDE;(S)-PROLINAMIDE;H-PRO-NH2;L-PROLINE AMIDE;L-(-)-PROLINAMIDE;L-PROLINAMIDE
• CAS NO: 7531-52-4
• Molecular Formula: C₅H₁₀N₂O
• Molecular Weight: 114.15
• EINECS: 231-397-0
• Product Categories: AMINOACIDS DERIVATIVES;APIs;Amino Acids;Proline [Pro, P];Amino Acids and Derivatives;Amides (Chiral);Chiral Building Blocks;Synthetic Organic Chemistry;Amino Acid Derivatives;Peptide Synthesis;Proline;Miscellaneous Reagents;Aromatics;Catalyst;Heterocycles;API;Pharmaceuticalintermediates
• Mol File: 7531-52-4.mol

Chemical Properties

• Melting Point: 95-97 °C(lit.)
• Boiling Point: 213.66°C (rough estimate)
• Flash Point: 137.4 °C
• Appearance: White to straw/Powder or Granules
• Density: 1.1008 (rough estimate)
• Vapor Pressure: 0.000923mmHg at 25°C
• Refractive Index: 1.4720 (estimate)
• Storage Temp.: -20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 16.21±0.20(Predicted)
• Water Solubility: Soluble in water and ethanol (50 mg/ml).
• BRN: 80807
• CAS DataBase Reference: L-Prolinamide(CAS DataBase Reference)
• NIST Chemistry Reference: L-Prolinamide(7531-52-4)
• EPA Substance Registry System: L-Prolinamide(7531-52-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 22-24/25-36/37/39-26
• WGK Germany: 3
• F: 10
• Hazardous Substances Data: 7531-52-4(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
L-Prolinamide is used as an important raw material and intermediate for organic synthesis, contributing to the development of various chemical compounds and products.
Used in Pharmaceutical Industry:
L-Prolinamide is used as a key component in the production of pharmaceuticals, playing a crucial role in the synthesis of drugs and medications.
Used in Agrochemicals:
L-Prolinamide is utilized as a vital intermediate in the agrochemical industry, aiding in the development of pesticides, fertilizers, and other agricultural products.
Used in Dye Industry:
L-Prolinamide is employed as a significant intermediate in the dye industry, contributing to the production of various dyes and colorants.
Used as Organocatalyst:
L-Prolinamide is used as an efficient organocatalyst for aldol reactions on water, facilitating the synthesis of complex organic molecules and enhancing the overall efficiency of the reaction process.

InChI:InChI=1/C5H10N2O/c6-5(8)4-2-1-3-7-4/h4,7H,1-3H2,(H2,6,8)/p+1/t4-/m1/s1

Synthetic route

Z-Pro-NH2 (34079-31-7) → L-prolinamide (7531-52-4)

Conditions	Yield
With 10% palladium on carbon; hydrogen In methanol for 7h;	100%
With hydrogen; palladium on activated charcoal In methanol for 9h; Ambient temperature;	88.4%
With hydrogen; palladium on activated charcoal In methanol under 2068.6 Torr; for 5h;	87%
With hydrogen; palladium In methanol for 3h;

N-acetyl-L-prolinamide (16395-58-7) → L-prolinamide (7531-52-4)

Conditions	Yield
With hydrogenchloride In water at 103℃; for 2h; Temperature;	95.3%

L-proline methyl ester monohydrochloride (2133-40-6) → L-prolinamide (7531-52-4)

Conditions	Yield
With ammonia In methanol	91%
With ammonia In methanol at 0 - 20℃; for 15h; Reagent/catalyst; Large scale;	85%
With ammonia In methanol at -25℃; for 96h; Sealed tube;	55%

methyl (2S)-pyrrolidine carboxylate (2577-48-2) → L-prolinamide (7531-52-4)

Conditions	Yield
With ammonia In methanol at 65℃; for 15h;	90%
With methanol; ammonia
With ammonium hydroxide
With ammonium hydroxide In butan-1-ol at 5 - 30℃;

(2S,1'S)-1-(1'-phenylethyl)pyrrolidine-2-carboxamide (929897-95-0) → L-prolinamide (7531-52-4)

Conditions	Yield
With hydrogen; palladium dihydroxide In ethanol; ethyl acetate at 20℃; under 760 Torr; for 14h;	77%

(S)-(9H-fluoren-9-yl)methyl 2-carbamoylpyrrolidine-1-carboxylate (115134-39-9) → L-prolinamide (7531-52-4)

Conditions	Yield
With morpholine In N,N-dimethyl-formamide for 1h;	73%
With alkylamine In N,N-dimethyl-formamide at 20℃; for 1h;

L-proline (147-85-3) → L-prolinamide (7531-52-4)

Conditions	Yield
Stage #1: L-proline With thionyl chloride In methanol for 2h; Heating; Stage #2: With ammonia In methanol at 20℃; for 96h; Further stages.;	72%
Multi-step reaction with 3 steps 1: sodium hydroxide / H2O / Ambient temperature 2: 1.) triethylamine, isobutyl chloroformate, 2.) ammonia / 1.) chloroform, 0 deg C, 2 h, 2.) chloroform, RT, overnight 3: 88.4 percent / hydrogen / 10percent palladium on carbon / methanol / 9 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / -5 - 70 °C 2: ammonium hydroxide / butan-1-ol / 5 - 30 °C View Scheme

L-prolyl-L-alanine (6422-36-2) → (2R,5S)-2-Methyl-1,3-diazabicyclo<3.3.0>octan-4-on + L-prolinamide (7531-52-4)

Conditions	Yield
With ammonium acetate anodic oxidation; Pt electrodes, i = 370 mA*cm-2, current equiv.: 6.2 F/mol;	A 49% B 41%

ethyl (2S)-pyrrolidine-2-carboxylate (5817-26-5) → L-prolinamide (7531-52-4)

Conditions	Yield
With methanol; ammonia

(S)-2-Carbamoyl-pyrrolidine-1-carboxylic acid 2-(4-methoxy-phenyl)-2-oxo-ethyl ester (125219-05-8) → 1-(4-methoxyphenyl)ethanone (100-06-1) + L-prolinamide (7531-52-4)

Conditions	Yield
Irradiation; mild conditions;

(S)-tert-butyl 2-carbamoylpyrrolidine-1-carboxylate (35150-07-3) → L-prolinamide (7531-52-4)

Conditions	Yield
With trifluoroacetic acid at 0℃; for 1h;
With trifluoroacetic acid acidolysis;
With trifluoroacetic acid In dichloromethane at 20℃; for 1h;
With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere;
With trifluoroacetic acid In dichloromethane at 20℃; for 2h;

L-proline benzyl ester → L-prolinamide (7531-52-4)

Conditions	Yield
With methanol; ammonia

Fmoc-Pro-OH (71989-31-6) → L-prolinamide (7531-52-4)

Conditions	Yield
Stage #1: Fmoc-Pro-OH With Rink amide resin; benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 3.5h; Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃; for 0.416667h; Stage #3: With trifluoroacetic acid
Multi-step reaction with 2 steps 1: pyridine; di-tert-butyl dicarbonate; ammonium bicarbonate / 20 °C 2: alkylamine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme

(2S,1'S)-5-hydroxy-2-(1'-phenylethylamino)pentanenitrile (929897-92-7) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NEt3; MsCl; DMAP / CH2Cl2 / 36 h / 0 - 20 °C 1.2: 3380 mg / aq. H2SO4 / CH2Cl2 / 48 h / 20 °C 2.1: 77 percent / H2 / Pd(OH)2/C / ethanol; ethyl acetate / 14 h / 20 °C / 760 Torr View Scheme
Multi-step reaction with 2 steps 1: 78 percent / aq. H2SO4 / CH2Cl2 / 48 h / 20 °C 2: 77 percent / H2 / Pd(OH)2/C / ethanol; ethyl acetate / 14 h / 20 °C / 760 Torr View Scheme

1-(tert-butoxycarbonyl)-L-proline (15761-39-4) + Boc-Thr(OBzl)-resin → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / Boc2O; pyridine; (NH4)2CO3 / dioxane / 18 h / 20 °C 2: TFA / CH2Cl2 / 1 h / 20 °C View Scheme

Fmoc-Pro-OH (71989-31-6) + Fmoc-Arg(Pbf)-OH → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / NH4HCO3; EEDQ / acetonitrile / 15 h / 20 °C 2: 73 percent / morpholine / dimethylformamide / 1 h View Scheme

(S)-2-Ethoxycarbonyloxycarbonyl-pyrrolidine-1-carboxylic acid benzyl ester → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3(gas) / CH2Cl2 / 1 h / -20 °C 2: 87 percent / H2 / 5percent Pd/C / methanol / 5 h / 2068.6 Torr View Scheme

N-Benzyloxycarbonyl-L-proline (1148-11-4) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-methylmorpholine / CH2Cl2 / 2 h / -20 - -15 °C 2: NH3(gas) / CH2Cl2 / 1 h / -20 °C 3: 87 percent / H2 / 5percent Pd/C / methanol / 5 h / 2068.6 Torr View Scheme
Multi-step reaction with 2 steps 1: 1.) triethylamine, isobutyl chloroformate, 2.) ammonia / 1.) chloroform, 0 deg C, 2 h, 2.) chloroform, RT, overnight 2: 88.4 percent / hydrogen / 10percent palladium on carbon / methanol / 9 h / Ambient temperature View Scheme

water (7732-18-5) + N-[[(Phenylmethoxy)-carbonyl]-D-phenylalanyl]-L-proline (17460-56-9) + isobutyl chloroformate (543-27-1) → L-prolinamide (7531-52-4)

Conditions	Yield
With 4-methyl-morpholine In tetrahydrofuran; ethyl acetate	1.5 g (72%)

proline acid chloride (175446-63-6) → L-prolinamide (7531-52-4)

Conditions	Yield
With ammonia In methanol at 20℃; for 72h;

(5S)-2,2-dimethyl-1,3-diazabicyclo<3.3.0>octan-4-one (97482-27-4) → (2S)-N-propan-2-ylpyrrolidine-2-carboxamide (174089-62-4) + L-prolinamide (7531-52-4)

Conditions	Yield
With sodium tetrahydroborate In methanol

(S)-Nα-(benzyloxycarbonyl)proline hydroxamic acid → L-prolinamide (7531-52-4)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol

C6H11N2OPol → L-prolinamide (7531-52-4)

Conditions	Yield
With trifluoroacetic acid In chloroform-d1 Inert atmosphere; solid phase reaction;

1-(tert-butoxycarbonyl)-L-proline (15761-39-4) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 4-methyl-morpholine; isobutyl chloroformate / tetrahydrofuran / 0.58 h / 0 °C 1.2: 4 h / 0 - 20 °C 2.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C View Scheme

(S)-acetylproline (68-95-1) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / dichloromethane / 6 h / 3 - 30 °C 2: ammonium hydroxide / dichloromethane / 3 h / 30 °C 3: hydrogenchloride / water / 2 h / 103 °C View Scheme

L-glutamic acid (56-86-0) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / 2 h / 1 - 25 °C 2.1: potassium borohydride / water / 4 h / 3 - 45 °C 3.1: chloroformic acid ethyl ester; triethylamine / dichloromethane / 1.5 h / -10 °C 3.2: 0.5 h / 25 °C View Scheme

(S)-2-Amino-pentanedioic acid 5-ethyl ester (1119-33-1) → L-prolinamide (7531-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium borohydride / water / 4 h / 3 - 45 °C 2.1: chloroformic acid ethyl ester; triethylamine / dichloromethane / 1.5 h / -10 °C 2.2: 0.5 h / 25 °C View Scheme

trifluoroacetic acid (76-05-1) + L-prolinamide (7531-52-4) + Wang resin-linked N1-tert-butyloxycarbonyl-N2-triflylguanidine → (S)-1-Carbamimidoyl-pyrrolidine-2-carboxylic acid amide; compound with trifluoro-acetic acid

Conditions	Yield
Stage #1: L-prolinamide; Wang resin-linked N1-tert-butyloxycarbonyl-N2-triflylguanidine In dichloromethane at 20℃; Stage #2: trifluoroacetic acid In dichloromethane Further stages.;	100%

2-Bromoacetyl bromide (598-21-0) + L-prolinamide (7531-52-4) → (S)-1-(2-bromoacetyl)pyrrolidine-2-carboxamide (253309-37-4)

Conditions	Yield
With dmap; triethylamine In dichloromethane for 2h; cooling;	100%
Stage #1: 2-Bromoacetyl bromide; L-prolinamide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With potassium carbonate In tetrahydrofuran at 0 - 20℃; for 4h;	85.8%

di-tert-butyl dicarbonate (24424-99-5) + L-prolinamide (7531-52-4) → (S)-tert-butyl 2-carbamoylpyrrolidine-1-carboxylate (35150-07-3)

Conditions	Yield
In 1,4-dioxane; water at 20℃;	100%
With triethylamine In dichloromethane at 0 - 20℃; for 6h;
With potassium carbonate In dichloromethane at 10 - 15℃; Inert atmosphere;
With triethylamine In dichloromethane at -15℃; for 12h; Concentration;
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In dichloromethane at 10 - 15℃; for 2h;

2,4-di-tertbutyl-6-chloromethylphenol (10193-84-7) + L-prolinamide (7531-52-4) → (2S)-1-(3,5-di-tert-butyl-2-hydroxybenzyl)pyrrolidine-2-carboxamide

Conditions	Yield
With sodium hydrogencarbonate In acetonitrile for 24h; Inert atmosphere; Schlenk technique; Reflux;	100%

N-[N-[(phenylmethoxy)carbonyl]-L-phenylalanyl]-L-leucine (4313-73-9) + L-prolinamide (7531-52-4) → Z-Phe-Leu-Pro-NH2

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	100%

2-((4-(4,6-bismorpholine-1,3,5-triazin-2-yl)phenyl)amino)-1H-benzo[d]imidazole-6-carboxylic acid + L-prolinamide (7531-52-4) → (S)-1-(2-((4-(4,6-bismorpholine-1,3,5-triazin-2-yl)phenyl)amino)-1H-benzo[d]imidazole-6-carbonyl)pyrrolidine-2-carboxamide

Conditions	Yield
Stage #1: 2-((4-(4,6-bismorpholine-1,3,5-triazin-2-yl)phenyl)amino)-1H-benzo[d]imidazole-6-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.666667h; Inert atmosphere; Stage #2: L-prolinamide In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere;	99.7%
Stage #1: 2-((4-(4,6-bismorpholine-1,3,5-triazin-2-yl)phenyl)amino)-1H-benzo[d]imidazole-6-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.666667h; Inert atmosphere; Stage #2: L-prolinamide In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere;	79%

fumaryl dichloride (627-63-4) + L-prolinamide (7531-52-4) → C14H16N4O2 (913978-88-8)

Conditions	Yield
Stage #1: fumaryl dichloride; L-prolinamide With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; Stage #2: With trifluoroacetic anhydride In dichloromethane at 0 - 20℃; for 24 - 48h;	98%

3,5,5-trimethyl hexanal (5435-64-3) + L-prolinamide (7531-52-4) → (7aS)-3-(2,4,4-trimethylpentyl)hexahydro-1H-pyrrolo[1,2-c]imidazol-1-one (1378479-21-0)

Conditions	Yield
With triethylamine In methanol for 18h; Inert atmosphere; Reflux;	98%

3-Phenylbutyraldehyde (16251-77-7) + L-prolinamide (7531-52-4) → (7aS)-3-(2-phenylpropyl)hexahydro-1H-pyrrolo[1,2-c]imidazol-1-one (1084907-50-5)

Conditions	Yield
With potassium carbonate In ethanol at 60℃; for 24h;	97%
With potassium carbonate In ethanol at 60℃; for 24h; Inert atmosphere;	97%

Z-Gly-(L)-Phe (1170-76-9) + L-prolinamide (7531-52-4) → Z-Gly-L-Phe-L-Pro-NH2

Conditions	Yield
With O-(3,4-dihydro-4-oxo-azabenzo-1,2,3-triazinyl)C(NMe2)2*PF6; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	96.5%
With 2,4,6-trimethyl-pyridine; [(Me2N)(1H-1,2,3-triazolo[4,5-b]pyridinyl-1)CH=]Me2N*PF6 3-O In N,N-dimethyl-formamide	96.5%
With 2,4,6-trimethyl-pyridine; 1-hydroxy-7-aza-benzotriazole; diisopropyl-carbodiimide In dichloromethane Condensation;	94.8%

chloroacetyl chloride (79-04-9) + L-prolinamide (7531-52-4) → (S)-1-(2-chloroacetyl) pyrrolidine-2-carboxamide (214398-99-9)

Conditions	Yield
With triethylamine In dichloromethane at 5℃; for 2h; Reagent/catalyst; Inert atmosphere;	96%
With triethylamine In dichloromethane at -5 - 0℃; for 0.5h; Inert atmosphere;	96.3%
In tetrahydrofuran at 0℃; Reflux; Large scale;	92%

cyclopropylcarbinyl bromide (7051-34-5) + L-prolinamide (7531-52-4) → (-)-(S)-1-cyclopropylmethyl-2-pyrrolidinecarboxamide (114812-44-1)

Conditions	Yield
With triethylamine In tetrahydrofuran for 24h;	96%

BOC-glycine (4530-20-5) + L-prolinamide (7531-52-4) → (S)-tert-butyl 2-(2-carbamoylpyrrolidine-1-yl)-2-oxoethylcarbamate (52293-28-4)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃;	95.8%
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃;	95.8%
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃;	95.8%
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃;	95.8%
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 dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h;	71%

(S)-N-(benzyloxycarbonyl)phenylglycine (5491-18-9, 17609-52-8, 53990-33-3, 60584-76-1) + L-prolinamide (7531-52-4) → Cbz-Phg-Pro-NH2

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; 3-hydroxy-4-oxo-3,4-dihydro-5-azabenzo-1,2,3-triazine In chloroform; 2,2,2-trifluoroethanol at 20℃;	95.4%
Stage #1: (S)-N-(benzyloxycarbonyl)phenylglycine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: L-prolinamide In N,N-dimethyl-formamide at 20℃; Further stages.;	93%
With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; 1-diethoxyphosphinyloxy-7-azabenzotriazole	92.8%

Z-Hle-OPfp + L-prolinamide (7531-52-4) → Z-Hle-Pro-NH2

Conditions	Yield
In N,N-dimethyl-formamide Ambient temperature;	95%

(Sa)-3,3'-diformyl-2,2'-dihydroxy-1,1'-binaphthalene + L-prolinamide (7531-52-4) → C32H30N4O4

Conditions	Yield
In ethanol for 3h; Reflux;	95%

2-chloro-6-(piperidin-1-ylmethyl)-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)thieno[2,3-d]pyrimidin-4-amine + L-prolinamide (7531-52-4) → (S)-1-(6-(piperidin-1-ylmethyl)-4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)thieno[2,3-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 150℃; for 5h; Microwave irradiation;	95%

1-chloro-2-(trifluoromethyl)benzene (88-16-4) + L-prolinamide (7531-52-4) → (S)-N'-((2-trifluoromethyl)phenyl)prolinylamide (403478-68-2)

Conditions	Yield
With 4-diphenylphosphino-13-dicyclohexylphosphino-[2.2]paracyclophane; water; palladium diacetate; caesium carbonate In 1,4-dioxane at 125℃; for 24h; Buchwald-Hartwig coupling;	94%

(2S)-2-[((2S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanoyl)amino]-3-methylbutanoic acid (13123-00-7) + L-prolinamide (7531-52-4) → Z-L-Phe-L-Val-L-Pro-NH2 (164861-48-7)

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; [Me2N(1H-1,2,3-triazolo[4,5-b]pyridinyl)CH=]Me2N 3-oxide*PF6; 4-(N,N-dimethylamino)-2,6-di-tert-butylpyridine In N,N-dimethyl-formamide at 20℃;	93.5%
With 2,4,6-trimethyl-pyridine; 1-hydroxy-7-aza-benzotriazole; 1-diethoxyphosphinyloxy-7-azabenzotriazole In N,N-dimethyl-formamide	93.4%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide Product distribution; Further Variations:; Reagents;	87.4%

4-oxo-1-pentyl-7-(phenylthio)-1,4-dihydroquinoline-3-carboxylic acid (1416564-42-5) + L-prolinamide (7531-52-4) → C26H29N3O3S (1416564-35-6)

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18.5h; Inert atmosphere;	93%

4-(5-((1-(2-ethyl-2-fluorobutyl)piperidin-4-yl)methyloxy)pyrimidin-2-yl)benzoic acid + L-prolinamide (7531-52-4) → (S)-1-(4-(5-((1-(2-ethyl-2-fluorobutyl)piperidin-4-yl)methoxy)pyrimidin-2-yl)benzoyl)pyrrolidine-2-carboxamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	93%

N-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)benzyl)-N-phenylethenesulfonamide + L-prolinamide (7531-52-4) → (S)-1-(2-(N-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)benzyl)-N-phenylsulfamoyl)ethyl)pyrrolidine-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	92.9%

L-prolinamide (7531-52-4) → L-proline (147-85-3)

Conditions	Yield
Stage #1: L-prolinamide With hydrogenchloride for 10h; Heating; Stage #2: With methyloxirane In ethanol at 20℃; for 5h;	92%

chloroacetyl chloride (79-04-9) + L-prolinamide (7531-52-4) → (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (207557-35-5)

Conditions	Yield
Stage #1: chloroacetyl chloride; L-prolinamide With potassium carbonate In acetonitrile at 0 - 15℃; Stage #2: With trifluoroacetic anhydride at 0 - 15℃;	92%
Stage #1: chloroacetyl chloride; L-prolinamide With potassium carbonate In acetonitrile at 0 - 20℃; Stage #2: With trifluoroacetic anhydride at 0 - 25℃;	92%
Stage #1: chloroacetyl chloride; L-prolinamide With trifluoroacetyl chloride In N,N-dimethyl-formamide at 50℃; for 1.5h; Stage #2: With trifluoroacetyl chloride In N,N-dimethyl-formamide at 60℃; for 1.5h; Reagent/catalyst; Temperature;	83.4%

(2S)-2-[(t-butoxycarbonyl)amino]-3-{4-[(5-nitropyridin-2-yl)oxy]phenyl}propanoic acid (1011521-39-3) + L-prolinamide (7531-52-4) → (2S)-1-{(2S)-2-[(t-butoxycarbonyl)amino]-3-[4-(5-nitro pyridin-2-yloxy)phenyl]propanoyl}pyrrolidine-2-carboxamide

Conditions	Yield
Stage #1: (2S)-2-[(t-butoxycarbonyl)amino]-3-{4-[(5-nitropyridin-2-yl)oxy]phenyl}propanoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: L-prolinamide In N,N-dimethyl-formamide at 20℃; for 15h;	92%

9-bromo-10-(bromomethyl)-2,3,6-trimethoxyphenanthrene (1215841-60-3) + L-prolinamide (7531-52-4) → (2S)-1-[(10-bromo-3,6,7-trimethoxy-9-phenanthryl)methyl]pyrrolidine-2-carboxamide (1309782-29-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 8h; Reflux;	92%

9-bromo-10-(bromomethyl)-2,3,6,7-tetramethoxyphenanthrene (1215841-59-0) + L-prolinamide (7531-52-4) → (S)-1-[(9-bromo-2,3,6,7-tetramethoxyphenanthren-10-yl)methyl]pyrrolidine-2-carboxamide (1309782-28-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 8h; Reflux;	92%
With potassium carbonate In N,N-dimethyl-formamide for 8h; Reflux;	92%

2’-cyano-3-fluoro-4’-((1-(2-fluoro-2-methylpropyl)piperidin-4-yl)methoxy)biphenyl-4-carboxylic acid + L-prolinamide (7531-52-4) → (S)-1-(2'-cyano-3-fluoro-4’-((1-(2-fluoro-2-methylpropyl)piperidin-4-yl)methoxy)biphenylcarbonyl)pyrrolidine-2-carboxamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	92%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	92%

Upstream product

• 5817-26-5 ethyl (2S)-pyrrolidine-2-carboxylate 
• 6422-36-2 L-prolyl-L-alanine 
• 34079-31-7 Z-Pro-NH₂ 
• 71989-31-6 Fmoc-Pro-OH 
• 1119-33-1 (S)-2-Amino-pentanedioic acid 5-ethyl ester 
• 56-86-0 L-glutamic acid 
• 16395-58-7 N-acetyl-L-prolinamide 
• 68-95-1 (S)-acetylproline 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 97482-27-4 (5S)-2,2-dimethyl-1,3-diazabicyclo<3.3.0>octan-4-one 
• 175446-63-6 proline acid chloride 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 7732-18-5 water 
• 17460-56-9 N-[[(Phenylmethoxy)-carbonyl]-D-phenylalanyl]-L-proline 

Downstream Products

• 789469-53-0 (S)-1-(2-Benzhydryloxy-ethyl)-pyrrolidine-2-carboxylic acid amide 
• 777833-33-7 (S)-1-{2-[Bis-(4-fluoro-phenyl)-methoxy]-ethyl}-pyrrolidine-2-carboxylic acid amide 
• 197709-31-2 (S)-3-Ethyl-3-methyl-hexahydro-pyrrolo[1,2-c]imidazol-1-one 
• 958852-30-7 (2S,αS)-α-(2-carbamoylpyrrolidin-1-yl)-α-phenylacetic acid methyl ester 
• 958852-31-8 (2S,αR)-α-(2-carbamoylpyrrolidin-1-yl)-α-phenylacetic acid methyl ester 
• 96948-23-1 1-[(2S)-N-Benzylpyrrolidin-2-yl]methanamine 
• 565453-39-6 (S)-1-[2-(3-hydroxyadamantan-1-ylamino)acetyl]pyrrolidine-2-carboxylic acid amide 
• 274901-16-5 vildagliptin 

Relevant articles and documents

Preparation method of L-prolinamide

The invention provides a preparation method of L-prolinamide. The preparation method comprises the following steps: by using L-proline as an initial raw material, firstly forming L-proline methyl ester hydrochloride, then carrying out ammonolysis to obtain a synthetic solution containing L-prolinamide, and dissociating the residual L-prolinamide hydrochloride in the synthetic solution into L-prolinamide through inorganic alkali in a non-aqueous environment, and removing by-products through a non-aqueous solvent system. According to the preparation method, the L-prolinamide hydrochloride can befully dissociated, the by-products and the impurities can be effectively removed, the yield and purity of the target product can be remarkably improved, the preparation method is simple and convenient in process, mild in condition and easy to control, expensive reagents are not needed, the production efficiency of the L-prolinamide can be improved, and the preparation method is suitable for large-scale industrial production and has important economic and social values.

Synthesis method of vildagliptin

The invention discloses a synthesis method of vildagliptin. The method comprises the following steps: performing esterification reaction on L-glutamic acid and ethanol to obtain L-glutamic acid-gamma-ethyl ester; reducing the L-glutamic acid-gamma-ethyl ester under the action of potassium borohydride to obtain L-proline; mixing L-proline with ethyl chloroformate for reaction to obtain acid anhydride; further reacting the acid anhydride with amine to obtain amide; dehydrating the amide under the action of phosphorus pentoxide to obtain an intermediate 1; performing substitution reaction on theintermediate 1 and chloroacetyl chloride to obtain an intermediate 2; and further reacting the intermediate 2 with 3-amino-1-adamantanol to obtain vildagliptin. The method has the advantages that fewimpurities are generated in the vildagliptin preparation process, the yield of the prepared vildagliptin is high, and compared with the prior art, the process is simpler, and the vildagliptin preparation cost is greatly reduced.

Synthesis method of L-prolinamide

The invention belongs to the field of organic synthesis, and discloses a synthesis method of L-prolinamide. The method comprises steps of S1, dissolving an initial material, L-proline, in water and then reacting with acetic anhydride, after reaction, extracting and drying to prepare N-acetyl-L-proline; S2, in a solvent system, performing a reaction on a raw material, N-acetyl-L-proline prepared inS1 and thionyl chloride, then concentrating and drying to obtain a compound; S3, dripping aqueous ammonia in the compound prepared in S2 as a raw material so as to react, filtering and preparing 1-acetyl-2-pyrrolidinecarboxamide; and S4, dripping HC1 into the 1-acetyl-2-pyrrolidinecarboxamide prepared in S3 as a raw material, so as to react, then concentrating, filtering and drying to prepare L-prolinamide. In the reaction process of the synthesis method provided by the invention, common reagent raw materials are used, the costs are low, the reaction conditions are mild, the chiral purity ishigh, the yield is high, the environment pressure is low, and the synthesis method is suitable for large-scale production.

Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus

In this study, bornyl- and cytisine-based cyanopyrrolidines as potent dipeptidyl peptidase-IV (DPP-IV) inhibitors were synthesised. The in vitro inhibiting activities of bornyl- and cytisine derivatives towards DPP-IV were evaluated. Bornyl-based cyanopyrrolidines were shown to have moderate inhibitory activity with regard to DPP-IV (1.27–15.78 μM). A docking study was performed to elucidate the structure-activity relationship of the obtained compounds. The in vivo hypoglycemic activities of the same compounds were evaluated with the oral glucose tolerance test (OGTT) in mice. Bornyl-based cyanopyrrolidines were shown to have good hypoglycemic activity.

Synthesis method of L-prolinamide

The invention relates to the technical field of medicines, in particular to a synthesis method of L-prolinamide. The synthesis method comprises the steps of (1) dissolving the L-prolinamide into an alcoholic solution, adding an esterification reagent for reacting, and obtaining an intermediate product II; (2) adding the product II of the step (1) into an alcoholic solution of ammonia, transferringto a high pressure reactor, and carrying out ammonia-feeding reaction; (3) decompressing and concentrating a reaction liquid in the step (2), and filtering to obtain a primary filter liquor; (4) desalinizing the primary filter liquor in the step (3), and filtering to obtain a secondary filter liquor; (5) decompressing and concentrating the secondary filter liquor of the step (4), adding a solventfor dissolving and crystalizing, cooling for suction filtration, and obtaining a product I. The synthesis method provided by the invention is simple to operate, less in waste water and waste gas, clean and environmentally-friendly. The total yield of the L-prolinamide is 78 percent, the product HPLC (High Performance Liquid Chromatography) purity is 99.6 percent, the maximum individual impurity is less than or equal to 0.3 percent, and a D type isomer is less than or equal to 0.3 percent.

HEMIAMINAL-TAG FOR PROTEIN LABELING AND PURIFICATION

The invention pertains to the synthesis, isolation, and characterization of hemiaminal for selective labeling of peptides, proteins, antibodies, and organic fragments with -C(=0) CH2NH2 and derivatives with -CH2NH2 group over -C(=0) CHRNH2 group (where R≠H). The invention also pertains to the method of single-site immobilization of proteins through N-terminus Gly on solid phase. The invention includes late-stage tagging of N-terminus Gly with an affinity tag, 19F NMR probe, and a fluorophore and a method for metal-free protein purification and isolation of analytically pure proteins.

Corresponding amine nitrile and method of manufacturing thereof

The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.

Synthetic method for chiral alpha-aminoamide compounds

The invention provides a synthetic method for chiral alpha-aminoamide compounds, belongs to the technical field of organic synthetic methodology, and concretely relates to a synthetic method for chiral alpha-aminoamide compounds, wherein the method has a simple process, low costs and good economy. The method comprises the following steps: 1, performing ammonolysis: adding substituted chiral alpha-aminocarboxylate hydrochloride into concentrated ammonia water, performing stirring for 4-12h under a room temperature, wherein each 1mmol substituted chiral alpha-aminocarboxylate hydrochloride is corresponding to 2-8mL the concentrated ammonia water; 2, after a reaction is finished, performing distillation for removing ammonia water after the reaction to obtain crude products chiral alpha-aminoamide compounds; and 3, performing filtration on the obtained crude products chiral alpha-aminoamide compounds by adopting a manner of adding a solvent or performing purification on the obtained crude products chiral alpha-aminoamide compounds through a manner of column chromatography which uses ammonia water as a mobile phase to obtain the products chiral alpha-aminoamide compounds. Compared with the prior art, a large number of an ammonia gas for ammonolysis is not needed in the method, the process and post-treatment are simple, costs are low and reaction time is short.

A method of refining prolinamides

The invention relates to a method for refining prolinamide, which includes the following steps: (a) dissolving prolinamide coarse product in an organic solvent, wherein the prolinamide coarse product contains ammonium chloride, prolinamide hydrochloride or mixture thereof; (b) adding inorganic alkali for treatment; and (c) separating to obtain the prolinamide. The method for refining prolinamide is simple, the content and optical purity of the obtained product are high, and the method is very suitable for industrial production.

A method for synthesizing allah Geleg sandbank (by machine translation)

The invention relates to a method for preparing anti-II type diabetes drug allah Geleg sandbank method for the synthesis of bulk drug (Anagliptin). The lack of commercial synthetic allah Geleg sandbank solve the technical problems of the method. Synthetic method comprises the following steps : (1) with vinyl ether and trichloro acetyl chloride as the raw material, passes through the three-step reaction to obtain the aldehyde protected intermediates 4 ; The 3-amino-5-methyl pyrazole condensation for dehydrating and gets pyrazolo pyrimidine mother nucleus; Carboxy b ester hydrolysis to obtain 2-methyl-pyrazolo [1,5-a] pyrimidin 6-carboxylic acid 6 ; (2) to L-proline as a raw material, passes through the methyl esterification, ammoniation, acetylation, Carbonitride reaction to obtain the chiral cyano pyrrolizinone intermediate 11 ; Chiral cyano pyrrolizinone intermediate 11 And diamine fragment 12 In alkaline conditions to obtain intermediate affinity substituted 13 ; Finally, intermediate 13 Under the conditions of the hydrochloric acid removal protection Boc base namely obtain cyanopentanoyl Azolylamine intermediate 14 ; (3) 2-methyl-pyrazolo [1,5-a] pyrimidine-6-carboxylic acid 6 The cyano Azolylamine intermediate 14 The condensation conditions to obtain the bulk drug allah Geleg sandbank coupled. (by machine translation)