[ CAS No. 86864-60-0 ] {[proInfo.proName]}

Name: 86864-60-0|(2-Bromoethoxy)(tert-butyl)dimethylsilane|96%
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Quality Control of [ 86864-60-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 86864-60-0 ]

CAS No. :	86864-60-0	MDL No. :	MFCD00209550
Formula :	C₈H₁₉BrOSi	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JBKINHFZTVLNEM-UHFFFAOYSA-N
M.W :	239.23	Pubchem ID :	3608067
Synonyms :

Calculated chemistry of [ 86864-60-0 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	4
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	57.39
TPSA :	9.23 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.19 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.19
Log Po/w (XLOGP3) :	3.62
Log Po/w (WLOGP) :	3.4
Log Po/w (MLOGP) :	2.69
Log Po/w (SILICOS-IT) :	1.22
Consensus Log Po/w :	2.82

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.34
Solubility :	0.109 mg/ml ; 0.000457 mol/l
Class :	Soluble
Log S (Ali) :	-3.5
Solubility :	0.0754 mg/ml ; 0.000315 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.38
Solubility :	0.1 mg/ml ; 0.000419 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.98

Safety of [ 86864-60-0 ]

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 [ 86864-60-0 ]

* 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 [ 86864-60-0 ]
Downstream synthetic route of [ 86864-60-0 ]

[ 86864-60-0 ] Synthesis Path-Upstream 1~7

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[ 86864-60-0 ]
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Yield	Reaction Conditions	Operation in experiment
35%	With tetrabutyl ammonium fluoride; potassium carbonate In tetrahydrofuran; ethyl acetate; N,N-dimethyl-formamide	Preparatory Example 56 1-(2-Hydroxyethyl)imidazole STR299 3.56 g of 2-bromoethyl t-butyldimethylsilyl ether and 1.97 g of imidazole were dissolved in 70 ml of N,N-dimethylformamide, to which 4 g of potassium carbonate were added, followed by agitation at 90° C. for 2 hours and 40 minutes. After removal of the solvent by distillation, ethyl acetate was added, followed by washing with water and drying with anhydrous magnesium sulfate. This was filtered and, after removal of the solvent by distillation, m the resultant residue was dissolved in tetrahydrofuran, to which 12.6 ml of tetrabutylammonium fluoride (1M tetrahydrofuran solution), followed by agitation at room temperature. After completion of the reaction, the solvent was distilled of and the resultant residue was subjected to silica gel column chromatography (developing solvent: dichloromethane) to obtain 0.59 g of the caption compound (yield 35percent). ¹ H-NMR(90 MHz, CDCl₃) δ:3.28(bs,1H), 3.6-4.2(m,4H), 6.84(bs,1H), 7.28(bs,1H)

Reference： [1] Patent: US5221671, 1993, A,

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Reference： [1] Chemistry Letters, 2004, vol. 33, # 9, p. 1146 - 1147

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Yield	Reaction Conditions	Operation in experiment
100%	With dmap; triethylamine In dichloromethane at 20℃; for 15 h;	To a solution of 2-bromoethanol (3.5 mL, 49.3 mmol) in DCM (20 mL) was added tert-butyldimethylsilyl chloride (8.17 g, 54.2 mmol) followed by triethylamine (13.85 mL, 98.6 mmol) and finally 4- dimethylaminopyridine (55 mg, 0.394 mmol). The mixture was stirred at room temperature for 15 hrs, and then concentrated IN-VACUO. The residue was partitioned between IN HCI and ethyl acetate. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated IN-VACUO to afford a yellow oil, which was purified by column chromatography. Eluting with n-hexane gave 11.8 g, 49.3 mmol (100percent), of [ (2- bromoethyl) oxy] (1, l-dimethylethyl) dimethylsilane as a colorless OIL. LH NMR (400 MHz, CDC13) : 3.89 (t, 2H), 3.40 (t, 2H), 0.91 (s, 9H), 0.091 (s, 6H); GC/MS for C8HLGBROSI : 239 (M+).
100%	Stage #1: With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 0.5 h; Stage #2: at 20℃; for 16 h;	In a round bottom flask, TBDMSC1 (10.61 g, 70.42 mmol) and imidazole (6.23 g, 91.55 mmol) were dissolved in DMF (12.5 mL) and the solution was stirred for 30 mmat rt. Then, 2-bromoethanol (5 mL, 70.42 mmol) was added and the mixture was stirred at rt for 16 hours. The reaction mixture was partitioned between Et20 and water. The organic layer was dried over MgSO4, filtered and concentrated under vacuum to give 17 g of intermediate 33 (quant. yield, colorless oil).
100%	With dmap; triethylamine In dichloromethane at 20℃; for 15 h;	To a solution of 2-bromoethanol (3.5 mL, 49.3 mmol) in DCM (20 mL) was added tert-butyldimethylsilyl chloride (8.17 g, 54.2 mmol) followed by triethylamine (13.85 mL, 98.6 mmol) and finally 4- dimethylaminopyridine (55 mg, 0.394 mmol). The mixture was stirred at room temperature for 15 hrs, and then concentrated IN-VACUO. The residue was partitioned between IN HCI and ethyl acetate. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated IN-VACUO to afford a yellow oil, which was purified by column chromatography. Eluting with n-hexane gave 11.8 g, 49.3 mmol (100percent), of [ (2- bromoethyl) oxy] (1, l-dimethylethyl) dimethylsilane as a colorless OIL. LH NMR (400 MHz, CDC13) : 3.89 (t, 2H), 3.40 (t, 2H), 0.91 (s, 9H), 0.091 (s, 6H); GC/MS for C8HLGBROSI : 239 (M+).

98.3%	With 1H-imidazole In DMF (N,N-dimethyl-formamide) at 20℃;	[0690] To a solution of P0026-0 (5.0g) and imidazole (3.3g) in DMF (40ml) was added portionwise TBDMSC1 (6.69g) at room temperature. After stirring overnight, water and hexane was added. The aqueous layer was separated and extracted twice with hexane. The combined organic layer was washed with water (twice) and brine, dried over MgSO4, filtered and evaporated under reduced pressure to give 9.49g (98.3percent) of P0026. [0691] IR (film): 2952.5, 2935.1, 1467.6, 1255.4, 1124.3, 1097.3, 838.9, 777.2 cm-1.
98.3%	With 1H-imidazole In DMF (N,N-dimethyl-formamide) at 20℃;	To a solution of P0054-0 (5. 0g) and imidazole (3.3g) in DMF (40ML) was added portionwise tert-butyldimethylsilyl chloride (TBDMSC1) (6.69g) at room temperature. After stirring overnight, water and hexane was added. The aqueous layer was separated and extracted twice with hexane. The combined organic layer was washed with water (twice) and brine, dried over MGS04, filtered and evaporated under reduced pressure to give 9.49g (98. 3percent) of P0054. IR (FILM) : 2952.5, 2935.1, 1467.6, 1255. 4,1124. 3,1097. 3,838. 9, 777.2 CM-1.
97%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 12 h;	Following a published procedure,²⁴ 2-bromoethanol (10.0 mL, 141 mmol) was added to a mixture of imidazole (12.5 g, 184 mmol) and toet-butyldimethylsilyl chloride (21.1 g, 140 mmol) in anhydrous DMF (25 mL). The reaction mixture was stirred at room temperature for 12 h. Water and diethyl ether were added. The phases were separated. The aqueous phase was extracted with diethyl ether. The combined organic phases were washed with water and brine. The solution was dried (Na₂SO₄). Evaporation of the solvent followed by bulb-to-bulb distillation (40-45 °C/0.05 mmHg) yielded a colorless liquid (32.5 g, 97percent): IR (film, v_max cm^"1) 2951, 2859, 1471; ¹H NMR δ 0.07 EPO <DP n="87"/>- 85 -(s, 6H), 0.89 (s, 9H), 3.36-3.41 (m, 2H), 3.85-3.90 (m, 2H); ¹³C NMR δ -5.06, 18.49, 26.04, 33.45, 63.74; EI-MS 137/139, 181/183, calcd 238.0389 (C₈H₁₉BrOSi); Anal. Calcd C, 40.17; H, 8.01. Found: C, 40.55; H, 8.25.
96%	at 20℃; for 3 h; Inert atmosphere	A modified procedure of Galka et al., J. Lab. Comp. Rad. 2005, 48, 11, 797-809, was used. A mixture of 2-bromoethanol (6.6 mmol; 0.83 g = 0.47 ml), fert.-butyldimethylsilylchloride (6.6 mmol, 1.0 g) and imidazole (7.3 mmol; 0.5 g) was stirred at RT for 3 hours under nitrogen atmosphere. The reaction was quenched with water, extracted with diethylether. The organic phases were dried over Na₂SO/i, filtered and concentrated. The purification was achieved by column chromatography (petrolether) to yield 2-bromoethoxy)(ieri.- butyl)dimethylsilane (6.4 mmol, 96 percent). ^.H NMR (300 MHz, CDC1₃) 3.91 (t; ³J = 6.5 Hz; 2H; OCH₂); 3.41 (t; ³J = 6.5 Hz; 2H; CH₂Br); 0.93 (s; 9H; C(CH₃)₃); 0.11 (s; 6H; 2xCH₃).
92%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 12 h;	To a solution of tert-butyldimethylsilyl chloride (TBS-Cl) (11.6 g, 77 mmol) in 25 mL of DMF was added imidazole (6.2 g, 91 mmol) followed by the dropwise addition of 2-bromoethanol (8.7 g, 70 mmol). The reaction mixture was stirred for 12 h at rt, extracted with EtOAc and washed with H₂O (x3). The combined organic fractions were dried over Na₂SO₄ and concentrated in vacuo to afford (2-bromoethoxy)(tert-butyl)dimethylsilane as a clear colourless oil (15.3 g, 92percent) The ¹H proton and ¹³C NMR shifts were confirmed in the report by Vader et al.
91%	With 1H-imidazole In dichloromethane at 20℃;	(2-Bromoethoxy)(tert-butyl)dimethylsilane (2)TBDMSO. ^„— BrTo a stirring solution of 2-bromoethanol (15.0 mL, 212 mmol) and imidazole (28.9 g, 425 mmol) in dichloromethane (200 mL) was added tert- butylchlorodimethylsilane (32.0 g, 212 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with water (300 mL) and extracted into dichloromethane (2 x 100mL). The organic layers were combined, washed with brine (100 mL), dried over sodium sulfate, filtered and evaporated to yield (2-bromoethoxy)(tert- butyl)dimethylsilane (46.3 g, 91 percent) as a colourless oil. 1 H NMR (400 MHz CDCI₃) ?_? ppm 0.00 (s, 6H); 0.82 (s, 9H); 3.27 (t, 2H); 3.80 (t, 2H).
91%	at 20℃; for 3 h; Inert atmosphere	A modified procedure of Galka et. al., J. Lab. Comp. Rad. 2005, 48, 11, 797-809 was used to prepare the title compound. A mixture of 2-bromoethanol (40 mmol), tert-butyldimethylsilylchloride (40 mmol) and imidazole (44 mmol)was stirred at rt for 3 hours under inert atmosphere. The reaction was quenched with water and extracted with diethylether.The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The purification was achieved by columnchromatography (PE/EE) to yield the title compound (36.4 mmol; 91 percent). 1H NMR (300 MHz, CDCl3) δ [ppm] = 3.91 (t;3J = 6.5 Hz; 2H; OCH2); 3.41 (t; 3J = 6.5 Hz; 2H; CH2Br); 0.93 (s; 9H; C(CH3)3); 0.11 (s; 6H; 2xCH3).
86%	With dmap; triethylamine In tetrahydrofuran at 0 - 20℃; for 10 h;	<Synthesis of Compound>Example 1-1Synthesis of Compound (M-1)In a 1 L reaction flask were charged 40 g of 2-bromoethanol (0.32 mol) and 53 g of t-butyldimethylchlorosilane, and thereto was added 400 mL of tetrahydrofuran (THF). The THF solution thus obtained was cooled to 0° C., and thereto was slowly added dropwise a THF solution prepared by dissolving 36 g of triethylamine (0.35 mol) and 3.9 g of N,N-dimethyl-4-aminopyridine (0.03 mmol) in 100 mL of THF, followed by stirring the mixture at room temperature for 10 hrs. After completing the reaction, precipitates thus generated were removed by suction filtration and then THF in the liquid layer was distilled off by an evaporator, and the residue was extracted with ethyl acetate, followed by washing with water and saturated saline and drying the organic layer over anhydrous magnesium sulphate. Thereafter, a residue obtained by vacuum concentration was purified by vacuum distillation to obtain 66.0 g (yield: 86percent) of a compound represented by the following formula (m-1).
83%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 16 h;	To a stirred solution of TBDMSC1 (3.5 g) in DMF (10 ml) was added imidazole (1.77 g). Then 2-bromoethan-l-ol (2.5 g) was added slowly dropwise and the reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with water and extracted with hexane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, gradient 0 - 3percent ethyl acetate in hexane). The title compound was obtained as colourless oil (3.96 g, 83percent). NMR complied with literature data.
77.5%	With 1H-imidazole In dichloromethane at 0 - 20℃; for 24 h;	Step 4: Preparation of (2-bromoethoxy)(teri-butyl)dimethylsilane To a solution of 2-bromoethanol (3.4 mL, 48.34 mmol) in dry DCM (25 mL) imidazole (9.86 g, 143 mmol) and ieri-butylchlorodimethylsilane (10.9gm, 72.52 mmol) were added at 0 °C. The reaction mixture was stirred at r.t. for 24 h. After completion of reaction, as confirmed by TLC, the reaction mixture was diluted with ethylacetate (350 mL) and washed with water (4 x 20 mL). The organic layer was dried over anhydrous Na₂S0₄ and' volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 0.2: 9.8 Ethyl acetate: Pet. Ether) to afford title compound (204 mg, 77.5 percent) as liquid. ESIMS (m/z): 239.1 (M+l).
77.5%	With 1H-imidazole In dichloromethane at 0 - 20℃; for 24 h;	Step 4: Preparation of (2-bromoethoxy)(tert-butyl)dimethylsilane To a solution of 2-bromoethanol (3.4 mL, 48.34 mmol) in dry DCM (25 mL) imidazole (9.86 g, 143 mmol) and tert-butylchlorodimethylsilane (10.9gm, 72.52 mmol) were added at 0 °C. The reaction mixture was stirred at r.t. for 24 h. After completion of reaction, as confirmed by TLC, the reaction mixture was diluted with ethylacetate (350 mL) and washed with water (4 x 20 mL). The organic layer was dried over anhydrous Na₂SO₄ and volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 0.2: 9.8 Ethyl acetate: Pet. Ether) to afford title compound (204 mg, 77.5 percent) as liquid. ESIMS (m/z): 239.1 (M+1).
76%	With dmap; triethylamine In dichloromethane at 20℃; for 16 h;	To a solution of 2.0 g (16.0 mmol, 1.0 eq.) of 2-bromoethanol in 10 mL of methylene chloride at 0 °C was added 3.2 g (32.0 mmol, 2.0 eq.) of triethylamine followed by 2.89 g(19.2 mmol, 1.2 eq.) of tert-butyldimethylsilyl chloride and 0.78 g (6.40 mmol, 0.4 eq.) of 4- dimethylamino pyridine and the mixture was stirred at room temperature for 16 h. The mixture was diluted with 50 mL of 1 M HC1 and extracted with 2 x 50 mL of methylene chloride. The combined organic extracts were washed with 30 mL of water, 30 mL of brine, dried (Na2SO4), filtered and the solvent removed in vacuo to provide 2.9 g (12.2 mmol, 76percent)of (2)-bromoethoxy)(tert-butyl)dimethylsilane. ‘H NMR (400 IVIFIz, CDC13): 3.79 (t, 2H),3.29 (t, 2H), 0.81 (s, 9H), -0.01 (s, 6H).
70%	With 1H-imidazole In dichloromethane at 20℃; for 2 h;	Tert-butyldimethylchlorosilane (6.4 g, 42 mmol) was added portionwise to a solution of compound 4 (5 g, 40 mmol) and imidazole (5.5 g, 80 mmol) in methylene chloride at room temperature for 2 hours at room temperature. The system was diluted with methylene chloride, washed with saturated aqueous sodium carbonate solution, washed with water,Saturated aqueous sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, filtered,Rotate to a yellow oil (6.7 g, 70percent).
62.4%	With dmap; triethylamine In dichloromethane at 20℃; for 15 h;	Example 123a (2-Bromoethoxy)(tert-butyl)dimethylsilane 123a To a solution of 2-bromoethanol (5.0 g, 40.3 mmol) in DCM (20 mL) was added tertbutyldimethylsilyl chloride (9.1 g, 60.5 mmol) followed by the additions of triethylamine (8.14 g, 80.6 mmol) and 4-dimethylaminopyridine (49.2 mg, 0.4 mmol). The mixture was stirred at room temperature for 15 h and concentrated in vacuo. The residue was partitioned between 1N HCl and ethyl acetate. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford yellow oil, which was purified by column chromatography eluting with PE:EA (50:1) to afford 123a as colorless oil (6.0 g, 62.4 percent). LCMS: (M+H)⁺ 241.
57%	With 1H-imidazole In acetonitrile at 20℃; for 12 h;	To a solution of 2-bromoethan-l-ol (6.5 g, 1.0 eq) in ACN (100 mL) at rt, TBDMSCl (5.0 g, 0.65 eq) and imidazole (3.4 g, 1.0 eq) were added and stirred at rt for 12 h. After TLC showed completion of starting material, the mixture was diluted with water (90 mL) and extracted with EtOAc (2 x 80 mL). The organic layer was washed with brine solution (20 mL), dried over anhydrous Na₂S0₄ and concentrated to provide (2-bromoethoxy)(tert-butyl)dimethylsilane (7.5 g, 57percent). 1H NMR (400 MHz, CDC1₃): δ 3.87 (t, 2H), 3.47 (t, 2H), 0.86 (s, 9H), 0.06 (s, 6H).
55%	With triethylamine In dichloromethane at 20℃; for 1.33333 h;	Dry DCM (25ml) in bromoethanol (9.912g, 79.32mmol) to a stirred solution of, in addition tert- butyldimethylsilyl chloride (13.212g, 85.03mmol) at a time, at room temperature the reaction mixture in the mixture was stirred. Then triethylamine in dry DCM (40ml) (8.865g, 12.3ml, 87.61mmol) was added dropwise over a solution for 1 hour and 20 minutes of. The reaction mixture was stirred for 3 days at room temperature, then water was added (30ml). The organic phase was separated, the aqueous phase was extracted with DCM (2 × 20ml). The combined organic extracts were washed with brine (30ml), dried (Na2SO4), the solvent was removed under reduced pressure, to give a pale yellow oil. It was distilled under reduced pressure to give the title compound (10.54g, 55percent) as a colorless oil.
53%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 20 h;	Intermediate (69) : Preparation of 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl] -methyl-amino}-ethanol; Step 1. Preparation of (2-bromo-ethoxy)-t-butyl-dimethyl-silane; 2-bromoethanol (1.Og, 8.0mmol) was dissolved in DMF (5ml). Therein, tert- butyldimethylsilyl chloride (1.45g, 9.6mmol) and imidazole (1.36g, 20.0mmol) were added, and the reaction mixture was stirred at room temperature for 20 hours. Thereafter, the reaction mixture was poured into diethyl ether, and washed with water and saturated sodium chloride aqueous solution. Combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (n-hexane=100percent) to give 1.Og (yield: 53percent, <n="113"/>colorless oil) of the target compound.[1197] ¹¹HH--NNMMIR (CD₃OD, 400D) δ 3.89(t/=6.6Hz, 2H), 3.40(t, J=6.6Hz, 2H), 0.90(s, 9H), 0.09(s, 6H)

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6
[ 288-32-4 ]
[ 18162-48-6 ]
[ 86864-60-0 ]

Reference： [1] Patent: US2001/41726, 2001, A1,

7
[ 86864-60-0 ]
[ 101166-65-8 ]

Reference： [1] Patent: US2001/34343, 2001, A1,
[2] Patent: US6423704, 2002, B1,
[3] Patent: US6194406, 2001, B1,
[4] Patent: WO2014/140241, 2014, A1, . Location in patent: Page/Page column 20; 38
[5] Helvetica Chimica Acta, 2016, vol. 99, # 7, p. 523 - 538

[ 86864-60-0 ] Synthesis Path-Downstream 1~88

1
[ 1618-26-4 ]
[ 86864-60-0 ]
[ 143681-96-3 ]

Reference： [1]Journal of the American Chemical Society,1992,vol. 114,p. 9836 - 9845

2
[ 879-37-8 ]
[ 86864-60-0 ]
[ 609826-37-1 ]

Yield	Reaction Conditions	Operation in experiment
97%		Indole Compound 1a (2.34 g, 20 mmol) and 3-bromopyridine (3.16 g, 20 [MMOL)] were dissolved in DMF (10 mL) and potassium carbonate (2.76 g, 20 mmol). [CUO] (130 mg, 1.6 [MMOL)] was added and the reaction was refluxed under argon for 16 h. The mixture was cooled to rt and partitioned between DCM (100 mL) and water (100 mL). The organic layer was washed with water (3 X 50 mL) and brine (2 X 50 mL), then dried [(NA2SO4)] and evaporated in vacuo to a brown oil. The product was purified via flash column chromatography (ethyl acetate: hexane; 1: 1) to give Compound [1B] (3.16 g, [81%)] as a colorless oil. The indole Compound [1B] (0.78 g, 4.0 mmol) in DCM (12 mL) was treated with [OXALYL] chloride (0.52 g, 4.1 mmol) with ice bath cooling and then stirred at ambient temperature for 16 h. The solution was cooled to-65 [C] and sodium methoxide (0.46 g, 8.0 [MMOL)] in methanol (10 mL) was added slowly ; the reaction was stirred at ambient temperature for 1 h and then evaporated in vacuo to a solid. The solid was extracted with chloroform (25 mL), filtered and the filtrate dried [(K2CO3)] and evaporated in vacuo to provide Compound 1c (0.73 g, 65%) as a grey [SOLID.'H] NMR [(CDC13)] [8] 8.88 (d, J = 2.3 Hz, 1 H), 8.77 (dd, [J = 4.] 7,1. 3 Hz, 1 H), 8.60 (s, 1 H), 8.54 (d, [J = 7.] 1 Hz, 1 H), 7.90 (m, 1 H), 7.56 (m, 1 H), 7.43 (m, 3H), 3.98 (s, 3H). ES-MS m/z 281 (MH+). The indole Compound 1d (5 g, 28.7 [MMOL)] in DMF (40 mL) was cooled in an ice bath followed by addition of 60% NaH (0.76 g, 31.6 mmol). The mixture was stirred at room temperature for 30 min. Silyl-protected [2-BROMO-1-ETHANOL] Compound 1e (7.55 g, 31.6 [MMOL)] was added and the mixture was stirred at rt for 8 h. Then water was added and extracted with EtOAc several times. The organic layers were combined and washed with brine, then dried [(NA2SO4)] and evaporated in vacuo to provide an oil. The oil was purified by flash column chromatography (95: 5: 0.5 ; DCM: MeOH : NH40H) to give an amide Compound 1f (9.22 g, 97%). 1H NMR [(CDC13)] [6] 7.69 (d, J =7.8 Hz, 1 H), 7.47 (d, J =8.2 Hz, [1H),] 7.30 (m, 3H), 5.78 (bd s, 1 H), 5.66 (bd s, 1 H), 4.34 (t, J =5.5 Hz, 2H), 4.03 (t, J =5.5 Hz, 2H), 3.84 (s, 2H), 0.94 (s, 9H), 0.01 (s, 6H). ES-MS m/z 333 (MH+). The methyl ester 1c (2.12 g, 6.37 [MMOL)] and amide Compound 1f (2.5 g, 8.92 mmol) were combined in dry THF (15 mL) under argon and cooled in an ice bath as [1M] potassium t-butoxide in THF (31 mL, 31 mmol) was added with stirring over a 15 min period. After 40 min, the reaction was quenched in an ice bath while 12 N HCI (4 mL, 48 [MMOL)] was slowly added. The mixture was stirred for 15 min at rt, made slightly basic by the addition of 3N [NAOH] and extracted with EtOAc. The organic layers were combined and washed with saturated [NAHC03] and brine, then dried [(NA2SO4)] and evaporated in vacuo to give a crude solid. The solid was then purified by flash column chromatography (97: 3: 0.3 ; DCM: MeOH : NH40H) to afford Compound 1 (1.24 g, 44%) as a red flaky solid. Compound 1 was dissolved in excess dilute [HCI,] then frozen and [LYOPHILIZED] to give the hydrochloride salt.'H NMR (CD30D) [6] 9.05 (s, [1H),] 8.79 (m, [1H),] 8.69 (m, [1H),] 8.14 (m, [1H),] 7.95 (s, [1H),] 7.91 (s, [1H),] 7.63 (d, J = 8.4 Hz, [1H),] 7.45 (d, J = 8.23 Hz, [1H),] 7.20 (m, 2H), 7.07 (t, J = 7.6 Hz, 1 H), 6.92 (t, J = 7.6 Hz, 1 H), 6.81 (d, J = 7.9 Hz, 1 H), 6.66 (t, J = 7.6 Hz, 1 H), 4.33 (t, J = 5.4 Hz, 2H), 3.89 (t, J = 5.3 Hz, 2H). ES-MS m/z 449 (MH+). Anal. Calcd. for [C27H20N403. 0. 98HCI. 0.] 89 H20: C, 64.83 ; H, 4.59 ; N, 11.2 ; Cl, 6.95 ; KF, 3.21. Found: C, 64.83 ; H, 4.45 ; N, 11.22 ; Cl, 7.13 ; KF, 3.29.
	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃;	EXAMPLE 1 10,11,12,13,14,16,17,18,19,20-decahydro-15-thio-2,9,12,18,21-pentaaza-1H-diindolo[1,2,3-m,n:3',2',1'-r,s]cyclononadec-14,16,18-trien[16,17-c]-pyrrole-2,5-dione (Compound 1); A mixture of Compound 1a (3.50 g, 20 mmol), Compound 1b (5.29 g, 22 mmol) and 60% NaH (0.88 g, 22 mmol) in DMF (350 mL) was stirred at 0 C. for 30 min and then r.t overnight. The reaction was quenched by slowly addition of water under ice bath. The mixture was extracted with EtOAc several times. The combined extracts were sequentially washed with water and brine and then dried (Na2SO4), evaporated in vacuo. The residue was separated by flash column chromatography (CH2Cl2/MeOH, 98:2) to give Compound 1c as a viscous oil. 1H NMR (CDCl3) delta 7.69 (d, J=7.9 Hz, 1H), 7.47 (d, J=8.2 Hz, 1H), 7.34 (m, 1H), 7.26 (m, 2H), 5.77 (bs, 1H), 5.62 (bs, 1H), 4.34 (t, J=5.5 Hz, 2H), 4.03 (t, J=5.5 Hz, 2H), 3.84 (s, 2H), 0.94 (s, 9H), 0.1 (s, 6H). ES-MS m/z 333 (MH+).

Reference： [1]Patent: WO2003/104222,2003,A1 .Location in patent: Page 49-51
[2]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3049 - 3053
[3]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 5171 - 5174
[4]Patent: US2007/88019,2007,A1 .Location in patent: Page/Page column 14

3
[ 18372-22-0 ]
[ 86864-60-0 ]
[ 609826-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 4h;	A mixture of Compound 1d (4.00 g, 19.7 mmol), Compound 1b (5.19 g, 21.7 mmol) and cesium carbonate (7.06 g, 21.7 mmol) in DMF (40 mL) was stirred at 50 C. for 4 h and then filtered. The filtrate was evaporated in vacuo and the residue was separated by flash column chromatography (EtOAc/heptane, 1:2) to give Compound 1e as a viscous oil. 1HNMR (CDCl3) δ 8.61 (m, 2H), 7.51 (m, 3H), 4.45 (t, J=5.1 Hz, 2H), 4.13 (m, 2H), 4.10 (s, 3H), 0.96 (s, 9H), 0.1 (s, 6H). ES-MS m/z 362 (MH+).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3049 - 3053
[2]Patent: US2007/88019,2007,A1 .Location in patent: Page/Page column 14

4
[ 86864-60-0 ]
[ 345627-80-7 ]
[ 345629-26-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

5
[ 29415-97-2 ]
[ 86864-60-0 ]
[ 325147-52-2 ]

Reference： [1]Journal of the American Chemical Society,2000,vol. 122,p. 12907 - 12908
[2]Journal of the American Chemical Society,2001,vol. 123,p. 12202 - 12206

6
[ 619-10-3 ]
[ 86864-60-0 ]
[ 953804-18-7 ]

Yield	Reaction Conditions	Operation in experiment
57%	With potassium carbonate; In N,N-dimethyl-formamide; at 40℃; for 96h;	Intermediate 287; fer?-Butvir2-(2-chloro-5-nitrophenoxy)ethoxyldimethylsilane; A mixture of <strong>[619-10-3]2-chloro-5-nitrophenol</strong> (6.0 g, 34.57 mmol), (2-bromoethoxy)-fer£- butyldimethylsilane (8.6 mL, 41.5 mmol) and potassium carbonate (7.15 g, 41.5 mmol), in DMF (40 mL) was heated at 4O0C for 4 days. The reaction mixture was filtered. Brine (200 mL) was added, and the mixture was extracted with EtOAc (3x 50 mL). The combined organic extracts were concentrated, and the residue purified by silica chromatography (hexanes/EtOAc gradient) to give 6.5 g (57%) of a white solid. 1H NMR: 7.94 (s, 1 H), 7.84 (dd, 1 H), 7.74 (d, 1 H), 4.325 (m, 2 H), 3.96 (m, 2 H), 0.82 (s, 9 H), 0.04 (s, 6 H).

Reference： [1]Patent: WO2007/119046,2007,A1 .Location in patent: Page/Page column 125

7
[ 15359-98-5 ]
[ 86864-60-0 ]
C₁₉H₃₄O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 45; 3 -(4-tert-Butoxyphenyl)-propan- 1 -ol (S4)S4 [00263] 3-(4-tert-Butoxyphenyl)-propan-l-ol (S4): A solution of 1 -tert-Butoxy-4- methylbenzene (S3) (8.81g, 53.7 mmol) in anhydrous THF (165 mL) was cooled to -15 0C under N2. KO'Bu (80.6 mL, 1 M in THF, 80.6 mmol) and M-BuLi (32.2 mL, 2.5 M in hexane, 80.6 mmol) were added; upon addition the reaction mixture turned a deep red color. After 1 h, (2-Bromoethoxy)-tert-butyl-dimethylsilane (17.3 mL, 80.6 mmol) was added by a syringe to the cold solution. The red color began to dissipate, and the reaction mixture was gradually warmed to room temperature and was stirred overnight under N2. The reaction mixture was poured into a separation funnel containing 400 mL H2O. The layers were separated, and the aqueous layer was extracted with EtOAc (3 x 200 mL). The extraction was monitored by TLC. The combined organic layers were dried over MgSO4, filtered and concentrated to give an oil. The crude oil was filtered through a silica gel plug with excess EtOAc. The filtrates were collected and concentrated to give a yellow oil.

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 6050 - 6055
[2]Patent: WO2007/112358,2007,A1 .Location in patent: Page/Page column 56

8
[ 3964-57-6 ]
[ 86864-60-0 ]
[ 570407-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 15h;	Reference Example 78 To a solution of 2.50 g of 3-chloro-4-hydroxybenzoic acid methyl ester in 25 ml of DMF, 2.78 g of potassium carbonate and 4.31 ml of 2-(tert-butyldimethylsilyloxy)ethylbromide were added, and the mixture was stirred at 50 C for 15 hours.. The solvent was evaporated, EtOAc was added to the residue, and the organic layer was washed with water and brine and dried over sodium sulfate.. After the evaporation of the solvent, the obtained residue was purified by silica gel column chromatography (eluent: hexane-EtOAc = 10:1?5:1) to obtain 4.88 g of 4-[2-(tert-butyldimethylsilyloxy)ethoxy]-3-chlorobenzoic acid methyl ester.

Reference： [1]Patent: EP1466912,2004,A1 .Location in patent: Page 21

9
[ 86864-60-0 ]
[ 76003-29-7 ]
[ 786683-69-0 ]

Yield	Reaction Conditions	Operation in experiment
50%		To a solution of /er/-butyl 3-oxopiperazine-l-carboxylate (cas: 76003-29-7, 2 g, 10 mmol) in DMF (20 mL) that had been pre-cooled in an ice-water bath was added NaH (800 mg, 2.0 equiv.) in portions under N2. The mixture was stirred for 0.5 hours. (2- bromoethoxy)(ter/-butyl)dimethylsilane (cas: 86864-60-0, 5.3 mL, 2.5 equiv.) was added to the solution at 0 C. The reaction mixture was stirred at 25 C for 12 hours. The reaction mixture was then diluted with water (50 mL) and extracted with EtOAc (3 x 80 mL). The combined organic extracts was then washed with water (50 mL), brine (50 mL), and dried over Na2S04, then concentrated under reduced pressure to a residue. The residue was purified by silica gel chromatography to afford ketopiperazine 1-321 as a pale oil (1.8 g, 50% yield, pale oil). MS (ESI, pos. ion) m/z: 381 (M+23
45%	With potassium hydroxide; tetrabutylammomium bromide; In tetrahydrofuran; at 20℃; for 4h;	a) A solution of (2-bromoethoxy)-tert-butyldimethylsilane (4.71 g, 19.7 mmol) in tetrahydrofuran (20 ml) was added dropwise at room temperature to a stirred solution of tert- butyl 3-OXOPIPERAZINE-1-CARBOXYLATE (3.94 g, 19.7 mmol), powdered potassium hydroxide -183- (1.32 g, 23.6 mmol) and tetrabutylammonium bromide (1.27 g, 3.94 mmol) in tetrahydrofuran (30 ml) and the resulting mixture was stirred for 4 hours. The mixture was filtered and then evaporated to leave a colourless viscous oil which was purified by silica gel chromatography eluting with methyl tert-butyl ether as eluent to give tert-butyl 4-(2-[TERT- butyl (dimethyl) silyl] OXY} ETHYL)-3-OXOPIPERAZINE-1-CARBOXYLATE (3.42 g, 45% yield) as a colourless oil: 1H-NMR (CDC13): 4.08 (s, 2H), 3.80 (t, 2H), 3.61 (m, 2H), 3.50 (m, 4H), 1.46 (s, 9H), 0.87 (s, 9H), 0.05 (s, 6H).
6.85 g		To solution of tert-butyl 3-oxopiperazine-1-carboxylate (1.00 g) in dimethylformamide (20 ml) was added at 0C sodium hydride (240 mg) in three portions and stirring was continued at22C for 30 mm. (2-Bromoethoxy)(tert-butyl)dimethylsilane (1.43 g) was added at 0C andstirring was continued at 22C for 4 h. The mixture was partitioned between water and ethylacetate, the organic layer was dried, evaporated and the residue purified by flashchromatography (silica gel, 0 - 5% methanol in dichloromethane) to give the title compound(6.85 g) as a light yellow oil.MS (ESI, m/z): 359.2 [(M+H)]

Reference： [1]Patent: WO2019/183577,2019,A1 .Location in patent: Page/Page column 246-247
[2]Patent: WO2004/94410,2004,A1 .Location in patent: Page 182-183
[3]Patent: WO2017/158147,2017,A1 .Location in patent: Page/Page column 80

10
[ 81721-87-1 ]
[ 86864-60-0 ]
C₁₆H₂₄N₂O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 80℃; for 12h;	A. To a solution of 6-nitro-2H-1,4-benzoxazin-3(4H)-one (0.50 g, 2.58 mmol) in 10 mL of MeCN was added potassium carbonate (0.53 g, 3.86 mmol) and (2-bromoethoxy)-t-butyldimethylsilane (0.55 mL, 2.58 mmol). The mixture was heated to 80 C. and stirred for 12 hours. The filtrate was collected from removing the solid and was concentrated under reduced pressure to residue, which was then purified by flash column chromatography with hexanes and ethyl acetate to afford the nitro compound.

Reference： [1]Patent: US2006/116368,2006,A1 .Location in patent: Page/Page column 65; 66

11
[ 86864-60-0 ]
[ 101166-65-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium iodide; In N-methyl-acetamide; acetone;	PREPARATION 57 4-(1-(2-Hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane Hydriodic Acid Salt Combine 2-(t-butyldimethylsilyloxy)ethyl bromide (116.2 g, 486 mmol), and sodium iodide (100 g, 663 mol) in acetone (350 mL) and dimethylformamide (25 mL). Heat to reflux. After 4 hours, cool, filter and evaporate in vacuo to give a residue. Distill the residue to give 2-(t-butyldimethylsilyloxy)ethyl iodide: bp; 60 C. at 0.5 mm Hg.
	With sodium iodide; In N-methyl-acetamide; acetone;	PREPARATION 57 4-(1-(2-Hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane Hydriodic acid salt Combine 2-(t-butyldimethylsilyloxy)ethyl bromide (116.2 g, 486 mmol), and sodium iodide (100 g, 663 mol) in acetone (350 mL) and dimethylformamide (25 mL). Heat to reflux. After 4 hours, cool, filter and evaporate in vacuo to give a residue. Distill the residue to give 2-(t-butyldimethylsilyloxy)ethyl iodide: bp; 60 C. at 0.5 mm Hg.
	With sodium iodide; In N-methyl-acetamide; acetone;	Preparation 57 4-(1-(2-Hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic Acid Salt Combine 2-(t-butyldimethylsilyloxy)ethyl bromide (116.2 g, 486 mmol), and sodium iodide (100 g, 663 mol) in acetone (350 mL) and dimethylformamide (25 mL). Heat to reflux. After 4 hours, cool, filter and evaporate in vacuo to give a residue. Distill the residue to give 2-(t-butyldimethylsilyloxy)ethyl iodide: bp; 60 C. at 0.5 mm Hg.

With sodium iodide; In acetone; at 70℃;

Step 3-A-alternative. J'ert-butyl(2-iodoethoxy)dimethylsilane A solution of (2-bromoethoxy)(tert-butyl)dimethylsilane (500 mg, 0.45 mL, 2.09 mmol) and sodium iodide (470 mg, 3.14 mmol) in 5.0 mL acetone was heated at 70 C with stir overnight. After cooling, solids were removed by filtration and the solid was washed with EtOAc. The combine filtrate and wash was evaporated to give pure title compound. 1H NMR (CDC13, 500 MHz)? 3.85 (t, 6.9 Hz, 2H), 3.22 (t, 7.0 Hz, 2H), 0.93 (s, 9H), 0.11 (s, 6H).

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 12951 - 12964
[2]Patent: US2001/34343,2001,A1
[3]Patent: US6423704,2002,B1
[4]Patent: US6194406,2001,B1
[5]Patent: WO2014/140241,2014,A1 .Location in patent: Page/Page column 20; 38
[6]Helvetica Chimica Acta,2016,vol. 99,p. 523 - 538

12
[ 288-32-4 ]
[ 86864-60-0 ]
[ 1615-14-1 ]

Yield	Reaction Conditions	Operation in experiment
35%	With tetrabutyl ammonium fluoride; potassium carbonate; In tetrahydrofuran; ethyl acetate; N,N-dimethyl-formamide;	Preparatory Example 56 1-(2-Hydroxyethyl)imidazole STR299 3.56 g of 2-bromoethyl t-butyldimethylsilyl ether and 1.97 g of imidazole were dissolved in 70 ml of N,N-dimethylformamide, to which 4 g of potassium carbonate were added, followed by agitation at 90 C. for 2 hours and 40 minutes. After removal of the solvent by distillation, ethyl acetate was added, followed by washing with water and drying with anhydrous magnesium sulfate. This was filtered and, after removal of the solvent by distillation, m the resultant residue was dissolved in tetrahydrofuran, to which 12.6 ml of tetrabutylammonium fluoride (1M tetrahydrofuran solution), followed by agitation at room temperature. After completion of the reaction, the solvent was distilled of and the resultant residue was subjected to silica gel column chromatography (developing solvent: dichloromethane) to obtain 0.59 g of the caption compound (yield 35%). 1 H-NMR(90 MHz, CDCl3) delta:3.28(bs,1H), 3.6-4.2(m,4H), 6.84(bs,1H), 7.28(bs,1H)

Reference： [1]Patent: US5221671,1993,A

13
[ 161876-64-8 ]
[ 86864-60-0 ]
[ 215660-85-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran;	Step (a) Synthesis of 4-ethyl-2-[2-(1,1-dimethylethyldimethylsilyloxy)-ethoxy]benzaldehyde This compound was prepared in a manner analogous to that of Step (b) of Example 1, using 17.0 grams (0.113 mole) of <strong>[161876-64-8]5-ethyl-2-formylphenol</strong>, 27.7 grams (0.116 mole) of 2-(1,1-dimethylethyldimethylsilyloxy)ethyl bromide, 19.2 grams (0.139 mole) of potassium carbonate, and a catalytic amount of 18-crown-6 in 200 mL of THF. The yield of the subject compound was 12.7 grams, following purification by column chromatography on silica gel. The NMR spectrum was consistent with the proposed structure.

Reference： [1]Patent: US1759,1998,H1

14
[ 86864-60-0 ]
[ 84905-80-6 ]
[ 871024-41-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h;	Production of 5-(2-[tert- butyl (dimethyl) silyl]oxy}ethyl)-4-chloro-5H-pyrrolo[3,2- d] pyrimidine4-Chloro-5H-pyrrolo [3, 2-d] pyrimidine (2.00 g) , (2- bromoethoxy) ( tert-butyl ) dimethylsilane (4.00 g) and cesium carbonate (6.40 g) were dissolved in N,N- dimethylformamide (10 mL) and the mixture was stirred at room temperature for 4 hr. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate:hexane=20: 80?40: 60) to give the title compound (3.02 g) as a brown solid.1H-NMR (DMSO-d6) delta: -0.24 (6H, s), 0.69 (9H, s), 3.90- 3.93 (2H, m) , 4.61-4.64 (2H, m) , 6.76 (IH, s), 8.00 (IH, s) , 8.61 (IH, s) .

Reference： [1]Patent: WO2007/64045,2007,A1 .Location in patent: Page/Page column 609

15
[ 617-27-6 ]
[ 86864-60-0 ]
[ 1069135-88-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 90℃; for 18h;	To a suspension of (D/L)-alanine ethyl ester hydrochloride (19.0 mmol, 2.92 g) in DMF (100 ml) was added potassium carbonate (42.75 mmol, 5.9 g) followed by Hunig's base (7.5 ml 42.8 mmol). The mixture was then heated to 90 C. and (2-bromoethoxy)-tert butyl dimethylsilane (3)(20.9 mmol, 5.0 g) added dropwise over 2 hours. The reaction mixture was maintained at 90 C. for a further 16 hours before being cooled to room temperature. The resultant suspension was filtered and washed with DMF (2×30 ml). The filtrate was concentrated in vacuo and taken through to the next step without any need for further purification. (Rf 0.55 DCM/ethyl acetate 8:3, anisaldehyde stain).

Reference： [1]Patent: US2008/255128,2008,A1 .Location in patent: Page/Page column 14-15

16
[ 86864-60-0 ]
[ 15944-34-0 ]
[ 1033589-07-9 ]

Yield	Reaction Conditions	Operation in experiment
62%		To a solution of 7-chloro-l,8-naphthyridin-2(lH)-one (2.7 g, 15.2 mmol) (J.Org.Chem. 1990, 55, 4744-4750) in N,N-dimethylformamide (4OmL) under nitrogen at O0C was added sodium hydride (0.73 g, 18.3 mmol). The slurry was stirred for ten minutes and then (2- bromoethoxy)-t-butyl dimethylsilane (4.3 g, 18.3 mmol) was added. The mixture was heated at 8O0C for two hours then cooled to room temperature. The reaction mixture was quenched with water and the product extracted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Chromatography <n="34"/>on silica gel with 20% acetone in n-hexane gave the product as an oil (3.2 g, 62%).MS CES): 338 (MH+) for C16H23N2SiClO21H NMR fDMSO-d): delta ppm -0.00 (s, 6H); 0.81 (s, 9H); 3.91 (t, 2H); 4.53 (t, 2H); 6.80 (d,IH); 7.45 (d, 1 H); 8.06 (d, IH); 8.29 (d, IH).

Reference： [1]Patent: WO2008/71964,2008,A1 .Location in patent: Page/Page column 32-33

17
[ 86864-60-0 ]
[ 84955-31-7 ]
7-[2-(t-butyldimethylsilanyloxy)ethyl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1; 7-(2-(4-(2,5-Difluorophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, Method A; A. 7-[2-(t-Butyldimethylsilanyloxy)ethyl]-<strong>[84955-31-7]4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong>; To a suspension of NaH (0.618 g, 15.45 mmol) in anhydrous DMF (15 mL) at 0 C. is added slowly a solution of <strong>[84955-31-7]4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong> (2 g, 11.86 mmol) in 5 mL of anhydrous DMF. The mixture is stirred at this temperature under N2 for 15 min, then (2-bromoethoxy)-t-butyldimethylsilane (4.0 mL, 18.64 mmol) is added at 0 C. The mixture is stirred at RT overnight. The reaction mixture is poured into water and extracted with ethyl acetate (EtOAc; 4×). The organic layer is dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuo. The crude product is purified by flash cromatography using EtOAc/cyclohexane (1/1) as eluent to yield 7-[2-(t-butyldimethylsilanyloxy)ethyl]-<strong>[84955-31-7]4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine</strong> as white needles: LC/MS (M+1=327). 1H NMR (CDCl3, 400 MHz) delta-0.08 (s, 6H), 0.84 (s, 9H), 3.88 (t, 2H, J=5.2 Hz), 4.17 (t, 2H, J=5.2 Hz), 4.89 (s, 2H, NH2), 6.35 (d, 1H, J=3.6 Hz), 6.90 (d, 11, J=16 Hz).

Reference： [1]Patent: US2008/242672,2008,A1 .Location in patent: Page/Page column 20

18
[ 374063-92-0 ]
[ 86864-60-0 ]
[ 1051316-14-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 113; l-(2-(7-Methoxyqumolin-4-yloxy)ethyl)-5-(4-methyIthiophen-2-yl)pyrazin-2(lH)-one <n="152"/>Cone. HCI, MeOH5-Bromo-l-(2-(ter*-butyldimethylsilyloxy)ethyl)pyrazin-2(lH)-one. 5- Bromopyrazin-2-ol (1.209 g, 6.91 mmol) was dissolved in DMF (10.0 mL) and sodium hydride (60% in mineral, 530 mg, 13.25 mmol) was added. The reaction flask was put in a water bath and stirred under argon for 15 minutes, and then (2- bromoethoxy)(tert-butyl)dimethylsilane (1.69 mL, 7.93 mmol) was added as a solution in DMF (4.7 mL total volume), followed by a -0.5 mL rinse with DMF. The reaction was stirred under argon at room temperature for 2 days. It was then quenched with water (50 mL) and extracted with EtOAc (3 x 50 mL). The organic extracts were combined, washed with water (4 x 50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated. The material was taken on crude to the next step.

Reference： [1]Patent: WO2008/103277,2008,A2 .Location in patent: Page/Page column 150-151

19
[ 5807-30-7 ]
[ 42492-57-9 ]
[ 38945-21-0 ]
[ 86864-60-0 ]
[ 267409-95-0 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: Treat a solution of 3,4-dichlorophenylacetic acid (25 g) with N-t-BOC-sarcosine methyl ester (24.3 g) (prepared from sarcosine methyl ester HCl and di-t-butyldicarbonate) according to a procedure similar to Example 11, Step 2, to give the desired product (36 g).Step 2 : Treat 2-bromoethanol (107 g) in CH2Cl2 (2 L) at 0 C with t-butyldimethylsilyichloride (143 g), NEt3 (130 g) and DMAP (11 g), allow the reaction mixture to warm to 23 C and stir for 18 h. Wash the mixture with H2O (250 mL), 20% HCl (250 mL), 20% NH4OH (250 mL), dry (MgSO4) and concentrate to give 2-(t-butyldimethylsilyloxy)-ethylbromide (197 g).Step 3 : Treat the product of Step 1 (57 g) in DMF (500 mL) at -10 C with NaH (8.6 g, 60% disp. in oil) and stir for 1 h. Add 2-(t-butyldimethylsilyloxy)ethylbromide (51.3 g) and Nal (6.4 g) and stir for 18 h. Add EtOAc (400 mL) and saturated NaCl solution (300 mL). Separate the organic portion, dry (MgSO4), filter and concentrate. Purify the crude oil by silica gel chromatography eluting with EtOAc/hexane mixtures to give product (60.1 g).Step 4 : Treat the product from Step 3 (28 g) with O-allylhydroxylamine HCl (17 g) according to a procedure similar to Example 1, to give the title compound (24.5 g).

Reference： [1]Patent: EP1032561,2004,B1 .Location in patent: Page 21

20
[ 86864-60-0 ]
[ 147460-41-1 ]
[ 811867-36-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 55℃;	Boc-T129a was produced from <strong>[147460-41-1]5-fluoro-2-bromophenol</strong> (129-1), TBDMS-protected 2-bromo-ethanol (129-2) and Boc-(R)-methylpropargylamine (129-4) using the reaction sequence presented in 48% overall yield.1H NMR (CDCl3, 300 MHz): delta 7.07-7.00 (m, 1H, aryl), 6.62-6.52 (m, 2H, aryl), 4.60 (bs, 1H, NHBoc), 4.08-3.90 (m, 4H, OCH2CH2OH)), 3.70-3.55 (m, 1H, CH3CHNHBoc), 3.18-3.32 (bs, 1H, OH), 2.75-2.42 (m, 2H, arylCH2), 1.92-1.50 (m, 2H, CH2CH2CH), 1.45 (s, 9H, C(CH3)3), 1.14 (d, J=6.6, 3H, CHCH3)MS: 327 (M+)

Reference： [1]Patent: US9181298,2015,B2 .Location in patent: Page/Page column 33: Sheet 11
[2]Patent: US2018/110824,2018,A1 .Location in patent: Paragraph 0450
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 8305 - 8320
[4]Patent: US2008/194672,2008,A1 .Location in patent: Page/Page column 56-57

21
[ 86864-60-0 ]
[ 186590-23-8 ]
[ 1047664-01-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 55℃;	The tether Boc-T85 was constructed starting from 2,3-difluorophenol (85-1, 20 g, 154 mmol) in 21% overall yield for 5 steps.TLC: Rf: 0.13 (25/75 AcOEt/Hex), detection: UV, ninhydrin1H NMR (CDCl3): delta 6.84 (m, 2H), 4.19 (m, 2H), 3.97 (m, 2H), 3.08 (m, 2H), 2.95 (m, 2H), 2.16 (s, 1H), 1.74 (m, 2H), 1.44 (m, 9H)LC-MS (Grad A4) tR: 6.31 min

Reference： [1]Patent: US2008/194672,2008,A1 .Location in patent: Page/Page column 35-36

22
[ 2040-89-3 ]
[ 86864-60-0 ]
[ 1047664-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 55℃;	Starting from 2-fluorophenol (86-1, 33.8 g, 302 mmol), Boc-T86 was prepared utilizing the five step process shown in 26% yield (corrected for recovered starting materials in step 3).TLC: Rf: 0.33 (50/50 AcOEt/Hex), detection: UV, ninhydrin1H NMR (CDCl3): delta 6.94 (m, 2H), 5.09 (m, 1H), 4.15 (m, 2H), 3.94 (m, 2H), 3.08 (m, 2H), 2.70 (m, 2H), 1.78 (m, 1H), 1.61 (m, 2H), 1.44 (s, 9H)LC-MS (Grad A4) tR: 6.81 min

Reference： [1]Patent: US2008/194672,2008,A1 .Location in patent: Page/Page column 36

23
[ 50820-65-0 ]
[ 86864-60-0 ]
[ 1191905-28-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 24h;	To a solution of lH-<strong>[50820-65-0]indole-6-carboxylic acid methyl ester</strong> (3.7 g, 21.2 mmol) and (2- bromoethoxy)(en-butyl)dimethylsilane (5.6 g, 23.3 mmol) in DMF (40 mL) was added K2CO3 (14.6 g, 106 mmol). The mixture was heated to 60 0C for 24 hr then cooled to room temperature and diluted with ethyl acetate (300 ml) and washed with H2O (2 X 200 ml). Then organic layer was dried (MgSO4), filtered and then concentrated to provide 8.2 g of crude methyl l-(2-ethoxy-tert- butyldimethylsilane)-lH-indole-6-carboxylate as an orange brown oil.

Reference： [1]Patent: WO2009/129335,2009,A2 .Location in patent: Page/Page column 140; 141

24
[ 86864-60-0 ]
[ 57531-37-0 ]
[ 1131005-03-2 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1317 - 1328

25
[ 86864-60-0 ]
[ 26621-44-3 ]
[ 1003013-08-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With caesium carbonate; In N,N-dimethyl-formamide; at 70℃; for 1h;Reflux; Inert atmosphere;	Example 119-(2-(ieri-Butyldimethylsilyloxy)ethyl)-3-nitro- lH-pyrazole 119a119a CGIPHARM60WOA 100-mL single-neck round-bottomed flask equipped with a reflux condenser and magnetic stirrer was purged with nitrogen and charged with 3-nitro-lH-pyrazole (500 mg, 4.42 mmol), 2-(tert-butyldimethylsilyloxy)- l-bromoethane (2.12 g, 8.85 mmol), cesium carbonate (5.76 g, 17.7 mmol) and anhydrous DMF (5 mL). After heating at 70 C for 1 h, the mixture was cooled to room temperature and diluted with methylene chloride (50 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by columnchromatography to afford an 85% yield (1.02 g) of 119a as a white solid: mp 76-77 C; ]H NMR (500 MHz, CDC13) delta 7.52 (d, 1H, J = 2.5 Hz), 6.87 (d, 1H, J = 2.5 Hz), 4.29 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, / = 5.0 Hz), 0.84 (s, 9H), -0.44 (s, 6H).
84%		A solution of <strong>[26621-44-3]3-nitro-1H-pyrazole</strong> (Intermediate 2, 250 mg, 2.21 mmol) was dissolved in anhydrous N,N-dimethylformamide (5 mL) was treated with a 60% dispersion of sodium hydride in mineral oil (93 mg, 2.32 mmol) was added while stirring under nitrogen. After the effervescence ceased, the reaction stirred for an additional 10 min. At this time, the reaction was treated with (2-bromo-ethoxy)-tert-butyl-dimethyl-silane (598 mg, 2.50 mmol). The reaction continued to stir under nitrogen for 2 h. At this time, the solution was diluted with ethyl acetate (200 mL), washed with water (2×75 mL), a saturated aqueous sodium chloride solution (75 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (Merck silica gel 60, 40-63 mum; 5-25% ethyl acetate/hexanes) afforded 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-<strong>[26621-44-3]3-nitro-1H-pyrazole</strong> (508 mg, 84%) as a yellow oil. 1H-NMR (400 MHz, DMSO-d6) delta 0.00 (6H, s), 0.86 (9H, s), 4.03 (2H, t, J=5.6 Hz), 4.40 (2H, t, J=5.2 Hz), 7.11 (1H, d, J=2.4 Hz), 8.06 (1H, d, J=2.4 Hz).

Reference： [1]Patent: WO2012/31004,2012,A1 .Location in patent: Page/Page column 103-104
[2]Patent: US2009/264434,2009,A1 .Location in patent: Page/Page column 26; 42

26
[ 40711-33-9 ]
[ 86864-60-0 ]
[ 1192313-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In N,N-dimethyl-formamide; at 0 - 60℃;	To a suspension of ethyl 5-oxo-2,5-dihydro-1 H-pyrazole-3-carboxylate (1.5 g, prepared with an analogous procedure to that described in Preparation 1 ) and Na2CO3 (1.22 g) in dry DMF (20 ml_), [(3-bromoethyl)oxy](1 ,1-dimethylethyl)dimethylsilane (1.11 ml.) was added drop wise and the mixture was stirred at 60 0C overnight. The reaction mixture was cooled down to rt and filtered to remove the Na2CO3. The filtrate was diluted with DMF and Na2CO3 (1.22g) and [(3-bromoethyl)oxy](1 ,1-dimethylethyl)dimethylsilane (2.1 ml.) were added and the mixture was stirred at 60 0C for additional 36h. After cooling, the mixture was diluted with Et2O, washed with chilly water, dried, filtered and evaporated under reduced pressure. The crude was dissolved in DCM (15 ml.) and 2,6-lutidine (1.08 ml.) and [(3-bromoethyl)oxy](1 ,1-dimethylethyl)dimethylsilane (0.86 ml.) were added at 0 0C and the mixture was stirred at rt for 1 h. The mixture was diluted in DCM, washed with NaHCO3sat and then with HCI 0.25N. The organic layer was dried and the solvent evaporated under reduced pressure. The crude was purified by flash chromatography on silica column eluting with Cy/AcOEt with a gradient of Cy from 100% to 80% to give the title compound as colourless oil (0.63 g).MS (m/z): 315 [MH]+.

Reference： [1]Patent: WO2009/130232,2009,A1 .Location in patent: Page/Page column 49-50

27
[ 623585-97-7 ]
[ 86864-60-0 ]
[ 1194373-99-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In ISOPROPYLAMIDE; at 120℃; for 20.0h;	To a solution of (3i?,55)-benzyl 3,5-dimethylpiperazine-l-carboxylate (Method 108, 5.0 g, 20.1 mmol) in DMA (25 mL) was added tetrabutylammonium iodide (7.44 g, 20.1 mmol), potassium carbonate (5.57 g, 40.3 mmol) and (2-bromoethoxy)(te/t- butyl)dimethylsilane (8.67 g, 36.2 mmol). The reaction mixture was stirred at 120 0C for 20 hours, then concentrated. DCM (5OmL) was added, and the organic layer was washed with H2O, dried (Na2SO4), concentrated and purified with silica chromatography to give 7.2g (88 %) of a brown oil

Reference： [1]Patent: WO2009/136191,2009,A1 .Location in patent: Page/Page column 97

28
[ 86864-60-0 ]
[ 72521-00-7 ]
[ 1232685-12-9 ]

Yield	Reaction Conditions	Operation in experiment
50.7%		Step 2; 1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-<strong>[72521-00-7]5-methyl-6-nitro-1H-indazole</strong>5-Methyl-6-nitro-1H-indazole (354 mg, 2.0 mmol) was dissolved in DMF (10 ml) and the mixture was cooled to 0 C. with stirring. Lithium hexamethyldisilazane (2.2 ml of 1.0 M toluene solution) was added dropwise. The mixture was allowed to stir for five minutes, and then (2-bromoethoxy)-tert-butyldimethylsilane (0.52 ml, 2.4 mmol) was added. The mixture was stirred for 30 minutes at 0 C., then allowed to warm to room temperature with stirring for four hours. The reaction was quenched with pH2 buffer solution, and the mixture was then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 4:1 hexanes/ethyl acetate) to give 340 mg (50.7%) of 142-(tert-butyl-dimethyl-silanyloxy)-ethyl]-<strong>[72521-00-7]5-methyl-6-nitro-1H-indazole</strong> as a white powder.
50.7%		Step 2 1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-<strong>[72521-00-7]5-methyl-6-nitro-1H-indazole</strong>5-Methyl-6-nitro-1H-indazole (354 mg, 2.0 mmol) was dissolved in DMF (10 ml) and the mixture was cooled to 0 C. with stirring. Lithium hexamethyldisilazane (2.2 ml of 1.0 M toluene solution) was added dropwise. The mixture was allowed to stir for five minutes, and then (2-bromoethoxy)-tert-butyldimethylsilane (0.52 ml, 2.4 mmol) was added. The mixture was stirred for 30 minutes at 0 C., then allowed to warm to room temperature with stirring for four hours. The reaction was quenched with pH2 buffer solution, and the mixture was then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 4:1 hexanes/ethyl acetate) to give 340 mg (50.7%) of 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-<strong>[72521-00-7]5-methyl-6-nitro-1H-indazole</strong> as a white powder.

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 8413 - 8426
[2]Patent: US2010/160373,2010,A1 .Location in patent: Page/Page column 29
[3]Patent: US2011/71143,2011,A1 .Location in patent: Page/Page column 37

29
[ 532967-21-8 ]
[ 86864-60-0 ]
[ 1239964-34-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 3h;	To a solution of <strong>[532967-21-8]2,6-difluoro-4-hydroxybenzaldehyde</strong> (5.00 g, 31.60 mmol) in DMF (80 mL) were added K2CO3 (6.50 g, 47.40 mmol) and (2-bromoethoxy)-tert- butyldimethylsilane (8.90 mL, 41.10 mmol). The reaction mixture was heated to 85 0C for 3h and was complete by LCMS analysis. The cooled mixture was combined with water and extracted with EtOAc (3 x 100 mL). The combined extracts were washed with brine, dried over anhyd Na2SO4, concentrated and purified by flash chromatography (20% EtO Ac/Hex) to achieve 4-(2-(fert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzaldehyde as a while solid (10.00 g, 100%). MS (EI) m/z 317.3 (MH+).

Reference： [1]Patent: WO2010/93845,2010,A1 .Location in patent: Page/Page column 158

30
[ 16292-95-8 ]
[ 86864-60-0 ]
[ 1309685-88-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 20.0h;	To a solution of <strong>[16292-95-8]3-methoxy-4-nitrophenol</strong> (1 g, 5.9 mmol) in anhydrous DMF (25 mL) were added K2CO3 (2.45 g, 17.7 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (1.7 g, 7.1 mmol) sequentially. The reaction mixture was heated at 70 C. for 20 h. The mixture was cooled to room temperature, and diluted with water. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (0-20% EtOAc in hexanes) to give tert-butyl-[2-(3-methoxy-4-nitro-phenoxy)-ethoxy]-dimethyl-silane as a light yellow oil (1.0 g, 52%).
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 20.0h;	Step b: To a solution of <strong>[16292-95-8]3-methoxy-4-nitrophenol</strong> (1 g, 5.9 mmol) in anhydrous DMF (25 mL) were added K2CO3 (2.45 g, 17.7 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (1.7 g, 7.1 mmol) sequentially. The reaction mixture was heated at 70 C. for 20 h. The mixture was cooled to room temperature, and diluted with water. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (0-20% EtOAc in hexanes) to give tert-butyl-[2-(3-methoxy-4-nitro-phenoxy)-ethoxy]-dimethyl-silane as a light yellow oil (1.0 g, 52%).
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 20.0h;	Step b: To a solution of <strong>[16292-95-8]3-methoxy-4-nitrophenol</strong> (1 g, 5.9 mmol) in anhydrous DMF (25 mL) were added K2CO3 (2.45 g, 17.7 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (1.7 g, 7.1 mmol) sequentially. The reaction mixture was heated at 70 C. for 20 h. The mixture was cooled to room temperature, and diluted with water. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (0-20% EtOAc in hexanes) to give tert-butyl-[2-(3-methoxy-4-nitro-phenoxy)-ethoxy]-dimethyl-silane as a light yellow oil (1.0 g, 52%).

52%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 20.0h;	To a solution of <strong>[16292-95-8]3-methoxy-4-nitrophenol</strong> (1 g, 5.9 mmol) in anhydrous DMF (25 mL) were added K2CO3 (2.45 g, 17.7 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (1.7 g, 7.1 mmol) sequentially. The reaction mixture was heated at 70 C. for 20 h. The mixture was cooled to room temperature, and diluted with water. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (0-20% EtOAc in hexanes) to give tert-butyl-[2-(3-methoxy-4-nitro-phenoxy)-ethoxy]-dimethyl-silane as a light yellow oil (1.0 g, 52%).
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 20.0h;	Step 2. To a solution of <strong>[16292-95-8]3-methoxy-4-nitrophenol</strong> (1 g, 5.9 mmol) in anhydrous DMF (25mL) were added K2CO3 (2.45 g, 17.7 mmol) and (2-bromoethoxy)(tertbutyl)dimethylsilane (1.7 g, 7.1 mmol) sequentially. The reaction mixture was heated at70 oC for 20 h. The mixture was cooled to room temperature, and diluted with water.The mixture was extracted with ethyl acetate three times. The combined organic extractwas washed with water, brine, dried over MgSO4, and concentrated. The residue waspurified by chromatography (0-20% EtOAc in hexanes) to give tert-butyl-[2-(3-methoxy-4-nitro-phenoxy)-ethoxy]-dimethyl-silane as a light yellow oil (1.0 g, 52%).

Reference： [1]Patent: US2011/130398,2011,A1 .Location in patent: Page/Page column 60
[2]Patent: US2011/269809,2011,A1 .Location in patent: Page/Page column 12
[3]Patent: US2012/46306,2012,A1 .Location in patent: Page/Page column 36
[4]Patent: US2012/71499,2012,A1 .Location in patent: Page/Page column 10
[5]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4001 - 4009

31
[ 86864-60-0 ]
[ 38767-72-5 ]
[ 1229704-12-4 ]

Yield	Reaction Conditions	Operation in experiment
41%		To a solution of <strong>[38767-72-5]4-aminopyridin-2(1H)-one</strong> (Molbridge) (0.9 g, 8.17 mmol) in DMF (30 mL) was added NaH (60%, 490 mg, 12.3 mmol). The mixture was stirred at room temperature for 30 min before (2-bromoethoxy)(tert-butyl)dimethylsilane (2.15 g, 8.99 mmol) was added. The reaction mixture was heated at 78 C. for 15 h. The mixture was cooled and poured into H2O (100 mL) and extracted with ethyl acetate (350 mL). The organic layers were combined, washed with H2O (550 mL), brine (50 mL), dried over MgSO4 and concentrated. The residue was purified by flash chromatography (silica gel, 40+S, 0% to 10% MeOH in EtOAc) to give 4-amino-1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyridin-2-one as a white solid (0.9 g, 41%).

Reference： [1]Patent: US2011/130398,2011,A1 .Location in patent: Page/Page column 23

32
[ 607373-82-0 ]
[ 86864-60-0 ]
[ 1309686-51-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 2h;	To a solution of <strong>[607373-82-0]4-methoxy-5-nitropyridin-2-ol</strong> (0.5 g, 2.9 mmol) in anhydrous DMF (12 mL) were added K2CO3 (0.82 g, 5.9 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (0.7 g, 2.9 mmol) sequentially. The reaction mixture was heated at 70 C. for 2 h. The mixture was cooled to room temperature, and diluted with water. The mixture was extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated to give 2-(2-(tert-butyldimethylsilyloxy)ethoxy)-4-methoxy-5-nitropyridine as a white solid (0.9 g, 93%).

Reference： [1]Patent: US2011/130398,2011,A1 .Location in patent: Page/Page column 81

33
[ 52805-46-6 ]
[ 86864-60-0 ]
C₁₆H₂₅NO₃Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 24h;Inert atmosphere;	To a solution of 3-Hydroxy-4-methoxybenzonitrile (8.0 g, 53.6 mmol) in anhydrous DMF (114 mL) at room temperature under N2, CS2CO3 (35.0 g, 107.3 mol) and (2-bromoethoxy)-tert-butyldimethylsilane (25.7 g, 107.3 mmol) were added. The mixture was heated to 50 C and stirred for 24 hours. The DMF was removed in vacuo and the reaction mixture was extracted with ethyl acetate. The organic layer was washed three times with water, dried over anhydrous MgSC^, and concentrated in vacuo. The crude material was purified by flash columnchromatography to yield a white solid (16.3 g, 99 %). 1H NMR (CDC13) delta: 7.26-7.28 (dd, J= 1.9, 8.4 Hz, 1H), 7.17-7.17 (d, J= 1.9 Hz, 1H), 6.87-6.89 (d, J= 8.4 Hz, 1H), 4.09-4.12 (m, 2H), 3.98-4.01 (m, 2H), 3.90 (s, 3H), 0.89 (s, 9H), 0.08 (s, 6H); 13C NMR (CDC13): 153.3, 148.7, 126.5, 119.2, 117.7, 116.1, 111.5, 103.7, 70.5, 61.8, 55.9, 25.8, 18.3, -5.4; HRMS(ESI+) m/z : (Calcd for Ci6H25N03Si H+ = 308.1682 found [M]+ = 308.1685).

Reference： [1]Patent: WO2012/122368,2012,A1 .Location in patent: Page/Page column 52; 53

34
[ 1306763-30-3 ]
[ 86864-60-0 ]
[ 1306763-41-6 ]

Yield	Reaction Conditions	Operation in experiment
80%		GENERAL PROCEDURE 9. ALKYLATION OF CYANO INDANE AMINES To a flame-dried flask under N2 was added the (R)- or (5)-cyano indane amine (1 eq) in anhydrous DMF (0.14 M). The reaction mixture was cooled to 0C and sodium hydride (5 eq, 60%> in oil, 160.6 mmol) was added portionwise. After stirring at 0C for 2.75 h, the alkyl halide was added. The ice bath was removed after 5 minutes and the reaction mixture was allowed to warm to room temperature. After 1.5 h, the reaction mixture was quenched by the slow addition of sat. NaHC03 at 0C. Once gas evolution was complete the reaction was extracted with EA. The organic layers were washed with water and brine, dried over MgS04 and concentrated. The product was purified by chromatography (EA / hexanes) or preparative HPLC. Compounds 85 - 91, 105, 107, and 143 were prepared using General Procedures 9, 3, and 4 sequentially. (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2 ,3-dihydro- lH-inden- 1- yl)carbamate INT-16) Prepared using General Procedure 9. To a flame-dried flask under N2 was added {R)-tert- vXy 4-cyano-2,3-dihydro-iH-inden-l-ylcarbamate INT-8 (8.3 g, 32.1 mmol) in anhydrous DMF (240 mL). The reaction mixture was cooled to 0C and sodium hydride (3.8 g, 60% in oil, 160.6 mmol) was added portionwise. After stirring at 0C for 2.75 h, (2-bromoethoxy)(tert-butyl)dimethylsilane (16.9 mL, 70.7 mmol) was added. The ice bath was removed after 5 mins and the reaction mixture was allowed to warm to room temperature. After 1.5 h, the reaction mixture was quenched by the slow addition of sat. NaHC03 at 0C. Once gas evolution was complete the reaction was extracted with EA. The organic layers were washed with water and brine, dried over MgS04 and concentrated. The product was purified by chromatography (EA / hexanes) to provide 10.76 g (80%) of {R)-tert-bvXy 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano- 2,3-dihydro-iH-inden-l-yl)carbamate INT-16 as a colorless oil. LCMS-ESI (m/z) calculated for C23H36N203Si: 416.6; found 317.2 [M-Boc]+ and 439.0 [M+Na]+, tR = 4.04 min (Method 1). 1H NMR (400 MHz, CDC13) delta 7.46 (d, J = 7.6, 1H), 7.38- 7.32 (m, 1H), 7.33 - 7.18 (m, 1H), 5.69 (s, 0.5 H), 5.19 (s, 0.5 H), 3.70 (ddd, J = 48.8, 26.6, 22.9, 1.5 H), 3.50 - 3.37 (m, 1H), 3.17 (ddd, J = 16.7, 9.4, 2.2, 2H), 2.93 (m, 1.5 H), 2.45 (s, 1H), 2.21 (dd, J = 24.5, 14.5, 1H), 1.56 - 1.37 (bs, 4.5H), 1.22 (bs, 4.5H), 0.87 - 0.74 (m, 9H), -0.04 (dd, J = 26.6, 8.2, 6H). 13C NMR (101 MHz, CDC13) delta 155.03, 146.55, 145.54, 131.16, 130.76, [128.11, 127.03], 117.58, 109.20, 79.88, [63.93, 61.88], [61.44, 60.34], [49.73, 46.76], 30.30, 29.70, 28.44, 28.12, [25.87, 25.62], -5.43.
80%		To a flame-dried flask under N2 was added (R)-tert-butyl 4-cyano-2,3- dihydro-1H-inden-i-ylcarbamate INT-8 (8.3 g, 32.1 mmol) in anhydrous DMF (240mL). The reaction mixture was cooled to 0C and sodium hydride (3.8 g, 60% in oil,160.6 mmol) was added portionwise. After stirring at 0C for 2.75 h, (2- bromoethoxy)(tert-butyl)dimethylsilane (16.9 mL, 70.7 mmol) was added. The ice bath was removed after 5 mins and the reaction mixture was allowed to warm to room temperature. After 1.5 h, the reaction mixture was quenched by the slow addition of sat.NaHCO3 at 0C. Once gas evolution was complete the reaction was extracted with EA. The organic layers were washed with water and brine, dried over Mg504 and concentrated. The product was purified by chromatography (EA / hexanes) to provide10.76 g (80%) of (R)-tert-butyl 2-(tert-butyldimethyl silyloxy)ethyl(4-cyano-2,3 -dihydro-JH-inden-1-yl)carbamate INT-14 as a colorless oil. LCMS-ESI (m/z)calculated for C23H36N2O3Si: 416.6; found 317.2 [M-Boc] and 439.0 [M+Na], tR =4.04 mm (Method 1). ?H NIVIR (400 MFIz, CDC13) 7.46 (d, J = 7.6, 1H), 7.38- 7.32(m, 1H), 7.33 -7.18 (m, 1H), 5.69 (s, 0.5 H), 5.19 (s, 0.5 H), 3.70 (ddd, J 48.8, 26.6,22.9, 1.5 H), 3.50 -3.37 (m, 1H), 3.17 (ddd, J= 16.7, 9.4, 2.2, 2H), 2.93 (m, 1.5 H),2.45 (s, 1H), 2.21 (dd, J= 24.5, 14.5, 1H), 1.56 - 1.37 (bs, 4.5H), 1.22 (bs, 4.5H), 0.87-0.74 (m, 9H), -0.04 (dd, J= 26.6, 8.2, 6H). ?3C NMR (101 MHz, CDC13) 155.03,146.55, 145.54, 131.16, 130.76, [128.11, 127.03], 117.58, 109.20, 79.88, [63.93, 61.88],[61.44, 60.34], [49.73, 46.76], 30.30, 29.70, 28.44, 28.12, [25.87, 25.62], -5.43. (S)-tertbutyl 2-(tert-butyldimethyl silyloxy)ethyl(4-cyano-2, 3 -dihydro- 1 H-inden- 1- yl)carbamate INT-15 is prepared in an analogous fashion using INT-9.
77%		[0470] ( R)-tert-butyl 2-( tert-butyldimethylsilyloxy )ethyl( 4-cyano-2, 3-dihydro-lH-inden-l- yl)carbamate (I -59)[0471] To (R)-tert-butyl 4-cyano-2,3-dihydro-lH-inden-l-ylcarbamate INT-52 (0.700 g, 2.7 mmol) was added anhydrous DMF (10 mL) and the reaction mixture was stirred in a 0C ice bath under N2. Sodium hydride (0.541 g, 13.5 mmol) was added and the mixture was stirred at 0C for 2 h. After 2 h, (2-bromoethoxy)-tert-butyldimethylsilane (1.43 g, 5.9 mmol) was added and the reaction mixture was allowed to warm to room temperature for 1 h. The reaction was cooled to 0C and quenched with MeOH followed by saturated NaHC03. The mixture was extracted with EA and brine. The combined organic layers were dried over MgS04, filtered, and concentrated to produce a brown oil. The crude product was purified by silica gel flash chromatography (20% EA/Hexanes) to afford 0.868 g (77%) of (R)-tert-butyl 2-(tert-butyldimemylsilyloxy)emyl(4-cyano-2,3-dihydro-lH-inden-l-yl)carbamate INT-59 as a yellow oil. LCMS-ESI (m/z) calculated for C23H36N203Si: 416.6; found 317.1 [M+H - Boc]+, tR = 4.05 min. NMR (400 MHz, (CD3)2SO) delta 7.50 (m, 1H), 7.37 (m, 1H), 7.26 (m, 1H), 5.78 (m, 1H), 4.02 (m, 2H), 3.51 (m, 2H), 3.29 (m, 1H), 2.97 (m, 1H), 2.26 (m, 2H), 1.40 (s, 9H), 0.83 (s, 9H), 0.09 (s, 6H).

Reference： [1]Patent: WO2015/66515,2015,A1 .Location in patent: Page/Page column 94-95
[2]Patent: WO2018/64356,2018,A1 .Location in patent: Page/Page column 68; 69
[3]Patent: WO2011/60389,2011,A1 .Location in patent: Page/Page column 95

35
[ 86864-60-0 ]
[ 10111-08-7 ]
[ 1431873-28-7 ]

Yield	Reaction Conditions	Operation in experiment
31%		NaH (724 mg; 18.1 1 mmol) was added portion wise to a solution of 2- imidazolecarboxaldehyde (1 .16 g; 12.07 mmol) in DMF (58 mL) at 5C under N2 flow. The reaction mixture was stirred at 5 C for 30 minutes and (2-bromoethoxy)-tert- butyldimethylsilane (3.1 1 mL; 14.49 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred all over the weekend. The reaction mixture was poured into ice water and extracted with EtOAc. The organic layer was washed with brine, dried over MgS04, filtered and dried. The residue was purified by chromatography over silica gel (irregular SiOH, 15-45 muetaiota, 40g; mobile phase: DCM 99%, MeOH 1 %). The pure fractions were collected and evaporated to dryness yielding 940 mg (31 %) of intermediate 51 .

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 730 - 734
[2]Patent: WO2013/61080,2013,A1 .Location in patent: Page/Page column 162; 163

36
[ 86864-60-0 ]
[ 55687-04-2 ]
[ 1437281-38-3 ]

Yield	Reaction Conditions	Operation in experiment
91.3%		[0070] In N,N-dimethylformamide (7 mL) was dissolved 55 <strong>[55687-04-2]2-chloroquinoxalin-6-ol</strong> (59.3 mg, 0.328 mmol) synthesized in the step 3-1, to which 38 potassium carbonate (90.8 mg, 0.657 mmol) was then added. The resultant was heat-stirred at 80 C. for 0.5 hour, and 57 (2-bromoethoxy)-tert-butyldimethylsilane (140 μL) was added thereto, which was then heat-stirred at 80 C. for further 2.5 hours. The reaction solution was cooled down to room temperature, and after separation and extraction with ethyl acetate (60 mL×2), the organic layer was dehydrated and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by silica-gel chromatography (ethyl acetate/hexane=1/10 (volume ratio)) to provide (58 26) in the scheme 3 (yield: 101.5 mg (91.3%)). [0071] 1H-NMR (400 MHz, deuterated chloroform) δ 8.71 (s, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.47 (dd, J=9.2, 2.8 Hz, 1H), 7.39 (d, J=2.8 Hz, 1H), 4.21 (t, J=4.8 Hz, 2H), 4.06 (t, J=4.8 Hz, 2H), 0.92 (s, 9H), 0.12 (s, 6H).

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 596 - 600
[2]Patent: US2014/88306,2014,A1 .Location in patent: Paragraph 0070-0071; 0154-0155

37
[ 1370261-96-3 ]
[ 86864-60-0 ]
[ 1439909-16-6 ]

Yield	Reaction Conditions	Operation in experiment
38%	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 20.0℃; for 72.0h;	4-(3-(2H-1,2,3-Triazol-2-yl)phenylamino)-2-((lR,2S)-2- aminocyclohexylamino)pyrimidine-5 -carboxamide was prepared by the same scheme shown in Example 1 for 4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-2-((1S,2R)-2- aminocyclohexylamino)pyrimidine-5-carboxamide. 4-(3-(2H-1,2,3-Triazol-2-yl)phenylamino)- 2-((1R,2S)-2-aminocyclohexylamino)pyrimidine-5-carboxamide (230 mg, 0.58 mmol) was dissolved in 6 mL NMP. To it were added DIEA (300 xL, 1.74 mmol) and (2-bromoethoxy)(tert- butyl)dimethylsilane (500 mu, 2.32 mmol). The mixture was stirred at RT for three days. It was diluted with 200 mL EtOAc, washed with brine three times, dried, concentrated and subjected to flash column to isolate 4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-2-((1R,2S)-2-(2-(tert- butyldimethylsilyloxy)ethylamino)cyclohexylamino)pyrimidine-5-carboxamide (120 mg, 38%). It was dissolved in 10 mL THF and treated with B^NF (l.OM in THF, 0.66 mL, 0.66 mmol) for 40 m. The mixture was concentrated in vacuo, acidized with TFA and subjected to reverse phase preparative HPLC to isolate the title compound (85 mg). MS found for C21H27N902 as (M+H)+ 438.4. UV: lambda=249 nm.

Reference： [1]Patent: WO2013/78468,2013,A1 .Location in patent: Paragraph 0345

38
[ 912369-50-7 ]
[ 86864-60-0 ]
[ 1560796-11-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With caesium carbonate; In acetonitrile; at 40℃;	A mixture of 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine (0.1 g, 0.5 mmol, from Boron Molecular), (2-bromoethoxy)(tert-butyl)dimethylsilane (0.18 g, 0.75 mmol) and cesium carbonate (0.32 g, 1.0 mmol) in acetonitrile (2.0 mL) was stirred at 40C. overnight. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-30%) to afford the desired product (0.2 g, 88%). LCMS calculated for C24H44BN2O3Si (M+H)+: m/z=447.3. Found 447.3.

Reference： [1]Patent: US2014/45814,2014,A1 .Location in patent: Paragraph 0354; 0355

39
[ 86864-60-0 ]
[ 158326-84-2 ]
[ 1581754-61-1 ]

Yield	Reaction Conditions	Operation in experiment
740 mg	With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere;	68.a Example 68 3-Fluoro-N-(l-(2-hydroxyethyl)-3,3-dimethyl-2-oxoindolin-6-yl)isonicotinamide a) 6-Bromo-l-(2-(tert-butyldimethylsilyloxy)ethyl)-3,3-dimethylindolin-2-one To a solution of 6-bromo-3,3-dimethylindolin-2-one (example 14a, 500 mg, 2.08 mmol) in DMF (16.7 ml) under an argon atmosphere were added (2-bromoethoxy)(tert-butyl)dimethylsilane (996 mg, 894 μ, 4.16 mmol) and cesium carbonate (1.36 g, 4.16 mmol). After 1 hour at 80 °C the reaction mixture was treated with water and the aqueous phase was extracted with EtOAc. The combined organic layers were dried over Na2S04 and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel using heptane/ ethyl acetate as eluent. The title compound was obtained as orange liquid (740 mg). MS ESI (m z): 398.5/ 400.5 [(M+H)+] . 1H NMR (CDCI3, 300 MHz) δ = 7.19 (d, J=1.6 Hz, 1H), 7.15 (dd, J=1.6, 7.9 Hz, 1H), 7.02 (d, J=7.9 Hz, 1H), 3.87 - 3.78 (m, 4H), 1.35 (s, 6H), 0.81 (s, 9H), -0.04 (s, 6H).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/40969, 2014, A1 Location in patent: Page/Page column 57-58

40
[ 13395-85-2 ]
[ 86864-60-0 ]
C₁₈H₃₁ClO₂Si [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 7731 - 7757

41
[ 552331-16-5 ]
[ 86864-60-0 ]
5-bromo-2-(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-methyl-2H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
492 mg	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 35℃; for 3h;	To a solution of 5-bromo-3-methyl-lH-indazole (2.0 g) in N, -dimethylformamide (20 ml) were added ( 2-bromoethoxy) (tert- butyl) dimethylsilane (2.5 g) and 60% sodium hydride (682 mg) at 0C, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (492 mg) . 1H NMR (400 MHz, CDCl3) delta 0.94 (9H, s) , 1.72 (6H, s) , 2.77 (3H, s), 4.26 (2H, t, J = 5.2 Hz), 4.60 (2H, t, J = 5.2 Hz), 7.44- 7.48 (1H, m) , 7.66 (1H, d, J = 9.2 Hz), 7.87 (1H, s)

Reference： [1]Patent: WO2015/5489,2015,A1 .Location in patent: Paragraph 0266

42
[ 876379-22-5 ]
[ 86864-60-0 ]
benzyl (3S)-3-[2-[tert-butyl(dimethyl)silyl]oxyethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		A solution of <strong>[876379-22-5]benzyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate</strong> (99.5 mg, 0.298 mmol) in DMF (0.6 ml) was cooled to 0C, sodium hydride (>60% oil, 17.9 mg, 0.448 mmol) was added, and the mixture was stirred for 15 minutes. 2-Bromoethoxy-tert-butyl-dimethylsilane (0.128 ml, 0.595 mmol) was added, and the mixture was stirred at room temperature for two hours. Water was added to the reaction mixture, then extraction with a mixed solvent of ethyl acetate and hexane was carried out. The organic layer was washed with a saturated aqueous sodium chloride solution three times and then dried over anhydrous sodium sulfate. The drying agent was removed by filtration, then concentration under reduced pressure was carried out. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give benzyl (3S)-3-[2-[tert-butyl(dimethyl)silyl]oxyethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]piperidine-1-carboxylate (89.0 mg, 61%) as a colorless oily substance. LCMS: m/z 493 [M+H]+

Reference： [1]Patent: EP2842946,2015,A1 .Location in patent: Paragraph 1682

43
[ 86864-60-0 ]
[ 6336-32-9 ]
C₃₄H₄₈N₂O₂Si₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 2879 - 2883

44
[ 20637-09-6 ]
[ 86864-60-0 ]
methyl 4-(4-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)phenyl)butanoate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 5336 - 5345

45
[ 20637-09-6 ]
[ 86864-60-0 ]
C₂₀H₃₅NO₃Si [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 5336 - 5345

46
[ 106291-80-9 ]
[ 86864-60-0 ]
C₁₆H₂₅BrO₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate; In acetonitrile; at 80℃;	a- Synthesis of Int. 177: A solution of Methyl 4-bromo-3 -hydro xybenzoate (2.5 g, 10.8 mmol), (2- bromoethoxy)-tert-butyldimethylsilane (2.5 mL, 1 1.9 mmol), K2C03 (2.2 g, 16.2 mmol) in ACN (50 mL) was stirred at 80C overnight. Water and EtOAc were added, the mixture was extracted, the organic layer was separated, dried over MgS04, filtered and evaporated. The residue was purified by prep. LC (Regular SiOH, 30 muiotaeta, 120g Grace, mobile phase: 80/20 heptane/EtOAc). The pure fractions were collected and the solvent was evaporated until drynes (76%).

Reference： [1]Patent: WO2015/144799,2015,A1 .Location in patent: Page/Page column 181

47
[ 22876-16-0 ]
[ 86864-60-0 ]
3-(2-((tert-butyldimethylsilyl)oxy)ethyl)-6-methylbenzo[d]oxazol-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 5h;	A solution of <strong>[22876-16-0]6-methylbenzo[d]oxazol-2(3H)-one</strong> (0.74g, 5.0mmol) in DMF (30mL) was added with (2-bromoethoxy) (tert-butyl)dimethylsilane (1.43g, 6.0mmol) and Cs2CO3 (1.95g, 6.0mmol). The reaction mixture was stirred at 50C. After 5h, the mixture was poured into water (60mL) and then was extracted with ethyl acetate (20mL×3). The combined organic layer was washed by water for two times and saturated sodium chloride solution for one time, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography to afford 3 as a white solid. Yield 85% (1.31g).1H NMR (400MHz, CDCl3) δ 7.01 (d, J=0.6Hz, 1H), 6.95 (d, J=1.0Hz, 2H), 3.90 (d, J=8.5Hz, 4H), 2.38 (d, J=0.4Hz, 3H), 0.81-0.78 (m, 9H),-0.06 to-0.09 (m, 6H). MS (ESI): 308.2 [M+H]+

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 115,p. 191 - 200

48
[ 53316-51-1 ]
[ 86864-60-0 ]
1-(2-((tert-butyldimethylsiIyl)oxy)ethyl)-4,5-dimethyl-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		Step 1 : l-(2-((tert-butyldimethylsiIyl)oxy)ethyl)-4,5-dimethyl-lH-imidazole [001009] A solution of 4,5-dimethyl- lH-imidazole hydrochloride (2.94 g, 22.2 mmol) was in N,N-dimethylformamide (30.0 mL, 387 mmol) was cooled to 0 C. Sodium hydride (3.55 g, 88.7 mmol) was slowly added and the solution was stirred for 30 mins at 0 C. Potassium iodide (4.417 g, 26.61 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (6.365 g, 26.61 mmol) were added and the mixture was allowed to warm to room temperature with stirring over 30 minutes. The reaction as quenched with methanol (3 mL) and diluted with water ( 150 ml). The resulting aqueous mixture was extracted with ethyl acetate (3 x 70 mL). The combined organic portions was washed with brine, dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (0 to 15% MeOH in EtOAc) to provide 4.34g (77%) of the title compound. NMR (400 MHz, Chloroform-<i) delta 7.33 - 7.39 (m, 1 H) 3.87 - 3.93 (t, 2 H) 3.73 - 3.84 (t, 2 H) 2.13 - 2.18 (s, 3 H) 2.12 (s, 3 H) 0.85 (s, 9 H) -0.04 (s, 6 H).

Reference： [1]Patent: WO2016/4136,2016,A1 .Location in patent: Paragraph 001009

49
[ 58546-89-7 ]
[ 86864-60-0 ]
N-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-1-benzofuran-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%		Step 1, Method 26: 7V-{2-[(teri-Butyldimethylsilyl)oxy]ethyl}-l-benzofuran-5- amine[0255] Sodium hydride (60% in mineral oil, 97 mg, 4.06 mmol) was suspended in anhydrous N,N-dimethylformamide (2 mL). l-Benzofuran-5 -amine (450 mg, 3.38 mmol) in N,N-dimethylformamide (3 mL) was added and the mixture stirred at 0 C for 5 minutes. The suspension was warmed to room temperature and stirred for 30 minutes, (2-bromoethoxy)(ter?-butyl)dimethylsilane (870 mu,, 4.06 mmol) was added and the reaction stirred at 60 C for 20 hours. Water (0.5 mL) was added and the reaction concentrated. The residue was purified by FCC (silica, 0-30% ethyl acetate in heptane) to give the title compound 364 mg (30% yield) as a yellow gum. 5H NMR (500 MHz, DMSO) 7.77 (d, J = 2.1 Hz, 1H), 7.28 (d, J = 8.8 Hz, 1H), 6.72 (d, J = 2.1 Hz, 2H), 6.64 (dd, J = 8.8, 2.4 Hz, 1H), 5.24 (t, J = 6.0 Hz, 1H), 3.74 (t, J = 6.2 Hz, 2H), 3.15 (q, J = 6.1 Hz, 2H), 0.87 (s, 9H), 0.04 (s, 6H). Tr(METCR1278) = 2.38 min, (ES+) (M+H)+292, 85%.

Reference： [1]Patent: WO2016/33460,2016,A1 .Location in patent: Paragraph 0255

50
[ 857530-80-4 ]
[ 86864-60-0 ]
[ 1346818-87-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With caesium carbonate; In acetonitrile; at 90℃;	1-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-3, 5-dimethyl-4-(4, 4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (B21.1) (0419) To a solution of <strong>[857530-80-4]3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (300 mg, 1.35 mmol) in CH3CN (5 mL) was added Cs2CO3 (800 mg, 2.702 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (50 mg, 1.892 mmol). The mixture was stirred at 90 C. over night concentrated and purified by flash Chromatography (silica gel, PE:EA=0-15%, UV254 &UV280) to give the title compound (300 mg, 77%) as a yellow oil. LC-MS: [M+H]+=381.7.
77%	With caesium carbonate; In acetonitrile; at 90℃;	To a solution of <strong>[857530-80-4]3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (300 mg, 1.35 mmol) in CH3CN (5 mL) was added C52CO3 (800 mg, 2.702 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (50 mg, 1.892 mmol). The mixture was stirred at 90 C over night concentrated and purified by flash Chromatography (silica gel, PE:EA = 0-15%, UV254 &UV280) to givethe title compound (300 mg, 77%) as a yellow oil. LC-MS: [M+H] = 381.7.[00212] Intermediate B21: To a solution of B21.1 (300 mg, 0.79 mmol) in THF (6 mL)was added TBAF (412 mg, 1.58 mmol). The mixture was stirred at 30 C for 3 h,concentrated under reduced pressure to give the title compound (100 mg, 48%) as ayellow oil. LC-MS: [M+H]+ = 267.

Reference： [1]Patent: US2016/176882,2016,A1 .Location in patent: Paragraph 0418; 0419
[2]Patent: WO2017/221100,2017,A1 .Location in patent: Paragraph 00211

51
[ 86864-60-0 ]
[ 15965-30-7 ]
1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4,5-dichloro-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	Stage #1: 4,5-dichloroimidazole With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.0833333h; Stage #2: 2-(tert-butyldimethylsilyloxy)ethyl bromide In N,N-dimethyl-formamide; mineral oil at 60℃; for 1h;	1 Step 1: 1 -(2-((tert-Butyldimethylsilyl)oxy)ethyl)-4 ,5-dichloro- 1 H-imidazole NaH (60% dispersion in mineral oil, 240 mg, 6 mmol) was added to a solution of 4,5- dichloro-1H-imidazole (411 mg, 3 mmol) in DMF (10 mL). After 5 mi (2- bromoethoxy)(tert-butyl)dimethylsilane (718 mg, 3 mmol) was added to the mixture. The mixture was stirred at 60 °C for 1 h. The mixture was partitioned between EtOAc and H20. The organic layer was washed with brine, dried over Na2504, filtered, and concentrated underreduced pressure. The residue was purified by silica gel colunm chromatography (0-80% EtOAc in hexanes) to afford the title compound (274 mg, 3 1%).‘H NMR (500 MHz, acetone-d6) ö ppm 0.00 (s, 6H), 0.87 (s, 9H), 3.96 (t, J=5.0 Hz, 2H), 4.20 (t, J=5.2 Hz, 2H), 7.65 (s, 1H)

Reference： [1]Current Patent Assignee: PTC THERAPEUTICS INC - WO2016/109706, 2016, A1 Location in patent: Page/Page column 233

52
[ 135050-44-1 ]
[ 86864-60-0 ]
N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-chloro-4-iodoaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.5%		To a solution of <strong>[135050-44-1]3-chloro-4-iodoaniline</strong> (3.0 g, 11.84 mmol) in THF (18 mL) was cooled to 0C. 60% of NaH(1.16 g, 29.06 mmol) was added. The mixture was stirred for 1 h at room temperature. Then (2-bromoethoxy)(tertbutyl)dimethylsilane (3.48 g, 14.53 mmol) was added. The mixture was stirred for 12 h at 40C. The reaction wasquenched by sat aq (20 mL) and H2O (50 mL). The mixture was extracted with EA (40 mL 3), the organic layers werecombined and washed with brine (30 mL2), dried over Na2SO4. Filtered and filtrate was concentrated. The residue waspurified silica column (Eluent C) to afford N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-<strong>[135050-44-1]3-chloro-4-iodoaniline</strong> (3.5 g, yellowsolid), yield: 58.5%.MS m/z (ESI):412.0 [M+1]1H NMR (400 MHz, CDCl3) delta 7.51 (d, 1H), 6.74 (d, 1H), 6.27 (dd, 1H), 4.12 (t, 2H), 3.17 (t, 2H), 0.90 (s, 9H), 0.07 (s, 6H

Reference： [1]Patent: EP3042907,2016,A1 .Location in patent: Paragraph 0213; 0214

53
[ 135050-44-1 ]
[ 86864-60-0 ]
N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4,6-dichloro-N-(3-chloro-4-iodophenyl)pyrimidine-5-carboxamide [ No CAS ]

Reference： [1]Patent: EP3042907,2016,A1

54
[ 59557-90-3 ]
[ 86864-60-0 ]
4-bromo-N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3,5-dimethylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%		To NaH (60% purity, 40 g, 1000 mmol) was added a solution of <strong>[59557-90-3]4-bromo-3,5-dimethylaniline</strong> 1b (100 g, 500mmol) in THF (1 L) at ice-bath. The mixture was stirred at room temperature for 1h. To the mixture was added (2-bromoethoxy)(tert-butyl)dimethylsilane (179 g, 749 mmol), the mixture was stirred at 40C for 16 h. The reaction mixturewas cooled to room temperature, quenched excess NaH by adding dropwise slowly sat. NH4Cl solution (50 mL) andH2O (100 mL), extracted with EA (500 mL3) and H2O (500 mL2), combined the organic phase, saturation NaCl solution(300 mL*2), dried over Na2SO4, filtered, the filtrate was concentrated under reduced pressure. The residue was purifiedby silica column chromatography (Eluent C) to give title product 4-bromo-N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3,5-dimethylaniline 1c (180 g, yellow solid), yield:100%.MS m/z (ESI):358 [M+1]

Reference： [1]Patent: EP3042907,2016,A1 .Location in patent: Paragraph 0257; 0259

55
[ 2460-58-4 ]
[ 86864-60-0 ]
2-{2-[(tert-butyldimethylsilyl)oxy]ethoxy}-4-nitrobenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium carbonate; In acetonitrile; for 0.666667h;Reflux;	Room temperature dry MeCN (20ml) solution of <strong>[2460-58-4]2-hydroxy-4-nitro-benzaldehyde</strong> (0.500g, 2.992mmol) and anhydrous potassium carbonate (0.621g, 4.488mmol) to a stirred suspension of 2- bromo -1-tert- butyldimethylsiloxy ethane (83percent, 1.293g, 4.488mmol) was added, and the reaction mixture is heated under reflux for 40 minutes, it resulted in the emergence of rich dark red of the precipitate. The reaction mixture was allowed to cool to room temperature, it was added dry DMF (10ml). The reaction mixture was heated for 4 hours at 0.89 ° C., cooled, added to water (250 ml), and extracted with EtOAc (3 × 80ml). The combined organic extracts were water (3 × 100 ml), brine and washed with (100 ml), dried (Na2SO4), the solvent was removed under reduced pressure to give a pale brown solid, by flash chromatography (2: It was purified by 1 hexane / Et2O). Recrystallization from hexane, the title compound (0.621g, 64percent) was obtained as pale yellow crystals.

Reference： [1]Patent: JP5667058,2015,B2 .Location in patent: Paragraph 0905; 0906

56
[ 87687-75-0 ]
[ 86864-60-0 ]
C₂₃H₃₂O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1h;	Potassium carbonate (0.78 g, 5.7 mmol) was added to a solution of 12-3 (0.91 g, 3.7 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (0.87 mL, 4.0 mmol) in DMF (5 mL). The mixture was heated at 60 C. for 1 h. The mixture was diluted with EA, and washed with water and brine. The product was chromatographed (hexane:EA) to give 12-4 (0.91 g, 57%).

Reference： [1]Patent: US2016/244460,2016,A1 .Location in patent: Paragraph 0251; 0255

57
[ 404827-77-6 ]
[ 86864-60-0 ]
6-bromo-1-(2-(tert-butyldimethylsilyloxy)ethyl)-1H-indazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With caesium carbonate; In N,N-dimethyl-formamide; at 65℃; for 3h;	Intermediate 8. 6-bromo-1 -(2-(ieri-butyldimethylsilyloxy)ethyl)-1 H-indazol-3-amine To a solution of 6-bromo-1 /-/-indazol-3-amine (200mg, 0.94mmol) in dimethylformamide (2ml_) was added cesium carbonate (614mg, 1 .88mmol) and (2-bromoethoxy)(ie f- butyl)dimethylsilane (215mu, 1 .03mmol). The reaction mixture was stirred for 3 hours at 65C. Water was added into the crude mixture. A solid precipitates and it was dried to obtain the title compound as an orange solid (83% of yield), which was used in the next step without further purification. LRMS (m/z): 371 (M+1 )+

Reference： [1]Patent: WO2016/150971,2016,A1 .Location in patent: Page/Page column 24-25

58
[ 1306763-31-4 ]
[ 86864-60-0 ]
(S)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl-(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.01%	Stage #1: tert-butyl N-[(1S)-4-cyano-2,3-dihydro-1H-inden-1-yl]carbamate With sodium hydride In N,N-dimethyl-formamide at 0 - 10℃; for 2h; Inert atmosphere; Stage #2: 2-(tert-butyldimethylsilyloxy)ethyl bromide In N,N-dimethyl-formamide at 0 - 10℃; for 8h;	6 Example 6: Preparation of (S)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl-(4- cyano-2,3-dihydro-lH-inden-l-ylcarbamate, a compound of Formula 9: To a stirred solution of 20.0 gm of Formula 7 (0.0774 moles) and 200.0 of DMF under nitrogen atmosphere at 0-10°C,11.6 gm of sodium hydride (60%) (0.232 moles, 3.0eq.)was added at below 10°C. The reaction mixture was stirred for 2.0 hrs at 0-10°C. 37.0 gm of (2-bromoethoxy)-tert-butyldimethylsilane (Formula 8) (0.155 moles, 2.0eq.) was added and stirred for 8.0 hrs at 0-10°C. After completion, the reaction was quenched by the addition of saturated NaHCO3and the product was extracted with ethyl acetate. The organic layer was concentrated and purify through column chromatography by using ethyl acetate/hexane to obtain a light brown liquid of Formula 9 (24.2 gm, 75.01% yield) with HPLC Purity 99.95% & SOR -80.0° (c=0.1 in CHC13at 25°C).IR (Neat, cm-1): 2955, 2930, 2229, 1695, 1454, 1404, 1253, 1155, 1102, 837, 778; 1H-NMR(CDC13): δ 7.50-7.48 (d, 1H, J=7.53Hz), 7.41-7.34 (m, 1H), 7.29-7.25 (m, 1H), 5.72 (brs, 0.5H), 5.23 (brs, 0.5H) 3.81-3.44 (m, 3H), 3.24-3.18 (m, 2H), 3.01- 2.92 (m, 1.5H), 2.48 (brs, 1H), 2.35-2.19 (m, 1H), 1.50 (brs, 4.5Hz), 1.23 (brs, 4.5Hz), 0.85 (s, 9H), 0.03-0.01 (d, 6H);13C-NMR(CDC13): 155.86, 155.06, 147.23, 146.57, 145.51, 144.33, 131.18, 130.78, 128.40, 128.15, 127.24, 127.08, 117.59, 109.25, 108.97, 80.17, 79.90, 63.99, 61.91, 61.48, 60.36, 49.79, 46.82, 30.31, 29.73, 28.46, 28.15, 25.90, 18.28, 14.19, -5.36; MS (m/z): 417.3 [M+l]+, 361.1 [M-C(CH3)3]+, 317.2 [M-Boc]+.
53%	Stage #1: tert-butyl N-[(1S)-4-cyano-2,3-dihydro-1H-inden-1-yl]carbamate With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #2: 2-(tert-butyldimethylsilyloxy)ethyl bromide In N,N-dimethyl-formamide at 20℃; for 3h;	1.6 Preparation of (1S)-4-cyano-2,3-dihydro-1H-inden-1-yl N-[2-[(tert-butyldimethylsilyl)oxy]ethyl] carbamate To a solution of tert-butyl N-[(lS)-4-cyano-2,3-dihydro-lH-inden-l-yl]carbamate (1.7 g, 6.58 mmol, 1.00 equiv) in N,N-dimethylformamide (20 mL) was added sodium hydride (790 mg, 32.92 mmol, 3.00 equiv) at 0 °C. The resulting solution was stirred at room temperature for 2 h. To this was added (2-bromoethoxy)(tert-butyl)dimethylsilane (3.14 g, 13.13 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at room temperature. The reaction was then quenched by the addition of water/ice, extracted with ethyl acetate (3 x 50 mL) and the organic layers were combined. The resulting mixture was washed with brine (2 x 100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1 :20) to afford 1.47 g (53%) of tert-butyl (lS)-4-cyano-2,3-dihydro-lH-inden-l-yl N-[2-[(tert- butyldimethylsilyl)oxy] ethyl] carbamate as a light brown oil. LC-MS: m/z =417 [M+H]+.

Reference： [1]Current Patent Assignee: SUVEN LIFE SCIENCES LIMITED - WO2019/58290, 2019, A1 Location in patent: Page/Page column 21-22
[2]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2016/164180, 2016, A1 Location in patent: Paragraph 00156

59
[ 86864-60-0 ]
[ 1306763-31-4 ]
tert-butyl N-[2-[(tert-butyldimethylsilyl)oxy](²H₄)ethyl]-N-[(1S)-4-cyano-2,3-dihydro-1H-inden-1-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: tert-butyl N-[(1S)-4-cyano-2,3-dihydro-1H-inden-1-yl]carbamate With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #2: (2 bromoethoxy-1,1,2,2-d<SUB>4</SUB>)(1,1-dimethylethyl)dimethyl-silane In N,N-dimethyl-formamide at 20℃; for 3h;	4.1 Preparation of Tert-butylN-[2-[(tert-butyldimethylsilyl)oxy](²H4)ethyl]-N-[(1S)-4-cyano-2,3-dihydro-lH-inden-1-yl]carbamate To a solution of tert-butyl N-[(l S)-4-cyano-2,3-dihydro- lH-inden-l-yl] carbamate (1.9 g, 7.36 mmol, 1.00 equiv) in DMF (20 mL) was added sodium hydride (880 mg, 3.00 equiv) at 0 °C. The resulting solution was stirred for 2 h at room temperature. Then [2-bromo(2H4)ethoxy](tert-butyl)dimethylsilane (3.6 g, 14.80 mmol, 2.00 equiv) was added. The resulting solution was stirred for 3 h at room temperature. The reaction was then quenched by the addition of water/ice, extracted with 3x100 mL of ethyl acetate and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by SiC chromatography, eluted with ethyl acetate/petroleum ether (1 :20) to afford 1.94 g (63%) of tert-butylN-[2-[(tert-butyldimethylsilyl)oxy](2H4)ethyl]-N-[(l S) 4-cyano-2,3-dihydro-lH- inden-l-yl] carbamate as yellow oil. LC-MS: m/z = 421 [M+H]+.

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2016/164180, 2016, A1 Location in patent: Paragraph 00191

60
methyl 5-([6-(trifluoromethyl)pyridin-2-yl]carbonyl}amino)-1H-indazole-6-carboxylate [ No CAS ]
[ 86864-60-0 ]
[ 131747-42-7 ]
methyl 2-(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)-5-([6-(trifluoromethyl)pyridin-2-yl]carbonyl}amino)-2H-indazole-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
400 mg		1.00 g (2.66 mmol, 97%) of methyl 5-([6-(trifluoromethyl)pyridin-2-yl]carbonyl}amino)- lH-indazole-6-carboxylate (Intermediate 3-1) was initially charged in 50 ml of DMF, 1.10 g (7.99 mmol) of potassium carbonate and 221 mg (1.33 mmol) of potassium iodide were added while stirring, and the mixture was stirred at 25C for 30 min. Subsequently, 857 muIota (3.99 mmol) of (2-bromoethoxy)(tert-butyl)dimethylsilane were added and the mixture was stirred at 25C for 24 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were filtered through a hydrophobic filter and concentrated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate). This gave 400 mg of the title compound. UPLC-MS (Method Al): Rt = 1.58 min MS (ESIpos): m/z = 523(M+H)+ ^ N MR (300 MHz, DMSO-d6): delta [ppm] = -0.18 - -0.13 (m, 6 H), 0.74 (s, 9 H), 3.96 (s, 3 H), 4.08 (t, 2 H), 4.57 (t, 2 H), 8.15 - 8.25 (m, 1 H), 8.32 - 8.43 (m, 1 H), 8.43 - 8.52 (m, 3 H), 9.07 (s, 1 H), 12.53 (s, 1 H).

Reference： [1]Patent: WO2016/174183,2016,A1 .Location in patent: Page/Page column 55; 56

61
[ 86864-60-0 ]
[ 138786-86-4 ]
methyl 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-nitro-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 18h;	(2-Bromoethoxy)(tert-butyl)dimethylsilane (7.7g, 32 mmol) was slowly added to a stirred solution of methyl 4-nitro-lH-pyrazole-3-carboxylate, (6.0g, 28.9 mmol) in DMF (70mL) at 0 C. The reaction mass was stirred at room temperature for 18hr. Quenched the reaction mass with ice cold water and diluted with ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate (3x5 OmL). The combined organic layer was washed with brine, dried over Na2S04, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography afforded title compound (Polar spot in TLC) (4.3g, 47%). ESI-MS: m/z = 330.2 (M+H)+.

Reference： [1]Patent: WO2016/164754,2016,A1 .Location in patent: Page/Page column 45

62
[ 14733-73-4 ]
[ 86864-60-0 ]
C₁₅H₂₂BrNO₃Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.10 g	With sodium hydride; lithium bromide; In N,N-dimethyl-formamide; at 80℃; for 2h;	Compound Ia (4.20 g), 2- (tert-butyldimethylsilyloxy) ethyl bromide (5.10 mL), lithium bromide (3.50 g), sodium hydride (0.960 g) and DMF (100 mL) was stirred at 80 C. for 2 hours.Water was added to the reaction mixture and extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 8/1) to obtain compound II-a (3.10 g).

Reference： [1]Patent: JP2017/1991,2017,A .Location in patent: Paragraph 0267; 0268

63
[ 2042-14-0 ]
[ 86864-60-0 ]
2-(4-methyl-3-nitrophenoxy)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With caesium carbonate; sodium iodide; In 1-methyl-pyrrolidin-2-one; at 100℃; for 4h;	To a 100-mL round-bottom flask was placed a solution of <strong>[2042-14-0]4-methyl-3-nitrophenol</strong> (1.53 g,9.99 mmol) in NMP (40 mL) then Cs2CO3(4.24 g,13.01 mmol),NaT (1.5 g,10.00 mmol),and (2-bromoethoxy)(tert-butyl)dimethylsilane (3.11 g,13.00 mmol) were added. The reaction was stirred for 4 h at 100C,quenched by the addition of water,and extracted with EtOAc. The organic extracts were combined,washed with brine,dried over anhydrous Na2504,and concentrated under reduced pressure. The residue was purified by column chromatography eluting with EtOAc/petroleum ether (1:5)affording 1 g (51%) of the title compound as a yellow solid. 1H NMR (300 MHz,DMSO-d6):oe 7.50 (d,J 2.7 Hz,1H ),7.39 (d,J 8.5 Hz,1H ),7.23 (dd,J= 8.5,2.7 Hz,1H ),4.95 -4.80 (m,1H ),4.05 (t,J= 4.9 Hz,2H),3.71 (t,J= 4.9 Hz,2H),2.42 (s,3H).

Reference： [1]Patent: WO2017/62581,2017,A1 .Location in patent: Paragraph 0269

64
[ 2042-14-0 ]
[ 86864-60-0 ]
[ 873453-79-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With caesium carbonate; sodium iodide; In 1-methyl-pyrrolidin-2-one; at 100℃; for 6h;	To a 250-mL round-bottom flask was placed a solution of <strong>[2042-14-0]4-methyl-3-nitrophenol</strong> (1 g,6.53 mmol,1.00 equiv) in NMP (50 mL) then Cs2CO3 (2.77 g,8.50 mmol),NaT (980 mg),and (2-bromoethoxy)(tert-butyl)dimethylsilane (3.10 g,12.96 mmol) were added. The resulting solution was stirred for 6 h at 100C then the reaction was quenched with water and extractedwith EtOAc. The organic extracts were combined,washed with brine,dried over anhydrous Na2SO4,and concentrated under reduced pressure affording 1.48 g (73%) of the title compound as a white solid. 1H NMR(300 MHz,CDCl3): oe 8.14-8.03 (m,1H ),6.84-6.81 (m,2H),4.14-4.11 (m,2H),4.01-3.98 (m,2H),2.64 (s,3H),0.92 (s,9H),0.11 (s,6H).

Reference： [1]Patent: WO2017/62581,2017,A1 .Location in patent: Paragraph 0156

65
[ 7464-14-4 ]
[ 86864-60-0 ]
C₁₄H₂₄N₂O₄Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h;Sealed tube;	In a sealed tube, a mixture of <strong>[7464-14-4]2-hydroxy-5-methyl-3-nitropyridine</strong> (1.00 g, 6.49 mmol), (2-bromoethoxy)-tert-butyldimethylsilane (2.80 mL, 12.98 mmol) and K2C03 (2.70 g, 19.46 mmol) in DMF (13 mL) was stirred at 60 C for 2 h. The reaction mixture was cooled down to rt, poured onto a mixture of water and brine, then extracted with Et20. The organic layer was decanted, washed with brine, dried over MgSO4, filtered andevaporated to dryness. The residue was purified by column chromatography on silica gel (irregular SiOH, 80 g, mobile phase: heptane/EtOAc, gradient from 80:20 to 60:40). The pure fractions were collected and evaporated to dryness to give 1.68 g of intermediate 8i (83% yield, 94% purity based on LC/MS).

Reference： [1]Patent: WO2017/125534,2017,A1 .Location in patent: Page/Page column 341

66
[ 13659-23-9 ]
[ 86864-60-0 ]
(2-(2-bromo-5-chlorophenoxy)ethoxy)(dimethyl)(2-methyl-2-propanyl)silane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.5%	With potassium carbonate; potassium iodide; In 1-methyl-pyrrolidin-2-one; at 90℃; for 5h;	To a solution of<strong>[13659-23-9]2-bromo-5-chlorophenol</strong> (50 g, 241 rnmol) in NJVIP (500mL) wa. added K?C03 (66.51 g, 482 mmol), (2-bromoethoxy)-tert-butyl-25 dimethylsilane (56 8 mL 265.1 mmol) and catalytic amount of KJ (800 mg, 4.80mmol), and the suspension was heated to 90 oc for 5 h. On completion, thesuspension vas cooled to room temperature and diluted vvith water (500 mL).Aqueous phase was extracted with ethyl acetate (3 x 250 mL). Combined organic layer was washed ·with water (500 mL), brine (500 mL) and dried over sodiumsulphate. Solvent was removed tmder reduced pressure to afford crude materialwhich v.·as purified by column chromatography (1 00-200 mesh size silica gel,eluting with a gradient of 100();6 hexanes to 5% ethyl acetate in hexanes) affording5 pure (2-(2-bromo-5-chlorophenoxy)ethoxy)(dimethyl)(2-methyl-2-propanyl)silane(72 g, 83.5%) as light yellov oiL Rr: 0.8 in 5() Ethyl acetate in hexane.

Reference： [1]Patent: WO2017/147410,2017,A1 .Location in patent: Page/Page column 122; 123

67
[ 13659-23-9 ]
[ 86864-60-0 ]
diethyl 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)malonate [ No CAS ]

Reference： [1]Patent: WO2017/147410,2017,A1

68
[ 884-35-5 ]
[ 86864-60-0 ]
methyl 4-(2-[tert-butyl(dimethyl)silyl]oxy}ethoxy)-3,5-dimethoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 1h;	A mixture of (2-bromoethoxy)(tert-butyl)dimethylsilane (451 mg, 1.885 mmol), methyl 4- hydroxy-3,5-dimethoxybenzoate (200 mg, 0.943 mmol) and potassium carbonate (391 mg, 2.83 mmol) in N,N-dimethylformamide (5 mL) were stirred at 110 C for 1 hour. Then the mixture was cooled down to room temperature, diluted with water (15 mL), and extracted with ethyl acetate 3 times. The combined organic layers were dried over anhydrous Na2504, filtered and concentrated to give a residue which was purified by flash column chromatography on silica gel (loaded with CH2C12, elute:hexanes/ethyl acetate=0-.30%) to give the titled compound (340 mg, 0.9 18 mmol, 97% yield). LCMS (ESI) m/z 371.2 (M+H), RT = 2.283 minutes.

Reference： [1]Patent: WO2017/177004,2017,A1 .Location in patent: Paragraph 00747; 00748

69
[ 3034-38-6 ]
[ 86864-60-0 ]
1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5-nitro-1H-imidazole [ No CAS ]
1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-nitro-1H-imidazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 1241 - 1254

70
[ 86864-60-0 ]
[ 146093-46-1 ]
tert-butyl 4-(2-((tert-butyldimethlsilyl)oxy)ethyl)(methylamino)ethylpiperidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2018/5794,2018,A2

71
[ 86864-60-0 ]
[ 146093-46-1 ]
tert-butyl 4-(2-((((2-tert-butyldimethylsilyl)oxy)ethyl)amino)ethyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		To a suspension of activated molecular sieves in DMF (2.2 mL) was added CsOH H20 (74 mg, 0.44 mmol), and the mixture was stirred vigorously for 10 minutes. tert-Butyl 4-(2-aminoethyl)piperidine-l-carboxylate (99 mu, 0.44 mmol) was added, and the mixture was stirred for 30 minutes. Then (2-bromoethoxy)(fer^butyl)dimethylsilane (93 mu, 0.53 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction was filtered, washed with EtOAc, and partitioned between EtOAc and IN NaOH. The aqueous layer was extracted with EtOAc (3x). The combined organic layers were washed with brine, dried Na2S04), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to afford Intermediate 13 (72.6 mg, 43%). LCMS: m/z 387.6 (M+H)+. NMR (CDC13): delta 3.99 (br, 2H), 3.67 (t, 2H), 2.68- 2.59 (m, 6H), 1.76-1.54 (m, 5H), 1.10-1.09 (3H), 0.84 (s, 9H), 0.01 (s, 6H).

Reference： [1]Patent: WO2018/5794,2018,A2 .Location in patent: Page/Page column 87

72
[ 86864-60-0 ]
[ 35344-95-7 ]
C₁₂H₂₂N₂O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In acetonitrile; at 80℃; for 2h;	2-bromoethoxy- xit y Id i met y I si I ane (CAS [86864-60-0]) (2.4 mL; 1 1 .4 mmol ) was added to a solution of 1 H-pyrazo le-4-carbaldehyde (CAS [35344-95-7] ) (910 mg; 9.5 mmol ) and K2CO3 ( 1 .6 g; 1 1 .4 mmol) in ACN (18 mL ). The reaction was heated at 80C for 2h. The reaction mixture was partitioned between a saturated solution of NaHCO; and EtOAc. The organic layer was separated, dried over MgS04, filtered and evaporated till dryness. The residue was purified by chromatography ov er silica gel ( Stationary phase: irregular SiOH 40 iim 120g, mobile phase gradient from: 100% DCM, 0% MeOH to 95% DCM, 5% MeOH). The fractions containing product were collected and ev aporated to dryness yielding 1 .6 g (65%) of intermediate 12 .
65%	With potassium carbonate; In acetonitrile; for 2h;Reflux;	A solution of 2-bromoethoxy-tert-butyldimethylsilane(CAS [86864-60-0]), (2.44mL;11.37mmol), <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (CAS [35344-95-7]), (0.91g; 9.5mmol) and K2CO3 (1.57g; 11.37mmol) in ACN (18mL) was refluxed for 2 h. The mixture was cooled, poured into ice water and a saturated NaHCO3 solution, the aqueous layer was extracted with EtOAc. The organic layer was separated, dried over MgSO4, filtered and evaporated to dryness giving a crude compound which was purified by chromatography over silica gel (Stationary phase: irregular SiOH 15-40mum 120g, Mobile phase: Gradient from 100% DCM, 0% MeOH to 95% DCM, 5% MeOH). The fractions containing product were collected and evaporated to dryness yielding 1.56g (yield 65%) of intermediate 18.

Reference： [1]Patent: WO2018/50684,2018,A1 .Location in patent: Page/Page column 64-65
[2]Patent: WO2018/109088,2018,A1 .Location in patent: Page/Page column 72-73

73
[ 86864-60-0 ]
[ 81107-97-3 ]
C₁₅H₂₂BrF₃O₂Si [ No CAS ]

Reference： [1]Patent: US2018/110824,2018,A1 .Location in patent: Paragraph 0465

74
[ 86864-60-0 ]
[ 36725-28-7 ]
6-(4-aminophenyl)-2-(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		To a solution of intermediate 7 (4.01, 19.7 minol) in DMF (40 mL) was added sodium hydride(60% on mineral oil, 1.66 g, 41.4 minol) at r.t. and the solution stirred for 20 min. Then tetra-Nbutylaminonium iodide (0.73 g, 1.97 minol) was added and stirring continued for further 15 min. After cooling to 000 (2-bromoethoxy)(tert-butyl)dimethylsilane (5.66 g, 23.7 minol) was added slowly and the mixture was warmed to r.t.. After stirring for further 14 h the mixture was diluted with water and extracted with dichloromethane (3 x). The combined organic extracts werewashed with brine and filtered over a phase separator filter. After removal of the solvent under reduced pressure the crude product was purified by column chromatography (silica gel, hexanes/ethyl acetate gradient) to give the desired product (4.07 g, 10.5 minol, 53%).1H-NMR (400 MHz, DMSO-d6): 6 [ppm] = 7.51 (d, IH), 6.57 (d, IH), 5.55 (s, IH), 4.00-3.93 (m, IH), 3.79 (t, 2H), 3.69-3.61 (m, IH), 3.32-3.23 (m, IH), 2.09 (s, IH), 1.04 (d, 3H), 0.83 (s, 9H),0.01 (d, 6H)LC-MS (Method 1): R = 1.36 min; MS (ESIpos): mz = 363 [M÷H]

Reference： [1]Patent: WO2018/86703,2018,A1 .Location in patent: Page/Page column 266; 267

75
[ 86864-60-0 ]
[ 259808-67-8 ]
tert-butyl 4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3,3-dimethylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 70℃; for 16h;	To a stirred solution of <strong>[259808-67-8]tert-butyl 3,3-dimethylpiperazine-1-carboxylate</strong> (2.0 g, 9.33 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (3.35 g, 14.0 mmol) in ACN (5 mL) was added K2CO3 (3.87 g, 28.0 mmol) at RT. The reaction mixture was stirred at 70 C for 16 hours. The resulting mixture was diluted with water (50 mL) and extracted with EA (3 x 50 mL). The combined organic layers were washed with brine (3 x 50 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with a gradient of 1 - 10% EA in PE to afford the title compound. LCMS (ESI) calc?d for C19H40N2O3Si [M + 1]+: 373, found 373.

Reference： [1]Patent: WO2019/18186,2019,A1 .Location in patent: Page/Page column 54

76
[ 42923-79-5 ]
[ 86864-60-0 ]
2-(2-(tert-butyldimethylsilyloxy)ethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 6h;	To a stined solution of <strong>[42923-79-5]7-nitro-1,2,3,4-tetrahydroisoquinoline</strong> (3.0 g, 16.85 mmol) in DMF (80 mL) was added K2C03 (9.3 g, 67.42 mmol) followed by (2- bromoethoxy)(tert-butyl)dimethylsilane (8.0 g, 33.71 mmol). The reaction was stined at RT for 6 h. Water (200 mL) was added, and the mixture was extracted with Et20 (2 x 200 mL). The combined organic layers were washed with brine (100 mL), dried (Na2504) and concentrated. The crude mixture was purified by column chromatography (5i02, 15% EA/pet. ether) to afford 2-(2-(tert-butyldimethylsilyloxy)ethyl)-7-nitro- 1,2,3,4- tetrahydroisoquinoline (2.0 g, 35%) as a brown oil; MS (LCMS) mlz 337.2 [M+H].

Reference： [1]Patent: WO2019/28008,2019,A1 .Location in patent: Paragraph 0169

77
[ 86864-60-0 ]
[ 418759-58-7 ]
C₁₇H₂₇NO₆Si [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 8450 - 8461

78
[ 4831-43-0 ]
[ 86864-60-0 ]
C₁₄H₂₉NO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a slurry of 447.7 mg (5.0 equiv.) of sodium hydride (60% dispersion in mineral oil) in DMF (5 mL) that had been cooled to 0- 5 C was added a solution of 2,2- dimethylpyrollidinone (253.3 mg, 2.238 mmol) in DMF (7 mL). The reaction mixture was stirred at 0- 5 C for 10 minutes and (2-bromoethoxy)(/er/-butyl)dimethylsilane (642.5 mg, 1.2 equiv.) was added in one portion. The reaction mixture was stirred for 10 minutes at 0- 5 C, then allowed to warm to ambient temperature. After 18 hours, the reaction mixture was cooled to 0- 5 C, and the reaction was quenched with saturated aqueous NH4CI (10 mL). The reaction mixture was diluted with 50% brine (100 mL) and extracted with EtOAc (3 x 50 mL). The organic extracts were combined, dried (Na2S04), and concentrated to afford a colorless oil which was then dissolved in THF (12 mL). Aqueous HC1 (1M, 4 mL) was added, and the reaction mixture was stirred at ambient temperature for 5 hours. The reaction was quenched with saturated aqueous NaHCO, (10 mL) and diluted with brine (50 mL), then extracted with EtOAc (3 x 50 mL). The organic extracts were combined, dried (Na2S04) and concentrated to afford a colorless oil, which was purified by silica gel chromatography (Hexanes/Acetone 0- 100% gradient) to afford intermediate alcohol 1-83 (183.8 mg, 52% yield over 2 steps) as a colorless oil.

Reference： [1]Patent: WO2019/183577,2019,A1 .Location in patent: Page/Page column 165-166

79
[ 23789-83-5 ]
[ 86864-60-0 ]
C₁₅H₃₁NO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		To a solution of <strong>[23789-83-5]3,3-dimethylpiperidin-2-one</strong> (240 mg, 1.88 mmol) in DMF (5 mL) at 0 C under N2 was added a slurry of NaH (574 mg of 60% dispersion in mineral oil, 3.0 equiv.) in DMF (15 mL). After 20 minutes, (2-bromoethoxy)(/er/-butyl)dimethylsilane (673 mg, 1.5 equiv.) was added. The reaction mixture was allowed to warm to ambient temperature. After 18 hours, the reaction mixture was quenched with saturated aqueous NH4CI (10 mL) and diluted with water (50 mL). The aqueous phase was extracted with EtOAc (3 x 50 mL). The combined EtOAc extracts were dried (Na2S04) and concentrated to afford a colorless oil. Purification by silica gel chromatography (12 g pre-packed column, 0 to 25% EtOAc in Hexanes) afforded 181 mg (34% yield) of the silyl ether 1-142 as a colorless oil. This material (90 mg, 0.315 mmol) was dissolved in THF (3 mL) and treated with 1M TBAF solution in THF (0.95 mL, 3 equiv.) and the resulting solution was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated under reduced pressure to afford a residue, which was purified by preparative HPLC (H20/MeCN with 0.1% TFA) to provide 37.7 mg of alcohol 1-143 (70% yield).

Reference： [1]Patent: WO2019/183577,2019,A1 .Location in patent: Page/Page column 186-187

80
[ 20196-21-8 ]
[ 86864-60-0 ]
4-(2-((tert-butyldimethylsilyl)oxy)ethyl)thiomorpholin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		To a solution of <strong>[20196-21-8]thiomorpholin-3-one</strong> (cas: 20196-21-8, 1.17 g, 10 mmol) in anhydrous DMF (10 mL) was added sodium hydride (cas: 7646-69-7, 1.20 g, 30 mmol, 3.0 equiv.) in ice bath under N2. After 30 minutes, (2-bromoethoxy)(/er/-butyl)dimethylsilane (cas: 86864-60-0, 3.59 g, 1.5 equiv.) was added to the solution at 0 C . The reaction mixture was allowed to warm to ambient temperature and stirred for 5 hours. Once complete, the reaction was quenched with water (5 mL), extracted with EtOAc (3 x 500 mL). The combined organic extracts were then washed with water (50 mL), brine (50 mL), and dried with Na2S04, then concentrated under reduced pressure to a residue, which was purified by silica gel chromatography to afford 1-344 (1.40 g, 54% yield) as a pale yellow oil. MS (ESI, pos. ion) m/z: 276. l(M+l).

Reference： [1]Patent: WO2019/183577,2019,A1 .Location in patent: Page/Page column 255

81
[ 2555-05-7 ]
[ 86864-60-0 ]
1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-methylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		To a solution of 3-methylpyrrolidin-2-one (cas: 2555-05-7, 0.3 g, 3 mmol) in THF (10 mL) at 0- 5 C was added NaH (0.242 g, 2 equiv.) under N2. The reaction mixture was stirred for 0.5 hours, then (2-bromoethoxy)(/er/-butyl)dimethylsilane (cas: 86864-60-0, 0.86 g, 1.2 equiv.) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 5 hours. The reaction was then quenched with water (5 mL), and extracted with DCM (3 x 20 mL). The combined organic extracts were then washed with water (20 mL), brine (20 mL), dried with Na2S04 and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography to afford 1-405 (0.25 g, 32% yield) as a pale oil. MS (ESI, pos. ion) m/z: 258(M+l).

Reference： [1]Patent: WO2019/183577,2019,A1 .Location in patent: Page/Page column 276

82
[ 875781-17-2 ]
[ 86864-60-0 ]
5-bromo-1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2019/198692,2019,A1 .Location in patent: Paragraph 0150; 1023-1024

83
[ 32046-62-1 ]
[ 86864-60-0 ]
5-bromo-1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-benzo[d][1,2,3]triazole [ No CAS ]

Reference： [1]Patent: WO2019/198692,2019,A1 .Location in patent: Paragraph 1038-1039

84
[ 1184172-46-0 ]
[ 86864-60-0 ]
C₁₃H₂₁ClFNO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 3h;	Intermediate 35?? (620 mg, 4.20 mmol) was dissolved in DMF (12 mL), then (2-bromoethoxy)-tert-butyldimethylsilane (1.8 mL, 8.31 mmol) and K 2CO 3 (1.16 g, 8.39 mmol) were added and the mixture was stirred at 70 C for 3 h. Then the reaction was cooled to R.T., diluted with diethylether and washed with water and brine. The org. layer was dried over MgSO 4, filtered and concentrated. Flash column chromatography (80 g silica, Redisep, heptane/EtOAc, gradient 1:0 to 8:2) delivered intermediate 36?? as a yellowish oil (1.26 g, 98%).

Reference： [1]Patent: WO2019/208509,2019,A1 .Location in patent: Paragraph 0138

85
[ 86864-60-0 ]
[ 60290-21-3 ]
C₁₅H₂₃ClN₂OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		4-Chloro-lH-pyrrolo[3,2-c]pyridine [60290-21-3] (1.00 g, 6.55 mmol) was dissolved in DMF (52 mL). NaH (60% dispersion in mineral oil, 288 mg, 7.21 mmol) was added at 0 C and the reaction mixture was stirred at room temperature. When gas evolution stopped, (2-bromocthoxy)-/er/-butyldimcthylsilanc (2.1 mL, 9.83 mmol) was added at 0 C. The reaction mixture was stirred at room temperature for 3 h and quenched with water. The mixture was diluted with EtOAc. The aqueous layer was extracted with EtOAc (3 times). The combined organic layers were washed with brine, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica, DCM/MeOH, gradient from 100:0 to 98:2) to afford 1-97 (1.6 g, 79%).

Reference： [1]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 57

86
[ 704911-47-7 ]
[ 86864-60-0 ]
methyl 3-bromo-1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-1,2,4-triazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h;	A mixture of <strong>[704911-47-7]methyl 3-bromo-1H-1,2,4-triazole-5-carboxylate</strong> (100 mg, 0.49 mmol), (2-bromoethoxy)(tert-butyl)dimethylsilane (176 mg, 0.74 mmol) and Cs2CO3(318 mg, 0.98 mmol) in DMF (2 mL) was stirred at RT for 3 daysThe crude reaction mixture was then purified by RP-MPLC (0-100% ACN/H2O) to give I52 A (91m g, 51%) as a light yellow oil. LCMS m/z (M+H)+364.0/366.2. 1H NMR (CD3OD) delta 4.76 (t, J=5.0 Hz, 2H), 3.97 (t, J=5.3 Hz, 2H), 3.96 (s, 3H), 0.792 (s, 9H), -0.07 (s, 6H).

Reference： [1]Patent: US2020/131209,2020,A1 .Location in patent: Paragraph 0788; 0789

87
[ 86864-60-0 ]
[ 33513-42-7 ]
[ 60061-60-1 ]
4-bromo-1-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-3-isopropyl-1H-pyrazole-5-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 2-(tert-butyldimethylsilyloxy)ethyl bromide; 4-bromo-3-isopropyl-1H-pyrazole With caesium carbonate In acetonitrile at 20℃; for 6h; Cooling with ice; Inert atmosphere; Stage #2: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #3: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -78℃; for 1h;	4-Bromo-1-{2-[(tert-Butyldimethylsilyl)oxy]ethyl}-3-isopropyl-1H-pyrazole-5-carbaldehyde (7f) To a flask were added THF (0.88 mL) and i-Pr2NH (0.125 mL, 0.888mmol) at r.t. and the mixture was stirred in a dry ice/acetone bath. Tothe mixture was added n-BuLi solution (2.5 M in hexanes, 0.338 mL,0.846 mmol) dropwise and the mixture was stirred in a dry ice/acetonebath for 30 min. To the reaction mixture was added a solution ofpyrazole 12f (0.147 g, 0.352 mmol; corrected for 5:1 ratio of 12f:17)in THF (0.29 mL) dropwise and the mixture was stirred in a dryice/acetone bath for 30 min. To the mixture was added a solution ofDMF (0.059 mL, 0.761 mmol) in THF (0.29 mL) dropwise and the mixturewas stirred in a dry ice/acetone bath for 1 h. To the mixture wasadded 2-propanol (0.081 mL, 1.06 mmol) dropwise and then cooledin an ice/water bath. To the mixture was added sat. aq NH4Cl (10 mL)over 5 min and H2O (20 mL). The mixture was extracted with MTBE (3× 25 mL) and the combined organics were dried (Na2SO4) and concentrated.The resultant residue was purified by flash column chromatography(SiO2, eluting with 0-10% MTBE/heptane) to give pyrazolealdehyde 7f as a colorless oil; yield: 0.109 g (0.290 mmol, 82%).IR (neat): 2957, 2930, 1689, 1456, 1117 cm-1.1H NMR (400 MHz, CDCl3): = 9.85 (s, 1 H), 4.59 (t, J = 5.6 Hz, 2 H),3.90 (t, J = 5.5 Hz, 2 H), 3.07 (sept, J = 7.0 Hz, 1 H), 1.30 (d, J = 7.0 Hz, 6H), 0.79 (s, 9 H), -0.09 (s, 6 H).13C NMR (100 MHz, CDCl3): = 179.7, 155.5, 135.3, 102.1, 62.0, 53.9,26.6, 25.7, 21.4, 18.1, -5.7.HRMS (ESI+): m/z [M]+ calcd for C15H27BrN2O2Si: 374.1025; found:374.1014.

Reference： [1]Lindsay-Scott, Peter J.; Rivlin-Derrick, Eloise [Synthesis, 2020, vol. 52, # 1, p. 105 - 118]

88
[ 86864-60-0 ]
[ 60061-60-1 ]
4-bromo-1-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-3-isopropyl-1H-pyrazole [ No CAS ]
C₁₄H₂₇BrN₂OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In acetonitrile at 20℃; for 6h; Cooling with ice; Inert atmosphere; Overall yield = 75 percent; Overall yield = 0.750 g; regioselective reaction;	Alkylation of Pyrazoles; General Procedure 2 General procedure: The pyrazole 1 (1 equiv) was added to MeCN (8 mL/g) and the mixture was stirred in an ice/water bath. To the solution was added Cs2CO3(1.5 equiv) in one portion, followed by a solution of (2-bromoethoxy)-tert-butyldimethylsilane (6; 1.05 equiv) in MeCN (2 mL/g) dropwise.The reaction mixture was stirred at r.t. for 16 h, then to the mixture was added Cs2CO3 (1.5 equiv) in one portion, followed by 6 (0.5 equiv)dropwise. The mixture was stirred at r.t. for the time specified, then filtered through Celite, washing with MTBE (20 mL/g). The filtrate was concentrated to give a residue, which was purified as specified.

Reference： [1]Lindsay-Scott, Peter J.; Rivlin-Derrick, Eloise [Synthesis, 2020, vol. 52, # 1, p. 105 - 118]

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P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
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.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 86864-60-0 ] {[proInfo.proName]}

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[ 86864-60-0 ] Synthesis Path-Upstream 1~7

[ 86864-60-0 ] Synthesis Path-Downstream 1~88

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