Home Cart Sign in  
Chemical Structure| 17191-44-5 Chemical Structure| 17191-44-5

Structure of Cbz-Cyclo-Leu-OH
CAS No.: 17191-44-5

Chemical Structure| 17191-44-5

Cbz-Cyclo-Leu-OH

CAS No.: 17191-44-5

4.5 *For Research Use Only !

Cat. No.: A537727 Purity: 98%

Change View

Size Price

US Stock

Global Stock

In Stock
1g łÇʶÊÊ Inquiry Inquiry
5g łËʶÊÊ Inquiry Inquiry
25g łò˶ÊÊ Inquiry Inquiry
100g łË§ď¶ÊÊ Inquiry Inquiry

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • 1g

    łÇʶÊÊ

  • 5g

    łËʶÊÊ

  • 25g

    łò˶ÊÊ

  • 100g

    łË§ď¶ÊÊ

In Stock

- +

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 17191-44-5 ]

CAS No. :17191-44-5
Formula : C14H17NO4
M.W : 263.29
SMILES Code : O=C(O)C1(CCCC1)NC(OCC2=CC=CC=C2)=O
MDL No. :MFCD02094399
InChI Key :IXXMJXGMYKDTRQ-UHFFFAOYSA-N
Pubchem ID :1512635

Safety of [ 17191-44-5 ]

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

Computational Chemistry of [ 17191-44-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.43
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 69.23
TPSA ?

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

75.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.03
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

2.09
Log Po/w (WLOGP)?

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

2.16
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.

1.57
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

1.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.92

Water Solubility

Log S (ESOL):?

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

-2.63
Solubility 0.622 mg/ml ; 0.00236 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.31
Solubility 0.129 mg/ml ; 0.000492 mol/l
Class?

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

-3.3
Solubility 0.133 mg/ml ; 0.000506 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

Yes
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.

-6.42 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.

0.56

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<0.0
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)

2.32

Application In Synthesis of [ 17191-44-5 ]

* 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 [ 17191-44-5 ]

[ 17191-44-5 ] Synthesis Path-Downstream   1~34

  • 1
  • [ 949-67-7 ]
  • [ 17191-44-5 ]
  • [ 101813-77-8 ]
  • 3
  • [ 501-53-1 ]
  • [ 52-52-8 ]
  • [ 17191-44-5 ]
YieldReaction ConditionsOperation in experiment
78% To a solution of 1-aminocyclopentanecarboxylic acid (3.0 g, 23.2 mmol) in 1:1 dioxane/water (60 mL), was slowly added Na2CO3 (12.3 g, 116 mmol) followed by benzyl chloroformate (3.6 mL, 25.5 mmol) and the mixture stirred overnight at RT. The reaction mixture was carefully acidified to pH=2 with 1M HCl then extracted with EtOAc (3*30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to leave a pale yellow oil. LCMS and NMR showed the crude product to be a mixture of desired product and corresponding benzyl ester. The crude product was dissolved in 1:1 THF/water (60 mL) and treated with lithium hydroxide (2.67 g, 116 mmol). The mixture was stirred at RT overnight then washed with Et2O (3*30 mL), acidified to pH=2 and extracted with EtOAc (3*30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound (4.76 g, 78%). LCMS: m/z 264 [M+H]+.
78% To a solution of 1-aminocyclopentanecarboxylic acid (3.0 g, 23.2 mmol) in 1 :1 dioxane / water (60 ml), was slowly added Na2CO3 (12.3 g, 116 mmol) followed by benzyl chloroformate (3.6 ml, 25.5 mmol) and the mixture stirred overnight at RT. The reaction mixture was carefully acidified to pH 2 with 1 M HCI then extracted with EtOAc (3 x 30 ml). The combined organic extracts were washed with brine (30 ml), dried (MgSO4), filtered and concentrated in vacuo to leave a pale yellow oil. LCMS and NMR showed the crude product to be a mixture of desired product and corresponding benzyl ester. The crude product was dissolved in 1 :1 THF / water (60 ml) and treated with lithium hydroxide (2.67 g, 116 mmol). The mixture was stirred at RT over night then washed with Et2O (3 x 30 ml), acidified to pH 2 and extracted with EtOAc (3 x 30 ml). The combined organic extracts were washed with brine (30 ml), dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound (4.76 g, 78%). LCMS: m/z 264 [M+H]+.
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; A solution of benzyl chloroformate (0.290 g, 1.1 mmol) in dioxane (2.5 cm3) was added dropwise to a solution of 1 -aminocyclopentanecarboxylic acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 cm3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (Na2SO4), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70:30 mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the resonances at delta 5.31 and 7.29-7.40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit.1 82-86 C, ethyl acetate, petroleum ether); SH (400 MHz; CDCl3; Me4Si) 1.83 (4H, br s, 2 x cyclopentyl-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2.40 (2H, m, cyclopentyl- H2), 5.13 (2H, br s, OCH2Ph), 5.31 (0.7eta, br s, N-H) and 7.29-7.40 (5.3H, m, Ph and N-H*); deltac (100 MHz; CDCl3) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C),' denotes resonance assigned to minor conformer. <n="31"/>66.0 (quat., cyclopentyl-C), 66.8 (CH2, OCH2Ph), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat., NCO2) and 179.5 (quat., CO2H).
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; N-Benzyloxycarbonyl-1-aminocyclopentane-1-carboxylic acid 21 A solution of benzyl CHLOROFORMATE (0.290 g, 1.1 mmol) in dioxane (2.5 CM3) was added dropwise to a solution of L-AMINOCYCLOPENTANECARBOXYLIC acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 CM3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (NA2S04), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70: 30 mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the resonances at No. 5.31 and 7.29-7. 40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit. l 82-86 C, ethyl acetate, petroleum ether); IH (400 MHz; CDC13 ; Me4Si) 1.83 (4H, br s, 2 x CYCLOPENTYL-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2. 40 (2H, M, cyclopentyl- H2), 5.13 (2H, br s, OCH2Ph), 5.31 (0.7H, br s, N-H) and 7.29-7. 40 (5.3H, M, Ph and N-H*) ; DC (100 MHz; CDC13) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C), 66.0 (quat. , cyclopentyl-C), 66.8 (CH2, OCH2PH), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat. , NC02) and 179.5 (quat. , CO2H).
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; N-Benzyloxycarbonyl-l-aminocyclopentane-l-carboxylic acid 21 A solution of benzyl chloroformate (0.290 g, 1.1 mmol) in dioxane (2.5 cm3) was added dropwise to a solution of l-aminocyclopentanecarboxylic acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 cm3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (Na2SC>4), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70:30 mixture of conformers by NMR analysis (the ratio was estimated from the integration of the resonances at 6 5.31 and 7.29-7.40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit.1 82-86 C, ethyl acetate, petroleum ether); < (400 MHz; CDC; Me4Si) 1.83 (4H, br s, 2 x cyclopentyl-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2.40 (2H, m, cyclopenty[-H2), 5.13 (2H, br s, OCiPh), 5.31 (0.7H, br s, N-H) and 7.29-7.40 (5.3H, m, Ph and N-H*); <5fc (100 MHz; CDC13) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C), 66.0 (quat., cyclopentyl-C), 66.8 (CH2) OCH2Ph), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat, NC02) and 179.5 (quat., C02H).

  • 4
  • [ 17191-44-5 ]
  • [ 735247-38-8 ]
  • (R)-4-[(1-Benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-2-tert-butoxycarbonylamino-butyric acid methyl ester [ No CAS ]
  • 5
  • [ 1013-88-3 ]
  • [ 17191-44-5 ]
  • [ 39687-95-1 ]
  • {2-[(1-Benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-2,2-diphenyl-acetylamino}-acetic acid methyl ester [ No CAS ]
  • 6
  • [ 1013-88-3 ]
  • [ 17191-44-5 ]
  • [ 71015-20-8 ]
  • 2-{2-[(1-Benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-2,2-diphenyl-acetylamino}-2-methyl-propionic acid methyl ester [ No CAS ]
  • 7
  • [ 17191-44-5 ]
  • [ 60421-23-0 ]
  • [ 94999-60-7 ]
  • 9
  • [ 17191-44-5 ]
  • [ 101651-14-3 ]
  • Acetic acid (2S,3S)-3-[(1-benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-4-oxo-azetidin-2-yl ester [ No CAS ]
  • 10
  • [ 17191-44-5 ]
  • [ 221186-79-4 ]
  • (R)-1-{(S)-2-[(1-Benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-3-phenyl-propionyl}-pyrrolidine-2-carboxylic acid tert-butyl ester [ No CAS ]
  • 11
  • [ 17191-44-5 ]
  • 1-(2-amino-3-phenyl-propionyl)-piperidine-2-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]
  • 1-{2-[(1-benzyloxycarbonylamino-cyclopentanecarbonyl)-amino]-3-phenyl-propionyl}-piperidine-2-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]
  • 12
  • [ 17191-44-5 ]
  • [ 2133-40-6 ]
  • [ 842120-66-5 ]
  • 13
  • [ 17191-44-5 ]
  • [ 6011-14-9 ]
  • [1-(cyanomethyl-carbamoyl)-cyclopentyl]-carbamic acid benzyl ester [ No CAS ]
  • 14
  • [ 17191-44-5 ]
  • benzyl (1-cyanocyclopentyl)carbamate [ No CAS ]
  • 15
  • [ 17191-44-5 ]
  • [ 940868-36-0 ]
  • 16
  • [ 17191-44-5 ]
  • [ 519032-32-7 ]
  • 17
  • [ 17191-44-5 ]
  • 2-[(1-benzyloxycarbonylamino-cyclopentanecarboximidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester [ No CAS ]
  • 18
  • [ 17191-44-5 ]
  • 2-(1-benzyloxycarbonylamino-cyclopentyl)-5,6-dihydroxy-pyrimidine-4-carboxylic acid methyl ester [ No CAS ]
  • 19
  • [ 17191-44-5 ]
  • [ 519032-31-6 ]
  • 20
  • [ 17191-44-5 ]
  • (1-(((benzyloxy)carbonyl)amino)cyclopentane-1-carbonyl)-L-proline [ No CAS ]
  • 21
  • [ 17191-44-5 ]
  • 1-{2-[(1-amino-cyclopentanecarbonyl)-amino]-3-phenyl-propionyl}-piperidine-2-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]
  • 22
  • [ 17191-44-5 ]
  • C29H40N4O6 [ No CAS ]
  • 23
  • [ 17191-44-5 ]
  • C29H41N5O6 [ No CAS ]
  • 24
  • [ 17191-44-5 ]
  • C36H46N4O6 [ No CAS ]
  • 25
  • [ 17191-44-5 ]
  • C36H46N4O6 [ No CAS ]
  • 26
  • [ 17191-44-5 ]
  • 1-(2-[1-(7-benzyloxycarbonyl-2-<i>tert</i>-butoxycarbonylamino-heptanoylamino)-cyclopentanecarbonyl]-amino}-3-phenyl-propionyl)-piperidine-2-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]
  • 27
  • [ 17191-44-5 ]
  • 1-((S)-2-[1-((S)-2-Amino-7-benzyloxycarbonyl-heptanoylamino)-cyclopentanecarbonyl]-amino}-3-phenyl-propionyl)-piperidine-2-carboxylic acid tert-butyl ester; compound with trifluoro-acetic acid [ No CAS ]
  • 32
  • [ 17191-44-5 ]
  • N-(1-Amino-cyclopentancarbonyl)-L-tyrosin-aethylester [ No CAS ]
  • 33
  • [ 17191-44-5 ]
  • methyl (S)-2-methylpyrrolidine-2-carboxylate monohydrochloride [ No CAS ]
  • methyl N-benzyloxycarbonyl(cyclopentylglycyl)-L-2-methylprolinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
23% With 1-hydroxy-7-aza-benzotriazole; 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate; triethylamine; In 1,2-dichloro-ethane; at 20℃; for 19.1667h;Heating / reflux; Dry triethylamine (0.19 cm3, 1.4 mmol) was added dropwise to a solution of hydrochloride 10 (78 mg, 0.43 mmol), carboxylic acid 21 (0.15 g, 0.56 mmol) and 1- hydroxy-7-azabenzotriazole (Acros) (15 mg, 0.1 1 mmol) in dry 1 ,2-dichloroethane (24 cm3) under an atmosphere of nitrogen at room temperature, and the reaction mixture stirred for 10 min. 2-Chloro-l,3-dimethylimidazolidinium hexafluorophosphate (CIP) (Aldrich) (0.12 g, 0.43 mmol) was added and the resultant solution heated under reflux for 19 h, then washed successively with 10% aqueous hydrochloric acid (30 cm3) and saturated aqueous sodium hydrogen carbonate (30 cm3), dried (MgSO4), filtered and evaporated to dryness in vacuo. Purification of the resultant residue by flash column chromatography (60% ethyl acetate-hexane) yielded amide 22 (39 mg, 23%) as a white solid. Amide 22 was shown to exist as a 3:1 trans :cis mixture of carbamate conformers by 13C NMR analysis (the ratio was estimated from the relative intensities of the resonances at delta 154.1 and 155.7 assigned to the carbamate carbonyl-C atoms of the major and minor conformers, respectively): mp 200-203 0C; [alpha]D -54.5 (c 1.52 in CH2Cl2); vmax (filmycm"1 3432, 3239, 3042, 2953, 1736, 1712, 1627, 1540, 1455, 1417, 1439, 1374, 1282, 1256, 1216, 1194, 1171, 1156, 1136, 1100, 1081, 1042, 1020, 107, 953, 917, 876, 756 and 701 ; Sn (400 MHz, CDCl3) 1.33-1.53 (3H, br m, Proalpha-CH3), 1.62-2.20 (HH, m, Probeta-H2, Progamma-H2 and 7 x cyclopentyl-H), 2.59-2.71 (IH, br m, 1 x cyclopentyl-H), 3.31-3.42 (IH, br m, Prodelta-H4HB), 3.58-3.79 (4H, br m, OCH3 and Prodelta-HAH/?), 4.92-5.17 (3H, m, N-H and OCH2Ph) and 121-1 Al (5eta, s, Ph); deltac (100 MHz, CDCl3) 21.7 (CH3, Proalpha-CH3), 24. I* (CH2, cyclopentyl-C), 24.2 (CH2, cyclopentyl-C), 24.4 (CH2, Progamma-C), 24.5 (CH2, cyclopentyl-C), 36.4 (CH2, cyclopentyl-C), 37.1 (CH2, cyclopentyl-C), 37.2* (CH2, cyclopentyl-C), 37.7 (CH2, Probeta-C), 38.2* (CH2, cyclopentyl-C), 48.5 (CH2, Prodelta-C), 52.1 (CH3, OCH3), 66.6 (CH2, OCH2Ph), 66.9 (quat., Proalpha-C), 67.2 (quat., Glyalpha-C), 127.8 (CH, Ph), 128.2 (CH, Ph), 128.4 (CH, Ph), 136.6 (quat., Ph), 154.1 (quat., NCO2), 155.7* (quat., NCO2), 170.5 (quat., GIy-CO) and 174.7 (quat., CO2CH3); m/z (EI+) 388.1991 (M+. C2iH28N2O5 requires 388.1998).
23% METHYL N-BENZYLOXYCARBOT YL CYCLOPENTYL-GLYCYL-L-2-NAETHYLPROLINATE 22 Dry triethylamine (0.19 cm3, 1.4 mmol) was added dropwise to a solution of hydrochloride 10 (78 mg, 0.43 mmol), carboxylic acid 21 (0.15 g, 0.56 mmol) and 1- hydroxy-7-azabenzotriazole (ACROS) (15 mg, 0.11 mmol) in dry 1,2-dichloroethane (24 CM3) under an atmosphere of nitrogen at room temperature, and the reaction mixture stirred for 10 min. 2-CHLORO-1, 3-dimethylimidazolidinium hexafluorophosphate (CIP) (Aldrich) (0.12 g, 0.43 mmol) was added and the resultant solution heated under reflux for 19 h, then washed successively with 10% aqueous hydrochloric acid (30 CM3) and saturated aqueous sodium hydrogen carbonate (30 CM3), dried (MgSO4), filtered and evaporated to dryness in vacuo. Purification of the resultant residue by flash column chromatography (60% ethyl acetate-hexane) yielded amide 22 (39 mg, 23%) as a white solid. Amide 22 was shown to exist as a 3: 1 trans : cis mixture of carbamate conformers by 13C NMR analysis (the ratio was estimated from the relative intensities of the resonances at 8 154.1 and 155.7 assigned to the carbamate carbonyl-C atoms of the major and minor conformers, respectively): mp 200-203 C ; [A] D-54. 5 (c 1.52 in CH2Cl2) ; vmax (film)/cm-1 3432, 3239,3042, 2953,1736, 1712,1627, 1540,1455, 1417,1439, 1374,1282, 1256,1216, 1194, 1171,1156, 1136,1100, 1081,1042, 1020,107, 953,917, 876,756 and 701; No.H (400 MHz, CDCl3) 1.33-1. 53 (3H, br M, Proa-CH3), 1.62-2. 20 (11H, M, PROP-H2, PROY-H2 and 7 x cyclopentyl-H), 2.59-2. 71 (1H, br M, 1 x cyclopentyl-H), 3.31-3. 42 (1H, br m, PRO6-HAHB), 3.58-3. 79 (4H, br M, OCH3 and PRO8-HAHB), 4.92-5. 17 (3H, M, N-H and OCH2Ph) and 7.27-7. 42 (5H, s, Ph); (100 MHz, CDCl3) 21.7 (CH3, PROA-CH3), * denotes resonance assigned to minor conformer. 24.1* (CH2, cyclopentyl-C), 24.2 (CH2, cyclopentyl-C), 24.4 (CH2, Proy-C), 24.5 (CH2, cyclopentyl-C), 36.4 (CH2, cyclopentyl-C), 37.1 (GHZ, cyclopentyl-C), 37.2* (CH2, cyclopentyl-C), 37.7 (CH2, PROP-C), 38.2* (CH2, cyclopentyl-C), 48.5 (CH2, Pro8-C), 52.1 (CH3, OCH3), 66.6 (CH2, OCH2Ph), 66.9 (quat. , PROA-C), 67.2 (quat. , GLYalpha-C), 127.8 (CH, Ph), 128.2 (CH, Ph), 128.4 (CH, Ph), 136.6 (QUAT., Ph), 154.1 (quat. , NCO2), 155.7* (quat. , NCO2), 170.5 (quat. , Gly-CO) and 174.7 (quat. , C02CH3) ; m/z (EI+) 388.1991 (M+. C2LH28N205 requires 388.1998).
23% With 1-hydroxy-7-aza-benzotriazole; 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate; triethylamine; In 1,2-dichloro-ethane; for 19h;Inert atmosphere; Reflux; Methyl N~benzyloxycarbonyl cyclopentyl-glycyl-L-2-methylprolinate 22 Dry triethylamine (0.19 cm3, 1.4 mmol) was added dropwise to a solution of hydrochloride 10 (78 mg, 0.43 mmol), carboxylic acid 21 (0.15 g, 0.56 mmol) and 1 -hydroxy-7- azabenzotriazole (Acros) (15 mg, 0.11 mmol) in dry 1,2-dichloroethane (24 cm3) under an atmosphere of nitrogen at room temperature, and the reaction mixture stirred for 10 min. 2- Chloro-l,3-dimethylimidazolidinium hexafluorophosphate (CIP) (Aldrich) (0.12 g, 0.43 mmol) was added and the resultant solution heated under reflux for 19 h, then washed successively with 10% aqueous hydrochloric acid (30 cm3) and saturated aqueous sodium hydrogen carbonate (30 cm3), dried (MgS04), filtered and evaporated to dryness in vacuo. Purification of the resultant residue by flash column chromatography (60% ethyl acetate-hexane) yielded amide 22 (39 mg, 23%) as a white solid. Amide 22 was shown to exist as a 3:1 trans: cis mixture of carbamate conformers by l3C NMR analysis (the ratio was estimated from the relative intensities of the resonances at delta 154.1 and 155.7 assigned to the carbamate carbonyl-C atoms of the major and minor conformers, respectively): mp 200-203 C; [a]D -54.5 (c 1.52 in CH2C1 ); v,MX (film)/cm" 3432, 3239, 3042, 2953, 1736, 1712, 1627, 1540, 1455, 1417, 1439, 1374, 1282, 1256, 1216, 1194, 1171, 1156, 1136, 1100, 1081, 1042, 1020, 107, 953, 917, 876, 756 and 701; < (400 MHz, CDClj) 1.33-1.53 (3H, br m, Proa-C), 1.62-2.20 (11H, m, Prop-H2, Proy- and 7 x cyclopentyl-H), 2.59-2.71 (1H, br m, 1 x cyclopentyl-H), 3.31-3.42 (1H, br m, Pro5-HB), 3.58- 3.79 (4H, br m, OCH3 and Pro5-HA , 4.92-5.17 (3H, m, N-H and OCiPh) and 7.27-7.42 (5H, s, Ph); Sc (100 MHz, CDC13) 21.7 (CH3, Proa-CH3), 24.1* (C, cyclopentyl-C), 24.2 (CH2, cyclopentyl-C), 24.4 (CH2, Proy-C), 24.5 (CH2, cyclopentyl-C), 36.4 (CH2, cyclopentyl-C), 37.1 (CH2, cyclopentyl-C), 37.2* (CH2, cyclopentyl-C), 37.7 (CH2, RhoGammathetabeta-C), 38.2* (CH2, cyclopentyl- C), 48.5 (CH2, Pro6-C), 52.1 (CH3, OCH,), 66.6 (CH2j OCH2Ph), 66.9 (quat., Proct-C), 67.2 (quat., Glyc -C), 127.8 (CH, Ph), 128.2 (CH, Ph), 128.4 (CH, Ph), 136.6 (quat., Ph), 154.1 (quat., NC02), 155.7* (quat., NC02), 170.5 (quat., Gly-CO) and 174.7 (quat., C02CH3); m/z (EI+) 388.1991 (M+. C2,H28N205 requires 388.1998). * denotes resonance assigned to minor conformer.
  • 34
  • [ 5048-82-8 ]
  • [ 17191-44-5 ]
  • [ 494854-35-2 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; HATU; In N,N-dimethyl-formamide; at 40℃; for 48h; l-[(benzyloxy)carbonyl]amino}cyclopentanecarboxylic acid was dissolved in DMF (0.2 M). HATU (1 eq.) and triethylamine (3 eq.) were added, followed by ethyl (2u)-3-(4-aminophenyl)acrylate (0.95 eq.). The resulting mixture was stirred for 48 h at 40 0C. DMF was evaporated, the resulting oil taken up in EPO <DP n="18"/>EtOAc and the solution washed with hydrochloric acid (3x, 1 M), water, a solution of saturated aqueous NaHCO3 (2x) and brine. Drying over sodium sulfate and evaporation gave an orange solid, which was purified by flash chromatography on silica gel using PE/EtOAc (2.5 : 1, containing 1% EtOH) as the eluant. The resulting solid was immediately dissolved in DCM (0.1 M) and triflic acid (5 eq.) was added dropwise at RT. After 5 min at RT, the red mixture was poured into an aqueous solution OfNaHCO3. The organic phase was separated, the aqueous phase was extracted with DCM (4x) and the combined organic phases dried over sodium sulfate. Evaporation gave the title compound as an off-white solid, which was used without further purification. 1H NMR (400 MHz, DMSO-fi?6, 300 K) delta 1.26 (t, J 7.1, 3H), 1.48-1.61 (m, 2H), 1.63-1.87 (m, 4H), 1.96-2.10 (m, 2H), 4.188 (q, J7.1 Hz, 2H), 6.53 (d, J 16.0, IH), 6.60-7.30 (bs, 3H), 7.59 (d, J 16.0, IH), 7.67 (d, J8.5, 2H), 7.76 (d, J8.5, 2H); MS (ES+) m/z 303 (M+H)+.
Step 7; Ethyl (2E)-3 (4-{ [(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate; 1-[benzyloxy)carbonyl]amino}cyclopen(anecarboxylic acid was dissolved in DMF (0.2 M). HATU (1 eq.) and triethylamine (3 eq.) were added, followed by ethyl cinnamate (0.95 eq.). The resulting mixture was stirred for 48 h at 40 C. DMF was evaporated, the resulting oil taken up in EtOAc and the solution washed with HQ (3x, 1 M), water, a solution of saturated aqueous NaHC03 (2x) and brine. Drying over Na2SO4 and evaporation gave an orange solid, which was purified by flash chromatography on silica gel using PE/EtOAc (2.5 : 1. containing 1% EtOH) as the eluent The resulting solid was immediately dissolved in DCM (0,1 M) and triflic acid (5 eq.) was added dropwise at RT, After 5 mm at RT, the red mixture was poured into an aqueous solution of NaHCOj. The organic phase was separated, the aqueous phase was extracted with DCM (4x) and the combined organic phases dried over Na2SO4. Evaporation gave the title compound as an off-white solid, which was used without further purification.
 

Historical Records

Technical Information

Categories