[ CAS No. 102971-73-3 ] {[proInfo.proName]}

Name: 102971-73-3|Fmoc-Cys(tert-butoxycarnylpropyl)-OH|97%
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Quality Control of [ 102971-73-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 102971-73-3 ]

Product Details of [ 102971-73-3 ]

CAS No. :	102971-73-3	MDL No. :	MFCD11226818
Formula :	C₂₆H₃₁NO₆S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YUHBERDYPBZPQD-QFIPXVFZSA-N
M.W :	485.59	Pubchem ID :	11155983
Synonyms :

Safety of [ 102971-73-3 ]

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

Application In Synthesis of [ 102971-73-3 ]

* 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 [ 102971-73-3 ]
Downstream synthetic route of [ 102971-73-3 ]

[ 102971-73-3 ] Synthesis Path-Upstream 1~6

1
[ 28920-43-6 ]
[ 30845-10-4 ]
[ 102971-73-3 ]

Yield	Reaction Conditions	Operation in experiment
15%	With sodium carbonate In tetrahydrofuran	The compound 2 (2g, 7.60mmol) was dissolved in 10percent Na₂CO₃, and the Fmoc-Cl (2.94g, 11.4mmol) was added slowly, which was mixed with THF (7mL). After stirring overnight, 10percent citric acid was added to adjust PH 4 ~ 5. The THF was removed under reduced pressure and the residual solution was extracted by CH₂Cl₂. After washing successively with saturated NaCl solution, the organic phase was dried over anhydrous Na₂SO₄ and concentrated, the residue was purified by silica gel column chromatography (550mg, 15percent)_.¹H NMR (400 MHz, DMSO-d₆ ) δ 7.85 (d, J = 7.5 Hz, 2H), 7.77 ~7.61 (m, 3H), 7.37 (t, J = 7.5 Hz, 2H), 7.28 (t, J =7.4 Hz, 2H), 4.32~4.14 (m, 3H), 4.08 (qd, J = 8.8, 4.6 Hz, 1H), 2.86 (dt, J = 24.4, 10.2 Hz, 1H), 2.70(ddd, J = 15.2, 9.6, 5.6 Hz, 1H), 2.55 ~ 2.41 (m, 2H), 2.23 (t, J = 7.3 Hz, 2H), 1.68 (dd, J = 8.4, 6.1 Hz, 2H), 1.33 (s, 9H). ¹³C-NMR (100 MHz, DMSO-d₆ ): δ172.86, 172.31, 156.54, 144.32, 141.26, 141.24, 128.17, 127.59, 125.84, 125.80, 120.64, 80.13, 66.26, 54.58, 47.14, 34.11, 33.05, 33.04, 31.15, 28.24, 25.03.
10%	With sodium carbonate In tetrahydrofuran at 20℃;	Preparation of Compound 21: Compound 4 (2 g, 7.6 mmol) was dissolved with 10 ml of 10percent Na 2 CO 3 solution, Fmoc-Cl (2.94 g, 11.4 mmol) dissolved in THF was added, reacted overnight at room temperature, and the pH was adjusted with 10percent citric acid. 5, THF was removed under reduced pressure, extracted with CH2Cl2, the organic phase was washed with saturated NaCl solution, and dried under reduced pressure to give a brown yellow oil product 21 (200 mg, yield: 10percent);

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2375 - 2378
[2] Patent: CN107628975, 2018, A, . Location in patent: Paragraph 0142; 0143; 0144; 0145; 0146; 0147

2
[ 30845-10-4 ]
[ 82911-69-1 ]
[ 102971-73-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 12, p. 2984 - 2994
[2] Collection of Czechoslovak Chemical Communications, 1992, vol. 57, # 6, p. 1335 - 1344

3
[ 3153-32-0 ]
[ 102971-73-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 12, p. 2984 - 2994
[2] Patent: CN107628975, 2018, A,
[3] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2375 - 2378

4
[ 6182-78-1 ]
[ 102971-73-3 ]

5
[ 30845-10-4 ]
[ 102774-86-7 ]
[ 102971-73-3 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 2000, vol. 65, # 3, p. 407 - 424

6
[ 110661-91-1 ]
[ 102971-73-3 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 1992, vol. 57, # 6, p. 1335 - 1344

[ 102971-73-3 ] Synthesis Path-Downstream 1~88

1
[ 771-61-9 ]
[ 102971-73-3 ]
[ 143870-20-6 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1992,vol. 57,p. 1335 - 1344

2
[ 30845-10-4 ]
[ 82911-69-1 ]
[ 102971-73-3 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994
[2]Collection of Czechoslovak Chemical Communications,1992,vol. 57,p. 1335 - 1344

3
[ 4530-20-5 ]
[ 15761-39-4 ]
[ 13139-15-6 ]
[ 102971-73-3 ]
Fmoc-Asn-OH, Fmoc-Gln-OH, Fmoc-Ile-OH, Boc-Tyr-OH [ No CAS ]
C₄₈H₇₇N₁₁O₁₃S [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1992,vol. 57,p. 621 - 624

4
[ 30845-10-4 ]
[ 102774-86-7 ]
[ 102971-73-3 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,2000,vol. 65,p. 407 - 424

5
[ 102971-73-3 ]
[ 106-95-6 ]
[ 276869-37-5 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994
[2]Collection of Czechoslovak Chemical Communications,2000,vol. 65,p. 407 - 424

6
[ 3153-32-0 ]
[ 102971-73-3 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994
[2]Patent: CN107628975,2018,A
[3]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2375 - 2378

7
[ 6182-78-1 ]
[ 102971-73-3 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994
[2]Patent: CN107628975,2018,A
[3]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2375 - 2378

8
[ 102971-73-3 ]
[ 276869-38-6 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994
[2]Collection of Czechoslovak Chemical Communications,2000,vol. 65,p. 407 - 424

9
[ 102971-73-3 ]
(E)-But-2-enoic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

10
[ 102971-73-3 ]
3-Methyl-but-2-enoic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

11
[ 102971-73-3 ]
Cyclopropanecarboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

12
[ 102971-73-3 ]
Furan-2-carboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

13
[ 102971-73-3 ]
Thiophene-2-carboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

14
[ 102971-73-3 ]
Pyrazine-2-carboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

15
[ 102971-73-3 ]
<i>N</i>-[1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-nicotinamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

16
[ 102971-73-3 ]
4-Methyl-pentanoic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

17
[ 102971-73-3 ]
Cyclopentanecarboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

18
[ 102971-73-3 ]
5-Oxo-pyrrolidine-2-carboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2984 - 2994

19
[ 110661-91-1 ]
[ 102971-73-3 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1992,vol. 57,p. 1335 - 1344

20
[ 13734-34-4 ]
C₁₃H₂₅N₄O₄Pol [ No CAS ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₄H₆₉N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

21
C₁₃H₂₅N₄O₄Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₄H₆₉N₁₁O₁₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

22
C₁₃H₂₅N₄O₄Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₃H₆₇N₁₁O₁₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

23
C₁₇H₂₅N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₈H₆₉N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

24
C₁₈H₂₇N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₉H₇₁N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

25
C₁₇H₂₄FN₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₈H₆₈FN₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

26
C₁₈H₂₇N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₉H₇₁N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

27
C₁₅H₂₃N₄O₃PolS [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₆H₆₇N₁₁O₁₂S₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

28
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-31-6 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 77128-72-4 ]
Carbetocin [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

29
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 244132-31-8 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 77128-72-4 ]
[ 1190083-08-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

30
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 244132-31-8 ]
[ 204384-72-5 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 1190083-13-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

31
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 244132-31-8 ]
[ 204384-72-5 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 1190083-10-3 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

32
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 77128-72-4 ]
[ 1190083-08-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

33
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 77128-72-4 ]
[ 189249-10-3 ]
[ 1190083-09-0 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

34
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 141743-13-7 ]
C₄₈H₆₉N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

35
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 1026539-56-9 ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₈H₆₈FN₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

36
[ 29022-11-5 ]
[ 35661-60-0 ]
Fmoc-PhEtGly-OH [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₉H₇₁N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

37
[ 13734-34-4 ]
C₁₄H₂₇N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₅H₇₁N₁₁O₁₁S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

38
C₁₄H₂₇N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
C₄₅H₇₁N₁₁O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

39
C₁₅H₂₉N₄O₃Pol [ No CAS ]
[ 71989-23-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 102971-73-3 ]
[ 1613409-00-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5306 - 5317

40
Pro-2-Cl-Trt resin [ No CAS ]
[ 68858-20-8 ]
Boc-D-Arg(Pbf)-OH [ No CAS ]
[ 132388-59-1 ]
[ 102971-73-3 ]
[ 109-89-7 ]
Fmoc-β-(2-thienyl)-L-alanine [ No CAS ]
[ 89483-06-7 ]
c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-D-Arg-NEt₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The 1-7 fragment was assembled manually starting from 7.8 g (6.9 nmol) of H-Pro-2- chiorotrityl AM resin (EMD Millipore. catalog number 856057, 0.88 mmol/g). D1C/HOBt mediated couplings in DMF were employed. Single cycles of at least 2 hours with a 3-fold excess of activated Fmoc-protected amino acids were used during the synthesis. The completeness of couplings was assessed with ninhydrine test. Removal of the Fmoc protecting group was achieved with a single 30 nun, wash of the peptide resin with 20% piperidine in DMF. The following amino acid derivatives were used to assemble residues 1-7 of the resin-hound peptide: Finoc-Cys(( H2)3C(O)OtRu)-OH, Fmoc-Asn(Trt)-OH, FmocVal-OH, Fmoc-Thi-OH and .After the 1-7 peptide fragment was assembled the resin was washed thoroughly with DOvI and treated with the DCM/HFTP 7:3 (v/v) cocktail (2 x I h. 30 mL each). The solvents were then evaporated and the residue was precipitated with ethyl ether, filtered and dried in vacuo.5. 79 g (4.63 mmoi, 67 %) of the crude protected linear peptide was obtained. (The remainder of this product was used in the synthesis of other compounds as described herein.)100441 WD.-Arg-.NEt2 x 2TFA. 2.81 g (5.4 mmoi) of I3oc-D-Arg(Phfl-OH (Chem Impex, cat 05282), 1.95 niL (11.2 mniol) of DIPEA and 2.13 g (5.6 mniol) of HBYLT were dissolved in 10 mL DMF. 0.62 mL (6 rnmoi) of diethylanuine was subsequently added to the solution. No substrate was detected by analytical HPLC after 5 mm. The reaction mixture was poured into 500 niL of water and the precipitate was separated by centrifugation and dried in ?auio. The residue was treated with 20 mL TFA/TIS/H20 (96/2/2, v/v/v) for I h and the solvents were evaporated. The residue was treated with ethyl ether and decanted. 1.65 g (3.6 mmol, 67%) of semisolid derivative was obtained which was used in the subsequent step without purification. 100451 Coupling with HJDArgNEt2. 2.3 g (c.a. 1.86 mmol) of the linear protected peptide and 0.76 g (2 inmol) of HBTIJ were dissolved in 10 mL DMF containing 0.73 mL (4.2 unnuol) DIPEA. 0.93 g (2.05 nunol) of H-D-Arg(Pbf-OH x 2TFA in I niL DMF was subsequently added to the reaction mixture. No substrate was detected after 5 mm by HPLC. The product was precipitated with I 1/ of water, filtered off and dried in vacuo. 2.6 g (1.78 nunol, 96%) of crude protected hruear peptide was obtained. The fully? protected peptide was treated with 20 mL TFAIT1S/T-120 (96/2/2, v/v/v) for I h and the solvent was evaporated. The unprotected linear peptide was precipitated with ethyl ether and lyophilized. Yield 1.82. g (1.55 nnnoi, 83%). 100461 The entire amount of the linear peptide was dissolved in 50 niL of DMF. A solution of 0.59 g (c.a. 1.55 mmol) HBTU in 10 niL of DMF was also prepared. The peptide solution and the activator solution were added interchangeably to 50 mL of vigorously stirred DMF containing 200 9L of DIPEA in 10 portions of 5 mL and I mL, respectively. The pH was maintained at 9-10 with the addition of neat DIPEA. No substrate peak was detected by HPLC afier the last portions of the activator and peptide solutions have been added. The reaction mixture was dihited with 0.1% AcOH to 1 L. The obtained solution was loaded directly onto an HPLC prep column and purified with buffer system T eluted with a gradient of component B (see table above). The fractions with a purity exceeding 93%, determined by reverse-phase analytical HPLC, were pooled and reloaded onto the column. The colunm was washed with 5 volumes of 0.1M AcONH4 and the compound was subsequently eluted with buffer C to provide acetate salt. The fractions were pooled and lyophilized. 703.1 ing (0.60 nunol, 22% overall based on 89.6% peptide content) of white peptide powder was obtained. The product purity was determined by analytical HPIL as 99.7% and the observed M-tH was 1045.6 (calc. M-hH = 1045.5).

Reference： [1]Patent: WO2015/13690,2015,A1 .Location in patent: Paragraph 0043 - 0046

41
Pro-2-Cl-Trt resin [ No CAS ]
[ 68858-20-8 ]
Boc-D-Arg(Pbf)-OH [ No CAS ]
[ 132388-59-1 ]
[ 102971-73-3 ]
Fmoc-β-(2-thienyl)-L-alanine [ No CAS ]
[ 89483-06-7 ]
c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-D-Arg-NEt<SUB>2</SUB> [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The 1-7 fragment was assembled manually starting from 7.8 g (6.9 nmol) of H-Pro-2- chiorotrityl AM resin (EMD Millipore. catalog number 856057, 0.88 mmol/g). D1C/HOBt mediated couplings in DMF were employed. Single cycles of at least 2 hours with a 3-fold excess of activated Fmoc-protected amino acids were used during the synthesis. The completeness of couplings was assessed with ninhydrine test. Removal of the Fmoc protecting group was achieved with a single 30 nun, wash of the peptide resin with 20% piperidine in DMF. The following amino acid derivatives were used to assemble residues 1-7 of the resin-hound peptide: Finoc-Cys(( H2)3C(O)OtRu)-OH, Fmoc-Asn(Trt)-OH, FmocVal-OH, Fmoc-Thi-OH and .After the 1-7 peptide fragment was assembled the resin was washed thoroughly with DOvI and treated with the DCM/HFTP 7:3 (v/v) cocktail (2 x I h. 30 mL each). The solvents were then evaporated and the residue was precipitated with ethyl ether, filtered and dried in vacuo.5. 79 g (4.63 mmoi, 67 %) of the crude protected linear peptide was obtained. (The remainder of this product was used in the synthesis of other compounds as described herein.)100441 WD.-Arg-.NEt2 x 2TFA. 2.81 g (5.4 mmoi) of I3oc-D-Arg(Phfl-OH (Chem Impex, cat 05282), 1.95 niL (11.2 mniol) of DIPEA and 2.13 g (5.6 mniol) of HBYLT were dissolved in 10 mL DMF. 0.62 mL (6 rnmoi) of diethylanuine was subsequently added to the solution. No substrate was detected by analytical HPLC after 5 mm. The reaction mixture was poured into 500 niL of water and the precipitate was separated by centrifugation and dried in ?auio. The residue was treated with 20 mL TFA/TIS/H20 (96/2/2, v/v/v) for I h and the solvents were evaporated. The residue was treated with ethyl ether and decanted. 1.65 g (3.6 mmol, 67%) of semisolid derivative was obtained which was used in the subsequent step without purification. 100451 Coupling with HJDArgNEt2. 2.3 g (c.a. 1.86 mmol) of the linear protected peptide and 0.76 g (2 inmol) of HBTIJ were dissolved in 10 mL DMF containing 0.73 mL (4.2 unnuol) DIPEA. 0.93 g (2.05 nunol) of H-D-Arg(Pbf-OH x 2TFA in I niL DMF was subsequently added to the reaction mixture. No substrate was detected after 5 mm by HPLC. The product was precipitated with I 1/ of water, filtered off and dried in vacuo. 2.6 g (1.78 nunol, 96%) of crude protected hruear peptide was obtained. The fully? protected peptide was treated with 20 mL TFAIT1S/T-120 (96/2/2, v/v/v) for I h and the solvent was evaporated. The unprotected linear peptide was precipitated with ethyl ether and lyophilized. Yield 1.82. g (1.55 nnnoi, 83%). 100461 The entire amount of the linear peptide was dissolved in 50 niL of DMF. A solution of 0.59 g (c.a. 1.55 mmol) HBTU in 10 niL of DMF was also prepared. The peptide solution and the activator solution were added interchangeably to 50 mL of vigorously stirred DMF containing 200 9L of DIPEA in 10 portions of 5 mL and I mL, respectively. The pH was maintained at 9-10 with the addition of neat DIPEA. No substrate peak was detected by HPLC afier the last portions of the activator and peptide solutions have been added. The reaction mixture was dihited with 0.1% AcOH to 1 L. The obtained solution was loaded directly onto an HPLC prep column and purified with buffer system T eluted with a gradient of component B (see table above). The fractions with a purity exceeding 93%, determined by reverse-phase analytical HPLC, were pooled and reloaded onto the column. The colunm was washed with 5 volumes of 0.1M AcONH4 and the compound was subsequently eluted with buffer C to provide acetate salt. The fractions were pooled and lyophilized. 703.1 ing (0.60 nunol, 22% overall based on 89.6% peptide content) of white peptide powder was obtained. The product purity was determined by analytical HPIL as 99.7% and the observed M-tH was 1045.6 (calc. M-hH = 1045.5).

Reference： [1]Patent: WO2015/13690,2015,A1 .Location in patent: Paragraph 0043 - 0046; 0047; 0048

42
[ 68858-20-8 ]
Boc-D-Arg(Pbf)-OH [ No CAS ]
[ 78-81-9 ]
[ 132388-59-1 ]
[ 102971-73-3 ]
Fmoc-β-(2-thienyl)-L-alanine [ No CAS ]
[ 89483-06-7 ]
C₄₇H₆₉ClN₁₂O₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1 g (c,a. I mmnol) of FMPB AM resin (EMD Millipore, cat 4 855028) was swollen in15 ml of DCE/TMOF 1:1 mixture. To the resin suspension isobutyl amine (1.5 mL, 15 mmoi) was added followed by 3.2 g solid sodium triacetoxyborohvdride. The suspension was shaken overnight. The resin was washed with I1eOH, DMF and DCM and was subsequently acylated with Fmoc-D-Arg(Pbft-OH/D1C (4 eq) in DCM. The resin was washed with DMF and tested for acviarion completeness with the chioranil test (negative). The resin was split into three equal portions and the synthesis was continued at 0.33 nunol scale omi time Tribute Synthesizer. Single couplings mediated with HBTU/NMM in DMF or with DIC/HOBt (for Cys) with a 5-fold excess of Fin Soc-protected amino acids were used, The Finoc protecting group was removed with several consecutive 2 nun, washes with 20% piperidine in DMF. The following amino acid derivatives were used in the automatic synthesis: Fmoc-Pro-OH, Finoc-CysftCH2)3C(O)OtBu)-OH, Fmoc-Asn(Trt)-OH, Finoc-Val-OH, Fmoc-Thi-OH and Hoc-Cpa-OH. After the entire peptide sequence has been assembled the pepride was cleaved fronm the resin with 20 mnL of TF-iH2O/TIS 96:2:2 (v/v/v) for 2 h. The linear peptide was dissolved in 40 mL of DMF containing 200 qL of DIPEA. A solution of 152 mng (c.a. 0.4 mmoi) HBTU in 5 niL of DMF was also prepared. The peptide solution and the activator solution were added interchangeably to 40 mE of vigorously stirred DMF in 10 portions of 4 mnL amid 0.5 mE, respectively?. The p1-I was maintained at 9-10 with the addition of neat DIPEA. No substrate peak was detected by HPLC after the last portion of the activator solurion has been added. The reaction mixture was diluted with 0.1% AcOI-I to iL. The obtained solution was loaded directly onto an I-IPLC prep colunmnm. The conmpound was purified by three consecutive runs in buffer T. 100501 The fractions exceeding 97% purity were pooled and lyophiized. 49.0 mg (0.042mnmol, 12% overall, assuming 90% peptide content) of white peptide powder was obtained.The product purity was detennined by analytical HPLC as 99.5% and the observed M±H was1045.6 (calc. M+H = 1045.5).

Reference： [1]Patent: WO2015/13690,2015,A1 .Location in patent: Paragraph 0049; 0050

43
1,4-diaminobutane-2-chlorotrityl resin [ No CAS ]
[ 68858-20-8 ]
[ 71989-31-6 ]
[ 47375-34-8 ]
[ 132388-59-1 ]
[ 102971-73-3 ]
Fmoc-β-(2-thienyl)-L-alanine [ No CAS ]
C₄₁H₅₉N₉O₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		0.37 g (c.a. 0.3 mnniol) of 1,4-diaminobutane-2-chlorotrityi resin (EMD Millipore, cat // 856085) was swollen iii 10 niL of DMF and the resin placed in an automatic synthesis reaction vessel. The peptide assembly was carried out on the Tribute Synthesizer. Single couplings mediated with HBTU/NMM in DM1? or with D1C/HOBt (for Cys) with a 5-fold excess of Fmoc-protected amino acids were used. The Fmoc protecting group was renioved with several consecutive 2 nun. rashes with 20% piperidine in D11F. The following amino acid derivatives were used in the automatic synthesis: Fmoc-Pro-OH, FmocCys((CH 2)3C(O)OtBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Vai-OH, Fmnoc-Thi-OH and BocTyr(tflu)-O1-1. After the entire peptide sequence has been assembled the peptide was cleaved from the resin with 30 mE of HFIP/DCM 3:7 (v/v) for 2 h. The resin was filtered and the solvents were evaporated. The linear protected peptide was precipitated with anhydrous ethyl ether. The precipitate was decanted and suspended in 20 mnL acetonitrile. 111 mg (0.4 mnioi) of Z(2?Cl)-OSu and 0.136 mL (0.8mmol) DIPEA were subsequently added to the suspension. After the substrate has dissolved, the solvent was evaporated and the residue was treated with 20 mL of the TFAITIS/H20 95/2.5/2.5 cocktail for 1.5 h. TFA was then evaporated and the residue was precipitated rith diethvi ethex. The crude linear peptide vas dissolved in 100 mE of DMF containing 200 mL of DIPEA. A solution of 120mg (0.31 mmol) HBTU inS mL of DMF was subsequently? added to the vigorously stirred reaction mixture. After 30 miii. the reaction mixture was diluted with I L 0.1% AcOH and the obtained solution was uploaded onto prep HPLC cohmmn. The cychc peptide was eluted with fast (c.a. 3% MeCN/min.) in buffer system 1?. Fractions exceeding 97% purity by analytical HPLC were pooled and lyophihzed. ?The hophilizate ias? treated with 5 mL of the TMSBr/thioanisoie/TFA cocktail (1/1/6, v/v/v) for 1 h at 0C. TFA was evaporated and the peptide was precipitated with ethyl ether. The final product was purified by a single run in buffer T.j0052j The fractions exceeding 97% purity were pooled and lyophiized. 77.5 ing (0.079 mmoi, 26% overall, assuming 90% peptide content) of white peptide powder was obtained. The product purity was determined by analytical HPLC as 99.6% and the observed MI-H was 886.4 (calc. M+H 886.4).

Reference： [1]Patent: WO2015/13690,2015,A1 .Location in patent: Paragraph 0051 - 0052

44
[ 68858-20-8 ]
[ 204384-72-5 ]
C₃₇H₄₀ClN₄O₅PolS [ No CAS ]
[ 71989-31-6 ]
[ 132388-59-1 ]
[ 102971-73-3 ]
Fmoc-β-(2-thienyl)-L-alanine [ No CAS ]
C₄₅H₆₇N₁₁O₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		100531 0.43 g (c.a. 0.3 mmoi) of H Arg(Phf)-O-2chiorotrityl resin (EMD Mihhipore, cat 856067) was swollen in 10 mE of DMF and the resin placed in an automatic synthesis reaction vessel. The peptide assembly was carried out on the Tribute Synthesizer. Single couplings mediated with HBT IJ/NMM in DMF or with DIC/HOBt (for Cys) with a 54o1d excess of Fmoc-protected amino acids were used. The Fmoc protecting group was removed with several consecutive 2 mm. washes with 20% piper dme in DMF. The following amino acid derivatives were used in the automatic synthesis: FmocPro--OI-1, Fmoc Cys((CH2)3C(O)OtBu)-OH, Fmoc-Asn(Trt,)--OH, Fmoc-Vaf-OH and Fmoc?fh[-OH, A ffer the 38 peptide sequence has been assembled Fmoc-Phe(4-Et)--OH was coupled manually using DIC/HOBI method with 2-fold excess of reagents. The Frnoc group was then replaced with the Hoc group by treating the resin with 20% PIP/DMF for 30 mm. and acylating the N- terminal amino fOnction with Hoc2O in DMF, The linear peptide was cleaved from the resin with 30 mL of HFIP/DCy?f 3:7 (v/v) for 2 h. The resin was filtered and the solvents were evaporated. The linear protected peptide was precipitated with anhydrous ethyl ether. The precipitate was decanted and dried in vacuo.450 rug of the crude protected peptide was ohtained, The entire amount of the peptide (c.a. 0.3 mmoi) was dissolved in 10 mE 1,2- dichioroethane containing 0.5 niL DMF and 61 RL (0.45 nnnol) NMM. The solution was cooled to 0C on ice bath and 61 qL (0.45 mmol) of isobutyl chloroformate was added. The reaction mixture was magnetically stirred for 10 miii. at 0C. A solution of 160 rug (.4.5 mmol) sodium borohydride in 5 mE water was added in one portion. The reaction was diluted with 200 rnL water and the product was separated by? centrifugation arid dried in vacuo. The product was then was treated with 20 mL of the TFA/TIS/i-120 95/2.5/2.5 cocktail for 1.5 h. TFA was then evaporated and the residue was precipitated with diethyl ether. The crude linear peptide was dissolved in 80 mL of DMF containing 200 tL of D1PEA. A solution of6l nig (0.15 nnnoi) HBTIJ in 5 mE of DMF was subsequently added to the vigorously stirred reaction mixture. After 30 mm. the reaction mixture was diluted with I L 0.1% AcOH and the obtained solution was uploaded onto prep HPLC column. The cyclic peptide was purified by two consecutive runs in buffer T.100541 The fractions exceeding 97% purity were pooled and lyophilized. 41.7 rug (0.039mmoi, 13% overall, assuming 90% peptide content) of white peptide powder was obtained.The product purity was determined by analytical HPLC as 95.1% and the observed M+H was970.6 (calc. M+H 970.5).44

Reference： [1]Patent: WO2015/13690,2015,A1 .Location in patent: Paragraph 0053 - 0054

45
[ 2002-44-0 ]
[ 102971-73-3 ]
C₃₉H₅₃N₅O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%		Fmoc-Cys{(CH2)3COOtBu}-OH (38.0 grams; 78.3 mM) was dissolved in DMF (222 mL), and the solution was cooled to 0 to 5 C. Next, HOBt ( 12.0 grams, 78.3 mM) and <strong>[2002-44-0]H-Pro-Leu-Gly-NH2</strong> (26.64 grams, 93.7 mM) were added to the above solution at 0 to 5 C, and the stirring was continued for 5 min. To this solution, EDC.HC1 (25.3 grams, 132.0 mM; corrected for assay) was added while maintaining the temperature at 0 to 5 C. The reaction mixture was stirred for about 30 minutes while allowing the reaction mixture to warm to 25 to 30 C. The progress of the reaction was monitored by RP-HPLC. After the reaction was complete, it was quenched with a mixture of EtOAc and water, and the two layers were separated. The aqueous layer again extracted with the EtOAc. The combined organic layer was washed with 5% aqueous NaHC03, 1 % aqueous HS04, water, and 20% brine solution. The organic layer was dried with anhydrous Na2S04 and the solvents were removed under reduced pressure below 40 C. The residue was suspended in a mixture of DIPE and EtOAc, and stirred for 3 h. The solid was filtered, and washed with hexane, and dried under reduced pressure below 40-45 C for 3 hours to yield Fmoc-Cys{(CH2)3COOu)}-Pro-Leu-Gly-NH2 (53.5 grams; 71.2 mM; Yield: 91.0%; Purity RP -HPLC: 97.9%; [M+H]+ 752 amu)

Reference： [1]Patent: WO2017/175233,2017,A1 .Location in patent: Page/Page column 16; 23

46
[ 28920-43-6 ]
[ 30845-10-4 ]
[ 102971-73-3 ]

Yield	Reaction Conditions	Operation in experiment
15%	With sodium carbonate; In tetrahydrofuran;	The compound 2 (2g, 7.60mmol) was dissolved in 10% Na2CO3, and the Fmoc-Cl (2.94g, 11.4mmol) was added slowly, which was mixed with THF (7mL). After stirring overnight, 10% citric acid was added to adjust PH 4 ~ 5. The THF was removed under reduced pressure and the residual solution was extracted by CH2Cl2. After washing successively with saturated NaCl solution, the organic phase was dried over anhydrous Na2SO4 and concentrated, the residue was purified by silica gel column chromatography (550mg, 15%). 1H NMR (400 MHz, DMSO-d6 ) delta 7.85 (d, J = 7.5 Hz, 2H), 7.77 ~7.61 (m, 3H), 7.37 (t, J = 7.5 Hz, 2H), 7.28 (t, J =7.4 Hz, 2H), 4.32~4.14 (m, 3H), 4.08 (qd, J = 8.8, 4.6 Hz, 1H), 2.86 (dt, J = 24.4, 10.2 Hz, 1H), 2.70(ddd, J = 15.2, 9.6, 5.6 Hz, 1H), 2.55 ~ 2.41 (m, 2H), 2.23 (t, J = 7.3 Hz, 2H), 1.68 (dd, J = 8.4, 6.1 Hz, 2H), 1.33 (s, 9H). 13C-NMR (100 MHz, DMSO-d6 ): delta172.86, 172.31, 156.54, 144.32, 141.26, 141.24, 128.17, 127.59, 125.84, 125.80, 120.64, 80.13, 66.26, 54.58, 47.14, 34.11, 33.05, 33.04, 31.15, 28.24, 25.03.
10%	With sodium carbonate; In tetrahydrofuran; at 20℃;	Preparation of Compound 21: Compound 4 (2 g, 7.6 mmol) was dissolved with 10 ml of 10% Na 2 CO 3 solution, Fmoc-Cl (2.94 g, 11.4 mmol) dissolved in THF was added, reacted overnight at room temperature, and the pH was adjusted with 10% citric acid. 5, THF was removed under reduced pressure, extracted with CH2Cl2, the organic phase was washed with saturated NaCl solution, and dried under reduced pressure to give a brown yellow oil product 21 (200 mg, yield: 10%);

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2375 - 2378
[2]Patent: CN107628975,2018,A .Location in patent: Paragraph 0142; 0143; 0144; 0145; 0146; 0147

47
[ 102971-73-3 ]
C₂₃H₂₅NO₆S [ No CAS ]