[ CAS No. 34404-30-3 ] {[proInfo.proName]}

Name: 34404-30-3|Boc-D-Glu-OBzl|98%
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Quality Control of [ 34404-30-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 34404-30-3 ]

SDS Specification

Alternatived Products of [ 34404-30-3 ]

Product Details of [ 34404-30-3 ]

CAS No. :	34404-30-3	MDL No. :	MFCD00038266
Formula :	C₁₇H₂₃NO₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CVZUKWBYQQYBTF-CYBMUJFWSA-N
M.W :	337.37	Pubchem ID :	7010515
Synonyms :	Boc-D-Glu-OBzl	Chemical Name :	Boc-D-Glu-OBzl

Calculated chemistry of [ 34404-30-3 ]

Physicochemical Properties

Num. heavy atoms :	24
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.47
Num. rotatable bonds :	11
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	87.05
TPSA :	101.93 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.77 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.67
Log Po/w (XLOGP3) :	2.23
Log Po/w (WLOGP) :	2.34
Log Po/w (MLOGP) :	1.83
Log Po/w (SILICOS-IT) :	1.99
Consensus Log Po/w :	2.21

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.8
Solubility :	0.54 mg/ml ; 0.0016 mol/l
Class :	Soluble
Log S (Ali) :	-4.01
Solubility :	0.0333 mg/ml ; 0.0000987 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-3.64
Solubility :	0.0768 mg/ml ; 0.000228 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.39

Safety of [ 34404-30-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 34404-30-3 ]

* 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.

Upstream synthesis route of [ 34404-30-3 ]
Downstream synthetic route of [ 34404-30-3 ]

[ 34404-30-3 ] Synthesis Path-Upstream 1~4

1
[ 24424-99-5 ]
[ 79338-14-0 ]
[ 34404-30-3 ]

Reference： [1] Journal of Organic Chemistry, 2015, vol. 80, # 12, p. 6076 - 6082
[2] Patent: JP2015/166329, 2015, A, . Location in patent: Paragraph 0074-0075

2
[ 6893-26-1 ]
[ 34404-30-3 ]

Reference： [1] Roczniki Chemii, 1974, vol. 48, p. 1921 - 1927

3
[ 13303-10-1 ]
[ 34404-30-3 ]

Reference： [1] Roczniki Chemii, 1974, vol. 48, p. 1921 - 1927

4
[ 100-39-0 ]
[ 34404-28-9 ]
[ 34404-30-3 ]

Reference： [1] Roczniki Chemii, 1974, vol. 48, p. 1921 - 1927

[ 34404-30-3 ] Synthesis Path-Downstream 1~88

1
[ 1738-76-7 ]
[ 34404-30-3 ]
[ 71822-18-9 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1979,vol. 52,p. 1665 - 1671

2
[ 100-39-0 ]
[ 34404-28-9 ]
[ 34404-30-3 ]

Reference： [1]Roczniki Chemii,1974,vol. 48,p. 1921 - 1927

3
[ 17612-91-8 ]
[ 34404-30-3 ]
Boc-D-Glu(NHCH₂CH₂SAc)-OBzl [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1901 - 1921

4
[ 34404-30-3 ]
[ 107327-07-1 ]
[ 120059-65-6 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1184 - 1190

5
[ 34404-30-3 ]
[ 107326-81-8 ]
[ 115295-03-9 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1184 - 1190

6
[ 1149-26-4 ]
[ 1738-76-7 ]
[ 34404-30-3 ]
Boc-D-Arg(NO₂) [ No CAS ]
Z-L-Val-γ-D-Glu(Bzl)-D-Arg(NO2)-Gly-OBzl [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1998,vol. 46,p. 690 - 692

7
[ 34404-30-3 ]
[ 210963-67-0 ]

Yield	Reaction Conditions	Operation in experiment
76%		j0233j Compound A- Boc-Glu(OBn) (ig, 1 equiv) and N-Methylmorpholine (3.55 mmol, 1.2 equiv) were dissolved in 3 mL glyme and stirred at -15C. iso-Butyloxychloride (2.96 mmol, 1 equiv) was then added and stirred for an additional 15 mm. The resulting white precipitate was filtered off and NaBH4 (4.44 mmol, 1.5 equiv) was added to the filterate along with 4 mL of water and stirred for 15 mm. The reaction mixture was dissolved in EtOAc and extracted three times with brine. The organic layer was dried over Mg2504 and rotavapped at 40 C. Pure product was obtained on drying (0.726 g, 76%). Characterization confirmed formation of Compound A (Bergman, Y. Tetrahedron asymmetry, 19 (2008), 286 1-63).
33%		Preparation 50 Benzyl N-(ferf-butoxycarbonyl)-5-hvdroxy-D-norvalinate Triethylamine (12.4 mL, 89.02 mmol) and ethyl chloroformmate (1 1 .57 mL, 89.02 mL) were added to the solution of N-Boc-D-Glu(OBzl)OH (10 g, 29.6 mmol) in THF (100 mL) at -10C under an argon atmosphere. The mixture was stirred for 1 hour at - 10C. NaBH4 (4.39 g, 1 18.4 mmol) in water (100 mL) was added drop-wise to the reaction mixture at -10C, then the reaction mixture was stirred for 4 hours at room temperature. The reaction mixture was quenched with saturated aqueous NH4CI solution, extracted with EtOAc, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 30-40% EtOAc in petroleum ether to afford the title compound (3.1 g, 33%). 1H NMR (300MHz, CDCI3): delta ppm 1 .42 (s, 9H), 1 .70-1 .95 (m, 2H), 2.40- 2.50 (m, 2H), 3.53-3.70 (m, 3H), 4.8 (br s, 1 H), 5.1 (s, 2H), 7.30-7.40 (m, 5H). MS m/z 224 [M-Boc+H]+

Reference： [1]Patent: JP2015/166329,2015,A .Location in patent: Paragraph 0074-0075
[2]Patent: WO2014/143736,2014,A1 .Location in patent: Paragraph 0233
[3]Journal of Organic Chemistry,2015,vol. 80,p. 6076 - 6082
[4]Patent: WO2013/114250,2013,A1 .Location in patent: Page/Page column 161
[5]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

8
[ 34404-30-3 ]
[ 850742-49-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

9
[ 34404-30-3 ]
(R)-2-Amino-5-(2-amino-6-oxo-1,6-dihydro-purin-9-yl)-pentanoic acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

10
[ 34404-30-3 ]
[ 850742-50-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

11
[ 34404-30-3 ]
[ 850742-51-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

12
[ 34404-30-3 ]
[ 850742-61-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

13
[ 34404-30-3 ]
[ 850742-53-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

14
[ 34404-30-3 ]
[ 850742-55-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

15
[ 34404-30-3 ]
[ 850742-77-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

16
[ 34404-30-3 ]
[ 850742-59-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

17
[ 34404-30-3 ]
[ 850742-57-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 1058 - 1066

18
[ 34404-30-3 ]
[ 592530-93-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

19
[ 34404-30-3 ]
C₂₂H₂₉N₂O₆P [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

20
[ 34404-30-3 ]
C₂₂H₃₀N₃O₆P [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

21
[ 34404-30-3 ]
C₂₂H₃₀N₃O₆P [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

22
[ 34404-30-3 ]
[ 592530-94-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

23
[ 34404-30-3 ]
[ 592530-95-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2021 - 2024

24
[ 34404-30-3 ]
[ 173390-91-5 ]

Reference： [1]Tetrahedron,1998,vol. 54,p. 2059 - 2074

25
[ 34404-30-3 ]
Ac-D-γ-Glu-<N-MeΔAla>-D-Ala-Leu amide [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1995,vol. 49,p. 696 - 700

26
[ 34404-30-3 ]
[ 120059-55-4 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1184 - 1190

27
[ 34404-30-3 ]
[ 115295-05-1 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1184 - 1190

28
[ 34404-30-3 ]
[ 120085-40-7 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1184 - 1190

29
[ 34404-30-3 ]
gamma-D-Glutamyltaurine [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1901 - 1921

30
[ 34404-30-3 ]
(R)-2-Amino-4-(2-sulfo-ethylcarbamoyl)-butyric acid benzyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1901 - 1921

31
[ 34404-30-3 ]
(R)-2-tert-Butoxycarbonylamino-6-chloro-5-oxo-hexanoic acid benzyl ester [ No CAS ]

Reference： [1]Synthetic Communications,1990,vol. 20,p. 3097 - 3102

32
[ 34404-30-3 ]
(R)-2-tert-Butoxycarbonylamino-6-diazo-5-oxo-hexanoic acid benzyl ester [ No CAS ]

Reference： [1]Synthetic Communications,1990,vol. 20,p. 3097 - 3102

33
[ 34404-30-3 ]
[ 132286-83-0 ]

Reference： [1]Synthetic Communications,1990,vol. 20,p. 3097 - 3102

34
[ 6893-26-1 ]
[ 34404-30-3 ]

Reference： [1]Roczniki Chemii,1974,vol. 48,p. 1921 - 1927

35
[ 13303-10-1 ]
[ 34404-30-3 ]

Reference： [1]Roczniki Chemii,1974,vol. 48,p. 1921 - 1927

36
[ 6638-79-5 ]
[ 34404-30-3 ]
[ 1256386-07-8 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In dichloromethane; at 20℃; for 18h;	Example 1 General procedure for the synthesis of substituted hexahydro- pyrrolo [1,2-a] imidazol-3-one The general method is shown in Scheme 1. TBTU (1 eq) was added to a solution of N- (tert- butoxycarbonyl)-glutamine benzyl ester and NMM (1 eq) in dry DCM and the mixture stirred at room temperature for 30 minutes. A mixture of N, O-dimethylhydroxyamine hydrochloride (1. 5 eq) and NMM (1.5 eq) in DCM was separately stirred for 30 minutes. These two mixtures were combined and stirred at room temperature for 18 hours. The organic solvent was evaporated, the residue was loaded on a flash chromatograph column and eluted with ethyl acetate/hexane (v/v = 2/1) to give N- (tert-butoxycarbonyl)-5- (N, O-dimethyl-hydroxamide)-glutamine benzyl ester. N- (tert- butoxycarbonyl)-5- (N, O-dimethyl-hydroxyamide)-glutamine benzyl ester and a catalytic amount of palladium (10%) in carbon taken in methanol was stirred under 1 atm. hydrogen overnight at room temperature. After filtration and evaporation of solvent, a clear oily product was obtained which was used as is in next step. To a solution of N- (tert-butoxycarbonyl)-5- (N, O-dimethyl-hydroxamide)-glutamine (3.9 g, 13. 45 mmol) and NMM (1 eq) in THF at-15C was slowly added a THF solution of isobutyl chloroformate (1 eq). The mixture was stirred at this temperature for an additional 30 minutes. A solution of sodium borohydride (1.5 eq) in water was added in portions to the THF solution. After 20 minutes, the temperature was raised to room temperature and stirred for another 1 hour. The organic solvent was evaporated and the residue was purified on a column (10% methanol in DCM) to give N- (tert-butoxycarbonyl)-5- (N, O-dimethyl-hydroxamide)-glutaminol. To N- (tert-butoxycarbonyl)-5- (N, O-dimethyl-hydroxamide)-glutaminol and TEA (2 eq) in DCM at 0C was added methanesulfonyl chloride (2 eq) also in DCM. The solution was stirred at 0C for 20 minutes and at room temperature for an additional 45 minutes. The solvent was evaporated and the product extracted from water with ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. After removing solvent, the yield of mesylated product approached 100%. SCHEME 1 1) NHMe-OMe. HCI, I I NMM, TBTU, DCM O N-O 2) H2, Pd/C OBzI 3) i-BuOCOCI, NMM Boc-NH~OAr NaBH4-H20/THF 4) MsCI, Et3N, DCM 5) NaH, ArOH 1) TFA/DCM DMF, 80C 1) TFA/DCM D HN 2) Z-L-Lys (Boc)-OH, TBTU'" NMM, DCM 0 0 3) LAH, OC, THF N 4) TFA (cat.), DCM, reflux nit- Z H 1) H2, Pd/C, MeOH H2N 2) RCOOH, DIC, HOAt, DCM Ar 0 O N Nv Rd H 0 Sodium hydride (1.5 eq) was washed with hexane, the hexane was decanted and dry DMF was added. The suspension was mixed slowly with an aromatic alcohol (1.5 eq) at room temperature and the solution was stirred for 1 hour until no hydrogen was released. The mesylated compound in DMF was mixed with the above compound and stirred at room temperature for 24 hours. The solution was subsequently heated at 90C for an additional 24 hours. After cooling, the solution was poured into water and extracted twice with ethyl acetate. The combined organic layer was washed with water and brine and dried over sodium sulfate. The organic solvent was removed and the residue was purified on a silica gel column eluted by ethyl acetate/hexane (v/v = 2/1) to give 0-alkylated N- (tert-butoxycarbonyl)-5- (N, O-dimethyl-hydroxamide)-glutaminol. The compound synthesized in the preceding step was stirred in TFA/DCM (v/v = 1/4) for 1 hour. The solvent was removed and residue dried under vacuum. The residue was mixed with NMM (4 eq) in DCM. Separately, a DCM solution of Z-Lys (Boc) -OH (2 eq) and NMM (2 eq) was mixed with TBTU (2 eq) and stirred for 30 minutes. These two solutions were combined and stirred overnight at room temperature. After evaporating solvent and purification on an ethyl acetate column, O-alkylated N- (N-benzyloxy-N'-tert-butoxycarbonyl-L-lysyl)-5- (N, O-dimethyl-hydroxamide)- glutaminol was obtained in purified form. O-alkylated N- (N-benzyloxycarbonyl-N'-tert-butoxycarbonyl-L-lysyl)-5- (N, 0-dimethyl- hydroxamide)-glutaminol was dissolved in dry THF. The solution was cooled to 0C under nitrogen atmosphere. To this solution was slowly added LAH (1 M in THF, 1.25 eq). The solution was stirred at this temperature for 30 minutes and the reaction stopped by adding potassium hydrogen sulfate (1.5 eq) in water. After stirring for 30 minutes the solvent was removed and the residue re- dissolved in ether. The organic phase was washed with 1 N hydrochloric acid, saturated sodium hydrogen carbonate and brine. The ether layer was dried over sodium sulfate. Solvent was removed to yield an aldehyde derivative which was used for the next reaction without further purification. The aldehyde derivative was dissolved in DCM containing a catalytic amount of TFA and the solution refluxed for 5 hours. After removing solvent, the residue was purified on a column with DCM/acetone (v/v = 8/1) to give 2,5-substituted 1-benzyloxycarbonyl-hexa...

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109
[2]Patent: WO2005/79574,2005,A1 .Location in patent: Page/Page column 29-32

37
[ 67-56-1 ]
[ 34404-30-3 ]
[ 883985-06-6 ]

Yield	Reaction Conditions	Operation in experiment
	With diazomethyl-trimethyl-silane; In hexane; dichloromethane; at 0℃; for 1h;	To a solution of Boc-D-Glu-OBn (50.0 g, 148.2 mmol) in DCM (400 ml) and MeOH (100 ml) was added trimethylsilyldiazomethane (88.9 mL of 2.0 M solution in hexanes, 117.8 mmol) at 0 0C dropwise via an addition funnel. After 60 min the reaction was concentrated. This residue was diluted with CH3CN (400 mL) and (Boc)2O (48.5 g, 222.3 mmol) was added followed by DMAP (18.1 g, 14.8 mmol). After 24 h the reaction was concentrated and purified by silica gel chromatography (10% -> 60% ethyl acetate/ hexanes) to give the title compound (48.20 g, 72%). MS 252.2 (M+l - 2Boc).

Reference： [1]Patent: WO2006/44449,2006,A2 .Location in patent: Page/Page column 56

38
[ 34404-30-3 ]
[ 18107-18-1 ]
[ 883985-06-6 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; hexanes; dichloromethane; at 0℃; for 1h;	Step H. 1-Benzyl 5-methyl N.N-bisffe?-^butoxycarbonyl)-D-glutamate; To a solution of Boc-D-Glu-OBn (50.0 g, 148.2 mmol) in DCM (400 ml) and MeOH (100 ml) was added trimethylsilyldiazomethane (88.9 mL of 2.0 M solution in hexanes, 117.8 mmol) at 0 0C dropwise via an addition funnel. After 60 min the reaction was concentrated. This residue was diluted with CH3CN (400 mL) and (Boc)2O (48.5 g, 222.3 mmol) was added followed by DMAP (18.1 g, 14.8 mmol). After 24 h the reaction was concentrated and purified by silica gel chromatography (10% -» 60% ethyl acetate/ hexanes) to give the title compound (48.20 g, 72%). MS 252.2 (M+l - 2Boc).
	In methanol; hexanes; dichloromethane; at 0℃; for 1h;	Step H. 1 -Benzyl 5-methyl iV,N-bis(tgrt-butoxycarbonyl)-D-glutamate; To a solution of Boc-D-Glu-OBn (50.0 g, 148.2 mmol) in DCM (400 ml) and MeOH (100 ml) was added trimethylsilyldiazomethane (88.9 mL of 2.0 M solution in hexanes, 117.8 mmol) at 0 C dropwise via an addition funnel. After 60 min the reaction was concentrated. This residue was diluted with CH3CN (400 mL) and (Boc)2O (48.5 g, 222.3 mmol) was added followed by DMAP (18.1 g, 14.8 mmol). After 24 h the reaction was concentrated and purified by silica gel chromatography (10% -> 60% ethyl acetate/ hexanes) to give the title compound (48.20 g, 72%). MS 252.2 (M+l - 2Boc).

Reference： [1]Organic Letters,2008,vol. 10,p. 3235 - 3238
[2]Patent: WO2006/41830,2006,A2 .Location in patent: Page/Page column 66
[3]Patent: WO2006/44504,2006,A1 .Location in patent: Page/Page column 101

Yield	Reaction Conditions	Operation in experiment
		(c) N-[(1,1-Dimethylethoxy)carbonyl]-D-glutamic acid, 1-(phenylmethyl)ester A mixture of the ester product from part (b) (1 eq., 18.9 mmole, 4.32 g.) and benzyl alcohol (3 eq., 56.7 mmole, 5.9 ml., freshly distilled) in 10 ml. of dry tetrahydrofuran at room temperature under nitrogen is treated dropwise with a solution of dicyclohexylamine (1.1 eq., 20.8 mmole, 4.1 ml.) in 100 ml. of anhydrous ether. A white solid forms, and the thick suspension is mechanically stirred overnight. The solid is collected by filtration and washed with ether to yield the dicyclohexylamine salt as a gummy solid. The solid is dried at 40 under vacuum for one day. The solid is taken into 5% potassium bisulfate and extracted with ethyl acetate (4*100 ml.). The combined ethyl acetate layers are dried (MgSO4), filtered and the solvent stripped in vacuo to yield N-[(1,1-dimethylethoxy)-carbonyl]-D-glutamic acid, 1-(phenylmethyl)ester; m.p. 91-94.

40
[ 6373-46-2 ]
[ 34404-30-3 ]
C₃₀H₃₄N₂O₆ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 4963 - 4983

41
[ 4530-20-5 ]
4-methylbenzylhydrylamine resin [ No CAS ]
Boc-2Nal [ No CAS ]
[ 13734-34-4 ]
[ 84624-27-1 ]
[ 47689-67-8 ]
[ 34404-30-3 ]
[ 61315-61-5 ]
C₁₂₆H₁₃₄BrN₁₄O₁₉PolS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The sequence Boc-Phe-Tyr(2-Br-Z)-Lys(Fmoc)-DArg(Tos)-2Nal-Gly-DGlu(OBzl)-Lys(Fmoc) (SEQ ID NO:103) is manually assembled on MBHA resin using solid phase peptide synthesis Boc chemistry (Schnolzer et al. (1992) Int. J. Pept. Protein Res. 40:180-193) as outlined in Scheme 11. The chain assembly is carried out using the in situ neutralization/HBTU/DIEA activation procedure as described in Schnolzer et al. The side chain protecting group scheme is: Lys(Fmoc), DGlu(OBZl), DArg(Tos), Tyr(2-Br-Z). The alpha-amino group of all the amino acid building blocks is protected with tert-butoxycarbonyl (Boc). The stepwise chain assembly starts from the C-terminal end of the linear peptide and is accomplished in 8 steps as shown in Scheme 11. In step 1, five equivalents of protected amino acid Boc-Lys(2-Cl-Z) are activated with HBTU (4 eq)/DIEA (10 eq) in DMF, and coupled to MBHA resin. In step 2, five equivalents of Boc-DGlu(OBzl) are activated and coupled to the deprotected peptide resin from step 1 using neat TFA. These steps are repeated appropriately until step 8, the coupling of Boc-Phe. The Boc protecting group is removed with neat TFA, the resin is neutralized with DIEA, and washed with DMF and methanol and dried in air before HF cleavage. The linear peptide is simultaneously deprotected and cleaved from the resin using HF with 5% m-cresol or p-cresol as a scavenger for 1 hour at 0 C. The solvents are then evaporated and the crude peptide is precipitated and washed three times with cold diethyl ether.

Reference： [1]Patent: US2008/300177,2008,A1 .Location in patent: Page/Page column 27

42
[ 931-53-3 ]
[ 34404-30-3 ]
[ 1145788-30-2 ]
[ 1145788-29-9 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 1523 - 1525

43
C₂₉H₃₂N₂O₆*ClH [ No CAS ]
[ 34404-30-3 ]
[ 914981-88-7 ]

Reference： [1]Chemistry - A European Journal,2008,vol. 14,p. 10318 - 10330

44
C₃₂H₃₇N₃O₇*ClH [ No CAS ]
[ 34404-30-3 ]
[ 1192254-87-7 ]

Reference： [1]Chemistry - A European Journal,2008,vol. 14,p. 10318 - 10330

45
[ 34404-30-3 ]
Boc-D-pentahomoserine [ No CAS ]

Reference： [1]Journal of Natural Products,2009,vol. 72,p. 777 - 781

46
[ 24424-99-5 ]
[ 34404-30-3 ]
[ 18107-18-1 ]
[ 784156-32-7 ]

Yield	Reaction Conditions	Operation in experiment
72%		To a solution of Boc-D-Glu-OBn (50.0 g, 148.2 mmol) in DCM (400 ml) and MeOH(100 ml) was added trimethylsilyldiazomethane (88.9 mL of 2.0 M solution in hexanes, 117.8 mmol) at 0 0C dropwise via an addition funnel. After 60 min the reaction was concentrated. This residue was diluted with CH3CN (400 mL) and (Boc)2O (48.5 g, 222.3 mmol) was added followed by DMAP (18.1 g, 14.8 mmol). After 24 h the reaction was concentrated and purified by silica gel chromatography (10% -> 60% ethyl acetate/ hexanes) to give the title compound (48.20 g, 72%). MS 252.2 (M+l - 2Boc).
		To a solution of Boc-D-Glu-OBn (50.0 g, 148 mmol) in CH2Cl2 (400 mL) andMeOH (100 mL) at 0 0C was added (trimethylsilyl)diazomethane (2.0 M in hexanes, 89 mL, 118 mmol) dropwise via an addition funnel. After 1 h the reaction was concentrated under reduced pressure. This residue was diluted with CH3CN (400 mL) and di-tert-butyl dicarbonate (48.5 g, 222 mmol) was added, followed by DMAP (18.1 g, 14.8 mmol). The mixture was stirred at ambient temperature for 24 h, then concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane: EtOAc - 90:10 to 40:60, to give the title compound. MS: mlz = 252 (M - Ci0Hi5O4).

Reference： [1]Patent: WO2006/47196,2006,A2 .Location in patent: Page/Page column 57
[2]Patent: WO2008/153849,2008,A1 .Location in patent: Page/Page column 46

47
[ 34404-30-3 ]
[ 95-54-5 ]
[ 862403-36-9 ]

Yield	Reaction Conditions	Operation in experiment
		In 25 ml of chloroform was dissolved 2.50 g (7.41 mmol) of commercial Boc-D-glutamic acid benzyl ester, to which 2.13 g (11.1 mmol) of WSCI hydrochloride and 1.10 g (8.14 mmol) of HOBt were then added, and the solution was allowed to stand at room temperature for 5 minutes. It was added dropwise into 25 ml of chloroform solution of 0.962 g (8.89 mmol) of 1,2-phenylenediamine over a period of 2 hours, followed by stirring at room temperature for 18 hours. After the end of reaction, chloroform was supplemented thereto, followed by washing with hydrochloric acid, a sodium hydroxide aqueous solution, and a saturated saline solution. It was dried over anhydrous sodium sulfate before distilling off the solvent, followed by recrystallizing the residue from hexane/ethyl acetate to provide 1.96 g of the title compound as a white crystal.

Reference： [1]Patent: EP1707560,2006,A1 .Location in patent: Page/Page column 73

48
[ 34404-30-3 ]
[ 3171-45-7 ]
[ 862403-41-6 ]

Yield	Reaction Conditions	Operation in experiment
		In 25 ml of chloroform was dissolved 2.50 g (7.41 mmol) of commercial Boc-D-glutamic acid benzyl ester, to which 2.13 g (12.1 mmol) of WSCI hydrochloride and 1.10 g (8.14 mmol) of HOBt were then added, and the solution was allowed to stand at room temperature for 5 minutes. It was added dropwise into 25 ml of chloroform solution of 1.21 g (8.89 mmol) of 4,5-dimethyl-1,2-phenylenediamine over a period of 2 hours, followed by stirring at room temperature for 2 days. After the end of reaction, chloroform was supplemented, followed by washing with hydrochloric acid, a sodium hydroxide aqueous solution, and a saturated saline solution. It was dried over anhydrous sodium sulfate before distilling off the solvent, followed by purifying the residue using silica gel column chromatography (chloroform/ethyl acetate) to provide 1.96 g of the title compound as a white solid.

Reference： [1]Patent: EP1707560,2006,A1 .Location in patent: Page/Page column 74

49
[ 6366-70-7 ]
[ 34404-30-3 ]
[ 1257317-14-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 7422 - 7431

50
[ 34404-30-3 ]
[ 62-53-3 ]
[ 1257316-93-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 7422 - 7431

51
C₃₁H₃₈N₄O₄ [ No CAS ]
[ 34404-30-3 ]
N-butoxycarbonyl-O-benzyl-D-glutamyl-L-phenylalanyl-gem-L-phenylalanyl-benzyloxycarbonyl-retro-D-leucine [ No CAS ]

Reference： [1]Bulletin of the Korean Chemical Society,2012,vol. 33,p. 261 - 269

52
N-benzyloxycarbonyl-L-phenylalanyl-gem-L-phenylalanine [ No CAS ]
[ 34404-30-3 ]
N-benzyloxycarbonyl-L-phenylalanyl-gem-L-phenylalanyl-N-(t-butoxycarbonyl)-D-glutamyl-α-benzylester [ No CAS ]

Reference： [1]Bulletin of the Korean Chemical Society,2012,vol. 33,p. 261 - 269

53
[ 34404-30-3 ]
[ 784156-34-9 ]

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109
[2]Patent: WO2008/153849,2008,A1

54
[ 34404-30-3 ]
[ 1256386-08-9 ]

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109

55
[ 34404-30-3 ]
C₃₃H₄₁N₃O₆ [ No CAS ]

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109

56
[ 34404-30-3 ]
[ 1310382-07-0 ]

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109

57
[ 34404-30-3 ]
[ 1310382-09-2 ]

Reference： [1]Acta Chimica Slovenica,2011,vol. 58,p. 95 - 109

58
N^ε-(9-fluorenylmethoxycarbonyl)-L-lysine methyl ester hydrochloride [ No CAS ]
[ 34404-30-3 ]
[ 1380522-01-9 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 9343 - 9351

59
[ 34404-30-3 ]
[ 1380522-41-7 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 9343 - 9351

60
[ 34404-30-3 ]
[ 1380522-37-1 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 9343 - 9351

61
[ 34404-30-3 ]
[ 1380522-02-0 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 9343 - 9351

62
[ 34404-30-3 ]
[ 153-94-6 ]
[ 1401719-78-5 ]

Yield	Reaction Conditions	Operation in experiment
79%		Example 6 Preparation of H-D-Glu( -Trp-OH)-0-Bzl, Apo829 A. Preparation of Boc-D-Glu(D-Trp-OH)-0-Bzl Boc-D-Glu-OBz. ( 1.24 g, 33.3 mmol) was mixed with HOSu (3.83 g, 33.3 mrnol) and EDCI hydrochloride (6.38 g, 33.3 mmol) in DMF (80 mL) at room temperature and stirred for overnight. D-Trp-OH (10.2 g; 50 mmol) was added all at once and the reaction mixture was stirred at room temperature for another 6 h. The mixture was then quenched with a 0.5N HCI solution (250 mL) as a sticky solid formed. The liquid fraction was decanted and the residual sticky solid was dissolved in ethyl acetate (200 mL). The ethyl acetate layer was washed with a 0.5 N HCI solution (100 mL x 2), water (100 mL x 2) and brine, dried over MgS04 and filtered. The filtrate was concentrated in vacuo by rotary evaporation and the residue was triturated with ether to give Boc-D-Glu(D-Trp-OH)-0-Bzl as a white solid (6.60 g). The mother liquid was concentrated and triturated with 10 % ethyl acetate in hexanes to give a second crop of product as off-white solid (7.23 g). Combined yield = 13.82g (79%); 1H NMR (DMSO-DB, 400MHz) S (ppm): 10.82 (br. s, 1H), 8.09 (d, J = 7.1 Hz, 1H), 7.51 (d, J = 7.1 Hz, 1H), 7.27 - 7.41 (m, 7H), 7.11 (s, 1 H), 7.05 (t, J = 7.1 Hz: 1 H), 6.92 - 7.00 (m, 1 H), 5.01 - 5.21 (m, 2H), 4.39 - 4.51 (m, 1 H), 3.94 - 4.06 (m, 1 H), 3.08 - 3.19 (m, 1 H), 2.93 - 3.06 (m, 1 H), 2.05 - 2.26 (m, 2H), 1.82 - 1.98 (m, 1 H), 1 .67 - 1 .79 (m, 1 H), 1.37 (s, 9H); MS (m/z) 524 [M+1]+.

Reference： [1]Patent: WO2012/129671,2012,A1 .Location in patent: Page/Page column 38-39

63
[ 34404-30-3 ]
[ 1401720-11-3 ]

Reference： [1]Patent: WO2012/129671,2012,A1

64
[ 34404-30-3 ]
[ 1401719-58-1 ]

Reference： [1]Patent: WO2012/129671,2012,A1

65
[ 34404-30-3 ]
H-D-Glu(D-Trp-OH)-O-Bzl hydrochloride [ No CAS ]

Reference： [1]Patent: WO2012/129671,2012,A1

66
[ 34404-30-3 ]
[ 1401719-28-5 ]

Reference： [1]Patent: WO2012/129671,2012,A1

67
H-L-Trp-O-isoamyl hydrochloride [ No CAS ]
[ 34404-30-3 ]
[ 1401717-05-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	C. Preparation of Boc-D-Glu(L-Trp-0-isoamyl)-0-bzl Boc-D-Glu(L-Trp-0-isoamyl)-0-bzl was prepared from the reaction of H-L-Trp-O- isoamyl hydrochloride (7.65 g, 24.6 mmol), Boc-D-Glu-O-bzl (8.3 g, 24.6 mmol), EDCI (5.67 g , 29.5 mmoL), HOBt (3.5 g, 25.8 mmol) and DIPEA (8.6 mL, 49.2 mmol) in DMF (100 mL) The resulting mixture was stirred at room temperature for overnight. The reaction mixture was poured into a beaker of cold water (250 mL) with stirring. The mixture was extracted with ethyl acetate (100 mL x 3). The combined organic layers was successively washed with a 10% citric acid solution (30 mL), a saturated NaHC03 (50 mL) and brine (50 mL), and was then dried over MgS04. After solvent was removed in vacuo, Boc-D-Glu(L-Trp-O-isoamyi)- O-bzl was obtained as light yellowish oil (13.5 g). Yield = 93 %; 1H NMR (DMSO- d6 ,400MHz) delta ppm: 10.87 (br. s., 1 H), 8.30 (d, J = 7.1 Hz, 1 H), 7.48 (d, J = 8.1Hz, 1 H), 7.27 - 7.40 (m, 7 H), 7.15 (br. s., 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.91 - 7.03 (m, 1 H), 5.04 - 5.19 (m, 2 H), 4.48 (d, J = 6.1 Hz, 1 H), 3.97 (t, J = 6.1 Hz, 3 H), 3.12 (dd, J - 14.1 , 6.1 Hz, 1 H), 3.02 (dd, J = 14.1 , 8.1 Hz, 1 H), 2.14 - 2.29 (m, 2 H), 1.93 (d, J = 8.1 Hz, 1 H), 1 .67 - 1.83 (m, 1 H), 1 .41 - 1.55 (m, 2 H), 1.28-1.38 (m, 10 H), 0.80 (t, J = 6.1 Hz, 6 H); MS-ESI (m/z) 594 [M+lf.

Reference： [1]Patent: WO2012/129671,2012,A1 .Location in patent: Page/Page column 74-75

68
[ 872452-57-8 ]
[ 34404-30-3 ]
[ 1401717-05-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;Cooling with ice;	C. Preparation of Boc-D-Glu(L-Trp-O-isoamyl)-O-BzlTo a solution of Boc-D-Glu-O-Bzl (8.3 g, 24.6 mmol), H-L-Trp-O-isoamyl hydrochloride (7.65 g, 24.6 mmol), EDCI (5.67 g, 29.5 mmoL), and HOBt (3.5 g, 25.8 mmol) in DMF (100 mL) under ice-water bath cooling, was added DIPEA (8.6 mL, 49.2 mmol). The resulting mixture was stirred at room temperature for overnight. The reaction mixture was poured into a beaker of cold water (250 mL) with stirring. The mixture was extracted with ethyl acetate (100 mL x 3). The combined organic layers was successively washed with a 10% citric acid solution (30 mL), a saturated NaHCO3 (50 ml_) and brine (50 ml_), and was then dried over MgS04. After solvent was removed in vacuo, Boc-D-Glu(L-Trp-O-isoamyl)- O-bzl was obtained as light yellowish oil (13.5 g). Yield = 93 %; 1H NMR (DMSO- d6,400MHz) delta ppm: 10.87 (br. s., 1 H), 8.30 (d, J = 7.1 Hz, 1 H), 7.48 (d, J = 8.1 Hz, 1 H), 7.27 - 7.40 (m, 7 H), 7.15 (br. s., 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.91 - 7.03 (m, 1 H), 5.04 - 5.19 (m, 2 H), 4.48 (d, J = 6.1 Hz, 1 H), 3.97 (t, J = 6.1 Hz, 3 H), 3.12 (dd, J = 14.1 , 6.1 Hz, 1 H), 3.02 (dd, J = 14.1 , 8.1 Hz, 1 H), 2.14 - 2.29 (m, 2 H), 1.93 (d, J = 8.1 Hz, 1 H), 1.67 - 1.83 (m, 1 H), 1.41 - 1.55 (m, 2 H), 1.28-1.38 (m, 10 H), 0.80 (t, J = 6.1 Hz, 6 H); MS-ESI (m/z) 594 [M+1]+.

Reference： [1]Patent: WO2012/129680,2012,A1 .Location in patent: Page/Page column 37-38

69
[ 34404-30-3 ]
[ 784156-33-8 ]