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Chemical Structure| 62937-45-5 Chemical Structure| 62937-45-5

Structure of H-D-Pro-NH2
CAS No.: 62937-45-5

Chemical Structure| 62937-45-5

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Synonyms: (R)-Pyrrolidine-2-carboxamide

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of [ 62937-45-5 ]

CAS No. :62937-45-5
Formula : C5H10N2O
M.W : 114.15
SMILES Code : O=C(N)[C@@H]1NCCC1
Synonyms :
(R)-Pyrrolidine-2-carboxamide
English Name :D-Prolinamide
MDL No. :MFCD00153457
InChI Key :VLJNHYLEOZPXFW-SCSAIBSYSA-N
Pubchem ID :447554

Safety of [ 62937-45-5 ]

Computational Chemistry of [ 62937-45-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 33.66
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

55.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.71
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.87
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-1.16
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.78
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.42

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

0.07
Solubility 133.0 mg/ml ; 1.17 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.19
Solubility 178.0 mg/ml ; 1.56 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.34
Solubility 51.8 mg/ml ; 0.454 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.61 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.47

Application In Synthesis of [ 62937-45-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 62937-45-5 ]

[ 62937-45-5 ] Synthesis Path-Downstream   1~7

  • 2
  • [ 62937-45-5 ]
  • [ 247219-81-4 ]
  • [ 247219-83-6 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; dicyclohexyl-carbodiimide
  • 3
  • [ 62937-45-5 ]
  • [ 195311-28-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In tetrahydrofuran 18.C Amino Acid→diamine C) To a suspension of 0.380 gm of lithium aluminum hydride in 15 ml of dry tetrahydrofuran is carefully added a solution of the D-proline amide (prepared in B above) in 10 ml tetrahydrofuran. The mixture is refluxed for 2 hrs then cooled and quenched with 2 ml of 2.5N sodium hydroxide. The mixture is filtered through a pad of sodium sulfate and the filter cake washed with 2*50 ml of ether. The combined filtrates are concentrated in vacuo to yield 0.80 gm of desired 2-(1-pyrrolidinylmethyl) pyrrolidine.
With sodium hydroxide In tetrahydrofuran 18.C C C To a suspension of 0.380 gm of lithium aluminum hydride in 15 ml of dry tetrahydrofuran is carefully added a solution of the D-proline amide (prepared in B above) in 10 ml tetrahydrofuran. The mixture is refluxed for 2 hrs then cooled and quenched with 2 ml of 2.5N sodium hydroxide. The mixture is filtered through a pad of sodium sulfate and the filter cake washed with 2*50 ml of ether. The combined filtrates are concentrated in vacuo to yield 0.80 gm of desired 2-(1-pyrrolidinylmethyl) pyrrolidine.
  • 4
  • [ 70138-72-6 ]
  • [ 62937-45-5 ]
YieldReaction ConditionsOperation in experiment
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℃;
  • 5
  • [ 156899-02-4 ]
  • [ 62937-45-5 ]
  • [ 1246779-27-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 20℃; Intermediate 19tert-Butyl 2-(3-[(2R)-2-carbamoylpyrrolidin-1-yl]carbonyl}phenyl)-hydrazinecarboxylate 3-(2-Tert-butoxycarbonyl)hydrazinyl)benzoic acid (1.96 g, 7.77 mmol) was dissolved in NMP (10 ml) and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (5.91 g, 15.55 mmol), N-ethyl-N-isopropylpropan-2-amine (4.1 ml, 23.32 mmol) and (R)-pyrrolidine-2-carboxamide (0.89 g, 7.77 mmol) were added at room temperature. Stirring was continued overnight, the mixture was poured into aqueous HCl (0.5 M) and the product was extracted with EtOAc (3 times 100 ml). The combined organic extracts were washed with aqueous NaHCO3, brine and dried with Na2SO4. The crude product (1.3 g) was obtained after filtration and evaporation of the solvent in vacuo and was used in the next step without any further purification. APCI-MS m/z: 293 [MH+].
  • 6
  • [ 131477-20-8 ]
  • [ 62937-45-5 ]
YieldReaction ConditionsOperation in experiment
80% With ammonia In ethanol at 0 - 20℃; Large scale; 6 Preparation of D-prolinamide The D-proline ethyl ester hydrochloride obtained in Example 3 was dissolved in 400 L of ethanol, cooled to 0 to 10 ° C with stirring, and started to react with ammonia gas at a temperature of 15 to 20 ° C for 10 to 20 hours.At the end of the reaction, ethanol was evaporated to dryness under reduced pressure.700 L of methylene chloride was added to the solution, and the mixture was dissolved with stirring, and cooled to 0 to 10C.Began to drop concentrated concentrated potassium hydroxide solution (75kg dissolved in 45kg of water) drained, drop complete, heat stirring reaction 1 hour.The inorganic salt was removed by filtration.The filtrate was separated and the aqueous layer was extracted twice more with 250 ml of dichloromethane.The organic layers were combined and the dichloromethane was evaporated under reduced pressure.Ethyl acetate (50 L) was added and the residue was evaporated to dryness under reduced pressure.Adding ethyl acetate 440L dissolved in heat, activated carbon decolorization, hot filtration, cooling to 0-5 ° C stirring crystallization 2 hours.Filtered and dried in an oven at about 45 ° C under reduced pressure to obtain 79.3 kg of the target product D-prolinamide in a yield of 80.0%.Product purity (HPLC): 99.7%; titration content: 99.5%; L-prolinamide (GC): 0.15%.
  • 7
  • [ 24424-99-5 ]
  • [ 62937-45-5 ]
  • [ 70138-72-6 ]
YieldReaction ConditionsOperation in experiment
94.14 % With potassium carbonate In 1,4-dioxane; water at 20℃; 1, 2, 3 tert-Butyl (R)-2-carbamoylpyrrolidine-1-carboxylate: In a 5L four-mouth flask, add 2.5L of dioxacyclo, add 500g of D-prolinamide, stir to dissolve, add 2.5L of water and 362.6g of potassium carbonate, stir mechanically, add 1240g of Boc anhydride dropwise, and react for 15h at room temperature. After the reaction, dioxane was dihydrolated, extracted 3 times (3×0.15L) with ethyl acetate, the extract was concentrated, pulped with petroleum ether with a boiling range of 60-90 °C, and dried to obtain (R)-2-carbamoylpyrrolidine-1-carboxylic acid tert-butyl ester 881.7g, with a product yield of 94.14%.
 

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[ 62937-45-5 ]

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