[ CAS No. 33300-72-0 ] {[proInfo.proName]}

Name: 33300-72-0|(S)-1-((S)-2-((tert-Butoxycarbonyl)amino)propanoyl)pyrrolidine-2-carboxylic acid|97%
Brand: Ambeed
SKU: A191222
Price: 5.0 USD
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2D 3D

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Quality Control of [ 33300-72-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 33300-72-0 ]

SDS Specification

Alternatived Products of [ 33300-72-0 ]

Product Details of [ 33300-72-0 ]

CAS No. :	33300-72-0	MDL No. :	MFCD00134853
Formula :	C₁₃H₂₂N₂O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QGJDXUIYIUGQGO-IUCAKERBSA-N
M.W :	286.32	Pubchem ID :	11902919
Synonyms :

Calculated chemistry of [ 33300-72-0 ]

Physicochemical Properties

Num. heavy atoms :	20
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.77
Num. rotatable bonds :	7
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	75.79
TPSA :	95.94 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.19 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.26
Log Po/w (XLOGP3) :	1.21
Log Po/w (WLOGP) :	0.59
Log Po/w (MLOGP) :	0.28
Log Po/w (SILICOS-IT) :	0.06
Consensus Log Po/w :	0.88

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-1.92
Solubility :	3.48 mg/ml ; 0.0121 mol/l
Class :	Very soluble
Log S (Ali) :	-2.82
Solubility :	0.432 mg/ml ; 0.00151 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-0.8
Solubility :	45.4 mg/ml ; 0.158 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.19

Safety of [ 33300-72-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 33300-72-0 ]

* 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.

Upstream synthesis route of [ 33300-72-0 ]
Downstream synthetic route of [ 33300-72-0 ]

[ 33300-72-0 ] Synthesis Path-Upstream 1~1

1
[ 33300-72-0 ]
[ 13485-59-1 ]

Reference： [1] Journal of the Chemical Society - Series Chemical Communications, 1988, # 4, p. 287 - 289
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 14, p. 3635 - 3638
[3] Journal of Photochemistry and Photobiology B: Biology, 2013, vol. 121, p. 75 - 85
[4] Journal of Organic Chemistry, 2014, vol. 79, # 23, p. 11792 - 11796

[ 33300-72-0 ] Synthesis Path-Downstream 1~85

1
[ 80465-33-4 ]
[ 33300-72-0 ]
Boc-Ala-Pro-ΔLeu*NCA [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846

2
[ 37519-04-3 ]
[ 33300-72-0 ]
[ 109953-03-9 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1986,p. 1655 - 1664

3
[ 74805-42-8 ]
[ 33300-72-0 ]
Boc-Ala-Pro-ΔPhe*NCA [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846

4
[ 35084-69-6 ]
[ 33300-72-0 ]

Yield	Reaction Conditions	Operation in experiment
	palladium-carbon; In methanol;	C. N-t-butyloxycarbonyl-L-alanyl-L-proline N-t-butyloxycarbonyl-L-alanyl-L-proline benzyl ester (6.4 g, 17 m mole) was dissolved in methanol (100 ml). Hydrogen was passed for 3 hours through the solution in the presence of 10% palladium-carbon as a catalyst. The catalyst was removed by filtration and the filtrate was distilled under reduced pressure leaving a residue. The residue was crystallized in ethyl acetate-n-hexan to give N-t-butyloxycarbonyl-L-alanyl-L-proline (4.5 g, yield: 92.4%) having melting point of 155 to 157 C. and specific rotatory power [alpha]D25 =-90.5 (C-1, ethanol). The product gave a single spot on thin layer chromatography.
	palladium-carbon; In methanol;	C. N-t-butyloxycarbonyl-L-alanyl-L-proline N-t-butyloxycarbonyl-L-alanyl-L-proline benzyl ester (6.4 g, 17 m mole) was dissolved in methanol (100 ml). Hydrogen was passed for 3 hours through the solution in the presence of 10% palladium-carbon as a catalyst. The catalyst was removed by filtration and the solvent was distilled off under reduced pressure. The residue was crystallized in ethyl acetate-n-hexan to give N-t-butyloxycarbonyl-L-alanyl-L-proline (4.5 g, yield: 92.4%) having melting point of 155 to 157 C. and specific rotatory power [alpha]D25 =-90.5 (C=1, ethanol). The product gave a single spot on thin layer chromatography.
	palladium-carbon; In methanol;	C. N-t-butyloxycarbonyl-L-alanyl-L-proline N-t-butyloxycarbonyl-L-alanyl-L-proline benzyl ester (6.4 g, 17 m mole) was dissolved in methanol (100 ml). Hydrogen was passed for 3 hours through the solution in the presence of 10% palladium-carbon as a catalyst. The catalyst was removed by filtration and the filtrate was distilled under reduced pressure leaving a residue. The residue was crystallized in ethyl acetate-n-hexan to give N-t-butyloxycarbonyl-L-alanyl-L-proline (4.5 g, yield: 92.4%) having melting point of 155 to 157 C. and specific rotatory power [alpha]D25 =-90.5 (C=1, ethanol). The product gave a single spot on thin layer chromatography.

palladium-carbon; In methanol;

C. N-t-butyloxycarbonyl-L-alanyl-L-proline N-t-butyloxycarbonyl-L-alanyl-L-proline benzyl ester (6.4 g, 17 m mole) was dissolved in methanol (100 ml). Hydrogen was passed for 3 hours through the solution in the presence of 10% palladium-carbon as a catalyst. The catalyst was removed by filtration and the solvent was distilled off under reduced pressure. The residue was crystallized in ethyl acetate-n-hexan to give N-t-butyloxycarbonyl-L-alanyl-L-proline (4.5 g, yield: 92.4%) having melting point of 155 to 157 C. and specific rotatory power [alpha]D25 =-90.5 (C=1, ethanol). The product gave a single spot on thin layer chromatography.

Reference： [1]International Journal of Chemical Kinetics,2006,vol. 38,p. 376 - 385
[2]Liebigs Annalen der Chemie,1989,p. 751 - 770
[3]Patent: US4590178,1986,A
[4]Patent: US4590178,1986,A
[5]Patent: US4472381,1984,A
[6]Patent: US4536395,1985,A

5
[ 77286-89-6 ]
[ 33300-72-0 ]
((S)-1-Methyl-2-{(S)-2-[(R)-1-(4-nitro-phenylcarbamoyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

6
[ 78834-50-1 ]
[ 33300-72-0 ]
[ 102721-58-4 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

7
[ 33300-72-0 ]
[ 120792-16-7 ]
[ 120792-17-8 ]

Reference： [1]Liebigs Annalen der Chemie,1989,p. 751 - 770

8
[ 33300-71-9 ]
[ 33300-72-0 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 3454 - 3457
[2]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846
[3]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285
[4]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1015 - 1017
[5]Journal of Photochemistry and Photobiology B: Biology,2013,vol. 121,p. 75 - 85

9
[ 3392-05-0 ]
[ 147-85-3 ]
[ 33300-72-0 ]

Yield	Reaction Conditions	Operation in experiment
91.1%		General procedure: Under argon protection, BSA (2.2equiv.) was added to a solution of amino acid (1.1equiv.) in anhydrous dichloromethane. After the mixture was stirred for 1-8h at 23C, a solution of N-Boc protected NHS ester (1equiv.) in dichloromethane was added. The reaction mixture was stirred at 23C under argon until all active ester was consumed as judged by TLC analysis. The reaction mixture was washed with brine, dried over Na2SO4 and concentrated in vacuo to provide a white solid. The isolated product was recrystallized from diethyl ether/n-hexane to yield the targeted dipeptide as a white solid.
80%		Suspension 1.3 g (11 muetaetaomicronIota) of proline, 1.6 g (11 muiotaetaomicronIota) K2CO3 and 0.1 g of tetrabutylammonium hydroxide in 10 ml of dioxane are stirred for 15 min, 2.9 g (10 muiotatauiotaomicronIota) of N-oxysuccinimide ether of tert-butyloxycarbonyl-L-alanine are added and stirred for 10 h. Then they are diluted with water (25 ml) and stirred for 1 h, extracted with hexane-ether mixture (1 :1 , 15 ml), the aqueous solution is acidified with 1 M hydrochloric acid to pH 2-3, extracted with ethyl acetate (50 ml + 20 ml), the extract is washed with brine, dried with magnesium sulfate and boiled off. 2.3 g (80%) of chromatographically pure tert-butyloxycarbonylalanylproline with melting point of 155- 156C, Rf 0.47 (toluene - acetone - acetic acid, 100:50:1) is obtained, which is used for amide obtainment at the next stage without further purification.

Reference： [1]Chinese Chemical Letters,2016,vol. 27,p. 357 - 360
[2]Patent: WO2014/54980,2014,A1 .Location in patent: Page/Page column 5; 6
[3]Journal of Molecular Structure,1994,vol. 317,p. 119 - 129

10
[ 33300-72-0 ]
[ 13485-59-1 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3635 - 3638
[3]Journal of Photochemistry and Photobiology B: Biology,2013,vol. 121,p. 75 - 85
[4]Journal of Organic Chemistry,2014,vol. 79,p. 11792 - 11796

11
[ 2483-49-0 ]
[ 147-85-3 ]
[ 33300-72-0 ]

Reference： [1]Synlett,2011,p. 1427 - 1430
[2]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

12
[ 1115-59-9 ]
[ 33300-72-0 ]
[ 189573-54-4 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

13
[ 330970-69-9 ]
[ 623-05-2 ]
[ 33300-72-0 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 369 - 373

14
[ 330970-69-9 ]
[ 33300-72-0 ]

Reference： [1]Chemistry - A European Journal,2002,vol. 8,p. 3362 - 3376

15
[ 33300-72-0 ]
Arg(NO₂)-Pro-Gly-OBz hydrochloride [ No CAS ]
Boc-Ala-Pro-Arg(NO₂)-Pro-Gly-OBz [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1015 - 1017

16
[ 15761-38-3 ]
[ 147-85-3 ]
[ 33300-72-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3635 - 3638

17
[ 33300-72-0 ]
[ 76-05-1 ]
Ala-Pro-OH trifluoroacetate [ No CAS ]

Reference： [1]International Journal of Chemical Kinetics,2006,vol. 38,p. 376 - 385

18
[ 15761-38-3 ]
[ 33300-72-0 ]

Reference： [1]International Journal of Chemical Kinetics,2006,vol. 38,p. 376 - 385
[2]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285
[3]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846
[4]Journal of Photochemistry and Photobiology B: Biology,2013,vol. 121,p. 75 - 85
[5]Chinese Chemical Letters,2016,vol. 27,p. 357 - 360
[6]Organic Letters,2017,vol. 19,p. 3454 - 3457

19
[ 16652-71-4 ]
[ 33300-72-0 ]

Reference： [1]International Journal of Chemical Kinetics,2006,vol. 38,p. 376 - 385
[2]Liebigs Annalen der Chemie,1989,p. 751 - 770

20
[ 33300-72-0 ]
(S)-1-[(S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3635 - 3638

21
[ 33300-72-0 ]
(S)-1-[(S)-2-((S)-2-Amino-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid; compound with GENERIC INORGANIC NEUTRAL COMPONENT [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3635 - 3638

22
[ 33300-72-0 ]
(S)-1-((S)-2-{(S)-2-[3-[(R)-1-(4-Fluoro-phenyl)-ethylcarbamoyl]-5-(methanesulfonyl-methyl-amino)-benzoylamino]-3-phenyl-propylamino}-propionyl)-pyrrolidine-2-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3635 - 3638

23
[ 15761-38-3 ]
resin-bond orthogonally protected Fmoc-Lys-(Boc) [ No CAS ]
[ 33300-72-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1015 - 1017

24
[ 33300-72-0 ]
Ala-Pro-Arg(NO₂)-Pro-Gly-OBz hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1015 - 1017

25
[ 15761-39-4 ]
Boc-MePhe-N(-CH₂-Merrifield resin)-Phe-OMeBoc-Leu-OH [ No CAS ]
[ 33300-72-0 ]

Reference： [1]Chemistry - A European Journal,2002,vol. 8,p. 3362 - 3376

26
[ 479494-08-1 ]
[ 33300-72-0 ]

Reference： [1]Chemistry - A European Journal,2002,vol. 8,p. 3362 - 3376

27
[ 15761-39-4 ]
Boc-Thr(OBzl)-resin [ No CAS ]
[ 33300-72-0 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 369 - 373

28
[ 330970-65-5 ]
[ 33300-72-0 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 369 - 373

29
[ 33300-72-0 ]
[ 169602-57-7 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

30
[ 33300-72-0 ]
[ 189573-57-7 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

31
[ 33300-72-0 ]
(S)-2-[(S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carbonyl]-amino}-propionic acid ethyl ester; hydrochloride [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

32
[ 33300-72-0 ]
[ 189573-56-6 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

33
[ 33300-72-0 ]
[ 189573-61-3 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

34
[ 33300-72-0 ]
[ 189573-62-4 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

35
[ 33300-72-0 ]
(S)-2-[((S)-1-{(S)-2-[(S)-2-((S)-2-[(S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carbonyl]-amino}-propionylamino)-3-(4-dimethylamino-phenyl)-propionylamino]-propionyl}-pyrrolidine-2-carbonyl)-amino]-propionic acid ethyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285
[2]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

36
[ 33300-72-0 ]
(S)-2-[((S)-1-{(S)-2-[(S)-2-((S)-2-[(S)-1-((S)-2-Amino-propionyl)-pyrrolidine-2-carbonyl]-amino}-propionylamino)-3-pyren-1-yl-propionylamino]-propionyl}-pyrrolidine-2-carbonyl)-amino]-propionic acid ethyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

37
[ 33300-72-0 ]
(S)-2-[((S)-1-{(S)-2-[(S)-2-((S)-2-[(S)-1-((S)-2-tert-Butoxycarbonylamino-propionyl)-pyrrolidine-2-carbonyl]-amino}-propionylamino)-3-(4-dimethylamino-phenyl)-propionylamino]-propionyl}-pyrrolidine-2-carbonyl)-amino]-propionic acid [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285
[2]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

38
[ 33300-72-0 ]
[ 189573-58-8 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285
[2]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

39
[ 33300-72-0 ]
(S)-2-[((S)-1-{(S)-2-[(S)-2-((S)-2-[(S)-1-((S)-2-tert-Butoxycarbonylamino-propionyl)-pyrrolidine-2-carbonyl]-amino}-propionylamino)-3-pyren-1-yl-propionylamino]-propionyl}-pyrrolidine-2-carbonyl)-amino]-propionic acid [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

40
[ 33300-72-0 ]
[ 189573-64-6 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 5277 - 5285

41
[ 33300-72-0 ]
H-Trp(Ppt)-Ala-Pro-OH [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

42
[ 33300-72-0 ]
Boc-Trp(Ppt)-Ala-Pro-OH [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

43
[ 33300-72-0 ]
H-Lys(Z)-Trp(Ppt)-Ala-Pro-OH [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

44
[ 33300-72-0 ]
Boc-Lys(Z)-Trp(Ppt)-Ala-Pro-OH [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

45
[ 33300-72-0 ]
(S)-1-{(S)-2-[(S)-2-{(S)-6-Benzyloxycarbonylamino-2-[((S)-5-oxo-pyrrolidine-2-carbonyl)-amino]-hexanoylamino}-3-(1-diphenylphosphanecarbothioyl-1H-indol-3-yl)-propionylamino]-propionyl}-pyrrolidine-2-carboxylic acid [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

46
[ 33300-72-0 ]
(S)-1-{(S)-2-[(S)-2-{(S)-6-Amino-2-[((S)-5-oxo-pyrrolidine-2-carbonyl)-amino]-hexanoylamino}-3-(1H-indol-3-yl)-propionylamino]-propionyl}-pyrrolidine-2-carboxylic acid; compound with trifluoro-acetic acid [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289
[2]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

47
[ 33300-72-0 ]
(S)-2-{(S)-5-Benzyloxycarbonylamino-1-[(S)-1-[(S)-2-((S)-2-carboxy-pyrrolidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-2-(1-diphenylphosphanecarbothioyl-1H-indol-3-yl)-ethylcarbamoyl]-pentylcarbamoyl}-5-oxo-pyrrolidine-1-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1988,p. 287 - 289

48
[ 33300-72-0 ]
[ 102779-11-3 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

49
[ 33300-72-0 ]
(S)-1-{(S)-2-[(S)-2-(2,4-Dinitro-phenylamino)-4-methyl-pentanoylamino]-propionyl}-pyrrolidine-2-carboxylic acid [(R)-2-methyl-1-(4-nitro-phenylcarbamoyl)-propyl]-amide [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

50
[ 33300-72-0 ]
[ 102721-64-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

51
[ 33300-72-0 ]
[ 102779-12-4 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1985,vol. 58,p. 3661 - 3662

52
[ 33300-72-0 ]
Boc-Ala-Pro-ΔLeu-Leu-OMe [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846

53
[ 33300-72-0 ]
Boc-Ala-Pro-ΔPhe-Leu-OMe [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1993,vol. 66,p. 1844 - 1846

54
aqueous KHSO₄ [ No CAS ]
[ 24424-99-5 ]
[ 13485-59-1 ]
[ 33300-72-0 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; sodium hydroxide; ethyl acetate;	f Preparation of N-(tert-butoxycarbonyl)-L-alanyl-L-proline: compound XIX 3 g of L-alanyl-L-proline in hydrate form (0.0147 mol) are dissolved in 30 cm3 of aqueous 0.5M NaOH and 30 cm3 of dioxane and the mixture is cooled to 0 C. with stirring. 3.53 g of di-tert-butyl dicarbonate (0.0162 mol) are introduced thereto at 0C, using a syringe. The reaction mixture is stirred at 0 C. for 30 minutes and then at 20 C for one hour. 30 cm3 of ethyl acetate are added and the mixture is cooled to 0 C. It is then treated with dilute aqueous KHSO4 until pH=2 is reached, and a precipitate forms. This is filtered off, washed with ether and dried under vacuum. The desired product is obtained. NMR (DMSO-d6, ppm): 6.9 (1H, d, NH); 4.2 (2H, m, alpha-CH alanine and proline); 3.5 (2H, m, methylene); 2.1 (1H, m, CH2 proline); 1.9 (3H, m, CH2 proline); 1.3 (9H, s, methyl); 1.1 (3H, d, methyl).

Reference： [1]Patent: US6403561,2002,B1

Yield	Reaction Conditions	Operation in experiment
		The benzyl ester protecting group was removed by dissolving Boc-Ala-Pro-OBzl (35 g, 92.8 mmoles) in 200 ml of methanol and hydrogenating for 1 hour in the presence of 0.5 g of 10% Pd/C. The catalyst was removed by filtration and the solvent evaporated. The residue was crystallized from ethyl acetate to yield 16.1 g of Boc-Ala-Pro-OH (mp 153.5-154.5 C.).

56
[ 16652-71-4 ]
[ 33300-72-0 ]
[ 54046-55-8 ]

Yield	Reaction Conditions	Operation in experiment
88.7%	With benzotriazol-1-ol; In dichloromethane; ethyl acetate;	D. N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester N-t-butyloxycarbonyl-L-alanyl-L-proline (4.3 g, 15 m mole), L-proline benzyl ester hydrochloride (3.7 g, 15.3 m mole) and HOBt (2.0 g, 15 m mole) were dissolved in methylene dichloride (40 ml). WSC (2.8 ml) was added dropwise to the above mixture while cooling to -15 C. and stirring. The reaction was carried out for 3 hours at a temperature of not more than 0 C., and then overnight at room temperature. The solvent was removed by distillation under reduced pressure leaving a residue. The residue was dissolved in ethyl acetate, and washed with 1N hydrochloric acid, water, 5% sodium bicarbonate and water, in order. The mixture was dried over anhydrous sodium sulfate. The thus obtained solution was distilled under reduced pressure leaving a residue. The residue was crystallized with a mixture of ethyl acetate and n-hexan to give a crystal of N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester (6.3 g, 88.7%) having melting point of 143 to 145 C. and specific rotatory power of [alpha]D25 =-131.0 (C-1, chloroform).
88.7%	With benzotriazol-1-ol; In dichloromethane; ethyl acetate;	D. N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester N-t-butyloxycarbonyl-L-alanyl-L-proline (4.3 g, 15 m mole), L-proline benzyl ester hydrochloride (3.7 g, 15.3 m mole) and HOBt (2.0 g, 15 m mole) were dissolved in methylene dichloride (40 ml). WSC (2.8 ml) was added dropwise to the above mixture while cooling to -15 C. and stirring. The reaction was carried out for 3 hours at a temperature of not more than 0 C., and then overnight at room temperature. The solvent was removed by distillation under reduced pressure leaving a residue. The residue was dissolved in ethyl acetate, and washed with 1N hydrochloric acid, water, 5% sodium bicarbonate and water, in order. The mixture was dried over anhydrous sodium sulfate. The solvent thus obtained solution was distilled under reduced pressure leaving a residue. The residue was crystallized with a mixture of ethyl acetate and n-hexan to give a crystal of N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester (6.3 g, 88.7%) having melting point of 143 to 145 C. and specific rotatory power of [alpha]D25 =-131.0 (C=1, chloroform).
88.7%	With benzotriazol-1-ol; In dichloromethane; ethyl acetate;	D. N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester N-t-butyloxycarbonyl-L-alanyl-L-proline (4.3 g, 15 m mole), L-proline benzyl ester hydrochloride (3.7 g, 15.3 m mole) and HOBt (2.0 g, 15 m mole) were dissolved in methylene dichloride (40 ml). WSC (2.8 ml) was added dropwise to the above mixture while cooling to -15 C. and stirring. The reaction was carried out for 3 hours at a temperature of not more than 0 C., and then overnight at room temperature. The solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, and washed with 1N hydrochloric acid, water, 5% sodium bicarbonate and water, in order. The mixture was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was crystallized with a mixture of ethyl acetate and n-hexan to give a crystal of N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester (6.3 g, 88.7%) having melting point of 143 to 145 C. and specific rotatory power of [alpha]D25 =-131.0 (C=1, chloroform).

Reference： [1]Patent: US4590178,1986,A
[2]Patent: US4472381,1984,A
[3]Patent: US4536395,1985,A

57
phenylmethyl ester, hydrochloride salt [ No CAS ]
[ 15761-38-3 ]
[ 147-85-3 ]
[ 543-27-1 ]
[ 33300-72-0 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; In chloroform; ethyl acetate;	(a) t-Butoxycarbonyl-L-alanyl-L-proline, phenylmethyl ester A solution of t-butoxycarbonyl-L-alanine (2.48 g., 13.1 mmole) in 23 ml. of dry chloroform at -15 (ice-salt bath) is treated with N-methylmorpholine (1.47 ml., 13.1 mmole) followed by isobutyl chloroformate (1.8 ml., 13.1 mmole) to give a precipitate. After 15 minutes, L-proline, phenylmethyl ester, hydrochloride salt (3.18 g., 13.1 mmole) and N-methylmorpholine (1.47 ml., 13.1 mmole) are added. Gas evolution ensues and the mixture is kept below -10 for one hour, then allowed to warm to room temperature, and stirred overnight under argon. The mixture is diluted with ethyl acetate, filtered, and the filtrate evaporated to dryness. The residue is taken up in ethyl acetate and washed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride, dried (Na2 SO4) and evaporated. The residue is purified by flash chromatography on silica gel (210 g.) eluding with ethyl acetate/hexane (1:2) to give t-butoxycarbonyl-L-alanyl-L-proline, phenylmethyl ester (4.37 g.) as a colorless oil; Rf (ethyl acetate/hexane, 1:1) is 0.47.

Reference： [1]Patent: US4432971,1984,A

58
[ 7524-52-9 ]
[ 33300-72-0 ]
[ 940603-04-3 ]

Reference： [1]Molecules,2008,vol. 13,p. 958 - 976

59
[ 1246291-63-3 ]
[ 33300-72-0 ]
[ 1246291-64-4 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 4530 - 4533

60
[ 5292-43-3 ]
[ 33300-72-0 ]
[ 1410925-00-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In acetonitrile; at 20℃;Inert atmosphere;	General procedure: To a solution of N-acetyl-(S)-leucylglycine5 (30 mg, 0.13 mmol) in acetonitrile (10 mL) was added tert-butyl bromoacetate (17 muL, 0.12 mmol) and potassium carbonate (90 mg, 0.65 mmol). The mixture was stirred at room temperature overnight under N2, before it was filtered and the filtrate was concentrated in vacuo. The residue was subjected to flash column chromatography on silica (DCM/methanol) to give tert-butyl Oalpha-(N-acetyl-(S)-leucylglycyl)glycolate (38 mg, 92%) as a colourless solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7015 - 7018

61
[ 33300-72-0 ]
[ 1410924-95-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7015 - 7018

62
[ 33300-72-0 ]
[ 109-73-9 ]
C₁₇H₃₁N₃O₄ [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2012,p. 4669 - 4674

63
[ 33300-72-0 ]
[ 1430326-45-6 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2013,vol. 108,p. 151 - 158

64
[ 33300-72-0 ]
[ 1190939-17-3 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2013,vol. 108,p. 151 - 158

65
[ 81377-00-6 ]
[ 33300-72-0 ]
[ 1430326-44-5 ]

Yield	Reaction Conditions	Operation in experiment
60.4%		<strong>[33300-72-0]Boc-Ala-Pro-OH</strong> (2.86 g, 10 mmol) was dissolved in dichloromethane (DCM, 20 mL). To this solution, EDCI (4.77 g, 25 mmol) was added at 0 C and the reaction mixture was stirred for 15 min. Ala-Pro-OMe (2.00 g, 10 mmol) was added followed by HOBT (2.74 g, 20 mmol) to the above reaction mixture under stirring. After 24 h, the reaction mixture was filtered; the residue was washed with DCM (30 mL) and added to the filtrate. The filtrate was washed with 5% sodium bicarbonate and saturated sodium chloride solutions. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography. Semisolid mass; Yield 60.4%; 1H NMR (CDCl3, ppm): 7.15 (1H, -NH, Amide), 5.50 (1H, -NH, Boc), 4.55-4.64 (2H, m, -CH, Ala), 4.41-4.50 (2H, t, -CH, Pro), 3.35-3.49 (4H, t, -CH2, Pro), 3.70 (3H, s, -OCH3), 2.02-2.30 (8H, m, -CH2, Pro), 1.35 (6H, -CH3, Ala), 1.42 (9H, s, tert-Butyl group). 13C NMR (CDCl3, ppm): 173 (-NCO), 171 (-COO), 155 (C=O, Boc), 14.42 (-CH3, Ala), 21.39 (-CH, Ala), 27.11 (-CH2, Pro), 51.67 (-CH2, Pro), 58.00 (-CH, Pro). ESI-MS (m/z): 469 [C22H36N4O7 + H]+.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2013,vol. 108,p. 151 - 158

66
[ 2577-48-2 ]
[ 33300-72-0 ]

Reference： [1]Journal of Photochemistry and Photobiology B: Biology,2013,vol. 121,p. 75 - 85

67
[ 33300-72-0 ]
[ 1586804-62-7 ]

Reference： [1]Patent: WO2014/54980,2014,A1

68
[ 33300-72-0 ]
[ 1586804-63-8 ]

Reference： [1]Patent: WO2014/54980,2014,A1

69
[ 33300-72-0 ]
[ 1586804-64-9 ]

Reference： [1]Patent: WO2014/54980,2014,A1

70
[ 33300-72-0 ]
[ 76338-87-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With pyridine; di-tert-butyl dicarbonate; ammonium bicarbonate; In acetonitrile; for 16h;	Suspension 2.2 g (7.7 pmol) of <strong>[33300-72-0]N-tert-butyloxycarbonyl-alanylproline</strong>, 1 g (13 pmol) of ammonium bicarbonate, 0.3 ml of pyridine and 2 ml (9 pmol) of di-tert- butylpyrocarbonate in 10 ml of acetonitrile are stirred for 16 h, diluted with water (30 ml), extracted with hexane-ether mixture (1:1 , 15 ml) and, then, with chloroform and n- propanol mixture of (9:1 ; 50 + 20 ml). Extracts are combined, washed with brine and dried. Solvent is boiled off, the residue is treated with ether-hexane mixture and 2.0 g (73%) of amide tert-butyloxycarbonyl-alanylproline in the form of white crystalline powder with melting point of 112-113C, [a]D -10.5 (s 1 , ethanol). Rf 0.35 (B) are obtained. Found %: C 54.3; H 7.6; N 14.5. C13H23N3O4. Calculated %: C 54.73 H 8.13 N 14.72

Reference： [1]Patent: WO2014/54980,2014,A1 .Location in patent: Page/Page column 6

71
[ 16029-98-4 ]
[ 33300-72-0 ]
C₁₆H₃₀N₂O₅Si [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 11792 - 11796

72
[ 1280225-71-9 ]
[ 147-85-3 ]
[ 33300-72-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In tetrahydrofuran; at 20℃; for 15h;	General procedure: A mixture of Boc-l-phenyl alanine-ASUDester (Table 1, entry 6) (3.0g, 6.7mmol), l-phenyl alanine methyl ester hydrochloride (1.46g, 6.7mmol), and triethylamine (1.71g, 16.9mmol) in dry THF (15mL) was stirred overnight at room temperature (15h). After completion of the reaction, the reaction mixture was filtered (remove TEA·HCl salt) and washed with THF (5mL). The filtrate was concentrated under vacuum to obtain an oily crude. The oily crude was dissolved in ethyl acetate, washed with 1.0% NaHCO3 solution and water. The ethyl acetate layer was dried over Na2SO4 and distilled under vacuum to give an oily crude product.

Reference： [1]Tetrahedron Asymmetry,2016,vol. 27,p. 487 - 491

73
[ 33300-72-0 ]
methyl (2-((1S,2S)-1-((S)-1-((tert-butoxycarbonyl)-L-phenylalanyl)pyrrolidine-2-carboxamido)-2-methylbutyl)oxazole-4-carbonyl)-L-alanyl-L-prolyl-L-prolylglycinate [ No CAS ]