62937-45-5

Basic information

• Product Name: D-Prolinamide
• Synonyms: (R)-PROLINAMIDE;(R)-PYRROLIDINE-2-CARBOXAMIDE;(R)-PYRROLIDINE-2-CARBOXYLIC ACID AMIDE;H-D-PRO-NH2;H-D-PYRD(2)-NH2;D-PROLINAMIDE;D-PROLINE AMIDE;D-PROLINE-NH2
• CAS NO: 62937-45-5
• Molecular Formula: C₅H₁₀N₂O
• Molecular Weight: 114.15
• EINECS: 1533716-785-6
• Product Categories: AMIDE;AMINOACIDS DERIVATIVES;Pyrrolidines;Proline [Pro, P];Amino Acids and Derivatives;amino acid
• Mol File: 62937-45-5.mol

Chemical Properties

• Melting Point: 95-97°C
• Boiling Point: 303.6 °C at 760 mmHg
• Flash Point: 137.4 °C
• Appearance: Crystalline
• Density: 1.106 g/cm³
• Vapor Pressure: 0.000923mmHg at 25°C
• Refractive Index: 1.491
• Storage Temp.: -15°C
• Solubility: DMSO, Ethanol
• PKA: 16.21±0.20(Predicted)
• Water Solubility: Soluble in water.
• BRN: 471499
• CAS DataBase Reference: D-Prolinamide(CAS DataBase Reference)
• NIST Chemistry Reference: D-Prolinamide(62937-45-5)
• EPA Substance Registry System: D-Prolinamide(62937-45-5)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 62937-45-5(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
D-Prolinamide is used as a key intermediate in the synthesis of proline derivatives, which serve as efficient organocatalysts for the aldol reaction on water. This reaction is a crucial carbon-carbon bond-forming process in organic chemistry, enabling the construction of complex molecular structures with potential applications in pharmaceuticals, agrochemicals, and materials science.
Used in Pharmaceutical Industry:
D-Prolinamide is also utilized in the development of novel pharmaceutical agents, particularly in the design of peptidomimetics and enzyme inhibitors. Its unique stereochemistry and hydrogen bonding capabilities allow for the creation of bioactive molecules with improved potency, selectivity, and pharmacokinetic properties.

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

Synthetic route

(2R)-2-carbamoyl-pyrrolidine-1-carboxylic acid benzyl ester (62937-47-7) → (R)-prolinamide (62937-45-5)

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;	87.3%

D-proline ethyl ester hydrochloride → (R)-prolinamide (62937-45-5)

Conditions	Yield
With ammonia In ethanol at 0 - 20℃; Large scale;	80%

Z-D-proline (6404-31-5) → (R)-prolinamide (62937-45-5)

Conditions	Yield
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: 87.3 percent / hydrogen / 10percent palladium on carbon / methanol / 9 h / Ambient temperature View Scheme

D-Prolin (344-25-2) → (R)-prolinamide (62937-45-5)

Conditions	Yield
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: 87.3 percent / hydrogen / 10percent palladium on carbon / methanol / 9 h / Ambient temperature View Scheme

(R)-2-carbamoylpyrrolidine-1-carboxylic acid tert-butyl ester (70138-72-6) → (R)-prolinamide (62937-45-5)

Conditions	Yield
Stage #1: (R)-2-carbamoylpyrrolidine-1-carboxylic acid tert-butyl ester With trifluoroacetic acid at 25℃; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃;

N-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)benzyl)-N-phenylethenesulfonamide + (R)-prolinamide (62937-45-5) → (R)-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%

2-([1,1'-biphenyl]-4-yl)-4-methyl-5-(2-(methylsulfonyl)pyrimidin-4-yl)thiazole + (R)-prolinamide (62937-45-5) → (R)-1-{4-[2-((1,1'-biphenyl)-4-yl)-4-methylthiazol-5-yl]pyrimidin-2-yl}pyrrolidine-2-carboxamide

Conditions	Yield
In N,N-dimethyl-formamide at 80℃;	92%

9-bromo-10-(bromomethyl)-2,3,6,7-tetramethoxyphenanthrene (1215841-59-0) + (R)-prolinamide (62937-45-5) → (R)-1-[(9-bromo-2,3,6,7-tetramethoxyphenanthren-10-yl)methyl]pyrrolidine-2-carboxamide (1394286-36-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 8h; Reflux;	91%

2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)thieno[3,2-d]pyrimidin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)thieno[3,2-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide hydrochloride

Conditions	Yield
Stage #1: 2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)thieno[3,2-d]pyrimidin-4-amine; (R)-prolinamide With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 130℃; for 18h; Microwave irradiation; Stage #2: With hydrogenchloride In water; acetonitrile	90%

2-((4-(4,6-bismorpholine-1,3,5-triazin-2-yl)phenyl)amino)-1H-benzo[d]imidazole-6-carboxylic acid + (R)-prolinamide (62937-45-5) → (R)-1-(2-((4-(4,6-bismorpholin-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: (R)-prolinamide In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere;	88%

Ph(3-Cl)(5-OCHF2)-(R,S)CH(OH)C(O)OH (433938-41-1) + (R)-prolinamide (62937-45-5) → (R)-3-chloro-5-difluoro-methoxy-mandelic acid D-prolinamide salt

Conditions	Yield
In water; 4-methyl-2-pentanone at 20 - 100℃; for 22.5h; Purification / work up; Resolution of racemate;	81.8%
In water; ethyl acetate at 0 - 75℃; for 3.16667 - 13.8333h; Product distribution / selectivity; Heating / reflux;	n/a
In water; ethyl acetate at 72 - 75℃; for 0.166667 - 0.5h; Purification / work up; Resolution of racemate; Heating / reflux;	n/a

2-chloro-7-isopropoxy-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)quinazolin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(7-isopropoxy-4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)quinazolin-2-yl)pyrrolidine-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 150℃; for 5h; Microwave irradiation;	81%

5-(4-chlorophenyl)-2-{[1-(4-chloropyridin-3-yl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one + (R)-prolinamide (62937-45-5) → 1-{3-[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-1-yl]pyridin-4-yl}-D-prolinamide

Conditions	Yield
In ethanol Reflux;	79%

5'-(cis-3-cycloheptyl-4-oxo-3,4,4a,5,8,8a-hexahydrophthalazin-1-yl)-2'-methoxy-[1,1'-biphenyl]-4-carboxylic acid + (R)-prolinamide (62937-45-5) → (R)-1-(5'-(cis-3-cycloheptyl-4-oxo-3,4,4a,5,8,8a-hexahydrophthalazin-1-yl)-2'-methoxy-[1,1'-biphenyl]-4-carbonyl)pyrrolidine-2-carboxamide

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; Inert atmosphere;	78%

2-chloro-7-tosyl-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(7-tosyl-4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide

Conditions	Yield
In isopropyl alcohol at 150℃; for 3h; Microwave irradiation;	75%

(R)-prolinamide (62937-45-5) + 4-guanidinophenyl N-benzoylglycinate (288608-40-2) → Bz-Gly-D-Pro-NH2

Conditions	Yield
With clostripain; HEPES buffer; sodium chloride; calcium chloride at 25℃; pH=8.0;	72.6%

5-(4-chlorophenyl)-2-{[1-(2-chloropyridin-3-yl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one + (R)-prolinamide (62937-45-5) → 1-{3-[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-1-yl]pyridin-2-yl}-D-prolinamide

Conditions	Yield
In ethanol Reflux;	70%

(R)-prolinamide (62937-45-5) + allyl (5R,6S)-2-<<(methylsulfonyl)oxy>methyl>-6-<(R)-1-<(tert-butyldimethylsilyl)oxy>ethyl>penem-3-carboxylate (88585-79-9) → allyl (5R,6S)-2-<((2R)-1-prolinamido)methyl>-6-<(R)-1-<(tert-butyldimethylsilyl)oxy>ethyl>penem-3-carboxylate (166374-72-7) + 2-[(S)-2-(tert-Butyl-dimethyl-silanyloxy)-1-((R)-2-carbamoyl-pyrrolidine-1-carbonyl)-propyl]-5-methyl-thiazole-4-carboxylic acid allyl ester

Conditions	Yield
With triethylamine In dimethyl sulfoxide for 20h; Ambient temperature;	A 66% B n/a

benzoylamino-acetic acid benzyl ester (19811-58-6) + (R)-prolinamide (62937-45-5) → Bz-Gly-D-Pro-NH2

Conditions	Yield
With syn-benzaldehyde oxime; triethylamine; diothiothreitol In toluene at 35℃; immobilized papain;	65%

(R)-prolinamide (62937-45-5) + Bz-D-Ala-OGp → Bz-D-Ala-D-Pro-NH2

Conditions	Yield
With clostripain; HEPES buffer; sodium chloride; calcium chloride at 25℃; pH=8.0;	60.7%

2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)-5,6,7,8-tetrahydroquinazolin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-2-carboxamide hydrochloride

Conditions	Yield
Stage #1: 2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)-5,6,7,8-tetrahydroquinazolin-4-amine; (R)-prolinamide In isopropyl alcohol at 150℃; for 3h; Microwave irradiation; Stage #2: With hydrogenchloride In water; acetonitrile	60%

2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)quinazolin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)quinazolin-2-yl)pyrrolidine-2-carboxamide hydrochloride

Conditions	Yield
Stage #1: 2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)quinazolin-4-amine; (R)-prolinamide With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 130℃; for 18h; Microwave irradiation; Stage #2: With hydrogenchloride In water; acetonitrile	58%

2-[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-1-yl]benzoyl chloride + (R)-prolinamide (62937-45-5) → 1-{2-[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-1-yl]benzoyl}-D-prolinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 1h;	57%

(R)-prolinamide (62937-45-5) → (S)-1-nitrosopyrrolidine-2-carboxamide

Conditions	Yield
With tert.-butylhydroperoxide; nitromethane; potassium iodide In water at 80℃; for 6h;	56%

5'-(cis-3-isopropyl-4-oxo-3,4,4a,5,8,8a-hexahydrophthalazin-1-yl)-2'-methoxy-[1,1'-biphenyl]-4-carboxylic acid + (R)-prolinamide (62937-45-5) → (R)-1-(5'-(cis-3-isopropyl-4-oxo-3,4,4a,5,8,8a-hexahydrophthalazin-1-yl)-2'-methoxy-[1,1'-biphenyl]-4-carbonyl)pyrrolidine-2-carboxamide

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; Inert atmosphere;	56%

2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)thieno[2,3-d]pyrimidin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)thieno[2,3-d]pyrimidin-2-yl)pyrrolidine-2-carboxamide hydrochloride

Conditions	Yield
Stage #1: 2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)thieno[2,3-d]pyrimidin-4-amine; (R)-prolinamide With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 130℃; for 18h; Microwave irradiation; Stage #2: With hydrogenchloride In water; acetonitrile	56%

2-(2-(4-(tert-butyl)phenyl)-4-methylthiazol-5-yl)-5-(methylsulfonyl)-1,3,4-oxadiazole + (R)-prolinamide (62937-45-5) → (R)-1-{5-[2-(4-(tert-butyl)phenyl)-4-methylthiazol-5-yl]-1,3,4-oxadiazol-2-yl}pyrrolidine-2-carboxamide

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃;	56%

2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine + (R)-prolinamide (62937-45-5) → (R)-1-(4-((1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide hydrochloride

Conditions	Yield
Stage #1: 2-chloro-N-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine; (R)-prolinamide With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 125℃; for 15h; Microwave irradiation; Stage #2: With hydrogenchloride In water; acetonitrile	55%

(R)-prolinamide (62937-45-5) + Bz-D-Leu-OGp → Bz-D-Leu-D-Pro-NH2

Conditions	Yield
With clostripain; HEPES buffer; sodium chloride; calcium chloride In N,N-dimethyl-formamide at 25℃; pH=8.0;	46.2%

(R)-prolinamide (62937-45-5) → (-)-(R)-2-aminomethylpyrrolidine (57734-57-3, 69500-64-7, 123654-27-3, 72300-69-7)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 33h; Heating;	46.1%
Stage #1: (R)-prolinamide With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; Reflux; Stage #2: With water In tetrahydrofuran	30%
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; Reflux;
With lithium aluminium tetrahydride
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 75℃;

(R)-prolinamide (62937-45-5) + Bz-D-Phe-OGp → Bz-D-Phe-D-Pro-NH2

Conditions	Yield
With clostripain; HEPES buffer; sodium chloride; calcium chloride In N,N-dimethyl-formamide at 25℃; pH=8.0;	44%

3-{(S)-1-[4-(6-fluoro-pyridin-3-yl)-phenyl]-ethyl}-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (1352754-29-0) + (R)-prolinamide (62937-45-5) → (R)-1-[5-(4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-phenyl)-pyridin-2-yl]-pyrrolidine-2-carboxylic acid amide (1352753-90-2)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 100℃;	43%

Upstream product

• 62937-47-7 (2R)-2-carbamoyl-pyrrolidine-1-carboxylic acid benzyl ester 
• 6404-31-5 Z-D-proline 
• 344-25-2 D-Prolin 
• 70138-72-6 (R)-2-carbamoylpyrrolidine-1-carboxylic acid tert-butyl ester 
• 131477-20-8 D-proline ethyl ester hydrochloride 

Downstream Products

• 146445-04-7 (R)-(+)-N-tritylprolinamine 
• 103305-52-8 Z-Pro-Leu-D-Pro-NH₂ 
• 57734-57-3 (-)-(R)-2-aminomethylpyrrolidine 
• 190654-11-6 1-[6-(3-chloro-phenylamino)-9-ethyl-9H-purin-2-yl]-pyrrolidine-2-carboxylic acid amide 
• 955946-56-2 1-{[3-(4-{[(2R)-4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)phenyl]carbonyl}-D-prolinamide 
• 565452-98-4 1-chloroacetyl-2-cyano-(R)-pyrrolidine 
• 146445-06-9 5-Iodo-2,3-dimethoxy-N-((R)-1-trityl-pyrrolidin-2-ylmethyl)-benzamide 
• 146445-07-0 (R)-(-)-2,3-dimethoxy-5-iodo-N-(2-pyrrolidinylmethyl)benzamide 
• 78664-39-8 Z-pGlu-Leu-D-Pro-NH₂ 
• 195311-28-5 (S)-(+)-1-[(2-pyrrolidin-1-yl)methyl]-pyrrolidine 
• 1075736-80-9 1-[(3-iodophenyl)carbonyl]-D-prolinamide 
• 1075736-85-4 1-{[3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl]carbonyl}-D-prolinamide 
• 1143507-09-8 1-[(3-{6-methyl-4-[(3,3,3-trifluoro-2-{[[(4-fluorophenyl)sulfonyl](1-methylethyl)amino]methyl}-2-hydroxypropyl)amino]-1H-indazol-1-yl}phenyl)carbonyl]-D-prolinamide 

Relevant articles and documents

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Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr = N-dimethyl-2(R)-aminomethylpyrrolidine)

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Synthesis, antitumor activity, and nephrotoxicity of the optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato) platinum(II)

The optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)platinum(II) (DWA2114, 1), which has potent antitumor activity against various tumors, were synthesized. They were examined for antitumor activity against Colon 26 carcinoma in a sc-iv system, and changes in urinary protein and sugar levels in drug-treated mice were used as an index of nephrotoxicity. In their effect on tumors, (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II) (6b) was more potent than the enantiomer 6a in that the effective dose of 6b was smaller than that of 6a; but, both drugs exhibited potent antitumor activity. On the other hand, a distinct difference between 6a and 6b was shown in their nephrotoxicity. Isomer 6b induced a great increase in urinary protein and sugar levels in mice, whereas 6a caused no increase in these levels.