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Chemical Structure| 35150-07-3 Chemical Structure| 35150-07-3

Structure of Boc-Pro-NH2
CAS No.: 35150-07-3

Chemical Structure| 35150-07-3

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Product Details of [ 35150-07-3 ]

CAS No. :35150-07-3
Formula : C10H18N2O3
M.W : 214.26
SMILES Code : O=C(N1[C@H](C(N)=O)CCC1)OC(C)(C)C
MDL No. :MFCD00190827

Safety of [ 35150-07-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 35150-07-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 59.5
TPSA ?

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

72.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.9
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

0.05
Log Po/w (WLOGP)?

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

0.49
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.

0.33
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

0.55

Water Solubility

Log S (ESOL):?

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

-0.94
Solubility 24.8 mg/ml ; 0.116 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.13
Solubility 15.9 mg/ml ; 0.0744 mol/l
Class?

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

Very 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

-0.59
Solubility 54.8 mg/ml ; 0.256 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.

-7.57 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

0.0
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)

2.58

Application In Synthesis of [ 35150-07-3 ]

* 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 [ 35150-07-3 ]

[ 35150-07-3 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 35150-07-3 ]
  • [ 228244-04-0 ]
YieldReaction ConditionsOperation in experiment
76% With 1,3,5-trichloro-2,4,6-triazine; In N,N-dimethyl-formamide; at 20℃; for 1h; General procedure: A mixture of compound 2 (5 g, 23.3 mmol) and cyanuric chiloride (2.58 g, 14.0 mmol) in DMF (10 mL) was stirred at room temperature for 1 h (monitored by TLC). After the reaction completed, the solution was extracted with EtOAc, washed, dried, concentrated, and purified by flash chromatography on silica gel, eluted with a mixture of PE/EA (1/1, v/v), to afford 3 (3.48 g, 76%) as a white solid. 1H NMR (300 MHz, CDCl3) delta 4.76 (s, 1H), 3.51 (s, 2H), 2.34-2.31 (m, 1H), 2.17-2.10 (m, 2H), 1.90-1.87 (m, 1H), 1.49 (s, 9H). MS (ESI) m/z 197 [M+H]+.
76% With 1,3,5-trichloro-2,4,6-triazine; In N,N-dimethyl-formamide; at 20℃; for 1h; A mixture of compound 9 (5 g, 23.3 mmol) and cyanuric chiloride (2.58 g, 14.0 mmol) in DMF (10 mL) was stirred at roomtemperature for 1 h (monitored by TLC). After the reaction completed, thesolution was extracted with EtOAc, washed, dried, concentrated, and purified byflash chromatography on silica gel, eluted with a mixture of PE/EA (1/1, v/v)to afford 10 (3.48 g, 76%) as a white solid. 1H NMR (CDCl3,300 MHz): delta4.76(s, 1H), 3.51 (s, 2H), 2.34-2.31 (m, 1H), 2.17-2.10 (m, 2H), 1.90-1.87 (m, 1H),1.49 (s, 9H). MS (ESI) m/z 197[M+H]+.
With 1,3,5-trichloro-2,4,6-triazine; N,N-dimethyl-formamide; In dichloromethane; at 20 - 40℃;Inert atmosphere; Dichloromethane (500 ml), L-Prolinamide (100 g), potassium carbonate (60.50 g) were mixed and stirred under nitrogen atmosphere in round bottom flask The reaction mass was cooled to 10-15C and then Di-tert-butyl dicarbonate (210.30 g) was added. Reaction mixture was stirred till completion of the reaction. After completion water (500m1) was added and product was extracted in dichloromethane. Dichloro methane was removed and then dimethyl formamide (140 ml) and dichloromethane (700 ml) were added under nitrogen atmosphere. Cyanuric chloride (72.70 g) was charged in 2-3 equal lots to the reaction mass at 20-25C under nitrogen atmosphere. The reaction mass was maintained at 35-40C for 4-5 hrs. After completion of the reaction solid was filtered and washed with MDC. Methane sulfonic acid (252.60 g) was added to the filtrate and heated the reaction mass to 40-45C for 3-4 hrs. After completion of the reaction the reaction mass was cooled at 0-5C and Triethyl amine (88.65 g) and Chloroacetyl chloride (118.70 g) were added. The reaction mass was maintained at 20-30C for 1-2 hrs under nitrogen atmosphere. After completion of the reaction water was charged and product was extracted in dichloromethane. Organic layer was washed first with dilute HC1 solution and then with ammonia solution. Organic solvent was removed and product was crystallized using isopropyl alcohol. Yield: 75.0gm
55 g With triethylamine; trifluoroacetic anhydride; In dichloromethane; at -15℃; for 3h; step 1:The first reaction solution containing the compound represented by Formula II was cooled to -15.0 C., 30.0 g of triethylamine,A dichloromethane solution containing 0.357 mol of trifluoroacetic anhydride (TFAA) was added dropwise,Dropping time 2h, after the addition was completed, incubated for 1h,Insulation temperature was -15.0 , TLC monitoring showed that the reaction was completed;Step 2: To the solution in Step 1 was added purified water 100mL, washed and stratified;The pH was adjusted to 1 with 1 M hydrochloric acid, the temperature was controlled below 0 C,Stirring for 30-45min, standing stratification;Step 3: The mass concentration of 5% -10% dilute salt water 100mL wash phase;The organic layer was dried over sodium sulfate, filtered and the methylene chloride removed under reduced pressure.55.0 g (0.280 mol) of an oil was obtained as a compound of the formula III.

  • 2
  • [ 79-37-8 ]
  • [ 35150-07-3 ]
  • [ 228244-04-0 ]
YieldReaction ConditionsOperation in experiment
66% With pyridine; In ethyl acetate; N,N-dimethyl-formamide; acetonitrile; Preparation 116 tert-butyl (2S)-2-cyano-1-pyrrolidinecarboxylate A solution of oxalyl chloride (11.0 ml, 0.126 mol) and DMF (11.4 ml, 0.138 mol) in MeCN (170 ml) was treated dropwise with a solution of N-Boc-L-proline amide (12.3 g, 0.57mol) and pyridine (20.4 ml, 0.253 mol) in MeCN (30 ml) at 0 C. and stirred at this temperature for 15 minutes. The reaction mixture was diluted with EtOAc and washed with H2O (*3). The organic extract was dried over anhydrous MgSO4 and filtered. The solvent was removed under reduced pressure. The residue was purified on a silica column eluding with a solvent gradient of pentane:EtOAc (80:20) gradually changing to (60:40) to afford the title compound (7.40 g, 66%). 1H nmr: (d6DMSO) 1.40 (9H, s), 1.88 (2H, brs), 2.05-2.30 (2H, m), 3.21 (1H, m), 3.35 (1H, brs), 4.60 (1H, d). MS: 214 (MNH4+)
  • 3
  • [ 108-77-0 ]
  • [ 35150-07-3 ]
  • [ 228244-04-0 ]
YieldReaction ConditionsOperation in experiment
71% In N,N-dimethyl-formamide; at 0℃; for 1h; [0530] (S)-tert-butyl 2-cyanopyrrolidine-1-carboxylate (71b): To a solution of (S)-tert-butyl 2- carbamoylpyrrolidine-1-carboxylate 71a (86 mg, 0.40 mmol) in DME (2 mL) at 0 C, 2,4,6-trichloro-1,3,5- triazine (104 mg, 0.56 mmol) was added. After stirring for one hour at 0C, the reaction mixture was quenched with a cold 0.5 M NaOH solution. The mixture was then extracted with ethyl acetate. Organic layers were combined and washed with water and brine twice, dried over Na2SO4, and concentrated via vacuum. The crude reside was purified by silica gel column chromatography (15% ethyl acetate hexane to yield 71b (56 mg, 71%) as an oil. 1H NMR (500 MHz, CDCI3) 6 4.56-4.39 (m, 1H), 3.58-3.22 (m, 2H),2.28-1.94 (m, 4H), 1.47 (d, i=16.4 Hz, 9H); 13C NMR (126 MHz, CDCI3) 6 153.09, 119.23, 81.50, 47.27,45.79, 31.74, 28.39, 23.89; HRMS (ESI+): Calcd for C10H17N2O2 [M+H]: 197.1290, Found: 197.1287.
 

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