[ CAS No. 78269-85-9 ] {[proInfo.proName]}

Name: 78269-85-9|2,5-Dioxopyrrolidin-1-yl (2-(trimethylsilyl)ethyl) carbonate|97%
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Quality Control of [ 78269-85-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 78269-85-9 ]

CAS No. :	78269-85-9	MDL No. :	MFCD02683467
Formula :	C₁₀H₁₇NO₅Si	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FLDNDAMSCINJDX-UHFFFAOYSA-N
M.W :	259.33	Pubchem ID :	5018386
Synonyms :

Calculated chemistry of [ 78269-85-9 ]

Physicochemical Properties

Num. heavy atoms :	17
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.7
Num. rotatable bonds :	6
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	65.91
TPSA :	72.91 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.58 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.43
Log Po/w (XLOGP3) :	1.83
Log Po/w (WLOGP) :	1.16
Log Po/w (MLOGP) :	0.64
Log Po/w (SILICOS-IT) :	-0.57
Consensus Log Po/w :	1.1

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.2
Solubility :	1.62 mg/ml ; 0.00624 mol/l
Class :	Soluble
Log S (Ali) :	-2.98
Solubility :	0.271 mg/ml ; 0.00104 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.61
Solubility :	6.34 mg/ml ; 0.0244 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.02

Safety of [ 78269-85-9 ]

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 [ 78269-85-9 ]

* 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 [ 78269-85-9 ]
Downstream synthetic route of [ 78269-85-9 ]

[ 78269-85-9 ] Synthesis Path-Upstream 1~4

1
[ 6066-82-6 ]
[ 20160-60-5 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In acetonitrile at 0 - 20℃; for 16 h; Inert atmosphere	TeocCl reagent S13 was dissolved in CH3CN (105 mL) at 0 °C. Then, NHS (5.22 g,45.4 mmol, 1.30 equiv) and Et3N (4.59 g, 45.4 mmol, 1.30 equiv; in 11.0 mL CH3CN) wereadded. The reaction mixture was stirred at 0 °C rt. After 16 h, the reaction mixture waspoured into H2O. The aqueous layer was extracted with Et2O (6×). The combined organiclayers were washed with H2O (2×), HCl (1.0 M), followed by H2O and subsequent dried overMgSO4, filtered a well as concentrated under reduced pressure. The desired TeocOSu S14(7.72 g, 29.8 mmol, 85percent over two steps) was collected as colourless solid.

Reference： [1] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 564 - 570
[2] Synthesis, 1987, # 4, p. 346 - 349
[3] Patent: US6627660, 2003, B1,
[4] Patent: US2004/116391, 2004, A1,

2
[ 74124-79-1 ]
[ 2916-68-9 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With triethylamine In acetonitrile at 20℃; for 3 h;	Compound 41; TEA (21.9 mL, 155.6 mmol, 3.0 eq.) was added to 2-trimethylsilanyl- ethanol (7.4 mL, 51.88 mmol, 1.0 eq.) in 260 mL MeCN, followed by di- succinimidyl carbonate (20 g, 1.5 eq.). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated and extracted using EtOAc/ saturated NaHCO₃. The organic layer was concentrated after dried over Na₂SO₄. Ether (100 mL) was added to the residue to form a precipitate. The precipitate was filtered and dried to give Compound 41 as a white solid (11.1 g, 84percent). ¹H NMR (300 MHz, CDCl₃): δ 4.42 (t, 3 H), 2.82 (s, 4 H), 1.16 (t, 2 H), 0.1 (s, 9 H).
82%	With triethylamine In acetonitrile at 25℃; for 16 h;	Example 5; methyl (l-l- ( {2- [ (2, 36)-3-amino-2-hydroxy-4-phenylbutyl]-2- benzylhydrazino} carbonyl)-2, 2-dimethylpropylcarbamate; Example 5A; 1- (f [2- (trimethylsilyl) ethoxy] carbonyl} oxy)-2, 5-pyrrolidinedione; Trimethylsilylethanol (7.4 mL, 52 mmol) was dissolved in acetonitrile (260 mL) and treated with disuccinimoyl carbonate (20 g, 1.5 equivalents) and triethylamine (33 mL, 3 equivalents) at 25°C for 16h. The solvents were evaporated, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was triturated with ether to form a solid which was filtered and dried to give 11.12 g (82percent) of the title compound.
82%	With triethylamine In acetonitrile	EXAMPLE 5A 1-([2-(trimethylsilyl)ethoxy]carbonyl}oxy)-2,5-pyrrolidinedione Trimethylsilylethanol (7.4 mL, 52 mmol) was dissolved in acetonitrile (260 mL) and treated with disuccinimoyl carbonate (20 g, 1.5 equivalents) and triethylamine (33 mL, 3 equivalents) at 25° C. for 16 h. The solvents were evaporated, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was triturated with ether to form a solid which was filtered and dried to give 11.12 g (82percent) of the title compound.

Reference： [1] Patent: WO2008/11117, 2008, A2, . Location in patent: Page/Page column 491
[2] Patent: WO2005/61487, 2005, A1, . Location in patent: Page/Page column 115
[3] Patent: US2005/159469, 2005, A1, . Location in patent: Page/Page column 59

3
[ 2916-68-9 ]
[ 32315-10-9 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In tetrahydrofuran	Example 43 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate To a solution of triphosgene (25 g, 0.5 eq.) in THF (200 mL) was added dropwise a mixture of 2-(trimethylsilyl)ethanol (20 g, 1 eq.) and TEA (25 mL, 1.1 eq.) in THF at 0° C. After being stirred at rt for 2 hr, a solution of HOSu (1 eq.) in THF (50 mL) was added into the reaction mixture at 0° C. The resulting mixture was stirred overnight. The resulted solid was removed away by filtration under reduced pressure. The filtrate was treated by chromatographic column on silica gel eluted by CH₂Cl₂. The collected fractions was condensed to 10 mL of volume and poured into pure hexanes. The precipitated solid 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate was collected in 78percent yield by filtration under reduced pressure. ¹H NMR (400 M) 4.4 (d, 2H), 2.9 (s, 4H), 2.2 (d, 2H), 0.1 (s, 1H); ¹³C NMR 172, 154, 74, 28, 19, 0.

Reference： [1] Patent: US2010/105607, 2010, A1,

4
[ 2916-68-9 ]
[ 78269-85-9 ]

Reference： [1] Synthesis, 1987, # 4, p. 346 - 349
[2] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 564 - 570

[ 78269-85-9 ] Synthesis Path-Downstream 1~88

1
[ 6066-82-6 ]
[ 20160-60-5 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; In acetonitrile; at 0 - 20℃; for 16h;Inert atmosphere;	TeocCl reagent S13 was dissolved in CH3CN (105 mL) at 0 C. Then, NHS (5.22 g,45.4 mmol, 1.30 equiv) and Et3N (4.59 g, 45.4 mmol, 1.30 equiv; in 11.0 mL CH3CN) wereadded. The reaction mixture was stirred at 0 C rt. After 16 h, the reaction mixture waspoured into H2O. The aqueous layer was extracted with Et2O (6×). The combined organiclayers were washed with H2O (2×), HCl (1.0 M), followed by H2O and subsequent dried overMgSO4, filtered a well as concentrated under reduced pressure. The desired TeocOSu S14(7.72 g, 29.8 mmol, 85% over two steps) was collected as colourless solid.
	With triethylamine; In acetonitrile;	Example 2 Preparation of 1-[2(Trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (Teoc-0Su) 2-Trimethylsilylethyl carbonochloridate (4.8 g, 26.9 mmol) was taken up in dry acetronitrile (50 mL). The solution was cooled to 0 and solid N-hydroxysuccinimide (4.0 g, 34.8 mmol) was added with vigorous stirring followed by a solution of dry triethylamine (3.2 g, 31.6 mmol) in dry acetonitrile (5 mL). The mixture was stirred at low temperature for 15 minutes, then at room temperature overnight. The mixture was poured into water (200 ml) and extracted with ether (450 mL). The organic extracts were combined, washed with water (260 mL), 1 normal hydrochloric acid (60 mL), again water (60 mL), brine (60 mL), dried with magnesium sulfate and evaporated to dryness. The residue was taken up in boiling hexane (200 mL) and the solution allowed to cool. Crystallization was completed by storage at -15 C. (yield: 1.70 g).

Reference： [1]Beilstein Journal of Organic Chemistry,2016,vol. 12,p. 564 - 570
[2]Synthesis,1987,p. 346 - 349
[3]Patent: US6627660,2003,B1

2
[ 72-18-4 ]
[ 78269-85-9 ]
[ 113306-60-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 15h;Inert atmosphere;	L-Valine (1.17 g, 10.0 mmol, 1.00 equiv) was dissolved in H2O (10.0 mL) at rt. Then, Et3N(1.52 g, 15.0 mmol, 1.50 equiv) in 1,4-dioxane (10.0 mL) was added, followed by TeocOSuS14 (2.85 g, 11.0 mmol, 1.10 equiv). The reaction mixture was stirred for 15 h at rt, thendiluted with H2O and acidified with saturated KHSO4 solution. Afterwards, the reactionmixture was extracted with EtOAc (6×). The combined organic layers were washed withH2O (4x) and subsequently dried over MgSO4, filtered as well as concentrated under reducedpressure. The product was directly used in the next step without further purifications.

Reference： [1]Synthesis,1987,p. 346 - 349
[2]Beilstein Journal of Organic Chemistry,2016,vol. 12,p. 564 - 570

3
[ 78269-85-9 ]
[ 284494-10-6 ]
[ 284494-11-7 ]

Reference： [1]Chemistry - A European Journal,2000,vol. 6,p. 1416 - 1430

4
[ 17400-34-9 ]
[ 78269-85-9 ]
[3-(2-trimethylsilanyl-ethoxycarbonylamino)-propyl]-carbamic acid benzyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 5569 - 5572

5
[ 2419-56-9 ]
[ 78269-85-9 ]
Teoc-Glu(O^δ-t-Bu)OH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃;	To a stirred solution of G1 - tBa)~OH (2.089 g, 0.28 tmxoi) and trie&yl amine (0.2,15 mL, 15.43 ramol) in J : 1 .Dioxane:water (v v) (31 mL) Teoc-OSa (3,2 g, 12.34 tnmo) vvss added in one portion. The mixture i. stirred at room .temperature overnight, then diluted with water (15 mL), acidified "with 4 HQ and 1 N HCJ, nd extracted vvfth ethyl acetate (3 40 mL). The combined organic layers are washed with brine (60 mL), dried with magnesium sulfate, filtered and evaporated to gi ve a erode oil (3,451 g, 96.6% yield) and dried overnight

Reference： [1]Organic Letters,2004,vol. 6,p. 4483 - 4485
[2]Patent: WO2018/31809,2018,A1 .Location in patent: Paragraph 0130-0131

6
[ 952685-53-9 ]
[ 78269-85-9 ]
[ 952685-54-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃;	Step 2. tert-Butyl (2S,3R)-4-(N-(4-cyanobenzyl)-N-(2-(trimethyl silyl)ethoxycarbonyl)amino)- 1 -cyclohexyl-3-hydroxybutan-2-ylcarbamate. A solution of tert-butyl (2S,3R)-4-(4-cyanobenzylamino)-l-cyclohexyl-3- hydroxybutan-2-ylcarbamate (600 mg, 1.5 mmol) in CH2Cl2 (30 mL) was treated with Teoc-OSu (762 mg, 3.0 mmol, 2.0 equiv) and Et3N (304 mg, 3.0 mmol, 2.0 equiv). The mixture was allowed to stir overnight at rt. LC-MS analysis showed that all of the free amine had been consumed. The solution was washed with water,1.0 M aq HCl5 and brine, then over dried over Na2SO4, filtered and evaporated to leave tert-butyl (2S,3R)-4-(N-(4-cyanobenzyl)-N-(2- (trimethylsilyl)ethoxycarbonyl)amino)-1-cyclohexyl-S-hydroxybutan-2-ylcarbamate.NMR analysis showed that the compound was of sufficient purity to use in the next step.

Reference： [1]Patent: WO2007/117557,2007,A2 .Location in patent: Page/Page column 96

7
[ 78269-85-9 ]
tert-butyl (2S,3S)-4-amino-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate [ No CAS ]
[ 952685-56-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate; In water; acetone; at 20℃; for 2h;	Step 2. 2-(Trimethylsilyl)ethyl (2S53S)-3-N-/-butoxycarbonyl-amino-4-cyclohexyl- 2-hydroxybutylcaxbamate. To a stirred solution of t°r/-butyl (2S,3S)-4-amino-l-cyclohexyl-3- hydroxybutan-2-ylcarbamate (0.21 g, 0.74 mmol) in acetone (10 mL) and water (3 mL), K2CO3 (0.31 g, 2.22 mmol) was added, followed by Teoc-OSu (0.19 g, 0.74 mmol). The resulting solution was stirred at rt until no starting materials remained (~2 h). Acetone was removed, and the aqueous solution was extracted with CHbCl2 (4 x 10 mL). The combined organic layers were washed with water (5 mL) and brine (5 mL). Upon removing solvent, the crude residue was purified by flash column chromatography to afford 2-(trimethylsilyl)ethyl (2S,3S)-3-N-/- butoxycarbonyl-amino-4-cyclohexyl-2-hydroxybutylcarbamate (0.27 g, 87%); 1H NMR (400MHz3 CDCl3) delta: 5.42 (br, 1 H), 4.60 (d, 1 H), 4.12 (m, 2 H)5 3.62 (m, 2 H), 3.36 (m, 1 H), 3.04 (m, 1 H), 1.78 (m, 1 H)5 1.64 (m, 5 H), 1.42 (s, 9 H), 1.38- 1.04 (m, 6 H), 0.96 (m, 2 H), 0.82 (m, 1 H), 0.02 (s, 9 H); MS m/z 453 (M+Na+).

Reference： [1]Patent: WO2007/117557,2007,A2 .Location in patent: Page/Page column 98

8
[ 1246845-95-3 ]
[ 78269-85-9 ]
[ 952685-66-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium carbonate; In dichloromethane; water; at 20℃; for 2h;	Step 11. tert-butyl (2S,3R)-3-hydroxy-4-(N-methyl-N-(2- (tri.methylsilyl)ethoxycarbonyl)amino)-l-(tetrahydro-2H-rhoyran-4-yl)butan-2- ylcarbamate. Solid TeocOSu was added to a vigorously stirred 2-phase solution of tert- butyl (2S53R)-3-hydroxy-4-(methylamino)-l-(tetrahydro-2H-pyran-4-yl)butan-2- ylcarbamate (200 mg, 0.66 mmol), K2CO3 (164 mg, 1.12 mmol), H2O (5 mL) and CH2Cl2 (10 mL). After stirring for 2 h at rt, the mixture was diluted with CH2Cl2 (30 mL), washed with satd aq NaHCO3 and brine, dried over Na2SO4, filtered and concentrated to give an oil. The residue was purified by chromatography to give tert-butyl (2S,3R)-3-hydroxy-4-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-l-(tetrahydro-2H-pyran-4-yl)butan-2- ylcarbaraate (180 mg, 53%).

Reference： [1]Patent: WO2007/117557,2007,A2 .Location in patent: Page/Page column 106-107

9
[ 480450-43-9 ]
[ 78269-85-9 ]
[ 720721-32-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In 1,4-dioxane; water; at 20℃; for 20h;	[Reference Example 15] (3R,4S)-4-[(benzyloxycarbonyl)amino]-3-[(tert-butoxycarbonyl)am ino]piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester To a solution of the compound obtained in Reference Example 14 (5.98 g) in dioxane (50 ml), a 9% aqueous solution of sodium hydrogen carbonate (150 ml) was added, the mixture was cooled to 0C, subsequently a dioxane solution (20 ml) of 1-[(2-trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dion e (4.83 g) was added, and the mixture was stirred for 20 hours at room temperature. Acetic acid ethyl ester and water were added to the reaction mixture, the organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate, a 10% aqueous solution of citric acid, and a saturated aqueous solution of sodium chloride, subsequently the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:acetic acid ethyl ester = 4:1 ? 2:1), to obtain the title compound (6.75 g). 1H-NMR(CDCl3)delta:0.00(9H, s), 0. 96 (2H, t, J=8.3Hz), 1.36-1.53 (1H, m), 1.41(9H, s), 1.82-2.00(1H, m), 2.85(1H, t, J=12.1Hz), 3.01(1H, d, J=13.4Hz), 3.66-3.81(1H, m), 3.87-4.25(5H, m), 4.63-4.81(1H, m), 5.06(2H, br.s), 5.22-5.69(1H, br), 7.23-7.40(5H, m). MS (ESI)m/z:394 (M-Boc)+.

Reference： [1]Patent: EP1864982,2007,A1 .Location in patent: Page/Page column 63-64

10
[ 74124-79-1 ]
[ 2916-68-9 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With triethylamine; In acetonitrile; at 20℃; for 3h;	Compound 41; TEA (21.9 mL, 155.6 mmol, 3.0 eq.) was added to 2-trimethylsilanyl- ethanol (7.4 mL, 51.88 mmol, 1.0 eq.) in 260 mL MeCN, followed by di- succinimidyl carbonate (20 g, 1.5 eq.). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated and extracted using EtOAc/ saturated NaHCO3. The organic layer was concentrated after dried over Na2SO4. Ether (100 mL) was added to the residue to form a precipitate. The precipitate was filtered and dried to give Compound 41 as a white solid (11.1 g, 84%). 1H NMR (300 MHz, CDCl3): delta 4.42 (t, 3 H), 2.82 (s, 4 H), 1.16 (t, 2 H), 0.1 (s, 9 H).
82%	With triethylamine; In acetonitrile; at 25℃; for 16h;	Example 5; methyl (l-l- ( {2- [ (2, 36)-3-amino-2-hydroxy-4-phenylbutyl]-2- benzylhydrazino} carbonyl)-2, 2-dimethylpropylcarbamate; Example 5A; 1- (f [2- (trimethylsilyl) ethoxy] carbonyl} oxy)-2, 5-pyrrolidinedione; Trimethylsilylethanol (7.4 mL, 52 mmol) was dissolved in acetonitrile (260 mL) and treated with disuccinimoyl carbonate (20 g, 1.5 equivalents) and triethylamine (33 mL, 3 equivalents) at 25C for 16h. The solvents were evaporated, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was triturated with ether to form a solid which was filtered and dried to give 11.12 g (82%) of the title compound.
82%	With triethylamine; In acetonitrile;	EXAMPLE 5A 1-([2-(trimethylsilyl)ethoxy]carbonyl}oxy)-2,5-pyrrolidinedione Trimethylsilylethanol (7.4 mL, 52 mmol) was dissolved in acetonitrile (260 mL) and treated with disuccinimoyl carbonate (20 g, 1.5 equivalents) and triethylamine (33 mL, 3 equivalents) at 25 C. for 16 h. The solvents were evaporated, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was triturated with ether to form a solid which was filtered and dried to give 11.12 g (82%) of the title compound.

With triethylamine; In acetonitrile; at 20℃;

To a solution of compound 16 (22.2 mL, 0.156 mol, 1.0 eq) in CH3CN (780 mL) was added Et3N (65.7 mL, 0.468 mol, 3.0 eq) and compound 17 (60 g, 0.234 mmol, 1.5 eq) at room temperature and stirred for overnight. After completion, concentrated and EA (500 mL) was added, washed with saturated NaHCCh (200 mL), NaCl (200 mL*3), dried over Na2S04. Filtered and concentrated to give yellow liquid (18, 54.2 g, crude) which was used into next step without purification.

Reference： [1]Patent: WO2008/11117,2008,A2 .Location in patent: Page/Page column 491
[2]Patent: WO2005/61487,2005,A1 .Location in patent: Page/Page column 115
[3]Patent: US2005/159469,2005,A1 .Location in patent: Page/Page column 59
[4]Patent: WO2019/118878,2019,A1 .Location in patent: Page/Page column 57

11
[ 78269-85-9 ]
[ 154876-20-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrazine; In tetrahydrofuran; at 0 - 25℃; for 16.1667h;	Example 5B; 2- (trimethylsilyl) ethyl hydrazinecarboxylate; Hydrazine hydrate (1.87 mL, 38 mmol) was dissolved in THF (16 mL) at 0C and treated with Example 5A (2 g, 0.2 equivalent) in THF (7 mL) over 10 min. The mixtyure was warmed to 25C for 16 hrs and diluted with ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over sodium sulfate and the solvents were evaporated to give 1.31 g (99%) of a crude oil which was redissolved in ethanol (14 mL) and treated with benzaldehyde (0.72 mL, 1 equivalent) at 25C for 2 days. The solvents were evaporated and the crude residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents were evaporated. The crude oil was crystallized by treatment with ether/hexane and filtered to give 1. 85 g (99%) of the title compound
99%	With hydrazine; In tetrahydrofuran; at 0 - 25℃; for 16h;	EXAMPLE 5B 2-(trimethylsilyl)ethyl Hydrazinecarboxylate Hydrazine hydrate (1.87 mL, 38 mmol) was dissolved in THF (16 mL) at 0 C. and treated with Example 5A (2 g, 0.2 equivalent) in THF (7 mL) over 10 min. The mixtyure was warmed to 25 C. for 16 hrs and diluted with ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over sodium sulfate and the solvents were evaporated to give 1.31 g (99%) of a crude oil which was redissolved in ethanol (14 mL) and treated with benzaldehyde (0.72 mL, 1 equivalent) at 25 C. for 2 days. The solvents were evaporated and the crude residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents were evaporated. The crude oil was crystallized by treatment with ether/hexane and filtered to give 1.85 g (99%) of the title compound.
79%	With hydrazine; In tetrahydrofuran; at 0℃; for 2h;	Compound 42; Hydrazine monohydrate (5.73 mL, 115.6 mmol, 5.0 eq.) was added to Compound 41 (6 g, 23.13 mmol, 1.0 eq.) in 50 mL THF at 00C. A precipitate formed. The reaction was monitored by 1H NMR. The reaction was complete after 2 hours. The reaction mixture was concentrated and extracted using EtOAc/ saturated NaHCO3 (IX) and brine (IX). The organic layer was concentrated and dried over Na2SO4 to give Compound 42 as a white solid (3.23 g, 79%). 1H NMR (300 MHz, CDCl3): delta 5.84(b, 1 H), 4.20 (t, 2 H), 1.00 (t, 2 H), 0.1 (s, 9 H).

Reference： [1]Patent: WO2005/61487,2005,A1 .Location in patent: Page/Page column 115-116
[2]Patent: US2005/159469,2005,A1 .Location in patent: Page/Page column 59
[3]Patent: WO2008/11117,2008,A2 .Location in patent: Page/Page column 491

12
[ 331281-25-5 ]
[ 78269-85-9 ]
[ 871115-50-3 ]

Yield	Reaction Conditions	Operation in experiment
64%	In DMF (N,N-dimethyl-formamide); at 20℃;	To a solution of 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (200 mg, 0.9 mmol) in DMF (2 mL) was added 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (246 mg, 1.0 mmol) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 1N HCl solution and saturated brine. The organic layer was dried over MgSO4, filtered and evaporated. The resulting residue was purified by silica gel column chromatography (n-hexanes:ethyl acetate=4:1) to give the desired product (210 mg, 64%). 1H NMR (400 MHz, CDCl3) delta 4.99 (br s, 1H), 4.22-4.18 (m, 2H), 3.93 (br d, J=12.0 Hz, 2H), 3.27-3.20 (m, 2H), 2.35 (br d, J=12.8 Hz, 2H), 1.79-1.69 (m, 2H), 1.45 (s, 9H), 1.02-0.98 (m, 2H), 0.03 (s, 9H).

Reference： [1]Patent: US2005/277633,2005,A1 .Location in patent: Page/Page column 19

13
[ 46460-73-5 ]
[ 78269-85-9 ]
[ 1021495-54-4 ]

Yield	Reaction Conditions	Operation in experiment
		More specifically, commercially available mono-Cbz (benzyloxycarbonyl) protected 1,3-diaminopropane (1 g, 4.08 mmol) was suspended in dry dichloromethane (10 mL). The reaction was cooled in an ice bath and sequentially treated with triethylamine (4.2 mmol, 0.58 mL) and 2-trimethylsilylethyl-N-succinimidyl carbonate (Teoc-Osu, 1.06 g, 4.1 mmol). After stirring at rt for 16 hr, the reaction was diluted with dichloromethane and extracted with 5percent HCl, saturated NaHCO3 solution, brine, dried (MgSO4) and concentrated. The crude residue obtained was dissolved in ethyl acetate (30 mL) and hydrogenated using 10percent Palladium/carbon using a hydrogen balloon. After 16 hr at room temp, the reaction was filtered through celite and the filter bed washed with additional ethyl acetate. The filtrate was concentrated and the crude residue was dissolved in a mixture of dichloromethane (10 mL) and methanol (30 mL). 3,5-Dibromobenzaldehyde (1.05 g, 4 mmol) and glacial acetic acid (1 mL) were added to the reaction. After stirring for 15 minutes at room temp, sodium cyanoborohydride (0.38 g, 6 mmol) was added to the reaction, which was stirred for an additional 16 h at room temp. The reaction was diluted with additional dichloromethane and the organic phase was sequentially washed with sat. NaHCO3 solution, brine, dried (MgSO4) and concentrated. The crude residue obtained was purified by chromatography on silica gel using ethyl acetate/hexanes. 1H NMR (300 MHz, CDCl3) delta 7.51 (s, 1H), 7.38 (s, 2H), 5.16 (s, br, 1H), 4.12 (t, 2H), 3.69 (s, 2H), 3.25 (m, 2H), 2.64 (t, 2H), 1.65 (m, 2H), 0.95 (t, 2H).

Reference： [1]Patent: US2006/30603,2006,A1 .Location in patent: Page/Page column 2

14
[ 913567-99-4 ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl [1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-5-methyl-1H-pyrazol-3-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 76h;	1-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-5-methyl-1 H-pyrazol-3-amine (82mg, 0.25mmol) was dissolved in dichloromethane (2ml) and triethylamine (60mul, 0.43mmol) added, followed by 1-[([2-(trimethylsilyl)ethyl]oxy}carbonyl)oxy]-2,5-pyrrolidinedione (71 mg, 0.3mmol). The mixture was stirred at room temperature for 76h. The solvent was evaporated and the residue purified by flash chromatography, eluting with 3:1 isohexane:ethyl acetate. The product was triturated with isohexane and diethyl ether to give the title compound as a white powder. (61 mg). LC/MS Rt = 4.28 min, [MH+] 472, 474.

Reference： [1]Patent: WO2006/114313,2006,A1 .Location in patent: Page/Page column 52

15
[ 2749-11-3 ]
[ 78269-85-9 ]
[ 181767-52-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine; In 1,4-dioxane; water; at 20℃;	To a stirred solution of the commercially available 2-(S)-amino propanol (17.4 g) in water (200 ml) was added a solution of triethylamine (32 ml) in dioxane (200 ml). To the solution was added commercially available l-[2-(Trimetylsilyl)ethoxy- carbonyloxy]pyrrolidin-2,5-dione (60 g). The mixture was stirred at rt overnight, then diluted with water (200 ml), acidified with 1 N HCl, and extracted with Et2O (2 x 500 ml). The combined organic phase was washed with brine, dried over MgSO4 and evaporated to afford the title compound (44.2 g; 87 %).1H-NMR delta (CDCl3): 0.02 (s, 9H), 0.90-1.05 (m, 2H), 1.20 (d, 3H), 2.80 (br s, IH), 3.40-3.80 (m, 3H), 4.10-4.20 (m, 2H), 4.85 (s, IH).

Reference： [1]Patent: WO2006/116157,2006,A2 .Location in patent: Page/Page column 70

16
C₁₆H₂₂N₄O₃S [ No CAS ]
[ 78269-85-9 ]
C₂₂H₃₄N₄O₅SSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃;	Method E. Step 10To a solution of 13 g of E12 (R6 = 4-thien-2-yl, R1 = Me) in 100 ml DCM was added Teoc-OSu (1.03 eq) and DIEA (1.1 eq) at 00C. The reaction was stirred until disappearance of E12 (R6 = 4-thien-2-yl, R1 = Me) before it was extracted withEtOAc/water. The organic layer was dried and solvent evaporated and the residue chromatographed to give E13 (R6 = 4-thien-2-yl, R1 = Me) as an oil.NMR(H1, CDCI3) for E13 (R6 = 4-thien-2-yl, R1 = Me): delta 10.40, br, m, 1 H; 7.22, br. s, 1 H; 6.90, 1 H; 4.20, m, 2H; 3.68-4.06, m, 4H; 3.47, m, 1 H; 3.30, s, 3H; 1.29, s, 9H; 1.01 , m, 2H; 0.03, s, 9H.

Reference： [1]Patent: WO2006/138264,2006,A2 .Location in patent: Page/Page column 45; 49

17
[ 78269-85-9 ]
[ 149423-46-1 ]
[ 884511-13-1 ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium carbonate; In dichloromethane; water; at 20℃; for 2h;	To a vigorously stirred biphasic solution of (S)-tert-butyl l-amino-3- cyclohexylpropan-2-ylcarbamate (10.5 g, 0.041 mol), K2CO3 (10.2 g, 73.8 mol), H2O (60 mL), and CH2Cl2 (120 mL) was added l-[2- trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (TeocOSu) (11.14 g, 0.043 mol). The mixture was stirred for 2 h at rt, and then the reaction was washed with brine (3x20 mL), dried over Na2Stheta4, decanted, stripped, and separated on 50 g of SiO2 to give (S)- tert-butyl l-(2-(trimethylsilyl)ethoxycarbonylamino)-3-cyclohexylpropan-2- ylcarbamate (8.5 g, 52%) as a clear oil. 1U NMR (400MHz, CDCl3): 5.52 (brs, IH), 4.42 (brs, IH), 4.11 (m, 2H), 3.73 (brs, IH), 3.30-3.03 (m,2H), 1.81-1.50 (m, 5H), 1.43 (s, 9H), 1.42-1.02 (m, 6H), 1.02-0.76 (m, 4H), 0.03 (s, 9H); MS (E/Z): 401 (M+H+).

Reference： [1]Patent: WO2007/70201,2007,A1 .Location in patent: Page/Page column 179
[2]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3541 - 3545

18
[ 884511-15-3 ]
[ 78269-85-9 ]
[ 884511-16-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium carbonate; In dichloromethane; water; at 20℃; for 2h;	To a vigorously stirred 2-phase solution of (S)-tert-butyl l-cyclohexyl-3-(methylamino)propan-2-ylcarbamate (7.25 g, 0.027 mol), K2CO3 (6.66 g, 0.048 mol),H2O (40 mL) and CH2Cl2 (80 mL) was added l-[2- trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (TeocOSu) solid (7.3 g, 0.028 mol). After stirring for 2 h at rt, the reaction was added to CH2Cl2 (20OmL), washed with satd aq NaHCO3 (3 x 15 mL) then brine (3 x 15 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on 40 g of silica gel to give (S)-tert-butyl l-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamate as a clear oil (5.78 g, <n="182"/>50%). 1HNMR (400MHz, CDCl3) delta 4.50 (d, J=7.6Hz, IH), 4.15 (t, J=7.6Hz, 2H), 3.89 (m, IH), 3.56-2.95 (m, 2H), 2.92&2.90 (s, 3H)3 1.82 (m, IH), 1.66 (m, 4H), 1.41 (s, 9H), 1.50-1.10 (m, 6H), 1.00-0.70 (m, 4H), 0.01 (s, 9H). MS (E/Z): 415 (M+Hi).

Reference： [1]Patent: WO2007/70201,2007,A1 .Location in patent: Page/Page column 180-181
[2]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3541 - 3545
[3]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4836 - 4843
[4]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 747 - 751

19
[ 78269-85-9 ]
[ 105590-97-4 ]
[ 1025029-48-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 24h;	Stage 1 : 5-benzyl l-tert-butyl N-[2-(trimethylsilyl)ethoxy]carbonyl}-L-glutamate5-Benzyl 1-tert-butyl L-glutamate hydrochloride (1.156 g, 3.51 mmol) in water (4 ml) was added to a stirred solution of triethylamine (1.232 ml, 8.76 mmol) in dioxane (4 ml). The resulting solution was treated with l-[2-(trimethylsilyl)ethoxycarbonyloxy] pyrrolidin-2,5- dione [TEOCOSu] (1 g, 3.86 mmol) and stirred at room temp for 24 h. The mixture was diluted with water (50 ml), acidified with solid NaHSO4 and extracted with ether (3 x 60 ml). The combined organic phases were washed with water (3 x 100 ml) and brine (100 ml), dried (MgSO4) and evaporated to give 5-benzyl 1-tert-butyl N-[2- EPO <DP n="66"/>(trimethylsilyl)ethoxy]carbonyl}-L-glutamate (1.67 g) as a clear colourless oil. m/z 438 (M+H)+

Reference： [1]Patent: WO2008/56120,2008,A1 .Location in patent: Page/Page column 64-65

20
[ 1093865-41-8 ]
[ 78269-85-9 ]
[ 1093865-42-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dichloromethane; water; at 20℃; for 16h;	A mixture of 3-((3-chlorophenyl)(2-(2,2,2- trifluoroacetamido)ethoxy)methyl)-N-((iS)- 1 -cyclohexyl-3 -(methylamino)propan-2- yl)benzamide, obtained as described above, TeocOSu (295 mg, 1.14 mmol), and K2CO3 (2.14 g) in CH2Cl2 and H2O was vigorously stirred at room temperature for 16 h. The mixture was diluted with saturated brine, extracted with CH2Cl2, and dried over Na2SO4. After the solvent was removed in vacuo, the crude product was purified by preparative HPLC (Phenomenex Luna 5mu Cl 8(2) 10OA, 250 x 21.20 mm, 5 micron, 70% ?90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then <n="132"/>90% CH3CN/H2O, 0.1% CF3COOH over 10 min, flow rate 25 mL/min) to give 2- (trimethylsilyl)ethyl (2S)-2-(3-((3-chlorophenyl)(2-(2,2,2- trifluoroacetamido)ethoxy)methyl)benzamido)-3- cyclohexylpropyl(methyl)carbamate. LC-MS (3 min) m/z: 698 (M+H+).

Reference： [1]Patent: WO2008/156817,2008,A2 .Location in patent: Page/Page column 129-131

21
[ 1192479-42-7 ]
[ 78269-85-9 ]
C₂₂H₃₃BrN₄O₅SSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃;	To a solution of 13 g of the N-debenzylated product (R6 = 4-bromothien-2-yl, R1 = Me) in 100 ml dichloromethane was added 1-[(2- trimethylsilyl)ethoxycarbonyloxy]-pyrrolidin-2,5-dione (1.03 eq) and DIEA (1.1 eq) at 00C. The reaction mixture was stirred until disappearance of starting material, before it was extracted with EtOAc/water. The organic layer was dried, the solvent was evaporated and the residue chromatographed to give racemic C10 (R6 = 4- bromothien-2-yl, R1 = Me) as an oil. 1H NMR (CDCI3) delta 10.40, br, m, 1 H; 7.22, br. s, 1 H; 6.90, 1 H; 4.20, m, 2H; 3.68-4.06, m, 4H; 3.47, m, 1 H; 3.30, s, 3H; 1.29, s, 9H; 1.01 , m, 2H; 0.03, s, 9H.

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9331 - 9345
[2]Patent: WO2009/131974,2009,A1 .Location in patent: Page/Page column 95

22
[ 1160247-58-4 ]
[ 78269-85-9 ]
(+/-)-tert-butyl 7-bromo-3-((2-(trimethylsilyl)ethoxy)carbonylamino)-2,3-dihydrospiro[indene-1,4'-piperidine]-1'-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran; water; at 20℃; for 72h;	Step 2To a stirred solution of crude (+/-)-tert-butyl 3-amino-7-bromo-2,3- dihydrospiro[indene-l,4'-piperidine]-l'-carboxylate (264 mg, 0.69 mmol) in THF (5 mL) was added 10% aq K2CO3 (10 mL), followed by Teoc-OSu (269 mg, 1.04 mmol). The mixture was stirred at rt for 3 d, diluted with ether (80 mL), washed with brine (25 mL) and dried over MgSO4. Removal of the solvent left an oil (240 mg) which was purified chromatography on a 12-g silica cartridge, eluted with a 0 - 50% EtOAc in hexanes gradient to afford (+/-)-tert-butyl 7-bromo-3-((2-(trimethylsilyl)ethoxy)carbonylamino)- 2,3-dihydrospiro[indene-l,4'-piperidine]-l'-carboxylate (85 mg, 31% for 2 steps). LC- MS Method 1 tR = 2.35 min, m/z = 425, 427, 547, 549.

Reference： [1]Patent: WO2009/108332,2009,A1 .Location in patent: Page/Page column 69

23
[ 721927-86-2 ]
[ 78269-85-9 ]
[ 721927-87-3 ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of the compound (3.30 g) obtained in Referential Example 407, 10% palladium carbon (1.50 g), methanol (50 ml) and ethyl acetate (70 ml) was stirred at room temperature for 2 hours under a hydrogen atmosphere. After the catalyst was filtered off, the solvent was distilled off under reduced pressure. A colorless powder thus obtained was suspended in dioxane (100 ml). 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (2.54 g), a saturated aqueous solution (100 ml) of sodium bicarbonate and water (100 ml) were added to the resulting suspension, followed by stirring at room temperature for 24 hours. 1-[2-(Trimethylsilyl) ethoxycarbonyloxy] pyrrolidine-2,5-dione (0.46 g) and dioxane (100 ml) were added further and the resulting mixture was stirred for 4 hours. Ethyl acetate (300 ml) and water (100 ml) were added to the reaction mixture to separate the layers. The organic layer was washed with saturated saline (200 ml) and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. Hexane was added to the residue to solidify the same, whereby the title compound (2.62 g) was obtained.1H-NMR(CDCl3) delta: 0.04(9H,s), 0.96-1.03(2H,m), 1.44(9H,s), 3.48(1H,dt,J=14.5,6.0Hz), 3.52-3.63(1H,m), 4.14-4.20(2H,m), 4.21-4.26(1H,m), 5.18(1H,br s), 5.50(1H,br s), 6.12(1H,br s), 6.70(1H,br s).

Reference： [1]Patent: EP1577302,2005,A1 .Location in patent: Page/Page column 223

24
[ 1185734-58-0 ]
[ 78269-85-9 ]
[ 1204765-98-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 16h;	Example 9 Preparation of 1 (free base): see Example 1, above. Preparation of intermediate U: To a slurry of 1 (0.10 g, 0.42 mmol) in water (2 mL) was added triethylamine (0.12 g, 0.63 mmol) and dioxane (2 mL). Solid 2-(trimethylsilyl)ethylcarbonate-O-succinimide (0.12 g, 0.46 mmol) was added and the resulting mixture was stirred at room temperature for 16 h. Ether was added, and the mixture was washed successively with saturated aqueous ammonium chloride and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure, and the crude residue so obtained was purified by flash chromatography (ethyl acetate/hexane) to afford U as a colorless oil (0.15 g).

Reference： [1]Patent: US2010/16312,2010,A1 .Location in patent: Page/Page column 25-26

25
[ 2916-68-9 ]
[ 32315-10-9 ]
[ 78269-85-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In tetrahydrofuran;	Example 43 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate To a solution of triphosgene (25 g, 0.5 eq.) in THF (200 mL) was added dropwise a mixture of 2-(trimethylsilyl)ethanol (20 g, 1 eq.) and TEA (25 mL, 1.1 eq.) in THF at 0 C. After being stirred at rt for 2 hr, a solution of HOSu (1 eq.) in THF (50 mL) was added into the reaction mixture at 0 C. The resulting mixture was stirred overnight. The resulted solid was removed away by filtration under reduced pressure. The filtrate was treated by chromatographic column on silica gel eluted by CH2Cl2. The collected fractions was condensed to 10 mL of volume and poured into pure hexanes. The precipitated solid 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate was collected in 78% yield by filtration under reduced pressure. 1H NMR (400 M) 4.4 (d, 2H), 2.9 (s, 4H), 2.2 (d, 2H), 0.1 (s, 1H); 13C NMR 172, 154, 74, 28, 19, 0.

Reference： [1]Patent: US2010/105607,2010,A1

26
[ 2177-63-1 ]
[ 78269-85-9 ]
C₁₇H₂₅NO₆Si [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 3685 - 3687

27
[ 1346627-17-5 ]
[ 78269-85-9 ]
[ 1346627-18-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In 1,4-dioxane; at 20℃;	To a solution of tert-butyl 4-(2-(piperidin-4-yloxy)benzo[d]thiazol-6-yl)- 5,6-dihydropyridine-l(2H)-carboxylate (450 mg, 1.083 mmol) in dioxane (10 mL) was added Et3N (0.45 mL, 3.25 mmol) followed by 2,5-dioxopyrrolidin-l-yl 2- (trimethylsilyl)ethyl carbonate (281 mg, 1.083 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with CH2CI2 (30 mL), washed with water (30 mL) and brine. The organic layer was dried (Na2S04), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 35% EtOAc) to afford tert-butyl 4-(2-(l-((2- (trimethylsilyl)ethoxy)carbonyl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6- dihydropyridine-l(2H)-carboxylate (555 mg, 0.991 mmol, 92% yield) as a white solid. LCMS (m/z) =560 (M+H)+.

Reference： [1]Patent: WO2011/140160,2011,A1 .Location in patent: Page/Page column 139

28
[ 5318-27-4 ]
[ 78269-85-9 ]
[ 1352835-65-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane;Inert atmosphere;	Example 25; 4-(3-(6-Chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(tetrahydrofuran-3-ylamino)- 9H-pyrido[3,4-b]indole- 1 -carboxamide; 1.; To a yellow, homogeneous solution of 1H-indol-6-amine (1.3007 g, 9.84 mmol) and DIPEA (2.58 mL, 14.76 mmol) in 1,4-dioxane (19.68 mL) under nitrogen was added 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (2.81 g, 10.83 mmol) The reaction was stirred overnight, diluted with EtOAc (1500 mL), washed with water (3 x 50 mL) and brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to give the desired product (2.666 g, 9.65 mmol, 98% yield) as a light tan solid.

Reference： [1]Patent: WO2011/159857,2011,A1 .Location in patent: Page/Page column 117-118

29
trans-1-benzyl-4-(3-fluorophenyl)pyrrolidin-3-ylamine [ No CAS ]
[ 78269-85-9 ]
[trans-1-benzyl-4-(3-fluorophenyl)pyrrolidin-3-yl]carbamic acid propyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃;	Trans- 1 -Benzyl-4-(3-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid propyl ester:1 -([2-(Trimethylsilyl)ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione (4.5 g; 17.37 mmol) was added to a solution of trans-1 -benzyl-4-(3-fluorophenyl) pyrrolidin-3-amine (4.5 g; 16.87 mmol) and DIEA (4.5 ml; 25.30 mmol) in DCM (50 ml) at 05C, warmed to RT, and stirred for 1 hr at RT. The reaction solution was washed with brine, dried over MgS04, filtered, and concentrated. The crude material was purified was purified by Biotage eluting with a gradient of 30 to 60% EtOAc in hexane to provide the desired intermediate (6.0 g, yield 99%). LC-MS (M + H = 415, obsd = 415).

Reference： [1]Patent: WO2012/16001,2012,A1 .Location in patent: Page/Page column 32

30
[ 1678-68-8 ]
[ 78269-85-9 ]
[ 1398570-17-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In 1,4-dioxane; water; at 20℃; for 48h;	Ethyl trans-4-aminocyclohexanecarboxylate (J. Med. Chem., 1971, 14, 600-614) (29.5 g, 143 mmol) was dissolved in 1,4-dioxane (290 ml) and water (290 ml), triethylamine (30.0 ml, 215 mmol) and 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (40.8 g, 157 mmol) were added under ice cooling and the resulting mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated and then the residue was diluted with ethyl acetate and washed with 10% aqueous citric acid solution, saturated sodium bicarbonate solution, and brine in that order. The organic layer was dried over anhydrous sodium sulfate and the solvent was concentrated under reduced pressure to give 44.3 g (98%) of the title compound as colorless needle-like crystals.1H-NMR (500 MHz, CDCl3) delta: 0.03 (9H, s), 0.92-1.01 (2H, m), 1.08-1.18 (2H, m), 1.25 (3H, t, J=7.2 Hz), 1.48-1.59 (2H, m), 1.97-2.11 (4H, m), 2.21 (1H, tt, J=12.3, 3.7 Hz), 3.38-3.54 (1H, m), 4.07-4.19 (4H, m), 4.38-4.49 (1H, m).

Reference： [1]Patent: US2012/264738,2012,A1 .Location in patent: Page/Page column 129

31
[ 1678-68-8 ]
[ 78269-85-9 ]
[ 1398570-18-7 ]

Reference： [1]Patent: US2012/264738,2012,A1

32
[ 27019-47-2 ]
[ 78269-85-9 ]
C₁₆H₂₅NO₃Si [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 483 - 495

33
trans-1-benzyl-4-(4-trifluroromethoxy-phenyl)-pyrrolidin-3-ylamine [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl [trans-1-benzyl-4-(4-trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 1h;	1 -([2-(Trimethylsilyl)ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione (4.5 g; 17.37 mmol) was added to a solution of trans-1 -benzyl-4-(3-trifluoromethoxyphenyl) pyrrolidinyl-3-amine (4.5 g; 16.87 mmol) and DIEA (4.5 ml; 25.30 mmol) in DCM (50 ml) at 0SC. The reaction mixture was then warmed to RT and stirred for 1 hr at RT. The reaction solution was washed with brine, dried over MgS04, filtered, and concentrated. The crude material was purified by Biotage eluting with a gradient of 30 to 60% EtOAc in hexane to provide the title compound 6.0 g, yield 99%.

Reference： [1]Patent: WO2013/96194,2013,A1 .Location in patent: Page/Page column 34

34
[ 26177-44-6 ]
[ 78269-85-9 ]
[ 1448189-28-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In water; N,N-dimethyl-formamide; at 20℃; for 12h;	2-(trimethylsilyl)ethyl 4-bromobenzylcarbamate TeocHN 4-Bromobenzylamine hydrochloride (354 mg, 1.59 mmol, 1 eq) was dissolved in DMF (6.4 mL) and water (2.1 mL) and stirred at room temperature. Triethylamine (0.33 mL, 2.39 mmol, 1.5 eq) and TeocOSu (454 mg, 1.75 mmol, 1.1 eq) were then added. After 12 hours, the mixture was diluted with EtOAc, washed with 1M HC1, saturated sodium bicarbonate, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by column chromatography (10 to 20% EtOAc hexanes) gave a colorless oil (0.4158 g, 1.26 mmol, 79%). 1H NMR (500 MHz, CDC13) delta 7.48 - 7.43 (m, 2H), 7.17 (d, J = 8.1 Hz, 2H), 4.94 (s, 1H), 4.31 (d, J= 6.0 Hz, 2H), 4.23 - 4.15 (m, 2H), 1.04 - 0.93 (m, 2H), 0.04 (s, 9H). 13C NMR (126 MHz, CDCI3) delta 156.91, 137.95, 131.88, 129.32, 121.43, 63.53, 44.53, 17.92, -1.32. MS (ESI) 354.1 (M+H).
79%	With triethylamine; In water; N,N-dimethyl-formamide; at 20℃; for 12h;	4-Bromobenzylamine hydrochloride (354 mg, 1.59 mmol, 1 eq) was dissolved in DMF (6.4 mL) and water (2.1 mL) and stirred at room temperature. Triethylamine (0.33 mL, 2.39 mmol, 1.5 eq) and TeocOSu (454 mg, 1.75 mmol, 1.1 eq) were then added. After 12 hours, the mixture was diluted with EtOAc, washed with 1M HCl, saturated sodium bicarbonate, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by column chromatography (10 to 20% EtOAc/hexanes) gave a colorless oil (0.4158 g, 1.26 mmol, 79%). 1H NMR (500 MHz, CDCl3) delta 7.48-7.43 (m, 2H), 7.17 (d, J=8.1 Hz, 2H), 4.94 (s, 1H), 4.31 (d, J=6.0 Hz, 2H), 4.23-4.15 (m, 2H), 1.04-0.93 (m, 2H), 0.04 (s, 9H). 13C NMR (126 MHz, CDCl3) 156.91, 137.95, 131.88, 129.32, 121.43, 63.53, 44.53, 17.92, -1.32. MS (ESI) 354.1 (M+H).

Reference： [1]Patent: WO2013/106646,2013,A2 .Location in patent: Page/Page column 87-88
[2]Patent: US2014/356322,2014,A1 .Location in patent: Paragraph 0260 - 0262

35
[ 7425-63-0 ]
[ 13726-76-6 ]
[ 78269-85-9 ]
[ 1455474-90-4 ]
[ 1455474-67-5 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 9518 - 9523

36
[ 7425-63-0 ]
[ 13726-76-6 ]
[ 78269-85-9 ]
[ 1455474-58-4 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 9518 - 9523

37
[ 1404488-81-8 ]
[ 78269-85-9 ]
[ 1404488-99-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; at 20℃; for 67.5h;	Step 1 [0199] Compound (14) (23.8 g) was dissolved in 1,4-dioxane (500 ml). To the solution were added triethylamine (20.66 ml) and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (38.5 g), and the mixture was stirred at room temperature for 67.5 hours. After the reaction mixture was concentrated, to the mixture was added a saturated sodium bicarbonate solution, and this was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford compound (15) (47.7g, crude yield). 1H-NMR (CDCl3) delta: 0.04 (9H, s), 0.99 (2H, m), 1.74 (3H, s), 2.65 (1H, dd, J = 13.9, 7.0 Hz), 2.98 (1H, m), 4.12 (2H, m), 5.02 (1H, s), 5.07 (1H, m), 5.47 (1H, m), 6.22 (1H, s), 7.34 (1H, dd, J = 5.2, 1.7 Hz), 7.54 (1H, d, J = 1.7 Hz), 8.35 (1H, d, J = 5.2 Hz).

Reference： [1]Patent: EP2703401,2014,A1 .Location in patent: Paragraph 0199

38
[ 306-37-6 ]
[ 78269-85-9 ]
[ 1610596-16-1 ]

Yield	Reaction Conditions	Operation in experiment
64%		Synthesis of HIPS-AF594 A hydrazinyl-indole detectable label conjugate (HIPS-AF594) was synthesized as illustrated in Scheme 1, below: Compound 20 (2-(trimethylsilyl)ethyl 1,2-dimethylhydrazinecarboxylate) was synthesized from Compound 10 as follows. To a vigorously stirred suspension of sym-dimethylhydrazine dihydrochloride (7.5 mmol) in 15 mL MeCN was added triethylamine (18.8 mmol). The resulting white suspension was filtered and cooled to 0 C. While stirring, N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (3.7 mmol) in 2 mL MeCN was added dropwise over 10 min. The reaction was allowed to warm to RT over 16 hr with stirring. The crude reaction was concentrated in vacuo, then partitioned between 100 mL EtOAc and 30 mL water. The organic phase was washed 3*30 mL brine, dried over MgSO4, filtered and concentrated in vacuo to afford the product in a 64% yield. The product required no further purification. 1H NMR (400 MHz, CDCl3) delta 4.5 (bs, 1H), 4.20 (dd, J=8.8, 8.4 Hz, 2H), 3.03 (s, 3H), 2.57 (s, 3H), 1.02 (dd, J=8.8, 8.4 Hz, 2H), 0.04 (s, 9H).

Reference： [1]Patent: US2014/141025,2014,A1 .Location in patent: Paragraph 0562; 0563

39
3-(pyrazin-2-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl 3-(pyrazin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;	To a solution of 3-(pyrazin-2-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (1.0 g, 5.0 mmol) and N,N-diisopropylethylamine (1.7 mL, 9.9 mmol) in DMF (15 mL) was added 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (1.5 g, 5.9 mmol). Stirred for 18 h and poured into ice cold brine (150 mL). Precipitate filtered and washed successively with water and ether to afford the desired product as a white solid (1.5 g, 89%). MS (ESI): mass calcd. for C15H22N6O2Si, 346.2; m/z found, 347.2 [M+H]+. 1H NMR (500 MHz, CDCl3) delta 9.50 (d, J=1.4 Hz, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.52-8.48 (m, 1H), 4.91 (s, 2H), 4.60-4.45 (m, 2H), 4.25-4.14 (m, 2H), 3.87 (t, J=5.3 Hz, 2H), 1.07-0.92 (m, 2H), 0.01-0.04 (m, 9H).

Reference： [1]Patent: US2014/275096,2014,A1 .Location in patent: Paragraph 0126; 0138

40
[ 1251001-95-2 ]
[ 78269-85-9 ]
1-(2-(trimethylsilyl)ethyl) 1'-tert-butyl spiro[indoline-3,3'-pyrrolidine]-1,1'-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 20℃; for 22h;Cooling with ice;	t-Butyl spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate (10.0 g, 36.4 mmol) was dissolved in methylene chloride (73 mL). Thereafter, triethylamine (15.2 mL, 109 mmol) and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (14.2 g, 54.8 mmol) were added to the above obtained solution under cooling on ice, and the thus obtained mixture was then stirred at room temperature for 22 hours. Thereafter, the reaction solution was diluted with water, and was then extracted with chloroform. The organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was purified by silica gel column chromatography (hexane : ethyl acetate = 5 : 1) to obtain 1-(2-(trimethylsilyl)ethyl) 1'-tert-butyl spiro[indoline-3,3'-pyrrolidine]-1,1'-dicarboxylate (16.1 g, quant.) in the form of a light yellow oily product. 1H-NMR (400 MHz, CDCl3) delta: 0.70 (9H, s), 1.12 (2H, br), 1.56 (9H, br), 2.00 (1H, m), 2.17 (1H, m), 3.38-3.75 (4H, m) , 3.90 (2H, m) , 4.32 (2H, m) , 7.00 (1H, t, J = 8.0 Hz), 7.13 (1H, d, J = 8.0 Hz), 7.25 (1H, d, J = 8.0 Hz), 7.89 (1H, br)

Reference： [1]Patent: EP2781521,2014,A1 .Location in patent: Paragraph 0659; 0660

41
4-(2-chloro-5-iodo-phenoxy)-piperidine [ No CAS ]
[ 78269-85-9 ]
4-(2-chloro-5-iodo-phenoxy)-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine; In tetrahydrofuran; for 1h;Reflux; Inert atmosphere;	c. 4-(2-Chloro-5-iodo-phenoxy)-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester (Intermediate Vc) To a stirred solution of Intermediate Vb (3.02 g, 8.94 mmol) and triethylamine (2.49 mL, 17.9 mmol) in THF (45 mL) was added 1-[2-(trimethylsilyl)ethoxy-carbonyloxy]pyrrolidin-2,5-dione (2.78 g, 10.7 mmol) and heated to reflux under a N2 atmosphere. After 1 h, the reaction was cooled, partitioned between H2O and DCM, and the organic layer separated, dried over MgSO4, concentrated in vacuo and subjected to FCC, eluting with 0-50% EtOAc/cyclohexane, to afford the title compound (4.26 g, 99%). LCMS (Method 3) Rt 5.34 min.
99%	With triethylamine; In tetrahydrofuran; for 1h;Reflux; Inert atmosphere;	To a stirred solution of Intermediate Vb (3.02 g, 8.94 mmol) and triethylamine (2.49 mL, 17.9 mmol) in THF (45 mL) was added l-[2-(trimethylsilyl)ethoxy- carbonyloxy]pyrrolidin-2,5-dione (2.78 g, 10.7 mmol) and heated to reflux under a N2 atmosphere. After 1 h, the reaction was cooled, partitioned between H20 and DCM, and the organic layer separated, dried over MgSC^, concentrated in vacuo and subjected to FCC, eluting with 0 - 50 % EtOAc/cyclohexane, to afford the title compound (4.26 g, 99%). LCMS (Method 3) Rt 5.34 min

Reference： [1]Patent: US2014/364412,2014,A1 .Location in patent: Paragraph 0565; 0566
[2]Patent: WO2014/195402,2014,A1 .Location in patent: Page/Page column 125; 126

42
C₁₀H₁₃F₃N₂O*2ClH [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl 5-amino-2-(2,2-difluoroethoxy)-3-fluorobenzyl(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-ethyl-N,N-diisopropylamine; In methanol; for 0.5h;	j00180j Intermediate 13D (0.5 g, 1.628 mmol) and 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (0.422 g, 1.628 mmol) were dissolved in MeOH (16.28mL). DIPEA (0.85 3 mL, 4.88 mmol) was added, and the reaction was allowed to stir for 30 mm. The reaction was concentrated in vacuo and diluted with EtOAc, washed with brine, dried (Na2504), filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromatography (0 to 100% EtOAc in hexanes) to yieldInermediate 13 (0.5 83 g, 95%). 1H NMR (400 MHz, CHLOROFORM-d) oe ppm 5.80 -6.45 (3 H, m), 4.46 (2 H, s), 4.05 - 4.27 (4 H, m), 3.61 (2 H, br. s.), 2.85 (3 H, br. s.), 1.02(2 H, br. s.), 0.05 (9 H, br. s.).

Reference： [1]Patent: WO2014/201073,2014,A1 .Location in patent: Paragraph 00180

43
4-(difluoromethoxy)-3-((methylamino)methyl)aniline dihydrochloride [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl 5-amino-2-(difluoromethoxy)benzyl(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With N-ethyl-N,N-diisopropylamine; In methanol; for 0.5h;	j00205j Intermediate 19B (0.5 g, 1.8 17 mmol) and 2,5-dioxopyrrolidin-1-yl 2- (trimethylsilyl)ethyl carbonate (0.471 g, 1.817 mmol) were dissolved in MeOH (18.17 mL). DIPEA (0.952 mL, 5.45 mmol) was added and the reaction was allowed to stir for 30 mm. The reaction was concentrated in vacuo and diluted with EtOAc, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude material waspurified by silica gel column chromatography (gradient from 0 to 100% EtOAc in hexanes) to yield Intermediate 19 (0.57 8 g, 92% yield). 1H NMR (400 MHz, CHLOROFORM-d) oeppm 6.92(1 H, d, J=8.53 Hz), 6.15 -6.67(3 H, m), 4.47(2 H, s), 4.18 - 4.28 (2 H, m), 3.63 (2 H, br. s.), 2.87 (3 H, br. s.), 1.02 (2 H, br. s.), 0.04 (9 H, br. s.).

Reference： [1]Patent: WO2014/201073,2014,A1 .Location in patent: Paragraph 00205

44
4-(cyclopropylsulfonyl)-3-((methylamino)methyl)aniline dihydrochloride [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl 5-amino-2-(cyclopropylsulfonyl)benzyl(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-ethyl-N,N-diisopropylamine; In methanol; at 20℃; for 0.0833333h;	Intermediate 2: 2-(Trimethylsilyl)ethyl 5-amino-2-(cyclopropylsulfonyl)benzyl(methyl)carbamate j00128j To a mixture of 4-(cyclopropylsulfonyl)-3 -((methylamino)methyl)aniline dihydrochloride (1.09 g, 4.54 mmol) and 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (1.176 g, 4.54 mmol) in MeOH (25 mL) was added DIPEA (2.376 mL, 13.61mmol) and stirred at rt for 5 mm. The reaction mixture was concentrated under reduced pressure, diluted with EtOAc, and washed with brine. The crude product was subjected to silica gel column chromatography (0-100% EtOAc/Hex gradient) to yield Intermediate 2 (1.744 g, 80%). 1H NMR 78017-063-02 (500 MHz, CD3OD) oe ppm 8.25 (d, J = 8.80Hz, 1 H) 7.30 (d, J = 8.25 Hz, 1 H) 7.22 (s, 1 H) 6.95 (s, 2 H) 5.54 (s, 2 H) 4.91 (d, J =17.60 Hz, 2 H) 3.68 (s, 3 H) 3.55 - 3.63 (m, 1 H) 1.66 - 1.85 (m, 6 H) 0.81 (d, J = 43.44 Hz, 9 H).

Reference： [1]Patent: WO2014/201073,2014,A1 .Location in patent: Paragraph 00128
[2]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 67 - 72

45
(2S,1'S,2'R)-3-(2-trifluoromethylcyclopropyl)alanine [ No CAS ]
[ 78269-85-9 ]
N-Teoc-(2S,1'S,2'R)-3-(2'-trifluoromethylcyclopropyl)alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%		A solution of TeocOSu (43 mg, 164 mumol) in acetone (1 mL) was added to a vigorously stirred solution of (2S,1'S,2'R)-3-(2'-trifluoromethylcyclopropyl)alanine (2S,1'S,2'R)-9a (27 mg, 137 mumol) and NaHCO3 (24 mg, 286 mumol) in water (1 mL) (if an emulsion formed, acetone and/or water was added to obtain a homogeneous solution), and stirring was continued for another 2 h. N,N-Dimethylaminopropylamine (8 muL, 6,4 mg, 52 mumol) was then added. After an additional 10 min, acetone was removed under reduced pressure, and the pH of the residual aqueous solution was adjusted to 2-3 with aq. 1 M KHSO4. The resulting emulsion was extracted with diethyl ether (50 mL), and the ethereal layer was washed with aq. 1 M KHSO4 (2 × 10 mL), water (3 × 10 mL), brine (2 × 5 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was dried overnight in vacuo to give a glass-like product (38 mg, 81%). Rf = 0.24 [EtOAc/hexane 1:3 (2% AcOH)]; = +22.80 (c = 0.46, CHCl3); 1H NMR (250 MHz, CDCl3): delta = 0.04 (s, 9H), 1.00 (dd, J = 9.5 Hz, 7.3 Hz, 2 H), 1.11-1.18 (m, 1 H), 1.60-1.95 (m, 2 H), 1.98-2.19 (m, 2 H), 4.14-4.23 (m, 3 H), 4.33-4.59 (m, 1 H), 5.33-5.46 (m, 1 H), 7.08-7.25 (bs, 1 H); 13C NMR (62.9 MHz, CDCl3): delta = -1.9 (+), 10.2 (-), 17.3 (-), 22.0 (+), 33.1 and 33.3 (-), 52.7 (+), 53.2 (+), 59.0 (+), 63.7 (+), 64.8 (-), 115.6 (q, J = 271.4 Hz), 157.4 (-), 174.5 and 174.8 (-).

Reference： [1]Beilstein Journal of Organic Chemistry,2014,vol. 10,p. 2844 - 2857

46
(2S,1'S,2'R)-3-(2-difluoromethylcyclopropyl)alanine [ No CAS ]
[ 78269-85-9 ]
N-Teoc-(2S,1'S,2'R)-3-(2'-difluoromethylcyclopropyl)alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%		A solution of TeocOSu (59 mg, 228 mumol) in acetone (1 mL) was added to a vigorously stirred solution of (2S,1'S,2'R)-3-(2'-difluoromethylcyclopropyl)alanine [(2S,1'S,2'R)-9b] (34 mg, 190 mumol) and NaHCO3 (34 mg, 396 mumol) in water (1 mL) (if an emulsion formed, acetone and/or water was added to obtain a homogeneous solution), and stirring was continued for another 2 h. N,N-Dimethylaminopropylamine (10 muL, 7.5 mg, 73 mumol) was then added. After an additional 10 min, acetone was removed under reduced pressure, and the pH of the residual aqueous solution was adjusted to 2-3 with aq. 1 M KHSO4. The resulting emulsion was extracted with diethyl ether (50 mL), and the ethereal layer was washed with aq. 1 M KHSO4 (2 × 10 mL), water (3 × 10 mL), brine (2 × 5 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was dried overnight in vacuo to give (2S,1'S,2'R)-53b (41 mg, 67%) as the glass-like product, Rf = 0.26 (EtOAc/hexane 1:3, +2% AcOH); = +20.2 (c = 0.26, CHCl3); 1H NMR (250 MHz, CDCl3, as the cyclohexylammonium salt): delta = 0.01 (s, 9 H), 0.38-0.57 (m, 1 H), 0.65-0.80 (m, 1 H), 0.85-1.49 (m, 9 H), 1.50-1.85 (m, 5 H), 1.85-2.03 (m, 2 H), 2.72-3.00 (m, 1 H), 3.89-4.22 (m, 3 H), 5.50 (td, J = 57.6 Hz, 4.1 Hz, 1 H), 5.71 (d, J = 7.3 Hz, 1 H), 7.35 (bs, 3 H); 13C NMR (62.9 MHz, CDCl3, major of two rotamers): delta = -1.6 (+), 7.2 (-), 110.6 (-), 17.6 (+), 20.4 (+, t, J = 24.0 Hz), 35.2 (-), 53.5 (+), 63.7 (-), 116.8 (+, t, J = 237.5 Hz), 156.3 (-), 176.3 (-).

Reference： [1]Beilstein Journal of Organic Chemistry,2014,vol. 10,p. 2844 - 2857

47
(2S,1'S,2'R)-3-(2-fluoromethylcyclopropyl)alanine [ No CAS ]
[ 78269-85-9 ]
N-Teoc-(2S,1'S,2'R)-3-(2'-fluoromethylcyclopropyl)alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%		A solution of TeocOSu (43 mg, 164 mumol) in acetone (1 mL) was added to a vigorously stirred solution of (2S,1'S,2'R)-3-(2'-fluoromethylcyclopropyl)alanine [(2S,1'S,2'R)-9c] (27 mg, 137 mumol) and NaHCO3 (24 mg, 286 mumol) in water (1 mL) (if an emulsion formed, acetone and/or water was added to obtain a homogeneous solution), and stirring was continued for another 2 h. N,N-Dimethylaminopropylamine (8 muL, 6.4 mg, 52 mumol) was then added. After an additional 10 min, acetone was removed under reduced pressure, and the pH of the residual water solution was adjusted to 2-3 with aq. 1 M KHSO4 solution. The resulting emulsion was extracted with diethyl ether (50 mL), and the ethereal layer was washed with aq. 1 M KHSO4 (2 × 10 mL), water (3 × 10 mL), brine (2 × 5 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was dried overnight in vacuo to give the glass-like product 53c (38 mg, 71%). Rf=0.24 [EtOAc/hexane 1:3 (2% AcOH)];S49= +28.2 (c = 0.34, CHCl3); 1H NMR (250 MHz, CDCl3): delta = 0.03 (s, 9 H), 0.99 (dd, J = 9.5 Hz, 7.3 Hz, 2 H), 1.05-1.13 (m, 1 H), 1.56-1.89 (m, 2 H), 2.01-2.22 (m, 2 H), 4.16-4.24 (m, 3 H), 4.32-4.54 (m, 1 H), 5.35-5.43 (m, 1 H), 7.00-7.30 (bs, 1 H); 13C NMR (62.9 MHz, CDCl3): delta = -1.9 (+), 3.3 (+), 10.1 (-), 12.0 (+), 17.7 (-), 34.3 (-), 52.3 (+), 64.6 (-), 105.1 (d, J = 275 Hz), 154.7 (Cquat), 175.2 (Cquat).

Reference： [1]Beilstein Journal of Organic Chemistry,2014,vol. 10,p. 2844 - 2857

48
[ 6638-79-5 ]
[ 75266-38-5 ]
[ 78269-85-9 ]
(Z)-2-(trimethylsilyl)ethyl (1-(methoxy(methyl)amino)-1-oxobut-2-en-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%		L-Vinylglycine hydrochloride M (320 mg, 2.33 mmol) was dissolved in dioxane/H2O (26 mL, 0.017M, 1:1 dioxane:H2O) and was treated with NaHCO3 (391 mg, 4.66 mmol) and N-[2-(Trimethylsilyl)ethoxycarbonyloxy]succinimide (633 mg, 2.44 mmol) sequentially at room temperature. The resulting mixture was stirred at room temperature for 24h and was then concentrated in vacuo to a volume of ca. 10 mL. The resulting solution was acidified with 10percent KHSO4 to ~pH6.5, was extracted with DCM (3 x 50 mL), dried over Na2S04 and concentrated to dryness. The resulting oil was dissolved in THF (23 mL) at ambient temperature and was treated with HOBt (944 mg, 6.99 mmol, 3.0 eq to VGly-HCl), HNMe(OMe)-HCl (341 mg, 3.5 mmol, 1.15 eq to VGly-HCl), EDC (671 mg, 3.5 mmol, 1.15 eq to VGly-HCl), and Et3N (975 mu^, 6.99 mmol, 3.0 eq to VGly-HCl) sequentially and the mixture was allowed to stir for lOh at ambient temperature. The crude mixture was filtered through a plug of celite and concentrated in vacuo. The resulting oil was purified by silica gel chromatography eluting with a gradient from hexanes to 60percentEtOAc/hexanes. Fractions containing the desired product were combined and concentrated in vacuo to provide (Z)- 2-(trimethylsilyl)ethyl (l-(methoxy(methyl)amino)-l-oxobut-2-en-2-yl)carbamate as a pale yellow oil (280 mg, 42percent from VGly-HCl). -NMR (500MHz, CDC13) delta 6.28 (s, 1H); 5.81-5.68 (m, 1H); 4.19-4.10 (m, 2H); 3.67 (s, 3H); 3.24 (s, 3H); 1.70 (d, J=7.0Hz, 3H); 1.03-0.91 (m, 2H); -0.01 (s, 9H). 13C-NMR (125MHz, CDCI3) delta 167.2, 154.2, 130.1, 121.2, 64.1, 61.1, 34.3, 17.8, 12.6, -1.34. HRMS (ESI-TOF) 289.1578 [M+H]+ (calculated for Ci2H25N204Si = 289.1584).

Reference： [1]Patent: WO2015/26796,2015,A1 .Location in patent: Paragraph 0082

49
(2S,5R)-5-(benzyloxyamino)piperidine-2-carboxylic acid dihydrochloride [ No CAS ]
[ 78269-85-9 ]
(2S,5R)-5-((benzyloxy)amino)-1-(2-trimethylsilylethoxycarbonyl)piperidine-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		Example 101 (2S,5R)-5-((Benzyloxy)amino)-1-(2-trimethylsilylethoxycarbonyl)piperidine-2-carboxylic acid (IV-a4) [0619] (2S,5R)-5-(benzyloxyamino)piperidine-2-carboxylic acid, dihydrochloride (3.23 g, 10 mmol) described in Example 11 were added 1,4-dioxane (10 mL), water (15 mL) and 5M sodium hydroxide (6 mL), and stirred under ice cooling. Potassium carbonate (1.38 g), N-(trimethylsilylethyloxycarbonyloxy)succinimide (2.85 g) were added further to the mixture, and the temperature was elevated to room temperature, followed by stirring overnight. The mixture was adjusted to pH 4 with citric acid · monohydrate, and extracted with ethyl acetate (50 mL) twice. The organic layer was washed with water and saturated brine and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate/hexane = 1:1 ? 1:0) to afford 3.41 g of the title compound (yield 86%). 1H NMR (400 MHz, CDCl3) delta 0.01 (s, 9H), 0.97 (t, J = 8.3 Hz, 2H), 1.59-1.68 (m, 2H), 1.97-2.02 (m, 2H), 3.00-3.25 (m, 2H), 4.08-4.19 (m, 3H), 4.65 (d, J = 11.3 Hz, 1H), 4.71 (d, J = 11.3 Hz, 1H), 4.72-4.89 (m, 1H), 7.23-7.32 (m, 5H); MS m/z 395 [M+H]+.

Reference： [1]Patent: EP2857401,2015,A1 .Location in patent: Paragraph 0619

50
2-((1S,2R,3S,5S)-3-aminobicyclo[3.1.0]hexan-2-yl)isoindoline-1,3-dione [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(1,3-dioxoisoindolin-2-yl)bicyclo[3.1.0]hexan-3-yl-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.5 g	With triethylamine; In 1,4-dioxane; toluene; at 20℃; for 1.5h;	A solution of 2-((1S,2R,3S,5S)-3-aminobicyclo[3.1.0]hexan-2-yl)isoindoline-1,3-dione (2.0 g, 8.264 mmol), 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (3.2 g, 12.396 mmol) and triethylamine (3.4 mL, 24.792 mmol) in dioxane/ water (100 mL, v/v=1/1) was stirred at room temperature for 1.5 hours. The reaction mixture was then diluted with ethyl acetate (100 mL), washed by 1 M hydrochloric acid (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and brine (50 mL). The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether=1:4) to afford the title compound (2.5 g, 78%) as a yellow oil. MS (ES+) C20H26N2O4Si requires: 386, found: 410 [M+23]+.

Reference： [1]Patent: US2015/119405,2015,A1 .Location in patent: Paragraph 0245; 0266; 0267

51
cis-tert-butyl 3-amino-4-(benzyloxycarbonylamino)piperidine-1-carboxylate [ No CAS ]
[ 78269-85-9 ]
cis-tert-butyl 4-(benzyloxycarbonylamino)-3-((2-(trimethylsilyl)ethoxy)carbonylamino)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine; In 1,4-dioxane; water; at 20℃; for 4h;	A solution of cis-tert-butyl 3-amino-4-(benzyloxycarbonylamino)piperidine-1-carboxylate (3.0 g, 8.6 mmol), 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (2.5 g, 9.5 mmol) and triethylamine in dioxane/ water (40 mL, v/v=1/1) was stirred at room temperature for 4 hours. After that, the solution was diluted with ethyl acetate (200 mL), and washed by 1 M hydrochloric acid (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4/1) to afford the title compound (3.5 g, 83%) as a white solid. MS (ES+) C24H39N3O6Si requires: 493, found: 516 [M+23]+

Reference： [1]Patent: US2015/119405,2015,A1 .Location in patent: Paragraph 0293; 0302; 0303

52
[ 78269-85-9 ]
[ 72648-80-7 ]
ethyl 2-((2-aminoethyl)((2-(trimethylsilyl)ethoxy)carbonyl)amino)acetate para-toluene sulphonate [ No CAS ]

Reference： [1]Patent: US2015/119385,2015,A1

53
[ 78269-85-9 ]
[ 72648-80-7 ]
ethyl 2-((2-((tert-butoxycarbonyl)amino)ethyl)((2-(trimethylsilyl)ethoxy)carbonyl)amino)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dichloromethane; water; at 20℃; for 20h;	[0790] 2,5-Dioxopyrrolidin-1-yl(2-(trimethylsilyl)ethyl)carbonate (5.44 g, 20.99 mmol) was added to a mixture ofethyl 2-((2-((tert-butoxycarbonyl)amino )ethyl)amino )acetate(intermediate 126, 4.70 g, 19.08 mmol) and K2C03(5.80 g, 42.0 mmol) in DCM (60 ml) and water (30 ml) atroom temperature. The reaction mixture was vigorouslystirred for 20 h at room temperature, partitioned betweensaturated aqueous NaHC03 solution and DCM, the mixture extracted with DCM (2x), the combined organic layers driedover Na2S04 and evaporated to give the title compound as ayellow solid. 1H NMR (400 MHz, DMSO-d6 ) o6.71 (d, br,lH), 4.16-3.93 (m, 6H), 3.30-3.21 (m, 2H), 3.09-3.00 (m,2H), 1.37 (s, 9H), 1.19 (t, 3H), 0.99-0.94 (m, lH), 0.90-0.85(m, lH), 0.05 (s, 9H).
	With potassium carbonate; In dichloromethane; water; at 20℃; for 20h;	2,5-Dioxopyrrolidin-1-yl (2-(trimethylsilyl)ethyl) carbonate (5.44 g, 20.99 mmol) was added to a mixture of ethyl 2-((2-((tert-butoxycarbonyl)amino)ethyl)amino)acetate (intermediate 126, 4.70 g,19.08 mmol) and K2C03 (5.80 g, 42.0 mmol) in DCM (60 ml) and water (30 ml) at room temperature. The reaction mixture was vigorously stirred for 20 h at room temperature, partitioned between saturated aqueous NaHCO3 solution and DCM, the mixture extracted with DCM (2x), the combined organic layers dried over Na2SO4 and evaporated to give the title compound as a yellow solid.1H NMR (400 MHz, DMSO-d5) 56.71 (d, br, IH), 4.16-3.93 (m, 6H), 3.30-3.21 (m, 2H),3.09-3.00 (m, 2H), 1.37 (s, 9H), 1.19 (t, 3H), 0.99-0.94 (m ,IH), 0.90-0.85 (m ,IH), 0.05 (s,9H).

Reference： [1]Patent: US2015/119385,2015,A1 .Location in patent: Paragraph 0790
[2]Patent: WO2015/59668,2015,A1 .Location in patent: Page/Page column 127; 128

54
[ 78269-85-9 ]
[ 17994-94-4 ]
methyl 7-(2-trimethylsilanylethoxycarbonylamino)-heptanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In dichloromethane; at 20℃; for 5h;Inert atmosphere;	Methyl 7-(2-trimethylsilanyl-ethoxycarbonylamino)-heptanoate Methyl 7-amino-heptanoate hydrochloride (7.0 g, 35.9 mmol) was dissolved in dichloromethane (75.4 mL), and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (10.0 g, 38.6 mmol) and triethylamine (10 mL, 71.7 mmol) were then added at room temperature. The mixture was stirred for 5 hours, and then quenched with water (100 mL), and separated. The aqueous layer was extracted with dichloromethane (50 mL). The organic layers were combined, then dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure to obtain 8.89 g (29.3 mmol, 82% yield) of methyl 7-(2-trimethylsilanyl-ethoxycarbonylamino)-heptanoate. 1H-NMR (CDCl3) delta: 0.04 (9H, s), 0.97 (2H, br.t, J = 8.4 Hz), 1.20-1.76 (8H, m), 2.31 (2H, t, J = 7.4 Hz), 3.07-3.23 (2H, m), 3.67 (3H, s), 4.14 (2H, br.t, J = 8.4 Hz), 4.50-4.70 (1H, m)

Reference： [1]Patent: EP2886530,2015,A1 .Location in patent: Paragraph 1399; 1401; 1402; 1403; 1404

55
[ 78269-85-9 ]
[ 7746-27-2 ]
2-trimethylsilylethyl 6-bromo-3-methylindazole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.44 g	With sodium hydride; In 1,4-dioxane; at 1 - 40℃; for 2h;	(3) Synthesis of 2-trimethylsilylethyl <strong>[7746-27-2]6-bromo-3-methylindazole</strong>-1-carboxylate [53-3] (hereinafter referred to as a compound [53-3]) To a solution of <strong>[7746-27-2]6-bromo-3-methyl-1H-indazole</strong> (1.0 g), which was obtained by the method described in the document (JP 2009-528363 W), in 1,4-dioxane (24 mL) were added sodium hydride (227 mg) and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (1.84 g) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (1.44 g) as a colorless oil. ESI-MS found: 355 [M + H]+

Reference： [1]Patent: EP2878594,2015,A1 .Location in patent: Paragraph 0633; 0634

56
2,2,2-trifluoro-1-((3aR,7aS)-octahydro-1H-pyrrolo[2,3-c]pyridin-1-yl)ethanone [ No CAS ]
[ 78269-85-9 ]
(3aS,7aS)-2-(trimethylsilyl)ethyl hexahydro-1H-pyrrolo[2,3-c]pyridine-6(2H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		Step 3. (3aS,7aS)-2-(Trimethylsilyl)ethyl hexahydro-1H-pyrrolo[2,3-c]pyridine-6(2H)-carboxylate. To a flask containing 2,2,2-trifluoro-1-((3aR,7aS)-octahydro-1H-pyrrolo[2,3-c]pyridin-1-yl)ethanone (3.29, 14.8 mmol) was added DCM (30 mL), TEA (10.3 mL, 73.9 mmol) and Teoc-OSuc (4.19 g, 16.3 mmol). The reaction mixture was stirred at 25 C. overnight and then poured into saturated NaHCO3/DCM. The layers were separated and the organic layer dried (Na2SO4) and the solvent removed to give (3aS,7aS)-2-(trimethylsilyl)ethyl hexahydro-1H-pyrrolo[2,3-c]pyridine-6(2H)-carboxylate. To (3aS,7aS)-2-(trimethylsilyl)ethyl hexahydro-1H-pyrrolo[2,3-c]pyridine-6(2H)-carboxylate (5.42 g, 14.8 mmol) was added MeOH (25 mL) and K2CO3 (4.09 g, 29.6 mmol). The mixture was stirred at rt for 4 hrs and then filtered and concentrated. The residue was taken up into DCM and washed with saturated NaHCO3 and brine. The organic extract was dried (Na2SO4) and the solvent removed to give the desired product (3.2 g, 80%). LC/MS (M+H) 271.2. 1H NMR (400 MHz, CDCl3) delta -0.17-0.03 (m, 9H) 0.80-1.00 (m, 2H) 1.26 (dd, 1H) 1.33-1.72 (m, 4H) 1.77-1.94 (m, 1H) 1.99-2.16 (m, 1H) 2.80-3.14 (m, 3H) 3.34 (dd, 1H) 3.56-3.76 (m, 2H) 4.04-4.21 (m, 2H) 5.27 (s, 1H).

Reference： [1]Patent: US2015/158864,2015,A1 .Location in patent: Paragraph 0399

57
(4-bromophenyl)methanamine hydrochloride [ No CAS ]
[ 78269-85-9 ]
[ 1448189-28-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In water; N,N-dimethyl-formamide; at 20℃; for 12h;	2-(trimethylsilyl)ethyl 4-bromobenzylcarbamate 4-Bromobenzylamine hydrochloride (354 mg, 1.59 mmol, 1 eq) was dissolved in DMF (6.4 mL) and water (2.1 mL) and stirred at room temperature. Triethylamine (0.33 mL, 2.39 mmol, 1.5 eq) and TeocOSu (454 mg, 1.75 mmol, 1.1 eq) were then added. After 12 hours, the mixture was diluted with EtOAc, washed with 1M HCl, saturated sodium bicarbonate, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by column chromatography (10 to 20% EtOAc/hexanes) gave a colorless oil (0.4158 g, 1.26 mmol, 79%). 1H NMR (500 MHz, CDCl3) delta 7.48-7.43 (m, 2H), 7.17 (d, J=8.1 Hz, 2H), 4.94 (s, 1H), 4.31 (d, J=6.0 Hz, 2H), 4.23-4.15 (m, 2H), 1.04-0.93 (m, 2H), 0.04 (s, 9H). 13C NMR (126 MHz, CDCl3) delta 156.91, 137.95, 131.88, 129.32, 121.43, 63.53, 44.53, 17.92, -1.32. MS (ESI) 354.1 (M+H).

Reference： [1]Patent: US2016/45607,2016,A1 .Location in patent: Paragraph 0258; 0259

58
[ 78269-85-9 ]
[ 157887-84-8 ]
C₁₇H₂₄N₂O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine; In dichloromethane; at 20℃;	Step 3: Compound 8b (lOOmg, 0.454 mmol) was dissolved in anhydrous DCM (4.5 mL) TEA (127 mu, 0.908 mmol) and 2,5-dioxopyrrolidin-l-yl (2-(trimethylsilyl)ethyl) carbonate (177 mg, 0.681 mmol) were added and the reaction stirred at room temperature overnight. The reaction was diluted with DCM, washed with brine, dried, filtered, and evaporated. The crude residue was purified by silica gel flash chromatography (EtO Ac/Hex, gradient, 0% to 40%) to obtain compound 8c (148mg, 89% yield). LCMS = 5.91 min (8 min method). 1H NMR (400 MHz, CDC13): delta 7.86-7.83 (m, 2H), 7.73-7.69 (m, 2H), 7.39 (bs, 1H), 4.26-4.20 (m, 2H), 3.94 (t, 2H, = 6.0 Hz), 3.83 (t, 2H, 6.9Hz), 2.06-1.98 (m, 2H), 1.05-0.98 (m, 2H),
148 mg	With triethylamine; In dichloromethane; at 20℃;	Compound 8b (lOOmg, 0.454 mmol) was dissolved in anhydrous DCM (4.5 mL) TEA (127 mu, 0.908 mmol) and 2,5-dioxopyrrolidin-l-yl (2-(trimethylsilyl)ethyl) carbonate (177 mg, 0.681 mmol) were added and the reaction stirred at room temperature overnight. The reaction was diluted with DCM, washed with brine, dried, filtered, and evaporated. The crude residue was purified by silica gel flash chromatography (EtO Ac/Hex, gradient, 0% to 40%) to obtain compound 8c (148mg, 89% yield). LCMS = 5.91 min (8 min method). 1H NMR (400 MHz, CDC13): delta 7.86-7.83 (m, 2H), 7.73-7.69 (m, 2H), 7.39 (bs, 1H), 4.26-4.20 (m, 2H), 3.94 (t, 2H, / = 6.0 Hz), 3.83 (t, 2H, 6.9Hz), 2.06-1.98 (m, 2H), 1.05- 0.98 (m, 2H), 0.04 (s, 9H).

Reference： [1]Patent: WO2017/4026,2017,A1 .Location in patent: Page/Page column 257; 258
[2]Patent: WO2016/36794,2016,A1 .Location in patent: Paragraph 454

59
C₈H₉NO₂*C₂HF₃O₂ [ No CAS ]
[ 78269-85-9 ]
C₁₄H₂₁NO₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium carbonate; In tetrahydrofuran; water; at 0 - 20℃;	10% Aqueoussodium carbonate (7.2 mL, 7.95 mmol, 5 eq) was added to a solution of crude (S)PheGly trifluoroacetate salt (545 mg, 1.59 mmol, 1 eq) in THF (8 mL). Themixture was cooled to 0C, then a solution of Teoc-OSu (415 mg, 1.59 mmol, 1eq) in THF (8 mL) was slowly added. The reaction mixture was left understirring for 1 hour at 0C, then overnight at rt. The solvent was partiallyremoved under reduced pressure, then the mixture was diluted with water (20 mL)and acidified with 1N HCl to pH 2-3. After extraction with CH2Cl2 (3 x 50mL) and drying with Na2SO4,the solvent was removed under reduced pressure, yielding pure 21 (453 mg, 1.53 mmol) as a white solid.Yield: 96% (2 steps). 1H NMR (400 MHz, acetone-d6): delta (ppm) 7.48 (d, J 7.6 Hz, 2H, H4), 7.36(m, 3H, H5, H6), 6.72 (bd, 1H, NH), 5.33 (d, J 7.6 Hz, 1H, H1), 4.12 (t, J 8.4Hz, 2H, H8), 0.97 (t, J 8.4 Hz, 2H, H9), 0.03 (s, 9H, H10).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4613 - 4619

60
[ 1096770-58-9 ]
[ 78269-85-9 ]
C₁₁H₂₃NO₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 16h;	A solution of compound 16 (4.00 g, 26.04 mmol) and triethylamine (5.44 mL, 39.06 mmol) in water (35 mL) and 1,4-dioxane (35 mL) was stirred at room temperature as compound 2 (7.428 g, 28.64 mmol) was added. The resulting mixture was stirred at room temperature overnight. After 16 h, the reaction mixture was diluted with water (125 mL) and extracted with ethyl acetate (125 mL×2). The extracts were washed with water (125 mL×1), combined, dried (Na2SO4), and concentrated. The residue was purified by column chromatography on silica gel (120 g column used with cartridge) using hexanes-ethyl acetate as eluents to get compound 17: 1H NMR (400 MHz, Chloroform-d) delta 4.68 (s, 1H), 4.23-4.13 (m, 2H), 4.01 (ddd, J=11.4, 4.8, 1.1 Hz, 1H), 3.92 (dd, J=12.0, 4.8 Hz, 1H), 3.56 (ddd, J=12.3, 9.7, 5.4 Hz, 1H), 3.48 (td, J=9.3, 4.8 Hz, 1H), 3.41 (td, J=11.9, 2.3 Hz, 1H), 3.14 (dd, J=11.4, 9.5 Hz, 1H), 1.99-1.87 (m, 1H), 1.55 (dtd, J=13.2, 11.6, 4.8 Hz, 1H), 1.06-0.91 (m, 2H), 0.04 (s, 9H). LCMS-ESI+ (m/z): [M+H-C2H4]+ calculated for C9H20NO4Si: 234.12. found: 233.95.

Reference： [1]Patent: US2016/289246,2016,A1 .Location in patent: Paragraph 0278; 0279

61
[ 78269-85-9 ]
[ 190792-70-2 ]
C₁₀H₂₁NO₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 16h;	A solution of the compound 32 (2.000 g, 19.39 mmol) and triethylamine (4.055 mL, 29.09 mmol) in water (15 mL) and 1,4-dioxane (15 mL) was stirred at rt as compound 2 (5.533 g, 21.33 mmol) was added. The resulting mixture was stirred at room temperature overnight. After 16 h, the reaction mixture was diluted with water (125 mL) and extracted with ethyl acetate (125 mL×2). The extracts were washed with water (125 mL×1), combined, dried (Na2SO4), and concentrated. The residue was purified by column chromatography on silica gel (120 g column) using hexanes-ethyl acetate as eluents to get compound 33: 1H NMR (400 MHz, Chloroform-d) delta 4.86 (d, J=6.3 Hz, 1H), 4.30 (dt, J=5.1, 2.5 Hz, 1H), 4.16 (dd, J=12.3, 4.9 Hz, 2H), 4.07-4.03 (m, 2H), 3.99 (tt, J=5.3, 2.2 Hz, 1H), 3.67 (ddd, J=20.4, 9.7, 2.9 Hz, 2H), 2.71 (s, 1H), 1.05-0.91 (m, 2H), 0.04 (s, 9H).

Reference： [1]Patent: US2016/289246,2016,A1 .Location in patent: Paragraph 0297; 0298

62
[ 1240390-32-2 ]
[ 78269-85-9 ]
C₁₁H₂₃NO₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; water; at 20℃; for 71h;	A solution of (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (1, 2667 mg, 22.77 mmol) and triethylamine (4.76 mL, 34.15 mmol) in water (23 mL) and 1,4-dioxane (23 mL) was stirred at room temperature as 1-[(2-trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (2, 6498 mg, 25.06 mmol) was added. The resulting mixture was stirred at room temperature. After 71 h, the reaction mixture was diluted with water (125 mL) and extracted with ethyl acetate (125 mL×2). The extracts were washed with water (125 mL×1), combined, dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel (120 g column) using hexanes-ethyl acetate as eluents and the product containing fractions were pooled and concentrated to get compound 3: 1H NMR (400 MHz, Chloroform-d) delta 4.81 (s, 1H), 4.25-4.09 (m, 2H), 4.09-3.97 (m, 1H), 3.91 (dt, J=11.6, 4.7 Hz, 1H), 3.69 (s, 1H), 3.52 (d, J=9.5 Hz, 1H), 3.46 (ddd, J=11.9, 9.1, 3.1 Hz, 1H), 3.21 (t, J=9.4 Hz, 1H), 2.46 (s, 1H), 2.01 (dddd, J=13.1, 5.4, 4.4, 3.2 Hz, 1H), 1.65 (dtd, J=13.2, 8.8, 4.1 Hz, 1H), 1.07-0.90 (m, 2H), 0.04 (s, 9H). LCMS-ESI+ (m/z): [M+H-C2H4]+ calculated for C9H20NO4Si: 234.12. found: 233.94.

Reference： [1]Patent: US2016/289246,2016,A1 .Location in patent: Paragraph 0262; 0263

63
[ 54987-14-3 ]
[ 78269-85-9 ]
5-(benzyloxy)-3-[2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)ethyl]-1H-indole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13.8 g	With triethylamine; In 1,4-dioxane; water; at 20℃;	[0163] In a mixture of 60.0 mL of dioxane and 60.0 mL of water was suspended 12.0 g of 3-(2-aminoethyl)-5-(benzyloxy)-1H-indole-2-carboxylic acid, and 18.9 mL of triethylamine and 12.0 g of N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimidewere added thereto, followed by stirring at room temperature overnight. After the completion of the reaction, thereaction mixture was concentrated under reduced pressure until the volume reached a half thereof. The reaction mixturewas adjusted to be acidic by adding 1 M hydrochloric acid and then ethyl acetate was added thereto. The precipitatedsolid was separated by filtration and the filtrate was extracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reducedpressure. The obtained solid was washed with hexane:ethyl acetate = 5:1 to obtain 13.8 g of 5-(benzyloxy)-3-[2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)ethyl]-1H-indole-2-carboxylic acid as a solid.

Reference： [1]Patent: EP3095781,2016,A1 .Location in patent: Paragraph 0163

64
[ 58578-45-3 ]
(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropane-1-amine [ No CAS ]
[ 78269-85-9 ]
[ 13831-31-7 ]
(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(hydroxyacetyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
312 mg		First, Intermediate C52 was reductively alkylated with benzyl (2S)-2- [(benzyloxy)carbonyl]amino} -4- oxobutanoate analogously to Intermediate C2. First, Intermediate C52 was reductively alkylated with benzyl (2S)-2- { [(benzyloxy)carbonyl] amino} -4-oxobutanoate analogously to C2. The secondary amino group was then acylated with 2-chloro-2-oxoethyl acetate as described for Intermediate C27, and the two ester groups were then hydrolysed with 2M lithium hydroxide solution in methanol. Theintermediate obtained in this manner was dissolved in ethanol, palladium on carbon (10%) was added and the mixture was hydrogenated at RT with hydrogen under standard pressure for 1 h.500 mg (0.886 mmol) of this frilly deprotected intermediate were taken up in 60 ml of dioxane, and 253 mg (0.975 mmol) of 1 -( { [2-(trimethylsilyl)ethoxy]carbonyl} oxy)pyrrolidine-2,5-dione and 198 jid of triethylamine were added. After 24 h of stirring at RT, the reaction was concentrated and the residue waspurified by preparative HPLC. Combination of the appropriate fractions, concentration under reduced pressure and drying under high vacuum gave 312 mg (50% of theory) of the title compound.

Reference： [1]Patent: WO2016/207090,2016,A2 .Location in patent: Page/Page column 258

65
N₁-[5-chloro-2-(methylsulfanyl)pyrimidin-4-yl]benzene-1,2-diamine [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl N-(2-[5-chloro-2-(methylsulfanyl)pyrimidin-4-yl]amino}phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In N,N-dimethyl-formamide; acetonitrile; at 70℃; for 5h;	Triethylamine (0.48 mL, 3.46 mmol) and 1-[2-(trimethylsilyl) ethoxycarbonyloxy]pyrrolidin- 2,5-dione (0.58 g, 2.26 mmol) were added to a stirred solution of A/1-[5-chloro-2- (methylsulfanyl)pyrimidin-4-yl]benzene-1 ,2-diamine (Preparation 7) (0.46 g, 1.73 mmol) in MeCN/DMF (1 :1 , 5 mL). The reaction was stirred at 70 C for 5 hours. The reaction was diluted with EtOAc (20 mL) and washed with a saturated solution of sodium bicarbonate (3 x 20 mL) and brine (3 x 20 mL). The organic phase was dried over MgS04 and the solvent was removed in vacuo. The crude product was purified by flash column chromatography with 3: 7 EtOAc: Petrol to give 2-(trimethylsilyl)ethyl A/-(2-[5-chloro-2-(methylsulfanyl) pyrimidin-4-yl]amino}phenyl) carbamate (0.50 g, 1.21 mmol, 80%) as a colourless oil. H NMR (400 MHz, DMSO-d6) delta ppm 9.13 (br s, 1 H), 8.69 (br s, 1 H), 8.27 (s, 1 H), 7.63-7.54 (m, 1 H), 7.44 (m, 1 H), 7.27-7.13 (m, 2H), 4.19 (t, J = 8.4 Hz, 2H), 2.30 (s, 3H), 1.01 (t, J = 8.4 Hz, 2H), 0.03 (s, 9H). LC-MS: [M+H]+ = 411.

Reference： [1]Molecular BioSystems,2016,vol. 12,p. 2867 - 2874
[2]Patent: WO2017/212329,2017,A1 .Location in patent: Page/Page column 23; 74

66
C₁₈H₂₄N₂O₄ [ No CAS ]
[ 78269-85-9 ]
C₂₄H₃₆N₂O₆Si [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 1698 - 1701

67
[ 78269-85-9 ]
[ 22483-09-6 ]
2-trimethylsilylethyl N-(2,2-dimethoxyethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
945 mg	With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 1h;	To the mixture of 2,2-dimethoxyethanamine (608.0 mg, 5.78 mmol) and triethylamine (1.07 mL, 7.71 mmol) in THF (10 mL) was added 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5- dione (1.0 g, 3.86 mmol) at 0 oC and the mixture was stirred at room temperature for 1h. The reaction was concentrated to dryness under reduced pressure. The residue was dissolved in DCM (150 mL) and the organic phase was washed with water and brine, dried over sodium sulfate and concentrated to afford 2-trimethylsilylethyl N-(2,2-dimethoxyethyl)carbamate (945 mg) as a colorless oil, which was used directly in the next step without further purification.1HNMR (400 MHz, CDCl3) delta 4.76(brs, 1H), 4.33 (t, J= 5.6 Hz, 1H), 4.12(t, J= 8.4 Hz, 2H), 3.36 (s, 6H), 3.27 (t, J=5.6 Hz, 2H), 0.94(t, J= 8.4Hz, 2H), 0.00(s, 9H).

Reference： [1]Patent: WO2017/108723,2017,A2 .Location in patent: Page/Page column 231

68
(S)-1-((1R,2R)-2-(((S)-6'-chloro-7-(((R)-hex-5-en-2-ylsulfonyl)carbamoyl)-3',4'-dihydro-2H,2’H-spiro[benzo[b][1,4]oxazepine-3,1'-naphthalen]-5(4H)-yl)methyl)cyclobutyl)prop-2-en-1-aminium chloride [ No CAS ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl ((S)-1-((1R,2R)-2-(((S)-6'-chloro-7-(((R)-hex-5-en-2-ylsulfonyl)carbamoyl)-3',4'-dihydro-2H,2’H-spiro[benzo[b][1,4]oxazepine-3,1’-naphthalen]-5(4H)-yl)methyl)cyclobutyl)allyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; at 20℃; for 0.333333h;	(S)-i-((IR,2R)-2-(((S)-6-chioro-7-(((R)-hex-5-en-2-ylsuifonyi)carbamoyl)-3.4-dihvdro-21-T.2H-spiro[benzo[b] [1.41 oxazepine-3 .1- naphthalen] -5(4H)-yl)methyi)cyclobutyi)prop-2-en- I -aminium chloride from Step 5 (240 rng, 0.392 rnmoi) in 1,4-dioxane (3.9 mL) was added 1-[(2- trimethylsilyl)ethoxycarbonyioxy jpyrrolidin-2,5-dione (132 ing, 0.51 0 mmol), followed by triethylamine (0.164 mL, 1.18 mmoi). The mixture was stirred atambient temperature for 20 minutes then was loaded into a silica gel cariridge and purified by colunm chromatography (0-30% EtOAc/ hexanes, 24g Si02) to afford 2-(trimethyisiiyl)ethyi ((S}- 1 -((IR.2R)-2-(((S)-6?-chioro-7-(((R)-hex-5-en-2- yisulfonvi)carbarnoyi)-3.4-dihvdro-2H,2H-spiro[benzo[b] [1.4] oxazepine-3 ,inaphthaien] -5(4H)-yi)methyl)cyciobutyi)aliyi)carbamate.

Reference： [1]Patent: WO2017/147410,2017,A1 .Location in patent: Page/Page column 410; 411

69
[ 40216-83-9 ]
[ 78269-85-9 ]
[ 128360-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile; at 20℃;	2,5-Dioxorhoyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (2.5 g, 9.64 mmol) was added to a solution of (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate, HCl salt (2.10 g, 11.6 mmol) and triethylamine (4.0 mL, 28.9 mmol) in acetonitrile (20 mL) and stirred at room temperature overnight. The reaction was quenched with water and ether. The organic layer was washed with 1.0 M HCl (2x) followed by brine. It was then dried with MgSO4, filtered and concentrated to afford crude (2S,4R)-2-methyl l-(2- (trimethylsilyl)ethyl) 4-hydroxypyrrolidine-l ,2-dicarboxylate which was used directly in the next step.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 43 - 48

70
[ 16012-70-7 ]
[ 25456-86-4 ]
[ 78269-85-9 ]
N²-acetyl-N⁶-[2-(trimethylsilyl)ethoxy]carbonyl}-L-lysyl-L-alanyl-L-alanyl-L-asparagine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;	N2-Acetyl-N6-[2-(trimethylsilyl)ethoxy]carbonyl}-L-lysyl-L-alanyl-L-alanyl-L-asparagine The synthesis of the title compound commenced with the coupling of N-[(benzyloxy)carbonyl]-L-alanyl-L-alanine and <strong>[25456-86-4]tert-butyl L-asparaginate</strong> in DMF in the presence of HATU and N,N-diisopropylethylamine and subsequent detachment of the Z protecting group by hydrogenation over 10% palladium on activated carbon in methanol under standard pressure. Subsequently, the deprotected intermediate was coupled with Intermediate L109 in DMF in the presence of HATU and N,N-diisopropylethylamine. This was followed by complete deprotection by stirring in a 7.5% solution of trifluoroacetic acid in DCM for 1 h. In the last step, the title compound was prepared by reprotecting the free amino group by reaction with 1-([2-(trimethylsilyl)ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione in DMF/water 1:1 in the presence of N,N-diisopropylethylamine. LC-MS (Method 1): Rt=0.71 min; MS (ESIpos): m/z=589 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1

71
[ 13623-85-3 ]
[ 78269-85-9 ]
C₁₄H₂₂N₂O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;	Example 101 ((4aR,8aR)-octahydro-1,7-naphthyridin-1(2H)-yl)(2-(5-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-3-yl)pyridin-4-yl)methanone Synthesis of 101 To a solution of 101A 5,6,7,8-tetrahydro-1,7-naphthyridine (250 mg, 1.207 mmol) and Teoc-O-Su (610 mg, 2.35 mmol) in dichloromethane (10 mL) at r.t. as Hunig's base (0.63 mL, 3.6 mmol) was added and the reaction mixture was stirred over weekend. The reaction mixture was washed with water, concentrated and absorbed onto silica, chromatographed with 10 to 100% gradient of ethyl acetate in hexanes, and product 101B was obtained. (161 mg, 47%). Compound 101B (12 mg) was dissolved in 1:1 mixture of ethanol and acetic acid and the solution was passed through H-Cube hydrogenation apparatus charged with 5% rhodium on carbon catalyst cartridge. After concentration, 20 mg of crude product 101C were obtained and used for next step without purification. Compound 101C was coupled with 1F as explained in Example 1 to get the product 101D. The Teoc group from product 101D was removed by treating it with 6N HCl in dioxane. The reaction mixture was concentrated and purified by HPLC to obtain the final product 101, as a TFA salt. LC/MS (M+H): 445.1; 1H NMR (6, 400 MHz, Methanol-d4), diagnostic signals: 8.87 (d, 1H, J=7.6 Hz), 8.72 (s, 1H), 8.66 (br s, 1H), 8.59 (d, 1H, J=6.0 Hz), 7.91 (d, 1H, J=3.6 Hz), 7.68 (d, 1H, J=5.2 Hz), 7.42 (d, 1H, J=7.2 Hz), 7.55 (dd, 1H, J=4.8, 1.2 Hz), 7.26 (dd, 1H, J=4.8, 4.0 Hz), 5.05 (dt, 1H, J=12.4, 5.2 Hz). Remaining area of the spectrum contains approximately 13 protons by integration.

Reference： [1]Patent: US2018/148457,2018,A1 .Location in patent: Paragraph 0966; 0967

72
[ 2576-47-8 ]
[ 78269-85-9 ]
[ 1354190-01-4 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In dichloromethane; at 20℃; for 5h;	2-Bromo-ethanolamine-HBr (944 mg, 4.6 mmol) and dichloromethane (5 mL) was mixed and Et3N (0.5mL, 6.9 mmol) was added, resulting in a slurry mixture. l-[2- (trimethylsilyl)ethoxycarbonyl oxy]pyrrolidine-2,5-dione (1 g, 3.9 mmol) was dissolved in dichloromethane (5 mL) and added to the mixture, which immediately dissolved the precipitate. The reaction was stirred at room temperature for 5 h and subsequently quenched with water and extracted with dichloromethane ( 3). The organic phase was dried over Na2SC>4, filtrated and solved was removed in vacou. Purification by silica gel chromatography (0-50% ethyl acetate in hexane) gave compound 33 (849 mg, 0.317 mmol, 82%). H-NMR (300 MHz, CDC ) : delta 5.03 (bs, 1H, NH), 4.13 (t, 2H, CH20), 3.53 (t, 2H, NHCH2), 3.42 (t, 2H, CH2Br), 0.96 (t, 2H, (CH3)3SiCH2), 0.0 (s, 9H, (CH3)3Si)).

Reference： [1]Patent: WO2018/115462,2018,A1 .Location in patent: Page/Page column 43

73
C₃₁H₃₇NO₄Si [ No CAS ]
[ 78269-85-9 ]
C₃₇H₄₉NO₆Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.6 g	With triethylamine; In 1,4-dioxane; at 40℃; for 16h;	A 200-mL round-bottomed flask was charged with isoxazolidine 44 (crude product from the preceding directed reduction step, theoretically 22.1 mmol). The starting material was dissolved in 1,4-dioxane (55 mL) and to the resulting solution, triethylamine (15.4 mL, 110 mmol, 5.00 equiv) and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (Teoc-OSu, 8.59 g, 33.1 mmol, 1.50 equiv) were added sequentially. The reaction mixture was heated to 40 C, and consumption of starting material was monitored by LCMS. After 16 h, the reaction was judged to be complete. The reaction mixture was then diluted in 450 mL of ethyl acetate, and the diluted product solution was washed with saturated aqueous ammonium chloride solution (3 x 50 mL). The combined aqueous washes were extracted with a portion of fresh ethyl acetate (100 mL), and the combined organic layers were then washed with saturated aqueous sodium chloride solution (50 mL). The washed organic product solution was dried over sodium sulfate, the dried solution was filtered, and the filtrate was (0804) concentrated to give a viscous orange oil. This material was purified by flash-column chromatography (1.00 kg silica gel, eluting with 5% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) to afford the product as a highly viscous, colorless oil (10.6 g, 73%, 2 steps). 1H NMR (600 MHz, CDC13): delta 7.78-7.74 (m, 4H), 7.48-7.44 (m, 2H), 7.42- 7.36 (m, 4H), 7.35-7.27 (m, 5H), 4.90 (app t, J = 3.8 Hz, 1H), 4.79 (dd, J = 6.2, 2.2 Hz, 1H), 4.67 (d, J = 11.8 Hz, 1H), 4.48 (d, J = 11.8 Hz, 1H), 4.25-4.12 (m, 4H), 3.65 (app p, J = 6.3 Hz, 1H), 3.31 (d, J = 3.9 Hz, 1H), 2.36 (d, J = 2.2 Hz, 1H), 1.33 (d, J = 6.2 Hz, 3H), 1.10 (s, 9H), 1.05-0.94 (m, 2H), 0.04 (s, 9H). HRMS (ESI+, m/z): [M+H]+ calcd for C37H49N06Si2, 660.3171; found 660.3161.

Reference： [1]Patent: WO2019/32936,2019,A1 .Location in patent: Paragraph 00419

74
[ 52-90-4 ]
[ 78269-85-9 ]
N-[2-(trimethylsilyl)ethoxy]carbonyl}-L-cysteine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	First, L-cysteine was converted with 1-([2-(trimethylsilyl)ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione in DMF in the presence of N,N-diisopropylethylamine into N-[2-(trimethylsilyl)ethoxy]carbonyl}-L-cysteine.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 72h;	A mixture of L-cysteine (CAS52-90-4, 470 mg, 3.88 mmol), 1-([2-(trimethylsilyl)- ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione (CAS 78269-85-9, 1.16 g, 4.46 mmol) and N,N- diisopropylethylamine (2.0 mL, 12 mmol) in DMF (12 mL) was stirred at r.t. for 3 days. Then toluene (100 mL) was added to the reaction solution and the mixture was concentrated under reduced pressure (azeotropic distillation with toluene was executed two times). The crude product was dissolved in DMSO and purified by preparative HPLC to give 770 mg of the title compound (90% purity, 67% yield) (1187) HPLC: Instrument: Labomatic HD-5000, pump head HDK-280, gradient module NDB-1000, fraction collector Labomatic Labocol Vario 2000, Knauer UV detector Azura UVD 2.1S, Prepcon 5 software. Column: Chromatorex C18 10muM 290x51 mm; Eluent A: water + 0.1% formic acid; Eluent B: acetonitrile; gradient: 0-20 min 10-70% B, 20-25 min 70% B. ; rate 250 mL/min, temperature 25C. (1188) LC-MS (Method 1): Rt = 0.81 min; MS (ESIneg): m/z = 264 [M-H]- (1189) 1H-NMR (400MHz, DMSO-d6) delta [ppm]: 0.03 (s, 9H), 0.93 (t, 2H), 2.65 - 2.75 (m, 1H), 2.81 - 2.90 (m, 1H), 4.03 - 4.11 (m, 1H), 4.05 (t, 2H), 7.35 (d, 1H), 12.81 (br s, 1H).

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2828-2830; 2837; 2844
[2]Chemistry - A European Journal,2019,vol. 25
[3]Patent: WO2019/149637,2019,A1 .Location in patent: Page/Page column 282

75
4-(4-(4-amino-1-methyl-1H-imidazole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid [ No CAS ]
[ 78269-85-9 ]
C₂₃H₂₉N₅O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.9%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 48h;	To 4-(4-(4-(tert-butoxy carbonylamino)- -methyl- lH-imidazole-2- carboxamido)phenyl)-l-methyl-l H-pyrrole-2-carboxylic acid (1 g, 2 275 mmol, was added HC1 (4.0 M in dioxane, (17.07 mL, 68.3 mmol), and the reaction mixture was stirred for 4 days at room temperature, then additional HC1 (4 0 M in dioxane, 24 mL, 96 mmol) was added. After 3 more days the reaction mixture was concentrated under reduced pressure to provide 4-(4-(4- amino-l -methyl- lH-imidazole-2-carboxamido)phenyl)-l -methyl- lH-pyrrole-2-carboxy lie acid (0.772 g, 100 % yield). ESI-MS calc for C rf f AK (M+H) 340.1; found 340.1. (2150) [01258] To 4-(4-(4-amino-l -methyl- lH-imidazole-2-carboxamido)phenyl)-l -methyl- 1H- pyrrole-2-carboxylic acid (0.772 g, 2.275 mmol) was added DCM (22.75 mL) and DIEA (0.396 mL, 2.275 mmol). The mixture was stirred at room temperature for 5 minutes the 2,5- dioxopyrrolidin-l-yl (2-(trimethyisiyl)ethyl) carbonate (0.590 g, 2 275 mmol), w'as added. After 24 hours, additional of 2,5-dioxopyrrolidin-l-yl (2-(trimethylsilyl)ethyl) carbonate (295 mg, 1.14 mmol) and DIEA (1.14 mmol, 200 pL) were added. After 24 hours, the reaction mixture was concentrated under reduced pressure. The crude product was purified on silica gel (0-45% MeOH in DCM) and then by reverse phase MPLC (10-100% MeCN in H2O with 0.1% HOAc) to provide compound 97 (0.648 g, 58.9 % yield). ESI-MS calc for CATLoN OsSr (M+H) 484.2; found 484.1.

Reference： [1]Patent: WO2019/126691,2019,A1 .Location in patent: Paragraph 01255; 01257; 01258

76
[ 78269-85-9 ]
[ 10270-94-7 ]
(S)-4-((tert-butoxycarbonyl)amino)-2-(((2-(trimethylsilyl)ethoxy)carbonyl)amino)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In 1,4-dioxane; water; at 20℃;	To a solution of compound 19a (25 g, 0.114 mol , 1.0 eq) in l,4-dioxane (180 mL) and H2O (180 mL) was added NaHCCh (23.2 g, 0.228 mol, 2.0 eq) and the solution of compound 2,5- dioxopyrrolidin-l-yl (2-(trimethylsilyl)ethyl) carbonate (18, 32.7 g, 0.12 mmol, 1.1 eq) in l,4-dioxane (100 mL) was added drop wise at room temperature and stirred for overnight. After completion, the remainder was added water (200 mL) and adjusted pH = 3-4 with 2N HC at 0C, extracted with DCM:MeOH=lO: l (100 mL*5), dried over Na2S04. Filtered and concentrated to give yellow liquid (10c, 43.6 g, crude) which was used into next step without purification. MS: (m-H)+: 361.1.

Reference： [1]Patent: WO2019/118878,2019,A1 .Location in patent: Page/Page column 57; 58

77
N₆-(tert-butoxycarbonyl)-L-lysine-3,3,4,4,5,5,6,6-d8 [ No CAS ]
[ 78269-85-9 ]
C₁₇H₂₆⁽²⁾H₈N₂O₆Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydrogencarbonate; In tetrahydrofuran; water; at 20℃; for 20h;	NaHCCh (3.30 g, 39.3 mmol) was suspended in water (31 mL), then 19c (1.00 g, 3.93 mmol), THF (31 mL) and teocOnsu (1.43 g, 5.50 mmol) was added. Biphasic mixture was allowed to vigorously stir at r.t. for 20h. Then reaction mixture was evaporated from THF and additional water (50 mL) was added and reaction mixture was washed with Et20 (2 x 20 mL). To aqueous layer was added citric acid to pH 3-4 and product was extracted with DCM (4x50 mL). Organic layers were combined and dried on Na2S04, filtered and evaporated to give product as a colorless oil (1.52, 97%). NMR (300 MHz, MeOD-rri) d: 4.15 (t, J= 8.1 Hz, 2H), 4.09 (s, 1H), 1.43 (s, 9H), 1.00 (t, J= 8.4 Hz, 2H), 0.05 (s, 9H).

Reference： [1]Patent: WO2019/118878,2019,A1 .Location in patent: Page/Page column 68; 69

78
C₃₁H₆₇NO₆Si₂ [ No CAS ]
[ 78269-85-9 ]
C₃₇H₇₉NO₈Si₃ [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 5471 - 5474

79
[ 5382-16-1 ]
[ 78269-85-9 ]
[ 840493-49-4 ]

Yield	Reaction Conditions	Operation in experiment
985 mg	With triethylamine; In tetrahydrofuran; at 25℃; for 2h;	To a solution of piperidin-4-ol (1.17 g, 11.57 mmol, 3 eq) in tetrahydrofuran (10 mL) was added triethylamine (1.17 g, 11.57 mmol, 1.61 mL, 3 eq), (2,5-dioxopyrrolidin-l-yl) 2- trimethylsilylethyl carbonate (1 g, 3.86 mmol, 1 eq) was added to the mixture, the reaction was stirred at 25 C for 2 h. The reaction mixture was quenched by water (30 mL) and extracted with ethyl acetae (20 mL x 2). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate= 5:1 to 0:1) to give compound 2-trimethylsilylethyl 4-hydroxypiperidine-l-carboxylate (985 mg) as a colorless oil. 1H-NMR (400MHz, CD3OD) d 4.22 - 4.16 (m, 4H), 3.71 - 3.67 (m, 10H), 3.60 - 3.56 (m, 1H), 3.31 - 3.13 (m, 1H), 1.81 - 1.61 (m, 2H), 1.50 - 1.47 (m, 2H), 1.47 (s, 9H), 1.27 (t, /= 7.2 Hz, 3H).

Reference： [1]Patent: WO2019/195609,2019,A2 .Location in patent: Paragraph 001466-001467

80
C₁₁H₁₄BrN*ClH [ No CAS ]
[ 78269-85-9 ]
C₁₇H₂₆BrNO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 1,4-dioxane; at 25℃; for 2h;	To a solution of lnt-2fc-1 (8.20 g, 28.2 mmol) and Teoc-OSu (8.03 g, 31.0 mmol) in 1 ,4- dioxane (200 ml_) was added TEA (8.55 g, 84 mmol) at 25 C. This mixture was stirred for 2 hours then quenched with water and extracted with petroleum ether (PE). The combined organic layers were concentrated under reduced pressure and the residue was purified by column chromatography over silica gel (eluting with a 1 %-10% gradient of EtOAc in PE) to give lnt-2fd-1. LC/MS: (M+Na+CH3CN)+:= 447.3, 449.3.

Reference： [1]Patent: WO2019/246349,2019,A1 .Location in patent: Page/Page column 99; 101

81
[ 62614-84-0 ]
[ 78269-85-9 ]
2-(trimethylsilyl)ethyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine; In tetrahydrofuran; at 0 - 20℃;	To a solution of 4-(piperidin-4-yl)phenol (1 g, 5.64 mmol) and Et3N (1.14 g, 11.3 mmol) in THF (10 mL) at 0C, 2,5-dioxopyrrolidin-l-yl (2-(trimethylsilyl)ethyl) carbonate (1.46 g, 5.6 mmol) was added. The mixture was warmed to room temperature overnight. The mixture was poured into water (20 mL) and extracted with EtOAc (2x30 mL). The organic layers were combined, washed with water (2x20 mL), brine (20 mL), dried (Na2S04), filtered and concentrated, and then purified by chromatography on silica gel (petroleum ether/EtOAc = 20/1) to give 2- (trimethylsilyl)ethyl 4-(4 hydroxyphenyl)piperidine-l-carboxylate (1.16 g, 63% ) as a yellow solid. 1H NMR (400 MHz, CDCl3): d 7.01 (d, 2H), 6.74 (d, 2H), 5.13 (s, 1H), 4.36-4.09 (m, 4H), 2.85- 2.74 (m, 2H), 2.55 (t, 1H), 1.76 (d, 2H), 1.63-1.42 (m, 2H), 1.02-0.93 (m, 2H), 0.6 (s, 9H); LCMS: 344.1 [M+Na]+.

Reference： [1]Patent: WO2019/241751,2019,A1 .Location in patent: Paragraph 00439

82
tert-butyl 4-(5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-yl)piperazine-1-carboxylate [ No CAS ]
[ 78269-85-9 ]
2-trimethylsilylethyl 3-(4-tert-butoxycarbonylpiperazin-1-yl)7,8-dihydro-5H-pyrido[3,4-b]pyrazine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60 mg	With sodium carbonate; In tetrahydrofuran; at 20℃; for 4h;	To a solution of ferf-butyl 4-(5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-yl)piperazine-l- carboxylate (compound 40h, 100 mg, 0.31 mmol) in TE1F (2 mL) was added sodium carbonate (83 mg, 0.78 mmol) and Teoc-OSu (162 mg, 0.63 mmol). After being stirred at 20 C for 4 hrs, the reaction mixture was concentrated and dissolved in EA (20 ml). The organic layer was washed with water (20 mL) twice and brine (20 mL) once, dried over Na2S04 and concentrated. The residue was purified by prep-TLC (PE:EA = 1:1) to give compound 40i (60 mg) as a yellow gum. MS: calc?d 464 (MEL), measured 464 (MEL).

Reference： [1]Patent: WO2019/238616,2019,A1 .Location in patent: Page/Page column 97-98; 100

83
2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine hydrochloride [ No CAS ]
[ 78269-85-9 ]
2-trimethylsilylethyl 2-chloro-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
270 mg	With sodium carbonate; In tetrahydrofuran; water; at 20℃; for 3h;	To the solution of 2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine hydrochloride (compound 51a, 190 mg, 0.92 mmol) and sodium carbonate (293 mg, 2.77 mmol) in THF (3 mL) and water (3 mL) was added 2,5-dioxopyrrolidin-l-yl(2-(trimethylsilyl) ethyl) carbonate (478 mg, 1.84 mmol). After being stirred at rt for 3 hrs, the reaction was quenched by addition of saturated NH4Cl (10 mL), diluted with water (30 mL) and extracted with EA (20 mL) for three times. The combined organic layer was washed with water (20 mL) twice and brine (20 mL) once, dried over Na2S04, concentrated and purified by prep-TLC (PE/EA = 3/1) to give compound 51b (270 mg) as a yellow gum. MS calc?d 314 (MEL), measured 314 (MEL).

Reference： [1]Patent: WO2019/238616,2019,A1 .Location in patent: Page/Page column 113-115

84
tert-butyl 4-(3-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperazine-1-carboxylate [ No CAS ]
[ 78269-85-9 ]
2-trimethylsilylethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-3-methyl-7,8-dihydro-5H-pyrido[3,4-b]pyrazine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
290 mg	With sodium carbonate; In 1,4-dioxane; water; at 20℃; for 1h;	To the solution of ferf-butyl 4-(3-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2- yl)piperazine- l-carboxylate (compound 60g, 250 mg, 0.75 mmol), sodium carbonate (159 mg, 1.50 mmol) in l,4-dioxane (6 mL) and water (1 mL) was added 2,5-dioxopyrrolidin-l-yl (2- (trimethylsilyl)ethyl) carbonate (583 mg, 2.25 mmol). After being stirred at rt for 1 h, the reaction mixture was concentrated and purified by flash column (PE/EA = 5/1) to give compound 60h (290 mg) as a yellow oil. MS: calc?d 478 (MH+), measured 478 (MH+).

Reference： [1]Patent: WO2019/238616,2019,A1 .Location in patent: Page/Page column 123-124; 126

85
[ 1159010-96-4 ]
[ 78269-85-9 ]
2-trimethylsilylethyl 3-bromo-7,8-dihydro-5H-1,6-naphthyridine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
400 mg	With sodium carbonate; In tetrahydrofuran; at 25℃; for 5.0h;	To a solution of 3-bromo-5,6,7,8-tetrahydro-1 ,6-naphthyridine hydrochloride (CAS:1159010-96-4, Vendor: PhamaBlock, 300 mg, 1.20 mmol), sodium carbonate (382 mg, 3.61 mmol) in THF (3 mL) and water (3 mL) was added N-[2- (trimethylsilyl)ethoxycarbonyloxyl succinimide (624 mg, 2.40 mmol). After being stirred at 25 C for 5 hrs, the reaction was quenched by addition of saturated NH4C1 (aq. 20 mL), diluted with 50 mL water, extracted with EA (30 mL) three times. The combined organic layer waswashed with water (30 mL) twice and brine (20 mL) once, dried over Na2SO4 and concentrated to give crude product which was purified by flash column (PE/EA = 10/1) to give compound 47a (400 mg) as a white solid. MS calc?d 357 (MHj, measured 357 (MHj.

Reference： [1]Patent: WO2019/238616,2019,A1 .Location in patent: Page/Page column 108-109

86
[4-(4-bromophenyl)thiazol-2-yl]methanamine [ No CAS ]
[ 78269-85-9 ]
2-trimethylsilylethyl N-[[4-(4-bromophenyl)thiazol-2-yl]methyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium hydrogencarbonate; In 1,4-dioxane; water; at 20℃; for 2h;	A solution of NaHCO3 (625 mg, 7.44 mmol) in water (8 mL) and 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (964 mg, 3.72 mmol) were added to a solution of [4-(4-bromophenyl)thiazol-2-yl]methanamine (1.033 g, 3.38 mmol) in dioxane (16 mL) at room temperature. The reaction mixture was stirred for 2 h and partitioned between EtOAc (20 mL) and water (20 mL). The organic extract was washed with brine (20 mL), dried and evaporated. The crude product was purified by chromatography on silica eluting with 0-50% EtOAc in hexane affording a white solid (948 mg, 68%). M/z 414 (M+H)+.

Reference： [1]Patent: EP3628672,2020,A1 .Location in patent: Paragraph 0552-0554

87
[ 78269-85-9 ]
[ 27854-96-2 ]
C₁₃H₂₂N₂O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24h;	Compound E91a (473 mg, 3.872 mmol) and TeocOSuc (1.19 g, 4.589 mmol) were dissolved in dichloromethane and stirred at room temperature as DIPEA (0.876 mL, 5.0 mmol) was added. Stirred for 24 h. The reaction mixture was washed with water and organic phase was concentrated, product chromatographed with 0 to 10% MeOH in CH2Cl2 gradient, product eluting at 5-7% MeOH. Obtained Compound E91b. 1H NMR (400 MHz, Chloroform-d) delta 8.61-8.55 (m, 2H), 7.28-7.21 (m, 2H), 4.96 (s, 1H), 4.83 (s, 1H), 4.21-4.09 (m, 2H), 1.48 (d, J=7.0 Hz, 3H), 0.99 (s, broad, 2H).

Reference： [1]Patent: US2020/108071,2020,A1 .Location in patent: Paragraph 1176-1177

88
[ 78269-85-9 ]
[ 66866-69-1 ]
N-trimethylsilylethoxycarbonyl-N-methyl-L-leucine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium hydrogencarbonate; In water; acetone; at 25℃;	(4) At 25C, in a 2L reaction flask equipped with a thermometer,Put 310mL acetone, 310mL water, 62.1g (0.34mol) in sequenceN-methyl-L-leucine hydrochloride,57.1g (0.68mol) sodium bicarbonate, 176.1g (0.68mol)N-[2-(Trimethylsilyl)ethoxycarbonyloxy]succinimide, stir and react overnight at 25C,Add 310mL water and 200mL petroleum ether, stir and extract,Separate the phases, adjust the aqueous phase to weak acidity with 3N hydrochloric acid, add 200mL ethyl acetate to extract the aqueous phase twice, combine the ethyl acetate phases, wash once with saturated sodium chloride, dry with anhydrous sodium sulfate, and concentrateObtain 86.8 g of N-trimethylsilyl ethoxycarbonyl-N-methyl-L-leucine, which is then recrystallized using ethyl acetate petroleum ether71.2g of N-trimethylsilylethoxycarbonyl-N-methyl-L-leucine was obtained, the yield was 72%, the chemical purity was 99.7%, and the chiral purity was 100%.

Reference： [1]Patent: CN112876502,2021,A .Location in patent: Paragraph 0078; 0083; 0102-0107

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P378
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P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
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P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
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P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
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P401
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Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
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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. 78269-85-9 ] {[proInfo.proName]}

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[ 78269-85-9 ] Synthesis Path-Upstream 1~4

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