[ CAS No. 18807-71-1 ] {[proInfo.proName]}

Name: 18807-71-1|Benzyl N-(2-aminoethyl)carbamate hydrochloride|97%
Brand: Ambeed
SKU: A161038
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2D 3D

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Quality Control of [ 18807-71-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 18807-71-1 ]

SDS Specification

Alternatived Products of [ 18807-71-1 ]

Product Details of [ 18807-71-1 ]

CAS No. :	18807-71-1	MDL No. :	MFCD00270150
Formula :	C₁₀H₁₅ClN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QMLKQXIAPAAIEJ-UHFFFAOYSA-N
M.W :	230.69	Pubchem ID :	12715871
Synonyms :

Calculated chemistry of [ 18807-71-1 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	6
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	59.98
TPSA :	64.35 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.61 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.54
Log Po/w (WLOGP) :	1.52
Log Po/w (MLOGP) :	1.25
Log Po/w (SILICOS-IT) :	0.77
Consensus Log Po/w :	1.02

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.14
Solubility :	1.67 mg/ml ; 0.00724 mol/l
Class :	Soluble
Log S (Ali) :	-2.5
Solubility :	0.728 mg/ml ; 0.00316 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.0
Solubility :	0.232 mg/ml ; 0.00101 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.07

Safety of [ 18807-71-1 ]

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 [ 18807-71-1 ]

* 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.

Upstream synthesis route of [ 18807-71-1 ]
Downstream synthetic route of [ 18807-71-1 ]

[ 18807-71-1 ] Synthesis Path-Upstream 1~9

1
[ 18807-71-1 ]
[ 72080-83-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydrogencarbonate In water	Preparation of benzyl (2-aminoethyl)carbamate To a solution of 2-(((benzyloxy)carbonyl)amino)ethanaminium chloride (1.0 g, 4.3 mmol) in water (5 mL) was added anhydrous Na₂CO₃ until litmus testing indicated pH 9. Solvent removal afforded a residue that was triturated with CH₂Cl₂ and filtered. The filtrate was concentrated to afford the desired free amine (0.93 g, 99percent yield).

Reference： [1] Patent: WO2015/81282, 2015, A1, . Location in patent: Paragraph 00714; 00715

2
[ 77153-05-0 ]
[ 18807-71-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydrogenchloride In methanol; ethyl acetate at 20℃; for 10 h;	Preparation of 2-(((benzyloxy)carbonyl)amino)ethanaminium chloride Benzyl tert-butyl ethane-1,2-diyldicarbamate (1.5 g, 6.3 mmol) in MeOH (10 mL) was treated with HCl/EtOAc (2 mL). The reaction was stirred at room temperature for 10 h and concentrated to give the title compound (1.0 g, 85percent yield).

Reference： [1] Bulletin of the Chemical Society of Japan, 1998, vol. 71, # 3, p. 699 - 709
[2] Journal of Peptide Science, 2013, vol. 19, # 1, p. 9 - 15
[3] Patent: WO2015/81282, 2015, A1, . Location in patent: Paragraph 00712; 00713

3
[ 13139-17-8 ]
[ 18807-71-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: With ethylenediamine In dichloromethane for 2.5 h; Stage #2: With hydrogenchloride In diethyl ether; hexane	Solid Phase Synthetic protocol: A solution of N-(benzyloxycarbonyloxy)succinimide (ZOSu, 100 g, 401 mmol) in dichloromethane (500 ml) was added dropwise over 2 hours to a solution of 5 ethylenediamine (1, 189 ml, 2.81 mol) in dichloromethane (750 ml). After 30 minutes the suspension was filtered and solids washed with dichloromethane. The filtrate was evaporated to dryness and the residue diluted with toluene (1.00 L) and water (0.50 L). The resulting mixture was filtered and the filtrate was separated to afford two phases. The aqueous phase contained the product; therefore it was extracted with 10 dichloromethane (2 x 250 ml). All organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was diluted with toluene (750 ml) and extracted with 2 M aqueous hydrochloric acid (500 ml) and 1 M aqueous hydrochloric acid (100 ml). Acidic aqueous phases were combined and basified with a solution of sodium hydroxide (60.0 g, 1.50 mol) in water (90 ml). The resulting mixture 15 was extracted with dichloromethane (4 x 200 ml), dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and diluted with hexanes (200 ml). 4 M Solution of hydrogen chloride in ether (100 ml, 400 mmol) was added to the solution, the resulting suspension was concentrated in vacuo and diluted with hexanes (1.00 L). The precipitated solid was filtered, washed with hexanes and dried in vacuo to give (2-amino20 ethyl)-carbamic acid benzyl ester hydrochloride as white powder. 25 Yield: 62.62 g (68percent). RF (Si02, dichloromethane/methanol 4: 1): 0.25 (free base). 1H NMR spectrum (300 MHz, Ac0D-d4, 80 °C, dH): 7.42-7.26 (m, 5 H); 5.16 (s, 2 H); 3.60 (t, J=5.7 Hz, 2 H); 3.32 (t, J=5.7 Hz, 2 H).

Reference： [1] Patent: WO2017/220706, 2017, A1, . Location in patent: Page/Page column 52; 53

4
[ 61495-86-1 ]
[ 18807-71-1 ]

Reference： [1] Patent: US6759509, 2004, B1,

5
[ 72080-83-2 ]
[ 18807-71-1 ]

Yield	Reaction Conditions	Operation in experiment
62.62 g	With hydrogenchloride In diethyl ether	A solution of N-(benzyloxycarbonyloxy)succinimide (ZOSu, 100 g, 401 mmol) in dichloromethane (500 mL) was added dropwise over 2 hours to a solution ofethylenediamine (1, 189 mL, 2.81 mol) in dichloromethane (750 mL). After 30 minutes the suspension was filtered and solids washed with dichloromethane. The filtrate was evaporated to dryness and the residue diluted with toluene (1.00 L) and water (0.50 L). The resulting mixture was filtered and the filtrate was separated to afford two phases. The aqueous phase contained the product; therefore it was extracted withdichloromethane (2 x 250 mL). All organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was diluted with toluene (750 mL) and extracted with 2 M aqueous hydrochloric acid (500 mL) and 1 M aqueous hydrochloric acid (100 mL). Acidic aqueous phases were combined and basified with a solution of sodium hydroxide (60.0 g, 1.50 mol) in water (90 mL). The resulting mixture was extracted with dichloromethane (4 x 200 mL), dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and diluted with hexanes (200 mL). 4 M Solution of hydrogen chloride in ether (100 mL, 400 mmol) was added to the solution, the resulting suspension was concentrated in vacuo and diluted with hexanes (1.00 L). Theprecipitated solid was filtered, washed with hexanes and dried in vacuo to give (2-amino- ethyl)-carbamic acid benzyl ester hydrochloride as white powder.Yield : 62.62 g (68percent).RF (Si02, dichloromethane/methanol 4: 1) : 0.25 (free base).1H NMR spectrum (300 MHz, AcOD-d4, 80 °C, dH) : 7.42-7.26 (m, 5 H); 5.16 (s, 2 H); 3.60 (t, J = 5.7 Hz, 2 H); 3.32 (t, J = 5.7 Hz, 2 H).

Reference： [1] Patent: WO2016/102562, 2016, A1, . Location in patent: Page/Page column 52

6
[ 886-64-6 ]
[ 18807-71-1 ]

Reference： [1] Synthesis, 1996, # 10, p. 1246 - 1258

7
[ 18807-67-5 ]
[ 18807-71-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 11, p. 1529 - 1532

8
[ 501-53-1 ]
[ 107-15-3 ]
[ 18807-71-1 ]

Reference： [1] Agricultural and Biological Chemistry, 1989, vol. 53, # 11, p. 3111 - 3112

9
[ 501-53-1 ]
[ 18807-71-1 ]

Reference： [1] Journal of Peptide Science, 2013, vol. 19, # 1, p. 9 - 15
[2] Patent: WO2015/81282, 2015, A1,

[ 18807-71-1 ] Synthesis Path-Downstream 1~88

1
[ 22906-75-8 ]
[ 18807-71-1 ]
[ 44604-32-2 ]

Reference： [1]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1968,vol. 349,p. 251 - 262

2
[ 1828-76-8 ]
[ 143-33-9 ]
[ 18807-71-1 ]
[ 80262-90-4 ]
[ 80262-86-8 ]

Reference： [1]Journal of Organic Chemistry,1982,vol. 47,p. 886 - 888
[2]Journal of Organic Chemistry,1982,vol. 47,p. 886 - 888

3
[ 16859-59-9 ]
[ 143-33-9 ]
[ 18807-71-1 ]
[ 80262-85-7 ]

Reference： [1]Journal of Organic Chemistry,1982,vol. 47,p. 886 - 888

4
[ 125342-48-5 ]
[ 18807-71-1 ]
[ 125342-49-6 ]

Reference： [1]Agricultural and Biological Chemistry,1989,vol. 53,p. 3111 - 3112

5
[ 82825-48-7 ]
[ 18807-71-1 ]
[ 82825-43-2 ]

Reference： [1]Acta Chimica Academiae Scientiarum Hungaricae,1982,vol. 109,p. 219 - 222

6
[ 501-53-1 ]
[ 107-15-3 ]
[ 18807-71-1 ]

Reference： [1]Agricultural and Biological Chemistry,1989,vol. 53,p. 3111 - 3112

7
[ 886-64-6 ]
[ 18807-71-1 ]

Reference： [1]Synthesis,1996,p. 1246 - 1258

8
[ 18807-71-1 ]
[ 74202-00-9 ]
[ 183444-81-7 ]

Reference： [1]Synthesis,1996,p. 1246 - 1258

9
[ 18807-71-1 ]
[ 183444-80-6 ]
[ 183444-82-8 ]

Reference： [1]Synthesis,1996,p. 1246 - 1258

10
[ 5241-66-7 ]
[ 18807-71-1 ]
[ 644996-22-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4103 - 4112

11
[ 18807-71-1 ]
[ 78444-90-3 ]
N-[((2-benzyloxycarbonylamino)ethylcarbamoyl)methyl]-3(R)-[N-(tert-butoxycarbonyl)amino]pyrrolidin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317

12
[ 873199-41-8 ]
[ 81-30-1 ]
[ 18807-71-1 ]
[ 873199-42-9 ]

Reference： [1]Chemistry - A European Journal,2005,vol. 11,p. 6525 - 6532

13
[ 906536-17-2 ]
[ 18807-71-1 ]
[ 906536-18-3 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4745 - 4761

14
[ 143-33-9 ]
[ 73274-87-0 ]
[ 18807-71-1 ]
[2-(1-cyano-4-methoxy-3-oxo-1,3-dihydro-isoindol-2-yl)-ethyl]-carbamic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1365 - 1379

15
[ 850038-83-4 ]
[ 143-33-9 ]
[ 18807-71-1 ]
[ 934634-52-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1365 - 1379

16
[ 850033-68-0 ]
[ 143-33-9 ]
[ 18807-71-1 ]
[ 850033-18-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1365 - 1379

17
[ 143-33-9 ]
[ 18807-71-1 ]
[ 94930-46-8 ]
[2-(1-cyano-4-fluoro-3-oxo-1,3-dihydro-isoindol-2-yl)-ethyl]-carbamic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1365 - 1379

18
[ 151838-62-9 ]
[ 18807-71-1 ]
C₉H₇NH₄CO₂COC₄H₈NCH₂CH₂NHCO₂CH₂C₆H₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 6876 - 6881

19
[ 18807-71-1 ]
benzyl 2-((2R,4R)-4-(naphthalen-2-ylmethoxy)pyrrolidine-2-carboxamido)ethylcarbamate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4745 - 4761

20
[ 18807-71-1 ]
{2-[2-((R)-3-Amino-2-oxo-pyrrolidin-1-yl)-acetylamino]-ethyl}-carbamic acid benzyl ester; compound with trifluoro-acetic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317

21
[ 18807-71-1 ]
[ 644996-23-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4103 - 4112

22
[ 18807-71-1 ]
[ 644996-24-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4103 - 4112

23
[ 18807-71-1 ]
H-Arg(Ts)-Eda-Z [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1998,vol. 71,p. 699 - 709

24
[ 18807-71-1 ]
[ 205874-98-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1998,vol. 71,p. 699 - 709

25
[ 18807-71-1 ]
[ 82825-44-3 ]

Reference： [1]Acta Chimica Academiae Scientiarum Hungaricae,1982,vol. 109,p. 219 - 222

26
[ 18807-71-1 ]
(S)-N-(2-Benzyloxycarbonylamino-ethyl)-3-tert-butoxycarbonylamino-succinamic acid [ No CAS ]

Reference： [1]Acta Chimica Academiae Scientiarum Hungaricae,1982,vol. 109,p. 219 - 222

27
[ 18807-71-1 ]
[ 82825-45-4 ]

Reference： [1]Acta Chimica Academiae Scientiarum Hungaricae,1982,vol. 109,p. 219 - 222

28
[ 850033-19-1 ]
[ 18807-71-1 ]
[ 850033-18-0 ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium cyanide; sodium acetate; In ethanol; acetic acid;	A stirring solution of N,N-diethyl-2-carboxaldhyde-6-trifluoromethoxybenzamide (2213 mg, 7.7 mmol) in 6 M hydrochloric acid (70 mL) was heated to reflux for 16 h. The reaction was cooled to room temperature and extracted with EtOAc (3×70 mL). The organic layers were combined, dried over Na2SO4, and conc in vacuo to a brown oil. The oil (1173 mg, 5.0 mmol) was added to a stirring solution of 1-(Benzyloxycarbonylamino)-2-aminoethane hydrochloride (1156 mg, 5.0 mmol, Aldrich) and sodium acatate (411 mg, 5.0 mmol, Aldrich) in ethanol (13.5 mL) and acetic acid (4.5 mL) followed by sodium cyanide (245 mg, 5.0 mmol, Aldrich). The reaction was stirred overnight and then conc in vacuo to a yellow solid. The solid was partioned between water (10 mL) and ethyl acetate (10 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×10 mL). The organic layers were combined, dried over Na2SO4, and conc in vacuo to a yellow oil. The oil was purified by radial chromatography (SiO2, 1:3, EtOAc:hexanes) to yield 1331 mg (63%) of the product as a colorless oil. MS (ESI) 420 (M+H)

Reference： [1]Patent: US2005/80074,2005,A1 .Location in patent: Page/Page column 22

29
[ 14418-84-9 ]
[ 18807-71-1 ]
[ 661480-77-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃;	A suspension of sodium allylsulfonate (2.0 g) in thionyl chloride (10.4 mL) was heated at 70C and stirred for 1.5 days. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure. The obtained residue was dissolved in dry tetrahydrofuran (10 mL), and the solvent was removed under reduced pressure. The obtained residue was again dissolved in dry tetrahydrofuran (10 mL), and the solvent was removed under reduced pressure to give <strong>[14418-84-9]allylsulfonyl chloride</strong> (1.26 g). To a suspension ofN-benzyloxycarbonyl-1,2-diaminoethane hydrochloride (0.82 g) and triethylamine (0.63 g) in dichloromethane (5 mL) was added <strong>[14418-84-9]allylsulfonyl chloride</strong> (0.25 g) at room temperature, and the mixture was stirred overnight. The reaction was quenched by addition of water, and the organic layer of the resulting mixture was separated. The organic layer was washed with 1 mol/L hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to giveN-(2-benzyloxycarbonylaminoethyl)allylsulfonamide (82 mg). This material was dissolved in acetonitrile (0.25 mL). To the solution were added 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-bromophenyl)methyl]-5-isopropyl-1H-pyrazole (70 mg), triethylamine (57 mg), palladium acetate (II) (3 mg) and tris(2-methylphenyl)phosphine (7 mg), and the mixture was refluxed overnight under shading the light. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (0.5 mL). To this solution was added 5 mol/L aqueous sodium hydroxide solution (0.25 mL), and the mixture was stirred at room temperature for 1 hour. The insoluble material was removed by filtration, and the filtrate was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 muL, 120A, 20x50mm, flow rate 30mL/minute linear gradient, water/methanol = 90/10 - 10/90) to give 4-({4-[(1E)-3-(2-benzyloxycarbonylaminoethylsulfamoyl)prop-1-enyl]phenyl}methyl)-3-(beta-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazole (14 mg). This material was dissolved in methanol (0.5 mL). To the solution was added 10% palladium-carbon powder (5 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give the title compound (10 mg).1H-NMR (CD3OD) delta ppm: 1.1-1.2 (6H, m), 2.0-2.1 (2H, m), 2.65-2.75 (4H, m), 2.85-2.95 (1H, m), 2.95-3.05 (4H, m), 3.25-3.45 (4H, m), 3.6-3.9 (4H, m), 5.0-5:1 (1H, m), 7.05-7.2 (4H, m)

Reference： [1]Patent: EP1544208,2005,A1 .Location in patent: Page/Page column 41-42

30
[ 307-35-7 ]
[ 18807-71-1 ]
[ 296239-32-2 ]

Reference： [1]Patent: EP1163231,2005,B1 .Location in patent: Page/Page column 24

31
[ 18807-71-1 ]
1H,1H,2H,2H-perfluorodecyloxyacetic acid [ No CAS ]
[ 296239-34-4 ]

Reference： [1]Patent: EP1163231,2005,B1 .Location in patent: Page/Page column 25

32
[ 56553-60-7 ]
[ 18807-71-1 ]
[ 96-22-0 ]
benzyl 2-[(1-ethylpropyl)amino]ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane;	Preparation 50 Benzyl 2-[(1-ethylpropyl)amino]ethylcarbamate Benzyl 2-aminoethylcarbamate hydrochloride (2 g, 8.65 mmol) was dissolved in dichloromethane (50 ml) and 3-pentanone (3.7 ml, 35 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature. Sodium triacetoxy borohydride (5.5 g, 26 mmol) was added and the reaction mixture was then stirred for 16 hours at room temperature. The solution was washed with saturated aqueous sodium hydrogen carbonate solution (40 ml). The dichloromethane phase was dried over anhydrous magnesium sulphate and the solvent was removed. The residue was purified by column chromatography on silica gel eluding with dichloromethane:methanol:0.88 concentrated aqueous ammonia (95:5:0.5 by volume). This gave the title compound as an oil (1.8 g). deltaH (300 MHz; CDCl3): 7.20-7.10 (5H, m), 5.30 (1H, bs), 5.10 (2H, s), 3.35-3.20 (2H, m), 2.85-2.70 (2H, m), 2.40-2.30 (1 H, m), 1.50-1.30 (4H, m), 0.90-0.80 (6H, m).

Reference： [1]Patent: US2002/32168,2002,A1

33
[ 357286-73-8 ]
[ 18807-71-1 ]
[2-(2-amino-5-cyano-6-furan-2-yl-pyrimidin-4-ylamino)-ethyl]-carbamic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,2-dimethoxyethane;	[2-(2-Amino-5-cyano-6-furan-2-yl-pyrimidin-4-ylamino)-ethyl]-carbamic acid benzyl ester From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, (2-amino-ethyl)-carbamic acid benzyl ester hydrochloride and DBU in DME. ES-MS m/e (%): 401 (M+Na+, 20), 379 (M+H+, 100).

Reference： [1]Patent: US2001/27196,2001,A1

Yield	Reaction Conditions	Operation in experiment
		Preparation Example 11 N-Benzenesulfonylethylenediamine: N-Benzyloxycarbonylethylenediamine hydrochloride (2.3 g, 10.0 mmol) obtained in accordance with the process described in Hoppe-Seyler's, Z. Physiol. Chem., 349, 251 (1968) and benzenesulfonyl chloride (1.2 ml, 0.95 mmol) were suspended in water (100 ml). After triethylarine (1.4 ml) was added to the suspension, a 1N aqueous solution (10 ml) of sodium hydroxide was gradually added over about 10 minutes, and the mixture was stirred at 70 C. for 30 minutes. Toluene was added to the reaction mixture, and the solvent was distilled off under reduced pressure.
		Under an atmosphere of dry argon, 24.3 g (0.128 mol) of N-CBZ-aminoacetonitrile (1e) was dissolved in anhydrous tetrahydrofuran (32 ml). The solution was stirred and 64 ml of borane-methylsulfide complex (2M in tetrahydrofuran) was added via syringe. The mixture was heated to reflux and stirred overnight. The mixture was cooled with an ice bath as 5 ml of water was added slowly, with vigorous stirring. The stirring was continued for ca. 5 minutes, then 75 ml of 6M HCl was slowly added. The mixture was stirred for 1 hour, then the excess tetrahydrofuran and dimethyl sulfide was removed in vacuo. The aqueous residue was extracted with ether (250 ml). The ether extracts were then discarded. The pH of the aqueous residue was raised to 11 by adding concentrated NH4 OH. The resulting aqueous solution was extracted with ethyl acetate (3100 ml) and the ethyl acetate extracts were combined and washed with brine (50 ml). After drying over anhydrous magnesium sulfate, the solution was filtered and concentrated in vacuo. The resulting oil was dissolved in 30 ml of anhydrous methanol, treated with cold methanolic HCl and concentrated in vacuo to produce a solid. The solid was triturated with ether and collected by filtration to give 15.1 g (51% yield) of N-CBZ-ethylenediamine hydrochloride (1f) as a white powder. 1 H NMR(D2 O) delta 3.15(m, 2H), 3.46(m, 2H), 5.14(s, 2H), 7.46(bs, 5H); 13 C NMR (D2 O) delta 41.1, 42.6, 70.4, 131.0, 131.3, 131.7, 132.0, 139.4, 161.7.

35
O-Benzyl-N-trifluoroacetyltyrosine [ No CAS ]
[ 541-41-3 ]
[ 18807-71-1 ]
O-benzyl-N-trifluoroacetyltyrosine-(2-carbobenzoxyaminoethylen)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; N-methyl-acetamide; (2S)-N-methyl-1-phenylpropan-2-amine hydrate;	(b) O-Benzyl-N-trifluoroacetyltyrosine-(2-carbobenzoxyaminoethylen)amide 18.5 g (50.4 mmol) of O-benzyl-N-trifluoro-acetyltyrosine (Example 9a) is dissolved in 200 ml of dry tetrahydrofuran, combined with 7 ml of Et3N, and then 4.8 ml (50.8 mmol) of chloroformic acid ethyl ester is added dropwise while maintaining the temperature at below -10 C. After this adding step is completed, the mixture is agitated for 30 minutes at this temperature, again combined with the same amount of precooled triethylamine, and an ice-cold solution of 11.6 g (50.4 mmol) of N-<strong>[18807-71-1](2-aminoethyl)carbamic acid benzyl ester hydrochloride</strong> in 100 ml of dimethylformamide is added dropwise. The mixture is stirred for another 30 minutes at -10 C., then allowed to warm up to room temperature under agitation, and thereafter heated for 10 minutes to 30 C. Then the solvent is removed by rotary evaporator and the mixture poured on 750 ml of ice water. The crystallized product is suctioned off, washed with ice water, and dried. The yield is 26.9 g (94% of theory). Melting point: 189-190 C. Analysis Calcd: C 61.87; H 5.19; N 7.73; O 14.71; F 10.48. Found: C 61.90; H 5.08; N 7.77; F 10.43.

Reference： [1]Patent: US5693309,1997,A

36
[ 916731-80-1 ]
[ 18807-71-1 ]
[ 916733-47-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate; In dimethyl sulfoxide; at 115℃;	EXAMPLE 178; 4-[7-(2-Oxo-imidazolidin-1-yl)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a. 4-[7-(2-Oxo-imidazolidin-1-yl)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester; To a mixture of 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (458 mg, 1.38 mmol), which was prepared as described in Example 65b, and (2-amino-ethyl)-carbamic acid benzyl ester hydrochloride (446 mg, 1.93 mmol) in DMSO (1.0 mL) was added K2CO3 (1.52 g, 11.04 mmol). The mixture was stirred at 115 C. overnight and subsequently partitioned between EtOAc and water. The combined organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash column chromatography on silica gel (EtOAc as eluent) to afford the desired product as a white solid (400 mg, 73%). 1H NMR (CDCl3) delta 9.13 (s, 1H), 8.69 (dd, J=9.40 and 2.35 Hz, 1H), 8.08 (d, J=9.53 Hz, 1H), 7.42 (d, J=2.33 Hz, 1H), 5.25 (br, 1H), 4.31 (m, 2H), 4.09 (t, J=8.21 Hz, 2H), 3.69 (t, J=8.14 Hz, 2H), 3.63 (m, 1H), 2.95 (m, 2H), 1.77-2.04 (4H), 1.48 (s, 9H). Calcd for C21H28N5O3 (MH+) 398.3, found 398.3.

Reference： [1]Patent: US2006/281772,2006,A1 .Location in patent: Page/Page column 122

37
[ 403479-49-2 ]
[ 18807-71-1 ]
[ 543-27-1 ]
[ 797040-07-4 ]

Yield	Reaction Conditions	Operation in experiment
50.3%	With NMM; In tetrahydrofuran; ethyl acetate;	3d) H-iNip-DAE-ZHCl 497 mg (2.17 mmol) of Boc-isonipecotic acid were dissolved with 250 mul (2.27 mmol) of NMM in 10 ml of dry THF. 296 mul (2.27 mmol) of isobutyl chloroformate were added at -15 C., and the mixture was stirred for a further 10 min. Then 500 mg (2.17 mmol) of N-Z-1,2-diaminoethaneHCl and 250 mul (2.27 mmol) of NMM were added, and the mixture was stirred at -15 C. for a further 1 h and then at RT for 4 h. The solvent was removed in vacuo, and the residue was taken up in ethyl acetate and subjected to 3 acidic (5% KHSO4), 1 neutral (saturated NaCl solution), 3 basic (NaHCO3 saturated) and 3 neutral (saturated NaCl solution) washes. The ethyl acetate phase was then dried over Na2SO4, and the solvent was removed in vacuo, resulting in the product as amorphous substance (HPLC: 50.3% B). The crude product was dissolved in 20 ml 1 N of hydrogen chloride in glacial acetic acid and left to stand at RT for 1 h. The solvent was then removed in vacuo, and the product was lyophilized. Yield: 722 mg HPLC: 26.4% B

Reference： [1]Patent: US2007/55065,2007,A1

38
[ 61495-86-1 ]
[ 18807-71-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In acetic acid;	EXAMPLE 12 N-Carbobenzyloxyethylenediamine Hydrochloride N,N-Bis-Carbobenzyloxyethylenediamine 11 (23.91 g, 72.8 mmol) in glacial acetic acid (100 mL) was treated with 12M HCl (12.1 mL, 2 equiv). The stirred mixture was heated at reflux for 1 h and then left to stand at rt overnight. A small amount of solid was removed by filtration and the filtrate was diluted with ether (700 mL) and left to stand at rt for 2 h. The resulting white solid product was collected by filtration, washed repeatedly with ether, and dried in a vacuum dessicator overnight (9.2440 g, 55%). 1H-NMR (DMSO-d6) delta 2.87 (t, 2H), 3.30 (q, 2H), 5.04 (s, 2H), 7.33 (m, 5H), 7.49 (brt, 1H), 8.22 (br, 3H).

Reference： [1]Patent: US6759509,2004,B1

39
N-β-Boc-L-α,β-diaminopropionic acid methyl ester hydrochloride [ No CAS ]
[ 3406-84-6 ]
[ 18807-71-1 ]
[ 277329-79-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran;	Part A-Preparation of Methyl (2S)-3-[(tert-Butoxy)carbonylamino]-2-[(4-{4-[({2-[(phenylmethoxy)carbonylamino]ethyl}amino)sulfonyl]phenyl}phenyl)sulfonyl]amino}propanoate Biphenyl-4,4'-disulfonyl chloride (5.30 g, 15.0 mmol, freshly recrystallized from CHCl3) and DCM (400 mL) were placed in a 100 mL 3-neck flask fitted with a thermometer, an addition funnel, and a nitrogen line. The addition funnel was charged with a solution of <strong>[18807-71-1]benzyl N-(2-aminoethyl)carbamate hydrochloride</strong> (2.30 g, 10.0 mmol) and DIEA (1.80 mL, 10.0 mmol) in DCM (40 mL). The contents of the flask were cooled below 5 C., and the contents of the addition funnel were added to the flask with rapid stirring over 30 min while keeping the temperature of the flask below 5 C. The addition funnel was then charged with a solution of N-beta-Boc-L-alpha,beta-diaminopropionic acid methyl ester hydrochloride (5.10 g, 20.0 mmol) and DIEA (7.60 mL, 44.0 mmol) in DCM (40 mL). This solution was added to the flask with stirring at 5 C. over 15 min, and stirred at ambient temperatures for an additional 4 days. The reaction was concentrated and the resulting residue was partitioned between EtOAc (6 L) and 0.1 N HCl (600 mL). The organic solution was washed consecutively with water (3 L), and saturated NaCl (2 L), dried (MgSO4), and concentrated to give the title compound as a colorless solid (9.60 g). MS: m/e 591.2.

Reference： [1]Patent: US2004/208823,2004,A1

40
[ 51673-84-8 ]
[ 18807-71-1 ]
[ 1042124-57-1 ]

Reference： [1]Tetrahedron Letters,2008,vol. 49,p. 2316 - 2319

41
[ 13734-34-4 ]
[ 18807-71-1 ]
[ 146553-00-6 ]

Reference： [1]Tetrahedron Letters,2008,vol. 49,p. 2316 - 2319

42
[ 277315-90-9 ]
[ 18807-71-1 ]
[ 277316-24-2 ]

Yield	Reaction Conditions	Operation in experiment
56%		20 (8.20 g, 16.8 mmol) Was dissolved in DMF (70 niL, Dried over 3A molecular sieves). Diisopropyl ethyl amine (8.68 g, 67.1 mmol) was added and the mixture was stirred under nitrogen. The mixture was cooled in a cool water bath then HBTU, O-benzotriazol-l-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (7.64 g, 20.1 mmol) was added in portions at a temperature below 170C. The mixture was further stirred for 20 minutes. A solution of <strong>[18807-71-1]benzyl N-(2-aminoethyl)carbamate hydrochloride</strong>, 21, (4.65 g, 20.1 mmol) in DMF (21 mL, dried over 3A molecular sieves) was added drop wise at a temperature below 170C. The solution was further stirred for 30 minutes and was allowed to warm to ambient temperature. The reaction solution was then evaporated at 6O0C and 10 mbar. This gave a residue of 33.8 g. The residue was dissolved in dichloromethane (120 mL). The mixture was washed twice with 0.1 M HCl(aq.), 20 mL each. The mixture was then washed three times with 10 % NaHCCb, 20 mL each. Evaporation at 5O0C and 10 mbar gave 13.8 g residue.[0063] The residue was dissolved in methylene chloride (15 mL) and filtered through silica gel 60 (100 g, size 0.015-0.040 mm, Merck). Dry Column Vacuum Chromatography technique was applied. The silica was eluted with eluent from pure ethyl acetate to a mixture ethylacetate with 5 % methanol in small increments. Each with a 50 ml portions. Fractions 7-11 were combined as judged pure from TLC analysis. Evaporation gave 6.3 g foaming oil that solidified up on cooling (56%). Purity HPLC 254nm 97.7 %.In Process assay: HPLCProduct LD. : 1H NMR, 13C NMR, FT-IR, LC/MS, residual solvent analysis, elemental analysis, loss on drying, optical rotation.

Reference： [1]Patent: WO2008/70291,2008,A2 .Location in patent: Page/Page column 24

43
C₂₁H₃₁ClN₂O₈S [ No CAS ]
[ 18807-71-1 ]
[ 277316-24-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; In dichloromethane; N,N-dimethyl-formamide; for 1h;Product distribution / selectivity;	The crude product was redissolved in CH2CI2 (150 mL) and a solution of benzyl N-(2- aminoethyl)carbamate hydrochloride, 21 (1.52 g, 6.6 mmol) and 4-methylmorpholine (1.11 g, 11.0 mmol) in DMF was added. After 1 h, the reaction mixture was concentrated in vacuo and partitioned between EtOAc and water. After separation of the layers, the EtOAc solution was washed with dilute nuaHCU3 and water. The EtOAc solution was concentrated in vacuo to give the crude product. This material was purified by chromatography (97:3 EtOAc/MeOH) to give 2.80 g of product 22. Addition of ether to this material caused the oil to crystallize. Filtration of the resulting solid gave 2.44 g of purified 22 (65.5%).

Reference： [1]Patent: WO2008/70291,2008,A2 .Location in patent: Page/Page column 12; 23-24

44
[ 15159-40-7 ]
[ 18807-71-1 ]
C₁₅H₂₁N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 0.75h;	Morpholine-4-carbonyl chloride (1.5 g, 10.0 mmol) was dissolved in dichloromethane (10 mL) in a 25 mL round bottom flask and to this was added 2- aminoethyl carbamic acid benzyl ester hydrochloride (2.54 g, 11.0 mmol) followed by diisopropylethylamine amine (2.59 g, 20.0 mmol). This mixture was stirred for 45 minutes after which the mixture was poured into a separatory funnel and washed with water (10 mL) and brine (10 mL), and dried (MgSO4). After filtration the dichloromethane was removed under reduced pressure. The resulting crude residue was the dissolved in methanol (50 mL) and to this solution was added 10% Pd/C(1.06 g). The mixture was then stirred under a hydrogen atmosphere (introduced via a balloon) for 1 hour. The reaction mixture was then filtered through a pad of <n="41"/>CELITE and concentrated to obtain the desired product (1.7 g, 98%) as a clear, colorless oil. 1H NMR (600 MHz, D2O): delta 3.60 (t, 4H, J = 6 Hz), 3.29-3.25 (m, 4H), 3.17 (t, 2H, J = 6 Hz), 2.69 (t, 2H, J = 6 Hz).

Reference： [1]Patent: WO2008/83054,2008,A2 .Location in patent: Page/Page column 39-40

45
[ 96736-00-4 ]
[ 18807-71-1 ]
[ 848083-52-3 ]

Yield	Reaction Conditions	Operation in experiment
66.8%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 16h;	4- [2- (tert-Butoxycarbonyl) hydrazino] benzoic acid (Schwartz, D. A., et al. ; Bioconj. Chem. , 1991,2, 333-336) (1.8 g, 7.29 mmol) and diisopropylethylamine (2.0 mL, 11.5 mmol) were dissolved in N, N-dimethylformamide (8 mL) and stirred under nitrogen at room temperature. The solution was treated with PyBroP (3.4 g, 7.29 mmol) and benzyl N- (2-AMINOETHYL)-CARBAMATE hydrochloride (1.68 g, 7.29 mmol). Additional PyBroP (0.34 g, 0.729 mmol) and benzyl N- (2- aminoethyl) carbamate hydrochloride (0.17 g, 0.729 mmol) were added to the reaction solution at 2 hours. At 6 hours, additional PyBroP (0.68 g, 1.46 mmol) and benzyl N- (2-aminoethyl) carbamate hydrochloride (0.34 g, 1.46 mmol) were added. The solution was stirred a total of 8 hours and was concentrated under vacuum to give a dark amber oil. Crude product was crystallized (ether) to give 2.08 g (66.8%) of the title compound as a colorless solid in 100% purity by LC/MS.

Reference： [1]Patent: WO2005/23314,2005,A1 .Location in patent: Page/Page column 67

46
C₂₆H₃₅N₃O₅S₂ [ No CAS ]
[ 18807-71-1 ]
[ 1146685-03-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1340 - 1343

47
[ 18807-71-1 ]
[ 1160-54-9 ]
KCB₄-181 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1340 - 1343

48
[ 15761-39-4 ]
[ 18807-71-1 ]
[ 1192134-58-9 ]

Reference： [1]Synthesis,2009,p. 2509 - 2516

49
[ 18807-71-1 ]
[ 84358-13-4 ]
[ 1221567-05-0 ]

Reference： [1]Patent: WO2004/101507,2004,A2 .Location in patent: Page/Page column 55-56

50
[ 203798-34-9 ]
[ 18807-71-1 ]
[ 1204008-01-4 ]

Yield	Reaction Conditions	Operation in experiment
79%		Step 1. Synthesis of 3,6-Diamino-N2,N5-bis[2-(benzyloxycarbonyl)aminoethyl]pyrazine-2,5-dicarboxamide (15). A suspension of N-carbobenzoxy-1,2-diaminoethane hydrochloride (4.61 g, 20.0 mmol) in anhyd DMF (100 mL) was stirred with DIPEA (3.50 mL, 20.1 mmol) for 30 min in an atmosphere of N2. Then 3,6-diaminopyrazine-2,5-dicarboxylic acid (1.98 g, 10.0 mmol) was added, and after 15 min, HOBt.H2O (3.37 g, 22.0 mmol) and EDC.HCl (4.22 g, 22.0 mmol) were added, and the resulting dark suspension was stirred at r.t. overnight (ca. 16 h). Most of the DMF was removed under high vacuum and the slurry was stirred with anhyd Et2O-MeOH (1:3, v/v; 200 mL) for about 30 min. The precipitate was collected by filtration and thoroughly washed with MeOH and anhyd Et2O and dried under high vacuum to give the bisamide 15 (4.37 g, 79%) as a yellow powder: 1H NMR (DMSO-d6) 8.50 (t, 2, J = 5.5), 7.39-7.31 (m, 10), 6.50 (br s, 4), 5.02 (s,4), 3.37-3.34 (br q, 4), 3.20-3.17 (br q, 4); 13C NMR (DMSO-d6) 165.80, 156.74, 146.65, 137.60, 128.78, 128.22, 128.20, 126.83, 65.74, 40.44 (overlaps with solvent), 39.22 (overlaps with solvent); RP-LC/MS (ESI) m/z 551.2 (M + H)+, 573.2 (M + Na)+ (tR = 3.86 min, 25-95%B). Anal. Calcd for C26H30N8O6: C, 56.72; H, 5.49, N, 20.35. Found: C, 56.79; H, 5.49; N, 20.30.
79%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	Step 1. Synthesis of 3,6-Diamino-N2,N5-bis[2-(benzyloxycarbonyl)aminoethyl]pyrazine-2,5-dicarboxamide (15). A suspension of N-carbobenzoxy-1,2-diaminoethane hydrochloride (4.61 g, 20.0 mmol) in anhyd DMF (100 mL) was stirred with DIPEA (3.50 mL, 20.1 mmol) for 30 min in an atmosphere of N2. Then 3,6-diaminopyrazine-2,5-dicarboxylic acid (1.98 g, 10.0 mmol) was added, and after 15 min, HOBt.H2O (3.37 g, 22.0 mmol) and EDC.HCl (4.22 g, 22.0 mmol) were added, and the resulting dark suspension was stirred at r.t. overnight (ca. 16 h). Most of the DMF was removed under high vacuum and the slurry was stirred with anhyd Et2O-MeOH (1:3, v/v; 200 mL) for about 30 min. The precipitate was collected by filtration and thoroughly washed with MeOH and anhyd Et2O and dried under high vacuum to give the bisamide 15 (4.37 g, 79%) as a yellow powder: 1H NMR (DMSO-d6) 8.50 (t, 2, J=5.5), 7.39-7.31 (m, 10), 6.50 (br s, 4), 5.02 (s,4), 3.37-3.34 (br q, 4), 3.20-3.17 (br q, 4); 13C NMR (DMSO-d6) 165.80, 156.74, 146.65, 137.60, 128.78, 128.22, 128.20, 126.83, 65.74, 40.44 (overlaps with solvent), 39.22 (overlaps with solvent); RP-LC/MS (EST) m/z 551.2 (M+H)+, 573.2 (M+Na)+ (tR=3.86 min, 25-95% B). Anal. Calcd for C26H30N8O6: C, 56.72; H, 5.49, N, 20.35. Found: C, 56.79; H, 5.49; N, 20.30.

Reference： [1]Patent: EP2143716,2010,A1 .Location in patent: Page/Page column 23-24
[2]Patent: US2010/10223,2010,A1 .Location in patent: Page/Page column 19
[3]Synthesis,2010,p. 2383 - 2392

51
[ 18807-71-1 ]
[ 79-04-9 ]
[ 223742-32-3 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 1087 - 1090

52
[ 18807-71-1 ]
[ 94-36-0 ]
[ 533923-07-8 ]

Yield	Reaction Conditions	Operation in experiment
34.2%		To a solution of benzyl-7V-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHCO3 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgSO4, filtered and concentrated to a crude, which was purified on a 1 -inch reverse-phase HPLC column to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%):MS: m/z (M+H)+ calc. 315.13, obs. 315.0.
34.2%	With sodium hydrogencarbonate; sodium hydroxide; In dichloromethane; water;	To a solution of benzyl-7V-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHCO3 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgSO4, filtered and concentrated to a crude, which was purified on a 1-inch reverse-phase HPLC column to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%): MS: m/z (M+H)+ calc. 315.13, obs. 315.0.
34.2%		To a solution of benzyl -N-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHC03 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgS04, filtered and concentrated to a crude, which was purified on a 1-inch reverse-phase HPLC column (Method 2) to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%): MS: m/z (M+H)+ calc. 315.13, obs. 315.0.

34.2%		To a solution of benzyl-N-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHC03 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgS04, filtered and concentrated to a crude, which was purified on a 1-inch reverse-phase HPLC column (Method 2) to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%): MS: m/z (M+H)+ calc. 315.13, obs. 315.0.
34.2%	With sodium hydrogencarbonate; sodium hydroxide; In dichloromethane; water;	To a solution of benzyl-iV-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHC03 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgS04, filtered and concentrated to a crude, which was purified on a 1-inch reverse-phase HPLC column (Method 2) to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%): MS: m/z (M+H)+ calc. 315.13, obs. 315.0.
34.2%		To a solution of benzyl-7V-(2-aminoethyl)carbamate chloride salt (1, 540 mg, 2.34 mmol) in sat. aq. NaHCO3 (45 mL) was added 1 M NaOH (15 mL) and the reaction was stirred vigorously. DCM (30 mL) was added, followed by benzoylperoxide (1.13 g, 4.68 mmol) and the reaction was stirred overnight. The organic layer was separated and washed with brine, dried over MgSO4, filtered and concentrated to a crude, which was purified on a 1 -inch reverse-phase HPLC column to yield benzyl-2-(benzoyloxyamino)ethyl carbamate (2, 252 mg, 0.80 mmol, 34.2%):MS: m/z (M+H)+ calc. 315.13, obs. 315.0.

Reference： [1]Patent: WO2010/42850,2010,A1 .Location in patent: Page/Page column 55
[2]Patent: WO2010/132757,2010,A2 .Location in patent: Page/Page column 97-98
[3]Patent: WO2011/44501,2011,A2 .Location in patent: Page/Page column 65
[4]Patent: WO2011/44498,2011,A1 .Location in patent: Page/Page column 68
[5]Patent: WO2011/44538,2011,A1 .Location in patent: Page/Page column 93
[6]Patent: WO2010/42851,2010,A1 .Location in patent: Page/Page column 55

53
[ 18807-71-1 ]
[ 94-36-0 ]
[ 533923-13-6 ]

Reference： [1]Patent: WO2011/44501,2011,A2
[2]Patent: WO2011/44498,2011,A1
[3]Patent: WO2010/42851,2010,A1
[4]Patent: WO2011/44538,2011,A1

54
[ 677277-70-2 ]
[ 18807-71-1 ]
[ 1312762-59-6 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 20h;	STEP A: To an ice cold mixture of N-2-trifluoroacetamido-L-butanoic acid (1.0079 g, 5.00 mmol) and N-hydroxybenzotriazole (886 mg, 6.60 mmol) in dichloromethane (30 mL) was added N-carbobenzoxy-1,2-diaminoethane hydrochloride (1.5058 g, 6.50 mmol), triethylamine (2.3 mL, 16.5 mmol) and 1-[3-dimethylaminopropyl]-3-ethyl carbodiimide hydrochloride (1.2616 g, 6.60 mmol). The resulting mixture was stirred at 0 C. for 2 hours ("h?) and then at room temperature for 18 h. The resulting mixture was diluted with DCM (50 mL), then washed with aqueous sodium chloride (2*25 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting residue was purified by flash chromatography, eluting with 70% ethyl acetate in heptane to yield (S)-benzyl 2-(2-(2,2,2-trifluoroacetamido)butanamido)ethylcarbamate as a white solid. 1HNMR (DMSO-d6) delta 9.49 (d, J=7.88 Hz, 1H), 8.19-8.17 (m, 1H), 7.39 (m+s, 6H), 5.00 (s, 2H), 4.20-3.99 (m, 1H), 3.31-3.03 (m, 4H), 1.81-1.58 (m, 2H), 0.83 (t, J=7.34, 7.34 Hz, 3H). MS MH+=376.

Reference： [1]Patent: US2011/152287,2011,A1 .Location in patent: Page/Page column 15

55
[ 1313712-87-6 ]
[ 18807-71-1 ]
[ 1313712-88-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; at 20℃;	(1) ExampleNext, 4-(2-acrylamide ethylcarbamoyl)-3-fulorophenylboronic acid (hereinafter referred to as sample 1) was synthetized as an example of the phenylboronic acid monomer of the invention according to the synthetic scheme 1 shown in FIG. 1. In practice, the sample 1 of this example was synthesized by the following procedures.At first, to 27 mmol of carboxyfluorophenylboronic acid (formula (15)) was added 50 mL of thionyl chloride, and refluxed at 90 C. (degrees of Celsius) in an oil bath, then the solution was produced. Subsequently, the redundant thionyl chloride was removed from the reaction mixture, and dissolved in 90 mL of tetrahydrofuran (THF), then added with 40 mmol of the compound represented by the above formula (17). Triethylamine (TEA) 200 mmol was added thereto in an ice-water bath, then the mixture was stirred at room temperature for one day.To the solution thus produced was added a diluted hydrochloric acid solution saturated with sodium chloride salt, and the procedures for washing and separation of solution were repeated, then THF was removed. The residue was dissolved in 400 mL of ethanol, and added with 1 g of 10% palladium carbon catalyst, and was subjected to hydrogen reduction reaction carried out at 40 C. (degrees of Celsius). Then, the palladium carbon catalyst was filtered, and the intermediate compound represented by the formula (19) (in FIG. 1) was obtained from the filtered solution. Then, the obtained intermediate compound was added with 50 mmol of acryloyl chloride and 150 mL of buffer solution of a carbonate salt (100 mM, pH 10), and stirred, and thus sample 1 of the example was obtained.
	With triethylamine; In tetrahydrofuran; at 20℃; for 24h;Cooling with ice;	At first, 27 mmol of carboxyfluorophenylboronic acid (formula (11)) was added with 50 mL of thionyl chloride, and refluxed at 90 C. (degrees Celsius) in an oil bath, and then a solution was produced. Subsequently, the redundant thionyl chloride was removed from the reaction mixture, which was then dissolved in 90 mL of tetrahydrofurane (THF), added with mmol of the compound represented by the above formula (13), further added with triethylamine (TEA) 200 mmol in an ice water bath, and then the mixture was stirred at room temperature for one day.The product solution obtained in this manner was added with a diluted hydrochloric acid solution saturated with sodium chloride salt, and subjected to the procedures for washing and separating the solution, and then THF was removed. The residue was dissolved in 400 mL of ethanol, and added with 1 g of 10% palladium carbon catalyst, and subjected to hydrogen reduction reaction under the condition of 40 C. (degrees Celsius). Then, the palladium carbon catalyst was filtered out therefrom, and the intermediate represented by the formula (15) (FIG. 1) was obtained from the filtrated solution. Subsequently, the obtained intermediate was added with 50 mmol of acryloyl chloride and 150 mL of a buffer solution of a carbonate salt (100 mM, pH 10), and stirred. In this way, sample 1 as a working example was obtained.

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 2124 - 2128
[2]Patent: US2012/283403,2012,A1 .Location in patent: Page/Page column 4-5
[3]Patent: US2013/66264,2013,A1 .Location in patent: Paragraph 0060; 0061

56
[ 501-53-1 ]
[ 18807-71-1 ]

Reference： [1]Journal of Peptide Science,2013,vol. 19,p. 9 - 15
[2]Patent: WO2015/81282,2015,A1

57
[ 13798-75-9 ]
[ 18807-71-1 ]
[ 82825-43-2 ]

Reference： [1]Journal of Peptide Science,2013,vol. 19,p. 9 - 15

58
[ 18807-71-1 ]
[ 13526-66-4 ]
[ 1429324-48-0 ]

Yield	Reaction Conditions	Operation in experiment
54%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 150℃; for 72h;Sealed tube;	A mixture of 3-bromo-6-chloro-imidazo[2,1 -f]pyridazine (3.00 g, 12.90 mmol), benzyl N-(2- aminoethyl)carbamate hydrochloride ( .90 g, 51.60 mmol) and N,N-diisopropylethylamine (13.52 ml, 77.40 mmol) in n-butanol (38.7 ml) was heated for 72 hours at 150C in a sealed tube. The reaction mixture was cooled and ethyl acetate was added. The organic layer was washed with a 1 aqueous HCI solution, water and brine. The organic layer was dried, filtered and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography over silica gel Using dichloromethane and methanol as eluents (gradient elution from 0% to 3% methanol). The product fractions were collected and the solvent was evaporated.Yield: 2.70 g of intermediate 107 (54%)LCMS method 1 : MH+ = 391 , RT = 0.650 min

Reference： [1]Patent: WO2013/46029,2013,A1 .Location in patent: Page/Page column 167

59
[ 119-68-6 ]
[ 18807-71-1 ]
benzyl 2-(2-(methylamino)benzamido)ethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃;	First, 0.164 g (1.08 mmol) of 2-(methylamino)benzoic acid wassolved at 0 C in 20 ml of DMF and treated with 0.25 g of benzyl2-aminoethylcarbamateHCl (1.08 mmol), 0.38 ml (2.16 mmol) ofDIPEA, and 0.279 g (1.08 mmol) of benzotriazolyl-1-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP).The mixture was stirred for 15 min at 0 C and at room temperatureovernight. The solvent was removed in vacuo, and the intermediatebenzyl 2-(2-(methylamino)benzamido) ethylcarbamatewas purified by preparative reversed phase HPLC. The solventwas evaporated in vacuo, and the remaining oil was treated with3 ml of 32% HBr in acetic acid for 1 h. The product was precipitatedby the addition of diethyl ether, filtered, and purified bypreparative HPLC (brownish oil; HPLC: 14.5 min; MS: calc.193.1, found 194.1 (M+H)+; NMR: 13C NMR (101 MHz, DMSOd6):d [ppm] = 170.23, 150.59, 133.13, 128.92, 114.91, 114.36,111.10, 39.17, 37.31, 29.74).

Reference： [1]Analytical Biochemistry,2013,vol. 442,p. 223 - 230

60
[ 18807-71-1 ]
[ 13076-17-0 ]
C₁₀₂H₁₃₆N₂O₆₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tin octanoate; In toluene; at 120℃; for 12h;Inert atmosphere;	In this experimental example, aminated poly-L-lactic acid (a-PLA) was synthesized using L-lactide (compound 6) and N-carbobenzoxy-1,2-diaminoethane hydrochloride (compound 7) (Scheme 7). [0152] To N-carbobenzoxy-1,2-diaminoethane hydrochloride (compound 7) (310 mg, 1.60 mmol) served as a polymerization initiator, a dispersion liquid obtained by dispersing tin octanoate (6.91 mg) in toluene (1.0 mL) was added. The toluene was distilled away under reduced pressure, and then L-lactide (compound 6) (3.45 g, 24 mmol) was added to perform polymerization reaction at 120C under an Ar atmosphere. After 12 hours, the reaction container was air-cooled to room temperature to obtain a yellowish-white solid. The obtained yellowish-white solid was dissolved in a small amount of chloroform (about 10 mL). The resulting chloroform was dropped into cold methanol (100 mL) to obtain a white precipitate. The obtained white precipitate was collected by centrifugation and dried under reduced pressure. [0153] To a dichloromethane (1 mL) solution of the obtained white precipitate (500 mg), 25 v/v% hydrogen bromide/acetic acid (2.0 mL) was added, and the mixture was stirred for 2 hours under dry air atmosphere in a shading environment. After the completion of reaction, the resultant reaction solution was dropped into cold methanol (100 mL) so that a precipitate was deposited. The precipitate was collected by centrifugation. The obtained white precipitate was dissolved in chloroform, washed with a saturated aqueous NaHCO3 solution, and then dehydrated with anhydrous MgSO4. Then, the MgSO4 was removed by Celite filtration, and the white precipitate was vacuum-dried to obtain white amorphous powder of a-PLA (440 mg).

Reference： [1]Patent: EP2682131,2014,A1 .Location in patent: Paragraph 0151-0153

61
[ 122-78-1 ]
[ 18807-71-1 ]
[ 1556858-94-6 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 2445 - 2447

62
[ 104-53-0 ]
[ 18807-71-1 ]
[ 1556858-99-1 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 2445 - 2447

63
[ 1612184-09-4 ]
[ 18807-71-1 ]
[ 1612182-24-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 85℃;Sealed tube;	Example 273benzyl N-(2-[2-am ino-6-(2, 3-di methylphenyl)pyrimidin-4-yl]am ino}ethyl)carbamate.A mixture of 4-chloro-6-(2,3-dimethylphenyl)pyrimidin-2-amine (28 mg, 0.12 mmol), <strong>[18807-71-1]benzyl N-(2-aminoethyl)carbamate hydrochloride</strong> (39 mg, 0.17 mmol) andHunig?s base (42 pL, 0.24 mmol) in n-butanol (2 mL) was heated in a sealed tube at 85C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H] 392.
	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 85℃;Sealed tube;	Example 273 benzyl N-(2-[2-amino-6-(2,3-dimethylphenyl)pyrimidin-4-yl]amino}ethyl)- carbamate. A mixture of 4-chloro-6-(2,3-dimethylphenyl)pyrimidin-2-amine (28 mg, 0.12 mmol), <strong>[18807-71-1]benzyl N-(2-aminoethyl)carbamate hydrochloride</strong> (39 mg, 0.17 mmol) and Hunig's base (42 muIota_, 0.24 mmol) in n-butanol (2 mL) was heated in a sealed tube at 85C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 392.

Reference： [1]Patent: WO2014/84778,2014,A1 .Location in patent: Page/Page column 159
[2]Patent: WO2015/187089,2015,A1 .Location in patent: Page/Page column 158

64
3-(tert-butoxycarbonylamino)-2-hydroxy-4-(methoxymethoxy)benzoic acid [ No CAS ]
[ 18807-71-1 ]
N-(2-(benzyloxycarbonylamino)ethyl)-3-(tert-butoxycarbonylamino)-2-hydroxy-4-(methoxymethoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With dmap; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 24h;Inert atmosphere;	Compound 6 (223.0mg, 0.712mmol) was dissolved in DMF (12mL) and diisopropylethylamine (0.184mL, 1.424mmol), EDCI (136.5mg, 0.712mmol), DMAP (cat.) were added. To this mixture, N-Cbz-ethylenediamine HCl (213.5mg, 0.926mmol) was added and reacted for one day under argon atmosphere. The reaction mixture diluted with water and extracted by ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated. The residue was purified by silica-gel column chromatography (chloroform/methanol=20/1) to give 7 (170.0mg, 49%) as the slightly yellow oil. (0021) HR-FD-MS (positive): [M]+ Found m/z 489.21033, C24H31O8N3 requires m/z 489.21111; 1H NMR (270MHz, CDCl3, rt): 12.00 (1H, s, OH), 8.11 (1H, br s, NH), 7.62 (1H, d, J=8.9 Hz), 7.36-7.28 (5H, m), 6.70 (1H, d, J=8.9Hz), 6.50 (1H, br s, NH), 5.45 (1H, br s, NH), 5.24 (2H, s), 5.11 (2H, s), 3.55 (2H, br t, J=6.0Hz), 3.51 (3H, s), 3.44 (2H, br t, J=6.0Hz), 1.53 (9H, s); 13C NMR (67.8MHz, CDCl3, rt): 169.3, 157.3, 155.5, 155.0, 154.9, 136.5, 128.3, 127.9 (2C), 126.0, 115.0, 111.0, 105.3, 94.5, 80.9, 66.4, 56.2, 40.7, 40.1, 28.0ppm; IR (neat): 3332, 2978, 1708, 1499, 1366, 1272, 1160, 1050cm-1

Reference： [1]Tetrahedron,2015,vol. 71,p. 1419 - 1424

65
[ 1325688-35-4 ]
[ 18807-71-1 ]
N'-[2-(benzyloxycarbonylamino)ethyl]-N,N''-bis(tert-butoxycarbonyl)-N-pent-4-ynylguanidine [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2014,vol. 2014,p. 7595 - 7604

66
[ 18807-71-1 ]
[ 72080-83-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydrogencarbonate; In water;pH 9.0;	Preparation of benzyl (2-aminoethyl)carbamate To a solution of 2-(((benzyloxy)carbonyl)amino)ethanaminium chloride (1.0 g, 4.3 mmol) in water (5 mL) was added anhydrous Na2CO3 until litmus testing indicated pH 9. Solvent removal afforded a residue that was triturated with CH2Cl2 and filtered. The filtrate was concentrated to afford the desired free amine (0.93 g, 99% yield).

Reference： [1]Patent: WO2015/81282,2015,A1 .Location in patent: Paragraph 00714; 00715

67
[ 18807-71-1 ]
(2S,3R)-2,3-diacetoxy-4-((2-(((benzyloxy)carbonyl)amino)ethyl)amino)-4-oxobutanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/81282,2015,A1

68
[ 18807-71-1 ]
(2S,3R)-4-((2-(((benzyloxy)carbonyl)amino)ethyl)amino)-2,3-dihydroxy-4-oxobutanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/81282,2015,A1

69
[ 18807-71-1 ]
(9R,10S)-benzyl 9,10-dihydroxy-3,8,11-trioxo-1-phenyl-2-oxa-4,7,12-triazapentadecan-15-oate [ No CAS ]

Reference： [1]Patent: WO2015/81282,2015,A1

70
[ 18807-71-1 ]
(9R,10S)-benzyl 9,10-bis((tert-butyldimethylsilyl)oxy)-3,8,11-trioxo-1-phenyl-2-oxa-4,7,12-triazapentadecan-15-oate [ No CAS ]

Reference： [1]Patent: WO2015/81282,2015,A1

71
C₉H₁₀BrNO₃ [ No CAS ]
[ 18807-71-1 ]
C₁₉H₂₂BrN₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.73 g	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2.5h;	(6) To a mixture of compound (I5) (1.76 g), Z-ethylenediamine hydrochloride (1.87 g), DMF (40 mL), and DIEA (2.8 mL), HBTU (2.64 g) was added, and the resulting mixture was stirred at room temperature for 2.5 hours. Ethyl acetate (250 mL) and water (100 mL) were added thereto. The organic layer was separated, then washed twice with water (300 mL) and once with a saturated aqueous solution of sodium chloride (300 mL), and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was recrystallized from ethyl acetate to obtain compound (I6) (1.73 g). TLC Rf: 0.58 (ethyl acetate) HPLC (SunFire) rt (min): 13.60
1.73 g	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2.5h;	(6)(I5) (1.76 g), Z-ethylenediamine hydrochloride (1.87 g),HBTU (2.64 g) was added to a mixture of DMF (40 mL) and DIEA (2.8 mL)And the mixture was stirred at room temperature for 2.5 hours. Ethyl acetate (250 mL) and water (100 mL) were added,The organic layer was separated,Washed twice with water (300 mL) and once with saturated aqueous sodium chloride solution (300 mL)And dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure,The obtained residue was recrystallized from ethyl acetate to obtain (I6) (1.73 g).

Reference： [1]Patent: US2016/199520,2016,A1 .Location in patent: Paragraph 0275; 0281
[2]Patent: JP2016/183151,2016,A .Location in patent: Paragraph 0310; 0311; 0317

72
[ 18807-71-1 ]
C₃₉H₅₂N₆O₉S [ No CAS ]

Reference： [1]Patent: US2016/199520,2016,A1

73
C₂₁H₃₂N₂O₉S [ No CAS ]
[ 18807-71-1 ]
C₃₁H₄₄N₄O₁₀S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.4 g	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	(2) To a mixture of compound (K1) (3.13 g), DMF (13 mL), Z-ethylenediamine hydrochloride (1.48 g), and DIEA (2.3 mL), HBTU (2.55 g) was added, and the resulting mixture was stirred at room temperature for 1 hour. Water (16 mL) was added dropwise thereto, and the mixture was stirred for 2 hours. Then, water (16 mL) was added thereto, and the solid was collected by filtration to obtain compound (K2) (3.40 g). HPLC (CAPCELL PAK MG) rt (min): 14.98 LC/MS (ACQUITY) rt (min): 1.46 MS (ESI, m/z): 665.5 [M+H]+, 663.6 [M-H]-
3.40 g	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	(2)(K1) (3.13 g), DMF (13 mL),To a mixture of Z-ethylenediamine hydrochloride (1.48 g) and DIEA (2.3 mL)HBTU (2.55 g) was added, and the mixture was stirred at room temperature for 1 hour. Water (16 mL) was added dropwise,After stirring for 2 hours, water (16 mL) was added and the solid was collected by filtration to give (K 2) (3.40 g).

Reference： [1]Patent: US2016/199520,2016,A1 .Location in patent: Paragraph 0308; 0310
[2]Patent: JP2016/183151,2016,A .Location in patent: Paragraph 0344; 0345; 0347

74
C₃₄H₄₀FN₃O₆ [ No CAS ]
[ 18807-71-1 ]
C₄₄H₅₂FN₅O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
135 mg	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	(7) To a mixture of compound (Q6) (181 mg), z-ethylenediamine hydrochloride (89.6 mg), DMF (2 mL), and DIEA (200 muL), HBTU (147 mg) was added, and the resulting mixture was stirred at room temperature for 20 minutes. Ethyl acetate (60 mL) and water (10 mL) were added to the reaction mixture. The organic layer was separated, then washed twice with water (30 mL), then washed with a saturated aqueous solution of sodium chloride (30 mL), and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/methanol=10/0 to 9/1) to obtain compound (Q7) (135 mg). LC/MS (ACQUITY) rt (min): 1.32 MS (ESI, m/z): 782.4 [M+H]+
135 mg	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	(7)(Q6) (181 mg), Z-ethylenediamine hydrochloride (89.6 mg),HBTU (147 mg) was added to a mixture of DMF (2 mL) and DIEA (200 muL)And the mixture was stirred at room temperature for 20 minutes.Ethyl acetate (60 mL) and water (10 mL) were added to the reaction mixture.The organic layer was separated, washed twice with water (30 mL)Washed with saturated aqueous sodium chloride solution (30 mL)And dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure,The obtained residue was purified by silica gel column chromatography (ethyl acetate / methanol = 10/0 to 9/1) to obtain (Q7) (135 mg).

Reference： [1]Patent: US2016/199520,2016,A1 .Location in patent: Paragraph 0350; 0357
[2]Patent: JP2016/183151,2016,A .Location in patent: Paragraph 0392; 0393; 0400

75
C₁₉H₂₈N₂O₉S [ No CAS ]
[ 18807-71-1 ]
C₂₉H₄₀N₄O₁₀S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.11 g	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 1h;	(4) To a mixture of compound (Y3) (938 mg), Z-ethylenediamine hydrochloride (517 mg), DMF (14 mL), and DIEA (1.4 mL), HATU (877 mg) was added, and the resulting mixture was stirred at room temperature for 1 hour. Dichloromethane and water were added to the reaction mixture. The organic layer was separated, then dried over anhydrous sodium sulfate, and then purified by silica gel column chromatography (ethyl acetate) to obtain compound (Y4) (1.11 g). TLC Rf: 0.25 (dichloromethane/methanol=95/5)
1.11 g	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 1h;	(4)(Y 3) (938 mg), Z-ethylenediamine hydrochloride (517 mg),To a mixture of DMF (14 mL) and DIEA (1.4 mL)HATU (877 mg) was added, and the mixture was stirred at room temperature for 1 hour.Dichloromethane and water were added to the reaction mixture.The organic layer was separated, dried with anhydrous sodium sulfate,Purification by silica gel column chromatography (ethyl acetate)(Y4) (1.11 g).

Reference： [1]Patent: US2016/199520,2016,A1 .Location in patent: Paragraph 0405; 0409
[2]Patent: JP2016/183151,2016,A .Location in patent: Paragraph 0455; 0456; 0461

76
[ 18807-71-1 ]
[ 13076-17-0 ]
a-PLLA [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		As shown by the following chemical formula, aminated poly-L-lactic acid (a-PLEA) (average polymerization degree: 30) was first synthesized using L-lactide (compound 1) and N-carbobenzoxy-l ,2-diaminoethane hydrochloride (compound 2).
440 mg		To N-carbobenzoxy-1,2-diaminoethane hydrochloride (compound 2) (310 mg, 1.60 mmol) served as a polymerization initiator, a dispersion liquid obtained by dispersing tin octanoate (6.91 mg) in toluene (1.0 mL) was added. The toluene was distilled away under reduced pressure, and then L-lactide (compound 1) (3.45 g, 24 mmol) was added to perform polymerization reaction at 120 C. under Ar gas atmosphere. After 12 hours, the reaction container was air-cooled to room temperature to obtain a yellowish-white solid. The yellowish-white solid was dissolved in a small amount of chloroform (about 10 mL). The chloroform was dropped into cold methanol (100 mL) to obtain a white precipitate. The white precipitate was collected by centrifugation and dried under reduced pressure. (0388) To a dichloromethane (1 mL) solution of the obtained white precipitate (500 mg), 25 v/v % hydrogen bromide/acetic acid (2.0 mL), and the mixture was stirred for 2 hours under dry air atmosphere in a shading environment. After the completion of reaction, a resultant reaction solution was dropped into cold methanol (100 mL) so that a precipitate was deposited. The precipitate was collected by centrifugation. The obtained white precipitate was dissolved in chloroform, washed with a saturated aqueous NaHCO3 solution, and then dehydrated with anhydrous MgSO4. Then, the MgSO4 was removed by Celite filtration, and the white precipitate was vacuum-dried to obtain white amorphous powder of a-PLA (440 mg).

Reference： [1]Patent: US2016/120985,2016,A1 .Location in patent: Paragraph 0192
[2]Patent: US2019/105412,2019,A1 .Location in patent: Paragraph 0386-0388

77
[ 18807-71-1 ]
[ 13076-17-0 ]
C₁₀₀H₁₃₄N₂O₆₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 120℃;	As shown by the following chemical formula, aminated poly-L-lactic acid (a-PLEA) (average polymerization degree: 30) was first synthesized using L-lactide (compound 1) and N-carbobenzoxy-l ,2-diaminoethane hydrochloride (compound 2).

Reference： [1]Patent: US2016/120985,2016,A1 .Location in patent: Paragraph 0199

78
C₄₅H₈₀N₄O₁₄ [ No CAS ]
[ 18807-71-1 ]
C₅₅H₉₂N₆O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃;	2-(7-Aza-lH-benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HATU, 2.46 g, 6.48 mmol) and triethylamine (1.89 mL, 13.6 mmol) were subsequently added to a solution of the oil from above (2, 5.31 g, 5.89 mmol) in dry dichloromethane (23 mL). Triethylamine (1.36 mL, 9.72 mmol) was added to a suspension of (2-amino- ethyl)-carbamic acid benzyl ester hydrochloride (3, 1.49 g, 6.48 mmol) in drydichloromethane (35 mL) and the resulting mixture was added to the above solution. The mixture was stirred overnight at room temperature, and then it was evaporated in dryness. The residue was redissolved in ethyl acetate (70 mL); washed with 1 M aqueous hydrochloric acid (1 x 70 mL), 5% aqueous solution of sodium carbonate (2 x 70 mL), 1 M aqueous hydrochloric acid (4 x 70 mL) and brine (70 mL); dried over anhydrous sodium sulfate and evaporated. The residue was purified by flash columnchromatography (Silicagel 60, 0.040-0-063 mm; eluent: dichloromethane/methanol 95 : 5 to 92: 8) to afford a thick yellow oil.Yield : 2.81 g (44%).RF (Si02, dichloromethane/methanol 9 : 1) : 0.25.1H NMR spectrum (300 MHz, CDCI3, dH) : 7.41-7.29 (m, 6 H); 7.22-7.13 (m, 1 H); 6.93- 6.81 (m, 1 H); 6.62-6.58 (m, 1 H); 5.90-5.81 (m, 1 H); 5.68-5.55 (m, 1 H); 5.09 (s, 2 H); 4.42-4.33 (m, 1 H); 4.01-3.95 (m, 4 H); 3.75-3.30 (m, 20 H); 3.14-3.06 (m, 2 H); 2.31-2.01 (m, 11 H); 1.97-1.76 (m, 1 H); 1.65-1.52 (m, 4 H); 1.46 (s, 9 H); 1.44 (s, 9 H); 1.27 (bs, 12 H); 1.04-0.87 (m, 2 H).

Reference： [1]Patent: WO2016/102562,2016,A1 .Location in patent: Page/Page column 63

79
C₄₉H₈₈N₄O₁₄ [ No CAS ]
[ 18807-71-1 ]
C₅₉H₁₀₀N₆O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃;	2-(7-Aza-lH-benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HATU, 3.55 g, 9.34 mmol) and triethylamine (2.72 mL, 19.5 mmol) were subsequently added to a solution of intermediate 2 (8.13 g, 8.49 mmol) in dry dichloromethane (34 mL). Triethylamine (1.78 mL, 12.7 mmol) was added to a suspension of (2-amino-ethyl)- carbamic acid benzyl ester hydrochloride (2.15 g, 9.34 mmol) in dry dichloromethane (51 mL) and the resulting mixture was added to the above solution. The mixture was stirred overnight at room temperature, and then it was evaporated in dryness. The residue was redissolved in ethyl acetate (150 mL); washed with 1 M aqueous hydrochloric acid (1 x 100 mL), 5% aqueous solution of sodium carbonate (2 x 100 mL), 1 M aqueous hydrochloric acid (4 x 100 mL) and brine; dried over anhydrous sodium sulfate and evaporated. The residue was purified by flash column chromatography (Silicagel 60, 0.040-0-063 mm; eluent: dichloromethane/methanol 95: 5 to 92 : 8) to afford compound 4 as thick yellow oil.Yield : 5.59 g (58%).RF (Si02, dichloromethane/methanol 9 : 1) : 0.20.1H NMR spectrum (300 MHz, CDCI3, dH) : 7.41-7.31 (m, 6 H); 7.21-7.12 (m, 1 H); 6.92- 6.83 (m, 1 H); 6.58-6.52 (m, 1 H); 5.89-5.79 (m, 1 H); 5.62-5.51 (m, 1 H); 5.10 (s, 2 H); 4.43-4.32 (m, 1 H); 4.05-3.92 (m, 4 H); 3.75-3.30 (m, 20 H); 3.15-3.07 (m, 2 H); 2.33-2.03 (m, 11 H); 1.97-1.68 (m, 1 H); 1.67-1.51 (m, 4 H); 1.45 (s, 9 H); 1.44 (s, 9 H); 1.26 (bs, 20 H); 1.05-0.87 (m, 2 H).LC-MS purity: 100% (ELSD).LC-MS Rt (Kinetex, 4.6 mm x 50 mm, acetonitrile/water 70 :30 to 100 : 0 + 0.1% TFA) : 1.41 min.LC-MS m/z: 1136.0 (M + H) + .

Reference： [1]Patent: WO2016/102562,2016,A1 .Location in patent: Page/Page column 67; 68

80
(S)-22-(tert-butoxycarbonyl)-41,41-dimethyl-10,19,24,39-tetraoxo-3,6,12,15,40-pentaoxa-9,18,23-triazadotetracontanoic acid [ No CAS ]
[ 18807-71-1 ]
15-[(S)-3-(2-{2-[(2-{2-[(2-benzyloxycarbonylamino-ethylcarbamoyl)methoxy]ethoxy}ethylcarbamoyl)methoxy]ethoxy}ethylcarbamoyl)-1-tert-butoxycarbonyl-propylcarbamoyl]pentadecanoic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃;	2-(7-Aza-lH-benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HATU, 11.4 g, 30.1 mmol) and triethylamine (8.77 mL, 62.9 mmol) were subsequently added to a solution of (S)-22-(tert-butoxycarbonyl)-41,41-dimethyl-10, 19, 24,39- tetraoxo-3,6,12,15,40-pentaoxa-9,18,23-triazadotetracontanoic acid (22.4 g, 27.4 mmol) in dry dichloromethane (110 mL). Triethylamine (5.72 mL, 41.0 mmol) was added to a suspension of (2-amino-ethyl)-carbamic acid benzyl ester hydrochloride (6.94 g, 30.1 mmol) in dry dichloromethane (165 mL) and the resulting mixture was added to the above solution. The mixture was stirred at room temperature overnight, and then it was evaporated to dryness. The residue was re-dissolved in ethyl acetate (500 mL); washed with 1 M aqueous hydrochloric acid (2 x 200 mL), 5% aqueous solution of sodium carbonate (2 x 200 mL, very slow separation of phases), 1 M aqueous hydrochloric acid (8 x 200 mL) and brine; dried over anhydrous sodium sulfate and evaporated to dryness in vacuo. The residue was purified by flash column chromatography (Silicagel 60, 0.040- 0.060 mm; eluent: dichloromethane/methanol 95 : 5) to afford 15-[(S)-3-(2-{2-[(2-{2- [(2-benzyloxycarbonylamino-ethylcarbamoyl)-methoxy]-ethoxy}-ethylcarbamoyl)- methoxy]-ethoxy}-ethylcarbamoyl)-l-tert-butoxycarbonyl-propylcarbamoyl]- pentadecanoic acid tert-butyl ester as pale yellow thick oil.Yield : 23.84 g (88%)RF (Si02, dichloromethane/methanol 9 : 1) : 0.35 1H NMR spectrum (300 MHz, CDCI3, dH) : 7.39-7.26 (m, 6 H); 7.19 (t, J = 6.3 Hz, 1 H); 6.91 (t, J = 5.7 Hz, 1 H); 6.52 (d, J = 7.5 Hz, 1 H); 5.83 (t, J = 5.5 Hz, 1 H); 5.09 (s, 2 H); 4.41 (ddd, J = 12.3, 4.6 and 4.3 Hz, 1 H); 3.99 (s, 2 H); 3.97 (s, 2 H); 3.71-3.30 (m, 20 H); 2.33-2.08 (m, 7 H); 1.97-1.83 (m, 1 H); 1.67-1.51 (m, 4 H); 1.45 (s, 9 H); 1.44 (s, 9 H); 1.35-1.20 (m, 20 H).LCMS method 4Purity: 100%Rt (Kinetex 4.6 mm x 50 mm, acetonitrile/water 50 : 50 to 100 : 0 + 0.1% FA) : 4.18 min Found m/z, z= l : 994.9 (M + H) +
88%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃;	2-(7 -Aza-1 H-benzotriazole-1-yl)-1, 1,3,3-tetramethyluronium hexafluorophosphate (HATU, 11.4 g, 30.1 mmol) and triethylamine (8.77 ml, 62.9 mmol) were subsequently added to a solution of (S)-22-(tert-butoxycarbonyl)-41,41-dimethyl-10,19,24,3920 tetraoxo-3,6,12,15,40-pentaoxa-9,18,23-triazadotetracontanoic acid (22.4 g, 27.4 mmol) in dry dichloromethane (110 ml). Triethylamine (5. 72 ml, 41.0 mmol) was added to a suspension of (2-amino-ethyl)-carbamic acid benzyl ester hydrochloride (6.94 g, 30.1 mmol) in dry dichloromethane (165 ml) and the resulting mixture was added to the above solution. The mixture was stirred at room temperature overnight, and then it was 25 evaporated to dryness. The residue was re-dissolved in ethyl acetate (500 ml); washed with 1 M aqueous hydrochloric acid (2 x 200 ml), 5% aqueous solution of sodium carbonate (2 x 200 ml, very slow separation of phases), 1 M aqueous hydrochloric acid (8 x 200 ml) and brine; dried over anhydrous sodium sulfate and evaporated to dryness in vacuo. The residue was purified by flash column chromatography (Silicagel 60, 0.04030 0.060 mm; eluent: dichloromethane/methanol 95: 5) to afford 15-[(S)-3-(2-{2-[(2-{2[(2-benzyloxycarbonylamino-ethylcarbamoyl)-methoxy]-ethoxy}-ethylcarbamoyl)methoxy] -ethoxy} -ethylca rbamoyl) -1-tert-butoxycarbonyl-propylca rba moyl]pentadecanoic acid tert-butyl ester as pale yellow thick oil. Yield: 23.84 g (88%)

Reference： [1]Patent: WO2016/102562,2016,A1 .Location in patent: Page/Page column 54; 55
[2]Patent: WO2017/220706,2017,A1 .Location in patent: Page/Page column 52; 55; 56

81
[ 72080-83-2 ]
[ 18807-71-1 ]

Yield	Reaction Conditions	Operation in experiment
62.62 g	With hydrogenchloride; In diethyl ether;	A solution of N-(benzyloxycarbonyloxy)succinimide (ZOSu, 100 g, 401 mmol) in dichloromethane (500 mL) was added dropwise over 2 hours to a solution ofethylenediamine (1, 189 mL, 2.81 mol) in dichloromethane (750 mL). After 30 minutes the suspension was filtered and solids washed with dichloromethane. The filtrate was evaporated to dryness and the residue diluted with toluene (1.00 L) and water (0.50 L). The resulting mixture was filtered and the filtrate was separated to afford two phases. The aqueous phase contained the product; therefore it was extracted withdichloromethane (2 x 250 mL). All organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was diluted with toluene (750 mL) and extracted with 2 M aqueous hydrochloric acid (500 mL) and 1 M aqueous hydrochloric acid (100 mL). Acidic aqueous phases were combined and basified with a solution of sodium hydroxide (60.0 g, 1.50 mol) in water (90 mL). The resulting mixture was extracted with dichloromethane (4 x 200 mL), dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and diluted with hexanes (200 mL). 4 M Solution of hydrogen chloride in ether (100 mL, 400 mmol) was added to the solution, the resulting suspension was concentrated in vacuo and diluted with hexanes (1.00 L). Theprecipitated solid was filtered, washed with hexanes and dried in vacuo to give (2-amino- ethyl)-carbamic acid benzyl ester hydrochloride as white powder.Yield : 62.62 g (68%).RF (Si02, dichloromethane/methanol 4: 1) : 0.25 (free base).1H NMR spectrum (300 MHz, AcOD-d4, 80 C, dH) : 7.42-7.26 (m, 5 H); 5.16 (s, 2 H); 3.60 (t, J = 5.7 Hz, 2 H); 3.32 (t, J = 5.7 Hz, 2 H).

Reference： [1]Patent: WO2016/102562,2016,A1 .Location in patent: Page/Page column 52

82
3-(5-((((R)-2-((R)-1-(N-(benzyloxy)formamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)-5-ethoxybenzoic acid [ No CAS ]
[ 18807-71-1 ]
(R)-benzyl (2-(3-(5-(((2-((N-(benzyloxy)formamido)methyl)heptanamido)methyl)carbamoyl)furan-2-yl)-5-methoxybenzamido)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 1.25h;	To a solution of 3-(5-((((R)-2-((R)-1-(N-(benzyloxy)formamido)propyl) heptanamido)methyl)carbamoyl)furan-2-yl)-5-ethoxybenzoic acid (185 mg, 0.30 mmol), glycine methyl ester hydrochloride (38.2 mg, 0.30 mmol) and HATU (133 mg, 0.35 mmol) in dichloromethane (1.55 ml) was added DIPEA (0.17 ml, 0.94 mmol) and the reaction stirred at room temperature for 1 hr 15 minutes. The reaction was then concentrated and water (10 ml) and DCM (10 ml) were added to the residue. The organic was collected via hydrophobic frit and concentrated. The residue was purified via flash chromatography (ISCO Combiflash Rf, 25 g column, 20-100% ethyl acetate/hexanes) to give the title compound (83.6 mg, 41% yield). MS (m/z) 679.3 (M+H+). INTERMEDIATES 159-16 1 were prepared from benzyl (2-aminoethyl)carbamate, hydrochloride and the indicated acid by methods analogous to those described for Intermediate 154. Intermediates 159 and 161 used DMF as solvent instead of DCM.

Reference： [1]Patent: US2016/340328,2016,A1 .Location in patent: Paragraph 0602; 0603; 0605

83
[ 23500-04-1 ]
[ 18807-71-1 ]
N<SUP>2</SUP>-acetyl-N-(2-aminoethyl)-N<SUP>6</SUP>-(tert-butoxycarbonyl)-L-lysinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The title compound was synthesized with classical methods of peptide chemistry starting with coupling of N2-acetyl-N6-(tert-butoxycarbonyl)-L-lysine with benzyl (2-aminoethyl)carbamate hydrochloride (1:1) with HATU and N,N-diisopropylethylamine and subsequent removal of the Z-protecting group by hydrogenation in DCM/methanol 1:1 over 10% palladiumlactivated charcoal under normal pressure. LC-MS (Method 1): R1 = 0.43 mm; MS (ESIpos): mz = 331 (M+H)+.
		The titel compound was obtained by coupling of N2-acetyl-N6-(tert-butoxycarbonyl)-L-lysinebenzyl (2-aminoethyl)carbamate hydrochloride (1:1) in DMF in the presence of HATIJ and N,Ndiisopropylethylamine and subsequent deprotection of the benzyloxycarbonyl group by hydrognenation in dichloromethane/methanol 1:1 in presence of 10% Pd/C at room temperature for 1 h.LC-MS (Methode 1): R1 = 0.43 mm; MS (ESIpos): m/z = 331 (M+H)t
		N2-Acetyl-N-(2-aminoethyl)-N6-(tert-butoxycarbonyl)-L-lysinamide The title compound was prepared by conventional methods of peptide chemistry by HATU coupling of commercially available N2-acetyl-N6-(tert-butoxycarbonyl)-L-lysine with benzyl (2-aminoethyl)carbamate hydrochloride (1:1) in the presence of N,N-diisopropylethylamine and subsequent detachment of the Z protecting group by hydrogenation in DCM/methanol 1:1 over 10% palladium on activated carbon. LC-MS (Method 1): Rt=0.43 min; MS (ESIpos): m/z=331 (M+H)+.

Reference： [1]Patent: WO2016/207090,2016,A2 .Location in patent: Page/Page column 285
[2]Patent: WO2016/207090,2016,A2 .Location in patent: Page/Page column 288
[3]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2305-2307

84
[ 18807-71-1 ]
[ 36239-09-5 ]
ethyl 2-[(2-[(benzyloxy)carbonyl]amino}ethyl)carbamoyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide; for 0.5h;	Ethyl 3-chloro-3-oxopropanoate (480 mg, 3.17 mmol) was added dropwise over 5 min to an ice-cold mixture of <strong>[18807-71-1]benzyl N-(2-aminoethyl)carbamate hydrochloride</strong> (665 mg, 2.88 mmol) and DIPEA (1 ml, 6 mmol) in DCM (10 ml) and DMF (1 ml). The reaction mixture was stirred for 30 min, then quenched with saturated NaHC03 (aq) and extracted with DCM (3 x 50 ml). The combined organic extracts were dried (Na2S04), filtered and evaporated in vacuo. Purification by flash column chromatography (eluting with a gradient of 5-100% EtOAc / heptane followed by 5-20% MeOH / EtOAc) afforded the title compound (451 mg, 42%) as a yellow-orange solid. 1 H-NMR (CDCI3, 500 MHz): d[ppm]= 7.41 - 7.30 (m, 6H), 5.23 (s, 1 H), 5.12 (s, 2H), 4.22 (q, J = 7.1 Hz, 2H), 3.45 (q, J = 5.5 Hz, 2H), 3.38 (q, J = 5.5 Hz, 2H), 3.30 (s, 2H), 1.30 (t, J = 7.1 Hz, 3H) HPLCMS (Method A): [m/z]: 309.05 [M+H]+

Reference： [1]Patent: WO2017/68089,2017,A2 .Location in patent: Page/Page column 345

85
[ 18807-71-1 ]
C₂₆H₂₇N₃O₄ [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,2017,vol. 90,p. 568 - 573

86
[ 81-86-7 ]
[ 18807-71-1 ]
C₂₂H₁₇BrN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2%	With acetic acid; In N,N-dimethyl-formamide; at 100℃; for 26h;	HCl·NHCH2CH2NHZ (841 mg, 3.95 mmol,), 4-bromo-1,8-naphthalic anhydride (1.03 g, 3.74 mmol, 2.0 eq) and acetic acid (0.370 mL) were mixed in N,N-dimethylformamide (8.0 mL) and stirred for 26 h at 100 C in dry atmosphere. After evaporation of the solvent, residue was dissolved in chloroform and washed with 4wt% KHSO4 aq three times, and saturated NaCl aq. The organic layer was dried over by Na2SO4. After evaporation of the solvent, the residue was purified by silica gel column chromatography (chloroform-methanol, 50:1, as eluent). Yield: 98 mg, 0.224 mmol (2%) 1H NMR (400 MHz, CDCl3): delta(ppm) 8.46~7.25 (m, 11H, Ph, Nap-H, amide), 5.20 (s, 1H, amide), 4.98 (s, 2H, CH2Ph), 4.38 (m, 2H, NHCH2CH2Nap), 3.61 (m, 2H, NHCH2CH2Nap)

Reference： [1]Bulletin of the Chemical Society of Japan,2017,vol. 90,p. 568 - 573

87
[ 18807-71-1 ]
[ 152120-54-2 ]
C₂₁H₃₂N₄O₆ [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 11177 - 11180

88
[ 120153-08-4 ]
[ 18807-71-1 ]
[ 1313712-89-8 ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 7878 - 7882
Angew. Chem.,2018,vol. 130,p. 8004 - 8008,5

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H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 18807-71-1 ] {[proInfo.proName]}

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[ 18807-71-1 ] Synthesis Path-Upstream 1~9

[ 18807-71-1 ] Synthesis Path-Downstream 1~88

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Aryls

Amides

Amines

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[ 18807-71-1 ]