[ CAS No. 1262681-31-1 ] {[proInfo.proName]}

Name: 1262681-31-1|ACetylene-PEG4-biotin conjugate|95%
Brand: Ambeed
SKU: A752908
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Quality Control of [ 1262681-31-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1262681-31-1 ]

Product Details of [ 1262681-31-1 ]

CAS No. :	1262681-31-1	MDL No. :	MFCD22380755
Formula :	C₂₁H₃₅N₃O₆S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	457.58	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 1262681-31-1 ]

Physicochemical Properties

Num. heavy atoms :	31
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.81
Num. rotatable bonds :	19
Num. H-bond acceptors :	6.0
Num. H-bond donors :	3.0
Molar Refractivity :	125.95
TPSA :	132.45 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-9.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	4.34
Log Po/w (XLOGP3) :	-0.39
Log Po/w (WLOGP) :	-0.15
Log Po/w (MLOGP) :	-0.17
Log Po/w (SILICOS-IT) :	2.94
Consensus Log Po/w :	1.31

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.18
Solubility :	30.4 mg/ml ; 0.0665 mol/l
Class :	Very soluble
Log S (Ali) :	-1.93
Solubility :	5.4 mg/ml ; 0.0118 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-4.85
Solubility :	0.00649 mg/ml ; 0.0000142 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	4.9

Safety of [ 1262681-31-1 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1262681-31-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1262681-31-1 ]

[ 1262681-31-1 ] Synthesis Path-Downstream 1~30

1
[ 1404191-47-4 ]
[ 1262681-31-1 ]
[ 1429934-33-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With tetrakis(actonitrile)copper(I) hexafluorophosphate; N-ethyl-N,N-diisopropylamine at 20℃; for 5h; Inert atmosphere;

Reference： [1]Karsten, Sebastian; Nan, Alexandrina; Liebscher, Juergen [ARKIVOC, 2012, vol. 2012, # 9, p. 204 - 219]

2
[ 1262681-31-1 ]
5'-CGACT(([4-(azidomethyl)phenyl]methyl)carboxamidocytosine)AAGGC-3' [ No CAS ]
5'-CGACTN-([(4-[4-(13-amino-2,5,8,11-tetraoxatridecan-1-yl)-1H-1,2,3-triazol-1-yl]methyl}phenyl)methyl]cytosine-2-oxo-5-carboxamido-biotin)AAGGC-3' [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lumiprobe; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; ascorbic acid In dimethyl sulfoxide at 20℃;

Reference： [1]Lu, Xingyu; Song, Chun-Xiao; Szulwach, Keith; Wang, Zhipeng; Weidenbacher, Payton; Jin, Peng; He, Chuan [Journal of the American Chemical Society, 2013, vol. 135, # 25, p. 9315 - 9317]

3
[ 1262681-31-1 ]
4-azidophenyl glyoxal [ No CAS ]
C₂₉H₄₀N₆O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With 2,6-dimethylpyridine; sodium L-ascorbate; N-ethyl-N,N-diisopropylamine; copper(I) bromide In water; dimethyl sulfoxide at 20℃; for 1h;

Reference： [1]Thompson, Darren A.; Ng, Raymond; Dawson, Philip E. [Journal of Peptide Science, 2016, vol. 22, # 5, p. 311 - 319]

4
[ 1262681-31-1 ]
6-azidohexyl 2,3,5-tri-O-benzyl-β-D-arabinofuranoside [ No CAS ]
C₃₂H₅₆N₆O₁₁S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: copper(ll) sulfate pentahydrate; sodium L-ascorbate / water; <i>tert</i>-butyl alcohol / 20 °C 2: acetic acid; hydrogen; palladium 10% on activated carbon / methanol / 3.5 h / 40 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1

5
[ 1262681-31-1 ]
6-azidohexyl 2,3,5-tri-O-benzyl-β-D-arabinofuranoside [ No CAS ]
biotin-(PEG)4-triazolehexyl 2,3,5-tri-O-benzyl-β-D-arabinofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃;	3 Biotin-(PEG)₄-triazole-hexyl 2,3,5-tri-O-benzyl-β-D-arabinofuranoside (Compound S20) To a stirring solution of S19β (14 mg, 0.025 mmol) and biotin-PEG4-alkyne (11.5 mg, 0.025 mmol) in tBuOH/H2O (1:1, 0.07 M) were added CuSO4.5H2O (0.5 μmol) from a 0.01 M stock solution in H2O and sodium ascorbate (0.005 mmol) from a 0.01 M stock solution in H2O. THF (80 μL) was added to solubilize all reaction components. The reaction was stirred at room temperature overnight. The mixture was then concentrated in vacuo. The residue was purified by flash column chromatography (10% MeOH/CH2Cl2, Rf=0.38). S20 was isolated as a white film (14 mg, 56%). 1H-NMR (CDCl3, 400 MHz): δ 7.54 (s, 1H), 7.38-7.21 (m, 15H), 6.75 (broad s, 1H), 6.31 (broad s, 1H), 5.40 (broad s, 1H), 5.03 (s, 1H), 4.68 (s, 2H), 4.61-4.41 (m, 7H), 4.31 (t, J=7.2, 3H), 4.21-4.14 (m, 1H), 4.00 (dd, J=3.1, 1.1 Hz, 1H), 3.91 (dd, J=6.8, 3.2 Hz, 1H), 3.73-3.53 (m, 16H), 3.48-3.35 (m, 3H), 3.18-3.07 (m, 1H), 2.88 (dd, J=12.8, 5.0 Hz, 1H), 2.72 (d, J=12.7 Hz, 1H), 2.21 (t, J=7.4 Hz, 2H), 1.89 (pent, J=7.3 Hz, 2H), 1.80-1.51 (m, 6H), 1.51-1.25 (m, 6H). HRESI-MS calcd for C53H74N6O11S [M+NH4]+ 1020.5475. found 1020.5458.

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1 Location in patent: Paragraph 0211

6
[ 1262681-31-1 ]
12-azidododec-2-enyl 2,3,5,6-tetra-O-acetyl-β-D-galactofuranoside [ No CAS ]
C₄₇H₇₆N₆O₁₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 22h;	3 Biotin-(PEG)4-triazole-dodec-2-enyl 2,3,5,6-tetra-O-acetyl-β-D-galactofuranoside (Compound S3) Intermediate S2 (6.0 mg, 0.011 mmol) was dissolved in dimethyl sulfoxide (DMSO) (400 μL) and water (100 μL). Biotin-PEG4-alkyne (Click Chemistry Tools, LLC, 5.4 mg, 0.012) was added, followed by CuSO4 5H2O (0.4 mg) and sodium ascorbate (0.4 mg). The reaction was stirred at room temperature for 22 h. The solvent was removed under reduced pressure, and the crude product was dissolved in MeCN (1 mL). The product was purified by HPLC [Vydac Protein & Peptide C18 column; gradient elution from 5-95% MeCN/water (vol/vol), 0.05% trifluoroacetic acid (TFA) (vol/vol)] to provide 3.3 mg (30%) of S3. 1H-NMR (300 MHz, CDCl3): δ 7.58 (s, 1H), 5.72 (dt, J=15.4, 6.8 Hz, 1H), 5.57-5.43 (m, 1H), 5.43-5.30 (m, 1H), 5.23-4.95 (m, 2H), 4.69 (s, 2H), 4.60-4.47 (m, 1H), 4.45-3.82 (m, 8H), 3.80-3.55 (m, 12H), 2.95-2.65 (m, 2H), 2.25-1.96 (m, 16H), 1.95-1.80 (m, 2H), 1.76-1.50 (m, 6H), 1.49-1.15 (m, 12H), 0.95-0.77 (m, 6H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1 Location in patent: Paragraph 0188; 0191

7
[ 1262681-31-1 ]
12-azidododec-2-enyl 2,3,5,6-tetra-O-acetyl-β-D-galactofuranoside [ No CAS ]
C₃₉H₆₈N₆O₁₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: copper(ll) sulfate pentahydrate; sodium L-ascorbate / dimethyl sulfoxide; water / 22 h / 20 °C 2: methanol; sodium methylate / 2 h / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1

8
[ 1262681-31-1 ]
12-azidododec-2-enyl 2,3,5,6-tetra-O-acetyl-β-D-galactopyranoside [ No CAS ]
C₄₇H₇₆N₆O₁₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 22h;	3 Biotin-(PEG)₄-triazole-dodec-2-enyl 2,3,5,6-tetra-O-acetyl-β-D-galactopyranoside (Compound S8) Compound S7 (6.0 mg, 0.011 mmol) was dissolved in DMSO (400 μL) and water (100 μL). Biotin-PEG4-alkyne (5.4 mg, 0.012 mmol) was added, followed by CuSO4 5H2O (0.4 mg) and sodium ascorbate (0.4 mg). The reaction was stirred at room temperature for 22 h. The solvent was removed under reduced pressure, and the crude product was dissolved in MeCN (1 mL). The product was purified by HPLC [Vydac, Protein & Peptide C18 column; gradient elution from 5-95% MeCN/water (vol/vol), 0.05% TFA (vol/vol)] to provide 5.8 mg (53%) of S8. (300 MHz, CDCl3): δ 7.59 (s, 1H), 5.68 (dt, J=15.3, 6.8 Hz, 1H), 5.54-5.34 (m, 2H), 5.22 (dd, J=9.5, 7.9 Hz, 1H), 5.01 (dd, J=10.4, 3.4 Hz, 1H), 4.70 (s, 2H), 4.55-4.45 (m, 2H), 4.40-3.95 (m, 6H), 3.89 (td, J=6.4, 1.0, 1H), 3.77-3.56 (m, 12H), 3.43 (broad s, 2H), 3.20-3.05 (m, 1H), 2.97-2.80 (m, 1H), 2.71 (broad d, J=13.4 Hz, 1H), 2.24-2.13 (m, 6H), 2.11-1.95 (m, 11H), 1.94-1.80 (m, 2H), 1.76-1.54 (m, 4H), 1.52-1.15 (m, 12H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1 Location in patent: Paragraph 0196

9
[ 1262681-31-1 ]
6-azidohexyl 2,3,5-tri-O-acetyl-β-D-ribofuranoside [ No CAS ]
biotin-(PEG)4-triazolehexyl 2,3,5-tri-O-acetyl-β-D-ribofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃;	3 Biotin-(PEG)₄-triazole-hexyl 2,3,5-tri-O-acetyl-β-D-ribofuranoside (Compound S16) To a stirring mixture of intermediate S15 (9.5 mg, 0.024 mmol) and biotin-PEG4-alkyne (11 mg, 0.024 mmol) in tBuOH/H2O (1:1, 0.07 M) were added sodium ascorbate (4.8 μmol) from a 0.1 M stock solution in H2O and CuSO4.5H2O (0.5 μmol) from a 0.01 M stock solution in H2O. The mixture was stirred at room temperature overnight and then concentrated in vacuo. The residue was purified by flash column chromatography (1-100% MeOH/CH2Cl2). S16 was isolated in 75% yield (15.5 mg). 1H-NMR (CDCl3, 300 MHz): δ 7.58 (s, 1H), 6.79 (broad s, 1H), 6.32 (s, 1H), 5.43 (s, 1H), 5.29 (dd, J=6.6, 5.0 Hz, 1H), 5.20 (dd, J=4.8, 0.6 Hz, 1H), 4.96 (s, 1H), 4.67 (s, 2H), 4.53-4.44 (m, 1H), 4.38-4.24 (m, 4H), 4.15-4.03 (m, 1H), 3.75-3.50 (m, 16H), 3.47-3.30 (m, 3H), 3.19-3.08 (m, 1H), 2.89 (dd, J=12.9, 5.1 Hz, 1H), 2.72 (d, J=12.7 Hz, 1H), 2.20 (t, J=7.2 Hz, 2H), 2.14-2.00 (3s, 9H), 1.90 (pent, J=6.9 Hz, 2H), 1.80-1.15 (m, 12H). HRESI-MS calcd for C38H62N6O14S [M+Na]+ 881.3937. found 881.3838.

Reference： [1]Current Patent Assignee: UNIVERSITY OF WISCONSIN SYSTEM; WARF (in: University of Wisconsin) - US2016/131649, 2016, A1 Location in patent: Paragraph 0205

10
[ 1262681-31-1 ]
ethyl 2-(2-azidoethylamino)-2-(4-tert-butylphenyl)acetate [ No CAS ]
C₃₇H₅₉N₇O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7.5 mg	With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃; Inert atmosphere;

Reference： [1]Mazuela, Javier; Antonsson, Thomas; Johansson, Magnus J.; Knerr, Laurent; Marsden, Stephen P. [Organic Letters, 2017, vol. 19, # 20, p. 5541 - 5544]

11
[ 1422540-93-9 ]
[ 1262681-31-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol; water / 2 h / Reflux 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 16 h / 20 °C

Reference： [1]Nagano, Masanobu; Carrillo, Nancy; Otsubo, Nobumasa; Hakamata, Wataru; Ban, Hitoshi; Fuller, Roberta P.; Bashiruddin, Nasir K.; Barbas, Carlos F. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 21, p. 5952 - 5961]

12
[ 87450-10-0 ]
[ 1262681-31-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 5 h / 20 °C 2: hydrazine hydrate / ethanol; water / 2 h / Reflux 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 16 h / 20 °C

13
[ 1013921-36-2 ]
[ 58-85-5 ]
[ 1262681-31-1 ]

Yield	Reaction Conditions	Operation in experiment
179 g	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h;	Compound-S8 [3] To a solution of Biotin (127 mg, 0.519 mmol) in DMF (2 mL) was added EDC-HCl (99 mg, 0.519 mmol) and amine (7) (100 mg, 0.433 mmol), and the whole was stirred at rt for 16 h. The reaction mixture was co-evaporated with toluene (x3), followed by purification using flash chromatography (CH2Cl2/MeOH = 5:1) gave desired product S8 (179 g, 90%) as colorless oil. 1H NMR (400 MHz, MeOD): δ 4.49 (dd, J = 8.0, J = 5.0 Hz, 1H), 4.31 (dd, J = 7.9, J = 4.5 Hz, 1H), 4.19 (d, J = 2.5 Hz, 2H), 3.69-3.61 (m, 12H), 3.56 (t, J = 5.3 Hz, 2H), 3.36 (m, 2H), 3.20 (m, 1H), 2.93 (dd, J = 12.8, 5.0 Hz, 1H), 2.85 (t, 1H, J = 2.4 Hz), 2.71 (d, J = 12.7 Hz, 1H), 2.23 (t, J = 7.3 Hz, 2H), 1.77-1.41 (m, 6H).

14
[ 1262681-31-1 ]
C₁₉H₂₉N₇O₈ [ No CAS ]
C₄₀H₆₄N₁₀O₁₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With copper(ll) sulfate pentahydrate; sodium L-ascorbate; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol In water; N,N-dimethyl-formamide; <i>tert</i>-butyl alcohol at 20℃; for 1h;	DNP-biotin (1) To a solution of DNP-azide (4) (40 mg, 0.0827 mmol) and biotin-alkyne (S8) (38 mg, 0.0827 mmol) in DMF/tBuOH/H2O (1: 2: 2, 2mL) was added THPTA (50 mg/mL, 0.72 L, 0.0992 mmol), CuSO4-5H2O (50 mg/mL, 0.50 mL, 0.002 mmol) and sodium ascorbate (50 mg/mL, 0.40 mL, 0.0992 mmol), and the whole was stirred at rt for 1 h. To the reaction mixture was added H2O and extracted with 20% iPrOH/DCM (x2), then dried over Na2SO4. Evaporation in vacuo, followed by purification using flash chromatography (CH2Cl2/MeOH = 6:1) gave desired product 9 (38.7 mg, 50%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.27 (ddd, J = 9.2, 2.4 and 0.8 Hz, 1H), 8.60 (br s, 1H), 8.28 - 8.25 (m, 1H), 7.78 (s, 1H), 6.95 (d, J = 12 Hz, 1H), 6.82 (br s, 1H), 6.64 (br s, 1H), 5.92 (br s, 1H), 5.10 (br s, 1H), 4.67 (s, 2H), 4.56 - 4.53 (m, 2H), 4.51 - 4.47 (m, 2H), 4.32 - 4.29 (m, 2H), 3.90 - 3.88 (m, 2H), 3.72 - 3.54 (m, 30H), 3.46 - 3.40 (m, 8H), 3.16 - 3.10 (m, 2H), 2.90 (dd, J = 12.8, 5.2 Hz, 2H), 2.72 (d, J = 12.8 Hz, 2H), 2.29 - 2.18 (m, 4H), 1.77-1.41 (m, 6H);13C NMR (126 MHz, CDCl3) δ 176.6, 173.2, 172.4, 148.3, 144.6, 135.9, 130.4, 124.4, 124.0, 114.0, 70.5, 70.42, 70.40, 70.38, 70.3, 70.1, 70.0, 69.93, 69.92, 69.6, 69.4, 64.4, 61.7, 60.04, 60.03, 55.4, 50.2, 43.3, 40.6, 39.2, 39.1, 37.6, 35.8, 35.4, 28.2, 28.0, 25.5, 22.7; HRMS: calcd for C40H65N10O14S (M + H+) 941.4397, found 941.4404.

15
[ 1262681-31-1 ]
C₂₅H₂₉F₂N₅O₅ [ No CAS ]
N-((S)-7-amino-1-(2,6-difluorophenoxy)-2-oxoheptan-3-yl)-3-(4-(15-oxo-19-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-2,5,8,11-tetraoxa-14-azanonadecyl)-1H-1,2,3-triazol-1-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: copper(II) sulfate; sodium L-ascorbate / water; dimethyl sulfoxide / 0.17 h / 25 °C 2: trifluoroacetic acid / dichloromethane / 12 h / 25 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD.; CORTEXYME INC - WO2018/53353, 2018, A1

16
[ 1262681-31-1 ]
C₂₅H₂₉F₂N₅O₅ [ No CAS ]
C₄₆H₆₄F₂N₈O₁₁S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.79%	With copper(II) sulfate; sodium L-ascorbate In water; dimethyl sulfoxide at 25℃; for 0.166667h;	55 Example 55. Preparation of -((S)-7-amino-l-(2,6-difluorophenoxy)-2-oxoheptan-3-yI)- 3.(4.(15-oxo-19H(3aS,4S,6aR)-2-oxohexahydro-lH hieno[3,4-d]imidazol-4-yl)-2,5,8,ll- tetraoxa-14-azanonadecyl)-lH-l,2,3-triazol-l-yl)benzamide (59) [0418] To a solution of 59.3 (80 mg, 174.83 μιηο, 1 equivalent) in DM SO (2 mL) and H20 (0.2 mL) was added 33.5 (90.48 mg, 174.83 μηιο, 1 equivalent) and CuS04 (5.58 mg, 34.97 μιηο, 5.37 μΤ, 0.2 equivalent) and sodium ascorbate (69.27 mg, 349.66 μηιο, 2 equivalent). The mixture was stirred at 25 °C for 10 min. The reaction mixture was quenched by addition H20 10 mL at 25 °C and extracted with ethyl acetate (lOmL x 3). The combined organic layers were washed with saturated brines (5mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a crude product. The residue was purified by prep-TLC (Si02, DCM: MeOH = 10: 1) to give 59.4 (90 mg, 92.30 μιηο, 52.79% yield) was obtained as yellow oil; LCMS [M + H] : 951 ; RT= 1.160 min.

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD.; CORTEXYME INC - WO2018/53353, 2018, A1 Location in patent: Paragraph 0418

17
[ 58-85-5 ]
[ 1262681-31-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 25 °C 2: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 25 °C

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD.; CORTEXYME INC - WO2018/53353, 2018, A1

18
[ 1013921-36-2 ]
[ 101187-31-9 ]
[ 1262681-31-1 ]

Yield	Reaction Conditions	Operation in experiment
100 mg	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 12h;	55 Example 55. Preparation of -((S)-7-amino-l-(2,6-difluorophenoxy)-2-oxoheptan-3-yI)- 3.(4.(15-oxo-19H(3aS,4S,6aR)-2-oxohexahydro-lH hieno[3,4-d]imidazol-4-yl)-2,5,8,ll- tetraoxa-14-azanonadecyl)-lH-l,2,3-triazol-l-yl)benzamide (59) [0417] A mixture of 59.1 (127.28 mg, 432.36 μιηο, 1 equivalent), 59.2(100 mg, 432.36 μιηο, 1 equivalent), DIPEA (167.64 mg, 1.30 mmol, 225.93 μΕ, 3 equivalent) in DMF (3 mL) was stirred at 25 °C for 12 hours. The residue was purified by prep-HPLC (TFA condition) to give 59.3 (100 mg, 218.54 μηιο, 50.55% yield) as a white solid; LCMS [M + H]: 458; RT= 1.052 min.

Reference： [1]Current Patent Assignee: CORTEXYME INC; WUXI APPTEC CO., LTD. - WO2018/53353, 2018, A1 Location in patent: Paragraph 0417

19
[ 1262681-31-1 ]
C₂₅H₄₆N₈O₈ [ No CAS ]
C₄₆H₈₁N₁₁O₁₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With Cupric sulfate; sodium ascorbate powder; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol In water monomer; <i>tert</i>-butyl alcohol at 20℃; for 3h;
	With Cupric sulfate; sodium ascorbate powder; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol In <i>tert</i>-butyl alcohol at 20℃; for 18h;

Reference： [1]Gotsbacher, Michael P.; Codd, Rachel [ChemBioChem, 2020, vol. 21, # 10, p. 1433 - 1445]
[2]Gotsbacher, Michael P.; Codd, Rachel [Methods in Enzymology, 2022, vol. 665, p. 49 - 71]

20
[ 1262681-31-1 ]
C₂₄H₄₄N₈O₈ [ No CAS ]
C₄₅H₇₉N₁₁O₁₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(ll) sulfate pentahydrate; sodium L-ascorbate; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol In water; <i>tert</i>-butyl alcohol at 20℃; for 3h;