[ CAS No. 624-76-0 ] {[proInfo.proName]}

Name: 624-76-0|2-Iodoethanol|98% (stabilized with Copper)
Brand: Ambeed
SKU: A438982
Rating: 96 (35 reviews)

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Cat. No.: {[proInfo.prAm]}

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Quality Control of [ 624-76-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 624-76-0 ]

Product Details of [ 624-76-0 ]

CAS No. :	624-76-0	MDL No. :	MFCD00002830
Formula :	C₂H₅IO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QSECPQCFCWVBKM-UHFFFAOYSA-N
M.W :	171.97	Pubchem ID :	12225
Synonyms :

Calculated chemistry of [ 624-76-0 ]

Physicochemical Properties

Num. heavy atoms :	4
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	25.85
TPSA :	20.23 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.24
Log Po/w (XLOGP3) :	0.65
Log Po/w (WLOGP) :	0.41
Log Po/w (MLOGP) :	0.75
Log Po/w (SILICOS-IT) :	0.81
Consensus Log Po/w :	0.77

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	3.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.25
Solubility :	9.68 mg/ml ; 0.0563 mol/l
Class :	Very soluble
Log S (Ali) :	-0.65
Solubility :	38.5 mg/ml ; 0.224 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.06
Solubility :	15.0 mg/ml ; 0.0871 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.98

Safety of [ 624-76-0 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P501-P270-P262-P210-P264-P280-P370+P378-P361+P364-P301+P310+P330-P302+P352+P310-P403+P235-P405	UN#:	2810
Hazard Statements:	H300+H310-H227	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 624-76-0 ]

* 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 [ 624-76-0 ]
Downstream synthetic route of [ 624-76-0 ]

[ 624-76-0 ] Synthesis Path-Upstream 1~8

1
[ 110-91-8 ]
[ 624-76-0 ]
[ 622-40-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 6, p. 2607 - 2622

2
[ 624-76-0 ]
[ 66224-66-6 ]
[ 707-99-3 ]
[ 126595-74-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 7, p. 2812 - 2822

3
[ 624-76-0 ]
[ 540-51-2 ]

Reference： [1] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1889, p. 1321

4
[ 624-76-0 ]
[ 108-18-9 ]
[ 96-80-0 ]

Reference： [1] J. Gen. Chem. USSR (Engl. Transl.), 1962, vol. 32, p. 502 - 506[2] Zhurnal Obshchei Khimii, 1962, vol. 32, p. 511 - 515

5
[ 1072-53-3 ]
[ 2314-97-8 ]
[ 624-76-0 ]
[ 2240-88-2 ]

Reference： [1] Organic Letters, 2002, vol. 4, # 26, p. 4671 - 4672

6
[ 624-76-0 ]
[ 18162-48-6 ]
[ 101166-65-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 1H-imidazole In dichloromethane at 30℃; for 17 h;	(i) Preparation of (2-iodoethoxy)-tert-butyldimethylsilane To a stirred solution of 2-iodoethanol (17.2 g; 100 mmol) and imidazole (8.17 g; 120 mmol) in dichloromethane (100 mL) was added tert-butyldimethylsilyl chloride (15.83 g; 105 mmol) at such a rate that the reaction temperature did not rise above 30° C. Upon complete addition the solution was left stirring for 17 h, then washed with water (2*50 mL) and brine (50 mL) and dried over MgSO₄. Evaporation of the solvent afforded the target compound (28.0 g; 97.8 mmol; 98percent) as a colourless liquid. ¹H-NMR (400 MHz) (CDCl₃): δ=3.83 (t, 2H, J=7.0 Hz), 3.83 (t, 2H, J=7.0 Hz), 3.20 (t, 2H, J=7 Hz), 0.90 (s, 9H), 0.08 (s, 6H) ppm.
90%	With 1H-imidazole In N,N-dimethyl-formamide at 30 - 40℃; for 4 h;	Preparation of tert-butyl(2-iodoethoxy)dimethylsilane After 2-iodoethanol (1.72 g, 10 mmol) was dissolved in dimethylformamide (8 mL), imidazole (0.817 g, 12 mmol) and tert-butyldimethylsilyl chloride (1.66 g, 11 mmol) were added thereto, and the mixture was stirred for 4 hours at 30° C. to 40° C. Water (50 mL) was added to the reaction solution, and the result was extracted with an ethyl acetate/normal-hexane=1/1 solution (100 mL). The organic layer was washed again with salt water (30 mL*3), dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 2.85 g (90percent) of a target compound. This compound was used as it was for the next reaction without purification.
90%	With 1H-imidazole In N,N-dimethyl-formamide at 30 - 40℃; for 4 h;	Preparation of tert-butyl(2-iodoethoxy)dimethylsilane After 2-iodoethanol (1.72 g, 10 mmol) was dissolved in dimethylformamide (8 mL), imidazole (0.817 g, 12 mmol) and tert-butyldimethylsilyl chloride (1.66 g, 11 mmol) were added thereto, and the mixture was stirred for 4 hours at 30°C to 40°C. Water (50 mL) was added to the reaction solution, and the result was extracted with an ethyl acetate/normal-hexane=1/1 solution (100 mL). The organic layer was washed again with salt water (30 mLx3), dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 2.85 g (90percent) of a target compound. This compound was used as it was for the next reaction without purification.

Reference： [1] Chemistry - A European Journal, 2017, vol. 23, # 5, p. 1157 - 1165
[2] Analytical Chemistry, 2003, vol. 75, # 21, p. 6002 - 6010
[3] Patent: US2013/59970, 2013, A1, . Location in patent: Paragraph 0311; 0312; 0313
[4] Patent: US2014/249162, 2014, A1, . Location in patent: Paragraph 0234
[5] Patent: EP2781519, 2014, A1, . Location in patent: Paragraph 0232
[6] Organic Letters, 2014, vol. 16, # 11, p. 2862 - 2864
[7] Organic Letters, 1999, vol. 1, # 3, p. 379 - 381
[8] Patent: US5939439, 1999, A,
[9] Patent: WO2013/152269, 2013, A1, . Location in patent: Page/Page column 83

7
[ 288-32-4 ]
[ 624-76-0 ]
[ 18162-48-6 ]
[ 101166-65-8 ]

Reference： [1] Patent: US2013/59926, 2013, A1, . Location in patent: Page/Page column

8
[ 120-72-9 ]
[ 624-76-0 ]
[ 121459-15-2 ]

Reference： [1] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 1, p. 27 - 30

[ 624-76-0 ] Synthesis Path-Downstream 1~88

1
[ 624-76-0 ]
[ 2933-29-1 ]
2-(2-imino-4,5,6,7-tetrahydro-benzothiazol-3-yl)-ethanol [ No CAS ]

Reference： [1]Pharmaceutical Chemistry Journal,1978,vol. 12,p. 1423 - 1427
Khimiko-Farmatsevticheskii Zhurnal,1978,vol. 12,p. 30 - 34

2
[ 624-76-0 ]
[ 108-18-9 ]
[ 96-80-0 ]

Reference： [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 502 - 506
Zhurnal Obshchei Khimii,1962,vol. 32,p. 511 - 515

3
[ 110-87-2 ]
[ 624-76-0 ]
[ 96388-83-9 ]

Yield	Reaction Conditions	Operation in experiment
		Cesium carbonate (3.91 g) is added to a solution of N-(4-chlorobenzyl)-4-hydroxy-2- (hydroxymethyl) thieno [[2, 3-B] PYRIDINE-5-CARBOXAMIDE] (3.49 g, prepared as described in US 6,239, 142) and 2-(2-iodoethoxy)tetrahydro-2H-pyran (2.56 g, prepared by mixing equal molar amounts [OF 2-IODOETHANOL] and 3, 4-dihydro-2H-pyran) in DMF (20 mL). The reaction mixture is stirred at [100 C FOR] 17 hours. The solvent is evaporated and the residue is dissolved in 10% CH30H in [CH2C12.] The mixture is washed with water and the organic layer is dried (MgSO4), filtered, concentrated. The crude product is crystallized from EtOAc to afford 3.8 g of the title compound as a white solid. Physical characteristics. 1H NMR (400 [MHZ,] DMSO-d6) delta 10.59, 8.71, 7.39, 7.38, 7.29, 5.79, 4. [69,] 4.58, 4.54, 4. [48,] 3.96, 3.78, 3.30, 1.54, 1.39, 1. [29 ;] MS (EI) [RNLZ] 476 [(M"), HRMS (FAB) ] 477.1245 (M+H) +.
		Cesium carbonate (3.91 g) is added to a solution [OF N-(4-CHLOROBENZYL)-4-HYDROXY-2-] (hydroxymethyl) thieno [2, [3-B]] [PYRIDINE-5-CARBOXAMIDE] (3.49 g, prepared as described in US 6,239, 142) and [2- (2-IODOETHOXY) TETRAHYDRO-2H-PYRAN] (2.56 g, prepared by mixing equal molar amounts of <strong>[624-76-0]2-iodoethanol</strong> and 3, [4-DIHYDRO-2H-PYRAN)] in DMF (20 [ML).] The reaction mixture is stirred at [100 C] for 17 hours. The solvent is evaporated and the residue is dissolved in 10% CH30H in [CH2CI2.] The mixture is washed with water and the organic layer is dried (MgSO4), filtered, concentrated. The crude product is crystallized from EtOAc to afford 3.8 g of the title compound as a white solid. Physical characteristics. 1H NMR (400 [MHZ,] DMSO-d6) [8] 10.59, 8.71, 7.39, 7.38, 7.29, 5.79, 4.69, 4.58, 4. [54,] 4.48, 3. [96,] 3.78, 3.30, 1. [54,] 1. [39,] 1.29 ; MS [(EI)] [M/Z] 476 [(M) ;] HRMS (FAB) [M/Z] 477.1245 (M+H) +.
		Cesium carbonate (3.91 g) is added to a solution of N-(4-chlorobenzyl)-4-hydroxy-2- (hydroxymethyl) thieno [2, 3-B] pyridine-5-carboxamide (3.49 g, prepared as described in US 6,239, 142) and 2-(2-iodoethoxy)tetrahydro-2H-pyran (2.56 g, prepared by mixing equal molar amounts of <strong>[624-76-0]2-iodoethanol</strong> and 3, 4-dihydro-2H-pyran) in DMF (20 mL). The reaction mixture is stirred at 100 C for 17 hours. The solvent is evaporated and the residue is dissolved in 10% CH30H in CH2C12. The mixture is washed with water and the organic layer is dried (MgSO4), filtered, concentrated. The crude product is crystallized from EtOAc to afford 3.8 g of the title compound as a white solid. Physical characteristics. 1H NMR (400 MHz, DMSO-d6) 8 10.59, 8.71, 7. 39, 7. 38, 7. 29, 5.79, 4. 69, 4.58, 4.54, 4.48, 3.96, 3.78, 3.30, 1.54, 1.39, 1.29 ; MS (EI) m/z 476 (M) ; HRMS (FAB) TNLZ 477.1245 (M+H) +.

Reference： [1]Synthesis,1990,p. 135 - 137
[2]Journal of Organic Chemistry,1989,vol. 54,p. 2404 - 2409
[3]Journal of the American Chemical Society,2019
[4]Organic Letters,2006,vol. 8,p. 573 - 576
[5]Journal of Chemical Ecology,1997,vol. 23,p. 553 - 568
[6]Journal of Medicinal Chemistry,1997,vol. 40,p. 408 - 412
[7]Organic Letters,2002,vol. 4,p. 2691 - 2694
[8]Journal of Medicinal Chemistry,2007,vol. 50,p. 5090 - 5102
[9]Synlett,2008,p. 1627 - 1630
[10]Patent: WO2004/22567,2004,A1 .Location in patent: Page 32-33
[11]Patent: WO2004/22568,2004,A1 .Location in patent: Page 31
[12]Patent: WO2004/106345,2004,A2 .Location in patent: Page 34

4
[ 624-76-0 ]
[ 13154-24-0 ]
[ 93550-77-7 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 6410 - 6424
[2]Organic Letters,2013,vol. 15,p. 112 - 115
[3]Chemistry - A European Journal,2017,vol. 23,p. 14702 - 14706
[4]Helvetica Chimica Acta,1984,vol. 67,p. 1625 - 1629
[5]Journal of the American Chemical Society,1997,vol. 119,p. 6496 - 6511

5
[ 624-76-0 ]
[ 2019-34-3 ]
3-(4-Chlorophenyl)propionic acid 2-iodoethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With pyridine; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 16h;

Reference： [1]Pearson, Anthony J.; Lee, Kieseung [Journal of Organic Chemistry, 1994, vol. 59, # 8, p. 2257 - 2260]

6
[ 624-76-0 ]
[ 81927-55-1 ]
[ 54555-84-9 ]
[ 594-65-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With trifluorormethanesulfonic acid In dichloromethane; cyclohexane for 18h; Ambient temperature;

Reference： [1]Liu; Coward [Journal of Medicinal Chemistry, 1991, vol. 34, # 7, p. 2094 - 2101]

7
[ 624-76-0 ]
[ 113-98-4 ]
[ 122048-11-7 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1774 - 1781

8
[ 624-76-0 ]
[ 57292-44-1 ]
N-<(1,1-Dimethylethoxy)carbonyl>-4-chloro-D-phenylalanine 2-iodoethyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1994,vol. 59,p. 2257 - 2260

9
[ 624-76-0 ]
[ 76684-89-4 ]
[ 140660-49-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 3h;

Reference： [1]Huang; McGowan; Detwiler [Journal of Medicinal Chemistry, 1992, vol. 35, # 11, p. 2048 - 2054]

10
[ 624-76-0 ]
[ 2140-69-4 ]
5-(2-hydroxyethyl)-3-methyluridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	In water; acetonitrile for 24h; Irradiation;

Reference： [1]Hassan, Mohamed E. [Recueil des Travaux Chimiques des Pays-Bas, 1986, vol. 105, # 1, p. 30 - 32]

11
[ 624-76-0 ]
[ 42059-80-3 ]
[ 96626-13-0 ]

Reference： [1]Tetrahedron,1991,vol. 47,p. 9431 - 9438
[2]Journal of the Chemical Society. Chemical communications,1984,p. 1698 - 1699

12
[ 624-76-0 ]
[ 60-92-4 ]
6-Amino-9-((4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxo-tetrahydro-2λ⁵-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-1-(2-hydroxy-ethyl)-9H-purin-1-ium [ No CAS ]

Reference： [1]Tetrahedron,1984,vol. 40,p. 2405 - 2414

13
[ 624-76-0 ]
[ 507-09-5 ]
[ 41858-09-7 ]

Yield	Reaction Conditions	Operation in experiment
48%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; at 0 - 20℃; for 2h;	Add to the reaction bottleThioacetic acid (874 mg, 11.5 mmol),<strong>[624-76-0]2-iodoethanol</strong> (1.72 g, 10 mmol),Dissolved in 15 ml of anhydrous toluene,1,8-diazabicycloundec-7-ene (DBU, 1.75 g, 11.5 mmol) was added dropwise at 0 C.5 ml of toluene solution, plus,The reaction was stirred for 2 hours at room temperature.After TLC detects the reaction,Dilute with a small amount of water,Divide the organic phase,Washed with saturated brine and concentrated.Purified by column chromatography,The product was dried under vacuum to give 576 mg,yield: 48%.
42%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; at 20℃;Inert atmosphere;	0.874 g (11.5 mmol) of thioacetic acid was placed in a 100 mL three-necked flask under N2 protection,(10.0 mmol) of <strong>[624-76-0]2-iodoethanol</strong> and 1.749 g (11.5 mmol) of DBU were slowly added dropwise to the reaction solution. After completion of the dropwise addition, the mixture was left to stand at room temperature After the reaction, the reaction product was passed through a silica gel column (the particle size of the silica gel was 200 to 300 mesh), and the filtrate was collected to give 0.5 g of a yellow oily liquid, i.e., a middle The yield was 42%.

Reference： [1]Nucleosides and Nucleotides,1995,vol. 14,p. 763 - 766
[2]Journal of Medicinal Chemistry,1995,vol. 38,p. 3941 - 3950
[3]Patent: CN109485676,2019,A .Location in patent: Paragraph 0375; 0378; 0379; 0380
[4]Patent: CN104893710,2016,B .Location in patent: Paragraph 0044
[5]Nucleosides and Nucleotides,1995,vol. 14,p. 563 - 565

14
[ 624-76-0 ]
[ 91-63-4 ]
[ 64170-00-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	In ethanol; at 50℃; for 36h;	Add 7 mL of ethanol to the round bottom flask, then add 1.1 mL of 2-methylquinoline.Add 0.5mL of iodine solution,The reaction was heated to 50 C for 36 h, and after the reaction was completed, the reaction system was cooled to room temperature.Solid precipitated, filtered and washed with ethanolObtaining 1,2-dimethyl-quinoline iodide salt (Compound 2),The yield was 93%.Its nuclear magnetic resonance spectrum is shown in Figure 1.

Reference： [1]Patent: CN109851553,2019,A .Location in patent: Paragraph 0020
[2]Russian Chemical Bulletin,1995,vol. 44,p. 1084 - 1086
Izvestiya Akademi Nauk, Seriya Khimicheskaya,1995,p. 1122 - 1124

15
[ 624-76-0 ]
[ 58113-36-3 ]
[ 131742-16-0 ]

Reference： [1]European Journal of Medicinal Chemistry,1997,vol. 32,p. 651 - 659

16
[ 624-76-0 ]
[ 84661-56-3 ]
1,1'-Di(3-hydroxyethyl)-3,3'-methylenediimidazolium diiodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In butan-1-ol; for 5h;Heating / reflux;	The combination of two equivalents of 1-IODOETHANOL (formula 12) with bisimidazol (formula 11) in refluxing butanol gives the water soluble diol shown as formula 13. This compound has been characterized by both NMR and X-ray crystallography.

Reference： [1]Chemistry - A European Journal,2000,vol. 6,p. 1773 - 180
[2]Dalton Transactions,2010,vol. 39,p. 6339 - 6343
[3]Patent: WO2005/23760,2005,A2 .Location in patent: Page/Page column 8

17
[ 624-76-0 ]
[ 16834-13-2 ]
C₄₈H₄₆N₈O₄⁽⁴⁺⁾*4I^(1-) [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4509 - 4523
[2]Journal of Medicinal Chemistry,2001,vol. 44,p. 4509 - 4523

18
[ 624-76-0 ]
[ 18162-48-6 ]
[ 101166-65-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 1H-imidazole; In dichloromethane; at 30℃; for 17h;	(i) Preparation of (2-iodoethoxy)-tert-butyldimethylsilane To a stirred solution of 2-iodoethanol (17.2 g; 100 mmol) and imidazole (8.17 g; 120 mmol) in dichloromethane (100 mL) was added tert-butyldimethylsilyl chloride (15.83 g; 105 mmol) at such a rate that the reaction temperature did not rise above 30° C. Upon complete addition the solution was left stirring for 17 h, then washed with water (2*50 mL) and brine (50 mL) and dried over MgSO4. Evaporation of the solvent afforded the target compound (28.0 g; 97.8 mmol; 98percent) as a colourless liquid. 1H-NMR (400 MHz) (CDCl3): delta=3.83 (t, 2H, J=7.0 Hz), 3.83 (t, 2H, J=7.0 Hz), 3.20 (t, 2H, J=7 Hz), 0.90 (s, 9H), 0.08 (s, 6H) ppm.
90%	With 1H-imidazole; In N,N-dimethyl-formamide; at 30 - 40℃; for 4h;	Preparation of tert-butyl(2-iodoethoxy)dimethylsilane After 2-iodoethanol (1.72 g, 10 mmol) was dissolved in dimethylformamide (8 mL), imidazole (0.817 g, 12 mmol) and tert-butyldimethylsilyl chloride (1.66 g, 11 mmol) were added thereto, and the mixture was stirred for 4 hours at 30° C. to 40° C. Water (50 mL) was added to the reaction solution, and the result was extracted with an ethyl acetate/normal-hexane=1/1 solution (100 mL). The organic layer was washed again with salt water (30 mL*3), dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 2.85 g (90percent) of a target compound. This compound was used as it was for the next reaction without purification.
90%	With 1H-imidazole; In N,N-dimethyl-formamide; at 30 - 40℃; for 4h;	Preparation of tert-butyl(2-iodoethoxy)dimethylsilane After 2-iodoethanol (1.72 g, 10 mmol) was dissolved in dimethylformamide (8 mL), imidazole (0.817 g, 12 mmol) and tert-butyldimethylsilyl chloride (1.66 g, 11 mmol) were added thereto, and the mixture was stirred for 4 hours at 30°C to 40°C. Water (50 mL) was added to the reaction solution, and the result was extracted with an ethyl acetate/normal-hexane=1/1 solution (100 mL). The organic layer was washed again with salt water (30 mLx3), dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 2.85 g (90percent) of a target compound. This compound was used as it was for the next reaction without purification.

	With 2-(Dimethylamino)pyridine; N-ethyl-N,N-diisopropylamine; In dichloromethane;	Step 2 tert-Butyl-(2-iodo-ethoxy)-dimethyl-silane To 2-iodoethanol (20 gm, 116 mmol) suspended in methylene chloride (500 mL) was added dimethylaminopyridine (100 mg) followed by diisopropylethylamine (30 mL, 174 mmol) and tert-butyldimethylsilyl chloride (19 gm, 128 mmol). The reaction was stirred overnight and the solvent was removed in vacuo and the residue was passed through a short column of silica gel and eluted with 95:5 methylene chloride: methanol. The desired fractions were combined and the solvent was removed in vacuo to give the desired product. 1 H NMR (400 MHz, CDCl3) delta 3.84 (dd, 2H); 3.20 (dd, 2H); 0.9 (m, 9H); 0.1 (m, 6H).
	With 1H-imidazole; In dichloromethane; at 20℃; for 20h;Cooling with ice; Large scale;	Step C (1,1 -dimethylethyl)(2-iodoethoxy)dimethylsilane .OTBDMS Iodoethanol (2.68 kg, 15.4 mol), CH2CI2 (12 L) and imidizaole (1.556 kg, 22.63 mol) were chilled in an ice bath. A solution of t-butyldimethylchlorosilane (2.536 kg, 16.32 mol) in CH2CI2 (2.5 L) was added to the reaction over a 2 h period. The resulting white suspension was allowed to warm to rt over an 18 h. The reaction was worked up by washing with water and brine). The organic layer was dried (MgSC^) and evaporated under reduced pressure to provide the product of Step C as a light yellow oil. FontWeight="Bold" FontSize="10" H NMR (400MHz, CDC13) delta = 3.75 (t, J = 7.0 Hz, 2 H), 3.11 (t, J = 7.0 Hz, 2 H), 0.77 - 0.89 (m, 10 H), 0.00 (s, 6 H).

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 1157 - 1165
[2]Analytical Chemistry,2003,vol. 75,p. 6002 - 6010
[3]Patent: US2013/59970,2013,A1 .Location in patent: Paragraph 0311; 0312; 0313
[4]Patent: US2014/249162,2014,A1 .Location in patent: Paragraph 0234
[5]Patent: EP2781519,2014,A1 .Location in patent: Paragraph 0232
[6]Organic Letters,2014,vol. 16,p. 2862 - 2864
[7]Organic Letters,1999,vol. 1,p. 379 - 381
[8]Patent: US5939439,1999,A
[9]Patent: WO2013/152269,2013,A1 .Location in patent: Page/Page column 83

19
[ 624-76-0 ]
[ 442-51-3 ]
2-(7-methoxy-1-methyl-β-carbolin-9-yl)ethanol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4613 - 4623

20
[ 624-76-0 ]
[ 84057-84-1 ]
5-amino-6-(2,3-dichlorophenyl)-2,3-dihydro-3-imino-2-(2-hydroxyethyl)-1,2,4-triazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	In acetone; for 144h;Heating / reflux;	5(3)-Amino-6-(2,3-dichlorophenyl)-2,3(2,5)-dihydro-3(5)-imino-2-(2- hydroxy ethyl)- 1 ,2,4-triazine 2-Iodoethanol (3.44 g, 0.02 mol) was added to a stirred suspension of 3,5-diamino-6-(2,3-dichlorophenyl)-l,2,4-triazine (2.56 g, 0.01 mol) in acetone (200 ml). The mixture was stirred at reflux for 6 days, cooled and the solid collected by filtration. The solid was stirred with 0.88 aqueous ammonia (100 ml) and the mixture stirred for 0.5 h. The solid (ca. 2.7 g) was removed by filtration, dried in vacuo and recrystallised from methanol to give 1.14 g (38 %) of the title compound as a white crystalline solid, mp 217-218 0C <n="14"/>deltaH (500 MHz, dmso-de) 3.34 (3H, s, CH3OH), 3.68 (2H, brt, J = 6 Hz, OCH2), 3.96 (2H, m, NCH2), 5.5-7.0 (2H, vbrpeak, NH2), 7.36-7.46 (2H, m, aromatic H), 7.71 (IH, dd, J = 8,2 Hz, aromatic H). This compound is a methanol solvate Methanesulfonate salt mp 242-245 0C]

Reference： [1]Patent: WO2008/7149,2008,A2 .Location in patent: Page/Page column 12; 13

21
[ 624-76-0 ]
[ 100-61-8 ]
[ 93-90-3 ]

Yield	Reaction Conditions	Operation in experiment
64.5%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 70℃; for 16h;	N-methylaniline (5mls, 0.05mol) was reacted with 2-Iodoethanol (3.599mls, 0.05mol) and diisopropylethylamine (8.039mls, 0.05mol) in ACN at 70oC for 16 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound as a yellow orange oil (4.48g, 0.03mol, 64.5%yield). 1H NMR (400 MHz, Chloroform-d) delta 7.27 - 7.15 (m, 2H), 6.81 - 6.67 (m, 3H), 3.74 (t, J = 5.8 Hz, 2H), 3.42 (t, J = 5.8 Hz, 2H), 2.92 (s, 3H).
64.5%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 70℃; for 16h;	N-methylaniline (5 mls, 0.05 mol) was reacted with 2-Iodoethanol (3.599 mls, 0.05 mol) and diisopropylethylamine (8.039 mls, 0.05 mol) in ACN at 70 C. for 16 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound as a yellow orange oil, 2a (4.48 g, 0.03 mol, 64.5% yield). 1H NMR (400 MHz, Chloroform-d) delta 7.27-7.15 (m, 2H), 6.81-6.67 (m, 3H), 3.74 (t, J=5.8 Hz, 2H), 3.42 (t, J=5.8 Hz, 2H), 2.92 (s, 3H).

Reference： [1]Chemical Communications,2015,vol. 51,p. 6625 - 6628
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2951 - 2954
[3]Patent: US2013/230542,2013,A1 .Location in patent: Paragraph 0122
[4]Macromolecules,2005,vol. 38,p. 9526 - 9538

22
[ 624-76-0 ]
[ 51792-34-8 ]
[ 877459-72-8 ]

Reference： [1]Chemical Communications,2006,p. 275 - 277
[2]Journal of Materials Chemistry,2012,vol. 22,p. 100 - 108

23
[ 624-76-0 ]
[ 86-74-8 ]
[ 1484-14-6 ]

Yield	Reaction Conditions	Operation in experiment
65%		To a solution of carbazole 1 (2.0 g, 11.96 mmol) in distilled DMF (20 mL) was added NaH (60% dispersion in mineral oil, 956.9 mg, 23.92 mmol) under nitrogen condition and stirred at 0 C for 30 min. To the reaction mixture was added dropwise 2-iodoethanol (4.1 g, 23.92 mmol) and stirred at 70 C for 24 h. The mixture was extracted with EtOAc and washed with water and dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, n-hexane/ EtOAc = 3:1) to afford 1.64 g (7.84 mmol , 65%) of the title compound 2.: Rf = 0.18 (n-hexane/EtOAc = 2:1); IR (neat, cm-1) 3253, 3048, 2914, 1492, 1483, 1457, 1348, 1325; 1H NMR d (400 MHz, CDCl3) d 8.07 (2H, td, J = 7.6, 1.2 Hz), 7.44-7.39 (4H, m), 7.22 (2H, td, J = 7.6, 1.2 Hz), 4.38 (2H, t, J = 5.2 Hz); 13C NMR (100 MHz, CDCl3) d 140.9, 126.0, 123.1, 120.6, 119.4, 109.0, 61.6, 45.6.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3317 - 3321
[2]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3088 - 3092
[3]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3301 - 3304
[4]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 27 - 30

24
[ 624-76-0 ]
[ 59-02-9 ]
[ 200701-54-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydroxide; In DMF (N,N-dimethyl-formamide); at 20℃; for 24h;	2-(2,5,7,8-Tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy))ethan-1-ol (13) A solution of R,R,R-alpha-tocopherol (0.5 g, 1.16 mmol) in N,N-dimethylformamide (20 mL) was treated with iodoethanol (1.7 g, 10 mmol) and an excess of powdered NaOH (2.5 g, 63 mmol). The resulting yellow slurry was stirred vigorously for 24 h at room temperature. The reaction was acidified with 5 N HCl and extracted with diethyl ether (330 ml). The combined ether layers were washed with H2O (330 ml) and brine (130 ml), and then dried with Na2SO4. The ether solution was concentrated to a yellow oil that was purified by silica gel chromatography eluding with 30% (v/v) EtOAc and 2% acetic acid in hexanes. The resulting yellow liquid was dissolved in diethyl ether (30 ml), washed with H2O (320 mL) and brine (120 mL), and then dried with Na2SO4. The resulting solution was concentrated to a light yellow oil and dried in vacuo for 48 h. This yielded 13 as yellow oil (0.40 g, 73%). 1H-NMR (CDCl3/TMS, ppm): 0.87 (m, 12H, 4a'-, 8a'-, 12a'-, 13'-CH3), 1.0-1.6 (m, 24H, 4'-, 8'-, 12'-CH, 1'-, 2'-, 3'-, 5'-, 6'-, 7'-, 9'-, 10'-, 11'-CH2, 2a-CH3), 1.81 (m, 2H, 3-CH2), 2.07, 2.14, 2.16 (3s, 9H, 5a-, 7a-, 8a-CH3), 2.59 (t, J=6.6 Hz, 2H, 4-CH2), 3.79 (m, 2H, OCH2), 3.94 (m, 2H, OCH2); 13C-NMR (CDCl3, ppm): 11.7, 11.8, 12.7 (5a-, 7a-, 8a-CH3), 19.6, 19.7 (CH3), 20.6, 21.0 (CH2), 22.6, 22.7 (CH3), 23.8 (2a-CH3), 24.4, 24.8 (CH2), 28.0 (CH), 31.2 (3-CH2), 32.7, 32.8 (CH), 37.3, 37.4, 37.5, 39.4, 40.0 (CH2), 63.1, 69.2 (OCH2), 75.0 (2-C), 117.8, 123.4, 126.4, 128.3 (aryl C), 149.2, 149.5 (aryl C-O); MS (CI, m/z): 475 (M+H+, Calc. for C31H54O3 474.40729).

Reference： [1]Patent: JP2004/504268,2004,A .Location in patent: Page/Page column 22-23
[2]Patent: US6703384,2004,B2 .Location in patent: Page column 19-20

25
[ 624-76-0 ]
N-[((5S)-3-{4-[exo-(1R,5S)-3-azabicyclo[3.1.0]hex-6-yl]3-fluorophenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide [ No CAS ]
N-[((5S)-3-{3-fluoro-4-[exo-(1R,5S)-3-(2-hydroxyethyl)-3-azabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 65℃; for 2h;	To a solution OFN [ ( (SS)-3- {4- [EXO- (1R, SS)-3-AZABICYCLO [3.1. 0] hex-6-yl]-3- fluorophenyl}-2-oxo-1, 3-OXAZOLIDIN-5-YL) methyl] acetamide (0.12 g, 0.36 mmol, 1 equivalent) in DMF (4 mL), was added DIEA (0.125 mL, 0.72 mmol, 2.0 equiv. ), followed by <strong>[624-76-0]2-iodoethanol</strong> (0.059 mL, 0.76 mmol, 2.0 equiv. ). After being stirred at 65C for 2 hours, cooled down to 23C, diluted with saturated NaHC03 aqueous and extracted with CH2CL2 (3X100 mL). The combined organic layers were washed (H2O, brine), dried (NA2SO4), filtered and evaporated to dry. The crude product was purified by chromatography on a silica gel column, eluting with a gradient increasing in polarity from 0 to 10% methanol in methylene chloride. Relevant fractions were combined to give the title compound. Yield 0.079 g (58%). MS (m/z): [M+H] + = 378. IH NMR (300 MHz, DMSO-d6) : 1.75 (s, 2H), 1.81 (s, 3H), 2.30 (s, 1H), 2.53 (m, 4H), 3.32 (m, 2H), 3.39 (t, J=5. 7 Hz, 2H), 3.47 (m, 2H), 3.68 (m, 1H), 4.07 (t, J=9. 0 Hz, 1H), 4.46 (bs, 1H), 4.72 (m, 1H), 7.00 (t, J=8. 7 HZ, 1H), 7.18 (m, 1H), 7.42 (dd, J=12. 9 Hz, 2.4 Hz, 1H), 8.23 (t, J=5. 4 Hz, 1H).

Reference： [1]Patent: WO2004/89943,2004,A1 .Location in patent: Page 127-128

26
[ 624-76-0 ]
[ 920-46-7 ]
[ 35531-61-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In dichloromethane; at 0 - 20℃; for 2.5h;Inert atmosphere;	A thermometer and a dropping funnel a 300mL three-necked flask and stirred into characters, a nitrogen atmosphere, de 23.0g (0.220 mol) and dichloromethane was added to 160mL was uniformly dissolved. This solution was cooled to 0 , which was further stirred by the addition of 30.4g of triethylamine (0.300 mol). Then, it was added dropwise to 2-iodide in ethanol 34.4g (0.200 mol) over 30 minutes, the temperature was raised to room temperature, the reaction solution was stirred for 2 hours. Thereafter, the reaction solution was poured into a saturated aqueous ammonium chloride solution to the 300mL The organic layer was separated, and the aqueous layer was extracted twice with 200mL of dichloromethane. The organic layers are combined, washed sequentially with a saturated aqueous solution of sodium hydrogen carbonate and then 500g, 500g saturated brine, and concentrated under reduced pressure. The resulting residue was dried under reduced pressure at 30 to the viscous matter five days 44.6g (0.186 mol, yield: 93%) was obtained. 1H-NMR spectrum (solvent: deuterated chloroform) by the measurement, the obtained compound was confirmed to be the compound represented by the formula (2-a).
	With triethylamine; In dichloromethane; at 0 - 20℃; for 2.5h;	(a) Synthesis of compound (m-2) Under a nitrogen atmosphere, a three-necked flask equipped with a stirrer chip and a dropping funnel was charged with 20.9 g (200 mmol) of the compound (m-1), which was dissolved in 160 ml of dichloromethane. The dichloromethane solution was cooled to 0C and 30.4 g (300 mmol) of triethylamine was added, followed by further stirring. After adding 37.8 g (220 mmol) of ethanol diiodide dropwise over 30 minutes, the reaction solution was heated to room temperature and stirred for two hours. After the reaction, the reaction solution was added to 300 ml of saturated ammonia chloride water and the dichloromethane layer was extracted using a separating funnel. The remaining water layer was extracted twice with 200 ml of dichloromethane. After removing the solvent from the collected dichloromethane layer, the residue was separated using column chromatography to obtain a compound (m-2).

Reference： [1]Patent: KR2016/14596,2016,A .Location in patent: Paragraph 0318-0320
[2]Patent: WO2006/121096,2006,A1 .Location in patent: Page/Page column 70-72
[3]Patent: EP1961739,2008,A1 .Location in patent: Page/Page column 22

27
[ 624-76-0 ]
[ 915023-65-3 ]
[ 915023-66-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; at 0 - 5℃; for 18h;	2-Methoxy-2-methylthiopropionic acid S-(2-hydroxyethyr) ester (9); To 2.5 g (19 mmol) 8 in 20 ml of dry toluene at ice bath temperature under Ar was added 2.2 ml (14.6 mmol) DBU dropwise with stirring. <strong>[624-76-0]Iodoethanol</strong> (1.2 ml, 14.6 mmol) in 5 ml dry toluene was added slowly to the rapidly stirred solution at O0C. The reaction mixture was then stirred for 18 hours at 5 0C. Reaction mixture was diluted with 200 ml of EtOAc and washed with 3 x 50 ml H2O. EtOAc layers were dried with Na2SO4, and solvent was removed in vacuo to give 4.7 g crude material. Silica gel chromatography with 20% EtOAc in hexanes provided 2.66 g, 79 % yield of (9). NMR 300 MHz, CDCl3, delta 3,75 (q, 2H, J=6 Hz), 3.33 (S, 3H), 3.06 (t, 2H, J=6 Hz), 2.02 (t, IH) and 1.39 (s, 6H) ppm.

Reference： [1]Patent: WO2006/122207,2006,A1 .Location in patent: Page/Page column 11

28
[ 624-76-0 ]
[ 1640-39-7 ]
[ 50839-66-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	In chloroform; at 70℃; for 48h;Inert atmosphere;	Take a 50mL bottle,Add 2 mL of 2,3,3-trimethylhydrazine (6.22 mmol),1.46 mL <strong>[624-76-0]2-iodoethanol</strong> (9.33 mmol),And adding 20mL of CHCl3 as a solvent, under nitrogen protection,The reaction was carried out at 70 C for 48 h, cooled to room temperature and concentrated.A purple oil was obtained which was recrystallized twice from petroleum ether to give a purple solid.The yield was 70%.
68%	In acetonitrile; for 1h;Reflux;	A solution of 2,3,3-trimethyl-3H-indole (6.37 g, 40 mmol), 2-iodine propanol (6.88 g, 40 mmol) and acetonitrile (20 mL) was refluxed for 15 h. After the reaction mixture cooled to room temperature, the ethyl ether wasaddedand the precipitate was filtered to give white solid. Yield, 68%.1HNMR(400Hz,DMSO-d6)delta: 7.30-8.95 (m, 4H), 4.24 (s, 1H), 4.22 (t, 2H), 2.81 (t, 2H), 1.86 (s, 3H), 1.44 (s, 6H);13C NMR (100 MHz, DMSO-d6)delta: 196.5, 148.1, 141.4, 128.3, 125.0, 120.1, 111.0, 59.7, 55.2, 43.0, 27.2, 27.2, 43.0.
	In acetonitrile; for 24h;Heating / reflux;	A solution of 2,3,3-trimethyl-3H-indole (1 ml, 6.3 mmol) and <strong>[624-76-0]2-iodoethanol</strong> (0.56 ml, 8.8 mmol) in MeCN (4 mL) was refluxed for 1 day. After being cooled to r.t., the reaction mixture was suspended in hexane, and the precipitated solid was sonicated and filtered. A part of the obtained purple solid (53 mg out of 1.37 g) was dissolved in 1N KOH (2 mL) and stirred at r.t. for 30 min. After extraction with ether, the organic layer was evaporated to afford 4 as yellow oil, which was used for the next reaction without further purification. A solution of 5-nitrososalicylaldehyde (38 mg, 0.23 mmol) and the obtained 4 in EtOH (5 mL) was refluxed for 4 hours. The mixture was evaporated and purified by column chromatography (silica gel; eluent, hexane:AcOEt=1:1) to afford purple crystal 5 (56 mg, 66% based on 2,3,3-trimethyl-3H-indole). MS(EI): 352(M+, 15), 337(5), 321(9), 83(100); HRMS(EI): M+352.1411 (calc.352.1423); 1H NMR(CDCl3) delta1.20 (s, 3H), 1.30 (s, 3H), 3.34 (ddd, J=5.1, 5.1, 14.7 Hz, 1H), 3.47 (ddd, J=5.5, 7.3, 14.7 Hz, 1H), 3.69-3.82 (m, 2H), 5.89 (d, J=10.5 Hz, 1H), 6.67 (d, J=7.5 Hz, 1H), 6.77 (d, J=8.5 Hz, 1H), 6.90 (dd, J=7.5, 7.5 Hz, 1H), 6.91 (d, J=10.5 Hz, 1H), 7.10 (dd, J=1.1, 7.5 Hz, 1H), 7.50 (ddd, J=1.1, 7.5, 7.5 Hz, 1H), 8.00 (d, J=2.5, 1H), 8.03 (dd, J=2.5, 8.5 Hz, 1H).

	In toluene; for 18h;Reflux;	1.5 equivalents of <strong>[624-76-0]2-iodoethanol</strong> was added to 2,3,3-trimethylindolenine and refluxed for 18 hours in toluene solvent to obtain intermediate 1. One equivalent of N, N'-diphenylformamidine and one equivalent of triethyl orthoformate was added to Intermediate 1 obtained, and refluxed in an ethanol solvent for 16 hours to obtain Intermediate 2.
	In acetonitrile; for 24h;Inert atmosphere; Reflux;	A solution of 2,3,3-trimethyl-3H-indole (12.56 mmol) and 2-iodoethyl alcohol (12.56 mmol) in acetonitrile (30 mL) was refluxed for 24 h under nitrogen protection. After cooling down to room temperature, the solvent was removed under reduced pressure. The residue was suspended in hexane (30 mL) and the mixture was filtered. The resulting solid was recrystallized from chloroform (40 mL) to afford 1-(2-hydroxyethyl-2,3,3-trimethyl- 3H-indolium iodine (7). A solution of 7 (4.89 mmol) and KOH (7.83 mmol) in water (15 mL) was stirred at 25 C for 20 min, and then was extracted with diethyl ether (3 _ 30 mL). The organic phase was concentrated under reduced pressure to afford 8. Yield, 67%; Melting point, 44.3-45.1 C; 1H NMR (CDCl3, 400 MHz) d 7.19-7.08 (m, 2H), 6.98-6.92 (m, 1H), 6.78 (d, 1H, J = 6.6 Hz), 3.90-3.49 (m, 4H), 1.47 (s, 3H), 1.42 (s, 3H), 1.21 (s, 3H); 13CNMR (CDCl3, 101 MHz) d 150.6, 140.0, 127.5, 122.4, 121.7, 112.0, 109.0, 63.0, 50.1, 47.0, 28.1, 20.8, 17.6.

Reference： [1]RSC Advances,2015,vol. 5,p. 97681 - 97689
[2]Chem,2018,p. 1928 - 1936
[3]Patent: CN108864155,2018,A .Location in patent: Paragraph 0047; 0048
[4]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 2398 - 2404
[5]Angewandte Chemie - International Edition,2011,vol. 50,p. 4103 - 4107
[6]Patent: US2007/195309,2007,A1 .Location in patent: Page/Page column 46; 47
[7]Molecular Crystals and Liquid Crystals,2011,vol. 548,p. 272 - 283
[8]Patent: KR2018/76149,2018,A .Location in patent: Paragraph 0272; 0273
[9]Tetrahedron Letters,2018,vol. 59,p. 3829 - 3832

29
[ 624-76-0 ]
[ 36953-37-4 ]
[ 889865-56-9 ]

Yield	Reaction Conditions	Operation in experiment
7%	With potassium carbonate; In tetrahydrofuran; at 80℃; for 48h;	Step b: 4-Bromo-l-(2-hydroxyethyl)pyridin-2(lH)-one; To a solution of 4-bromopyridin-2(lH)-one (174 mg, 1.00 mmol) in THF (3.5 mL) was added K2CO3 (1.38 g, 10.0 mmol) and 2-iodoethanol (156 muL, 2.00 mmol). The reaction was stirred at 80 0C for 2 days before being cooled to room temperature and filtered. The filtrate was concentrated and purified by column chromatography (0 - 10% MeOH - CH2Cl2) to yield 4-bromo-l-(2-hydroxyethyl)pyridin-2(lH)-one as a pale yellow solid (30 mg, 7%). ESI-MS m/z calc. 217.0, found 218.3 (M+l)+. Retention time 0.33 minutes. 1H NMR (400 MHz, DMSO-lambda5) delta 7.57 (d, J = 7.2 Hz, IH), 6.70 (d, J = 2.2 Hz, IH), 6.44 (dd, J = 2.2, 7.2 <n="99"/>Hz, IH), 4.89 (t, J = 5.4 Hz, IH), 3.91 (t, J = 5.4 Hz, 2H), 3.59 (q, J = 5.4 Hz, 2H).

Reference： [1]Patent: WO2008/141119,2008,A2 .Location in patent: Page/Page column 97-98

30
[ 624-76-0 ]
[ 39242-17-6 ]
1,1'-(2,6-pyridinediyl)bis[3-(2-hydroxyethyl)-1H-imidazol-3-ium] diiodide [ No CAS ]

Reference： [1]Dalton Transactions,2009,p. 340 - 352

31
[ 624-76-0 ]
[ 26892-90-0 ]
[ 53976-99-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 1948 - 1956

32
[ 624-76-0 ]
[ 66224-66-6 ]
[ 707-99-3 ]
[ 126595-74-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2812 - 2822

33
[ 624-76-0 ]
[ 99365-69-2 ]
2-(7-nitro-3,4-dihydroisoquinolin-2-(1H)-yl)ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With potassium carbonate; In acetonitrile;Reflux;	7-nitro-l,2,3,4-tetrahydroisoquinoline hydrochloride (500 mg, 2.33 mmol) and potassium carbonate (1610 mg, 1 1.65 mmol) in acetonitrile (155 mL) was added 2-iodoethanol (0.22 mL, 2.79 mmol). After heating at reflux overnight, the reaction was concentrated and the crude material partitioned between ethyl acetate and water. The aqueous layer was washed with ethyl acetate (3x) and the organics were combined, dried over magnesium sulfate, filtered, and concentrated. The crude residue was purified by silica gel <n="132"/>chromatography (0-15percent methanol in dichloromethane) to give the title compound as a brown oil (159 mg, 0.72 mmol, 31percent yield); MS (ESI) MS (ESI) m/z 223.4 [M+l]+

Reference： [1]Patent: WO2009/89042,2009,A1 .Location in patent: Page/Page column 130-131

34
[ 624-76-0 ]
[ 3484-22-8 ]
[ 1146961-58-1 ]

Reference： [1]Chemistry - A European Journal,2009,vol. 15,p. 2560 - 2571

35
[ 624-76-0 ]
[ 315702-99-9 ]
[ 1187669-21-1 ]

Yield	Reaction Conditions	Operation in experiment
19%		Example 1-60 2-{3-Methyl[4-(4-pyridinyl)-l,3-thiazol-2-yl]anilino}ethanol (97). [0313] 2-{3-Methyl[4-(4-pyridinyl)-l,3-thiazol-2-yl]anilino}ethanol (97). NaH(107 mg, 2.7 mmol) was added to a stirred solution of amine 5 (649 mg, 2.4 mmol) in DMF (10 mL) and the mixture stirred at 20 0C for 2 min. Iodoethanol (0.19 mL, <n="134"/>2.4 mmol) was added dropwise and the mixture stirred at 20 0C for 48 h. The reaction was quenched with saturated aqueous NH4Cl solution (10 rnL) and the mixture extracted with EtOAc (3 x 15 mL). The combined organic fraction was dried and the solvent evaporated. The crude solid was purified by column chromatography, eluting with a gradient (50-100percent) of EtO Ac/pet, ether, to give (i) starting material 5 (0.22 g, 34percent) and (ii) amine 97 (0.15 g, 19percent) as a white powder: mp (EtOAc/pet. ether) 149-151 0C; 1H NMR delta 8.58 (dd, J= 4.5, 1.6 Hz, 2 H, H-2"', H-6"'), 7.78 (dd, J= 4.5, 1.6 Hz, 2 H, H-3"', H-5"'), 7.47 (s, 1 H, H-5"), 7.30-7.40 (m, 3 H, H-2', H-4', H-5'), 7.34 (br dd, J= 7.4 Hz, 1 H, H-6'), 4.80 (t, J = 5.5 Hz, 1 H, OH), 4.03 (t, J= 6.2 Hz, 2 H, H-2), 3.71 (dt, J= 6.2, 5.5 Hz, 2 H, H-I), 2.35 (s, 3 H, CH3); 13C NMR delta 169.4, 149.9 (2), 147.7, 144.8, 141.1, 139.4, 129.6, 127.9, 127.0, 123.6, 119.8 (2), 106.6, 57.7, 54.9, 20.8; MS m/z 312.6 (MH+, 100percent). Anal, calcd for Ci7Hi7N3OS: C, 65.57; H, 5.50; N, 13.49. Found: C, 65.87; H, 5.43; N, 13.65percent.

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 787 - 797
[2]Patent: WO2009/114552,2009,A1 .Location in patent: Page/Page column 132-133

36
[ 624-76-0 ]
[ 514196-22-6 ]
[ 1221413-85-9 ]

Yield	Reaction Conditions	Operation in experiment
79%		Example 58Preparation of Derivative 58 According to the Present InventionDerivative 58 having the following formula was prepared as follows. Sodium hydride (24.14 mg, 1.0 mmol, 60% dispersed oil) was added in 20 ml of DMF solution containing 5-4-(2-cyclohexylethoxy)benzylidene)thiazolidin-2,4-dione (200 mg, 0.60 mmol) and stirred at room temperature under nitrogen. The mixture was further stirred for 10 minutes, and <strong>[624-76-0]2-iodoethanol</strong> (123.81 mg, 0.72 mmol) dissolved in 5 ml of DMF was slowly added thereto. After being stirred at 60 C. for 48 hours, the reaction mixture was extracted with ethyl acetate and washed with water. The organic layer was dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residue was purified by silica gel chromatography (hexane:ethyl acetate=10:1) to afford Derivative 58 having the above formula, 5-[(4-(2-cyclohexylethoxy)benzylidene]-3-(hydroxyethyl)-1,3-thiazolidine-2,4-dione (180 mg, yield: 79%).1H NMR (300 MHz, CDCl3) delta 7.878 (s, 1H), 7.485 (d, J=14.4 Hz, 2H), 7.007 (d, J=14.4 Hz, 2H), 4.078 (t, J=13.2 Hz, 2H), 4.001 (t, J=10.2 Hz, 2H), 3.891 (t, J=10.2 Hz, 2H), 2.049 (m, 1H), 1.670-1.782 (m, 7H), 1.471-1.529 (m, 1H), 1.178-1.284 (m, 3H), 0.956-1.034 (m, 2H)

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 1428 - 1433
[2]Patent: US2011/269954,2011,A1 .Location in patent: Page/Page column 22-23

37
[ 624-76-0 ]
[ 83-67-0 ]
[ 1507-14-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydride; In N,N-dimethyl-formamide; for 4h;	taking theobromine 540mg (3mmoL), NaH 720mg (30mmol) dissolved in 80mL DMF, adding 2mmol of <strong>[624-76-0]2-iodoethanol</strong> under the drop, after 4 hours of reaction, quenching the reaction with water, spin dry, oil Ether: CH3CH2OCOCH3 = 3:1 (v/v) as a mobile phase over silica gel to give compound 1-ethylhydroxy-3-7-dimethylxanthine, yield 94%.

Reference： [1]Patent: CN109912598,2019,A .Location in patent: Paragraph 0054-0055; 0058-0059; 0062-0063
[2]Dalton Transactions,2009,p. 7308 - 7313
[3]Dalton Transactions,2015,vol. 44,p. 7563 - 7569

38
[ 120-72-9 ]
[ 624-76-0 ]
[ 121459-15-2 ]

Reference： [1]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 27 - 30

39
[ 624-76-0 ]
2-(difluoromethyl)-4-hydroxy-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole [ No CAS ]
[ 1246547-81-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A mixture of 85 mg (0.0196 mmol) of 2-(difluoromethyl)-l-[4,6-di(4- mophiholinyl)-l,3,5-triazin-2-yl]-ltf-benzimidazol-4-ol (WO 2004/037812), 37 mg (0.22 mmol) of <strong>[624-76-0]2-iodoethanol</strong>, and 83 mg (0.6 mmol) of powdered K2CO3 in 10 mL of DMF was stirred at room temperature overnight, and then diluted with water. The product was collected by filtration, dried, and purified by chromatography on silica eluting with EtOAc to give 47 mg (50% yield) of 2-({2-(difluoromethyl)-l-[4,6-di(4-morpholinyl)-l ,3,5-triazin-2- yl]-l//-benzimidazol-4-yl}oxy)ethanol: mp (EtOAc) 243-246 0C; 1H NMR (DMSO-d6) delta 7.89 (d, J = 8.1 Hz, IH), 7.70 (t, 7HF = 52.8 Hz, IH), 7.38 (t, J = 8.2 Hz, IH), 6.95 (d, 7 = 7.9 Hz, IH), 4.93 (t, J = 5.5 Hz, exchangeable with D2O, IH), 4.24 (t, J = 5.0 Hz, 2 ), 3.84- 3.79 (m, 10H), 3.69 (m, 8H); Anal. Calcd. for C2IH25F2N7O4: C, 52.83; H, 5.28; N, 20.53; Found: C, 52.86; H, 5.22; N, 20.5%.
50%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A mixture of 2 (85mg, 0.0196mmol), <strong>[624-76-0]2-iodoethanol</strong> (37mg, 0.22mmol), and powdered K2CO3 (83mg, 0.6mmol) in 10mL of DMF was stirred at room temperature overnight, and then diluted with water. The product was collected by filtration, dried, and purified by chromatography on silica eluting with EtOAc to give 7 (47mg, 50% yield): mp (EtOAc) 243-246C; 1H NMR (DMSO-d6) delta 7.89 (d, J=8.1Hz, 1H), 7.70 (t, JHF=52.8Hz, 1H), 7.38 (t, J=8.2Hz, 1H), 6.95 (d, J=7.9Hz, 1H), 4.93 (t, J=5.5Hz, exchangeable with D2O, 1H), 4.24 (t, J=5.0Hz, 2H), 3.84-3.79 (m, 10H), 3.69 (m, 8H); 13C NMR (DMSO-d6) delta 164.4 (C), 161.4 (C), 151.1 (C), 144.2 (t, JCF=26.7Hz, C-2), 134.5 (C), 131.6 (C), 126.8 (CH), 108.6 (t, JCF=237.4Hz, CHF2), 108.0 (C), 106.5 (C), 70.4 (CH2), 68.9 (CH2), 59.6 (CH2), 43.6 (CH2). Anal. Calcd for C21H25F2N7O4: C, 52.8; H, 5.3; N, 20.5. Found: C, 52.9; H, 5.2; N, 20.5%.

Reference： [1]Patent: WO2010/110686,2010,A1 .Location in patent: Page/Page column 55
[2]European Journal of Medicinal Chemistry,2013,vol. 64,p. 137 - 147

40
[ 624-76-0 ]
[ 858839-90-4 ]
[ 1193334-72-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2.0h;	To the mixture of <strong>[858839-90-4]4-iodopyridin-2(1H)-one</strong> (50 mg, 0.213 mmol) in DMF (3 mL) was added 2-iodoethanol (73 mg, 0.426 mmol), K2CO3 (88 mg, 0.638 mmol) at rt. The mixture was stirred for 2 h at rt. After the reaction was finished, the mixture was washed with water and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated to give the crude product, which was purified by TLC to provide 1-(2-hydroxyethyl)-<strong>[858839-90-4]4-iodopyridin-2(1H)-one</strong> (60 mg 100%).

Reference： [1]Patent: US2010/331320,2010,A1 .Location in patent: Page/Page column 48; 49

41
[ 624-76-0 ]
[ 1258440-18-4 ]
[ 1258852-45-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;	A solution of 2-[(1-methylethyl)oxy]-5-[5-(1 ,2,3,4-tetrahydro-5-isoquinolinyl)-1 ,3,4- thiadiazol-2-yl]benzonitrile hydrochloride (Preparation 56) (50mg, 0.12 mmol) and potassium carbonate (50mg, 0.36 mmol) in DMF (1 ml) was treated with 2- iodoethanol (0.014ml, 0.18 mmol) and the mixture stirred at 8O0C for 2h. The mixture was diluted with water (10ml) and extracted with ethyl acetate (3x 10ml). The combined organic phases were dried (Na2SO4) and concentrated in vacuo. Purification of the residue by flash chromatography (cyclohexane/methanol: 0 to 5% gradient) gave 5-{5-[2-(2-hydroxyethyl)-1 ,2,3,4-tetrahydro-5-isoquinolinyl]-1 ,3,4- thiadiazol-2-yl}-2-[(1-methylethyl)oxy]benzonitrile (36mg, 71%) as a clear oil. LCMS (Method formate): Retention time 0.85min, MH+ = 421

Reference： [1]Patent: WO2010/146105,2010,A1 .Location in patent: Page/Page column 231

42
[ 624-76-0 ]
[ 95-53-4 ]
[ 136-80-1 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 3710 - 3713

43
[ 624-76-0 ]
[ 768-94-5 ]
[ 3716-66-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	In benzonitrile; at 120℃; for 12h;	Example XII 2-(adamantan-1-ylamino)ethanol 1-Adamantylamine (1 g, 6.05 mmol) and <strong>[624-76-0]2-iodoethanol</strong> (1.20 g, 7.00 mmol) were dissolved in benzonitrile (2 ml). The mixture was heated at 120 C. for 12 h. After this, the precipitate was filtered off and carefully washed with petrolether (320 ml). The white solid was dissolved in DCM (30 ml) and washed with a saturated solution of Na2CO3 (350 ml). The organic layer was separated, dried with Na2SO4 and the solvent was removed under reduced pressure to yield the title compound as colourless oil (950 mg, 4.86 mmol, 80%). 1H NMR (250 MHz, CD2Cl2): delta=1.55 (m, 12H, -CH2-), 1.99 (bs, 5H, -CH- and over-lapping OH, NH), 2.65 (t, 2H, J=5 Hz, -CH2-), 3.44 (t, 2H, J=5.1 Hz, -CH2-); all spectroscopic data are in good agreement with previously reported ones, e.g. P. E. Aldrich, E. C. Herrmann, W. E. Meier, M. Paulshock, W. W. Prichard, J. A. Snyder, J. C. Watts, J. Med. Chem. 1971, 14, 535-543.
80%	In benzonitrile; at 120℃; for 12h;	Example XII 2-(adamantan-1-ylamino)ethanol 1-Adamantylamine (1 g, 6.05 mmol) and <strong>[624-76-0]2-iodoethanol</strong> (1.20 g, 7.00 mmol) were dissolved in benzonitrile (2 ml). The mixture was heated at 120 C. for 12 h. After this, the precipitate was filtered off and carefully washed with petrolether (320 ml). The white solid was dissolved in DCM (30 ml) and washed with a saturated solution of Na2CO3 (350 ml). The organic layer was separated, dried with Na2SO4 and the solvent was removed under reduced pressure to yield the title compound as colourless oil (950 mg, 4.86 mmol, 80%). 1H NMR (250 MHz, CD2Cl2): delta=1.55 (m, 12H, -CH2-), 1.99 (bs, 5H, -CH- and over-lapping OH, NH), 2.65 (t, 2H, J=5 Hz, -CH2-), 3.44 (t, 2H, J=5.1 Hz, -CH2-); all spectroscopic data are in good agreement with previously reported ones, e.g. P. E. Aldrich, E. C. Herrmann, W. E. Meier, M. Paulshock, W. W. Prichard, J. A. Snyder, J. C. Watts, J. Med. Chem. 1971, 14, 535-543.

Reference： [1]Advanced Synthesis and Catalysis,2010,vol. 352,p. 3001 - 3012
[2]Patent: US2012/108819,2012,A1 .Location in patent: Page/Page column 26-27
[3]Patent: WO2012/56419,2012,A1 .Location in patent: Page/Page column 67

44
[ 624-76-0 ]
[ 1218760-13-4 ]
[ 1218760-86-1 ]

Yield	Reaction Conditions	Operation in experiment
83%		Example 124 1-[3,5-bis(trifluoromethyl)phenyl]-3-[(3R,4R)-3-(4-fluorophenyl)-1-(2-hydroxyethyl)piperidin-4-yl]-1,3-dimethylurea monohydrochloride To a solution of the compound (0.18 g) obtained in Example 51 and <strong>[624-76-0]2-iodoethanol</strong> (0.055 mL) in DMF (6.0 mL) was added N,N-diisopropylethylamine (0.184 mL) at room temperature, and the mixture was heated to 40C and stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 0?100% ethyl acetate/hexane) and treated with 2N hydrogen chloride/2-propanol to give the title compound (0.16 g, 83%) as a white powder. MS(ESI+): 522 (M-HCl+H)

Reference： [1]Patent: EP2336105,2011,A1 .Location in patent: Page/Page column 127

45
[ 624-76-0 ]
[ 1163271-39-3 ]
[ 1187543-15-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃;	Example 31 2-Amino-6-([2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]pyridine-3,5-dicarbonitrile 100 mg (0.18 mmol) of the compound from Example 5 were dissolved in 1.5 ml of DMF, 90 mg (0.28 mmol) of cesium carbonate and 158 mg (0.92 mmol) of iodoethanol were added and the mixture was stirred at 80 C. overnight. Another 90 mg (0.28 mmol) of cesium carbonate were then added, and the reaction mixture was stirred at 80 C. for another 4 h. A little water and THF were added to the reaction such that a clear solution was formed, and the product was purified by preparative HPLC (acetonitrile/water 10:90?95:5, 0.1% TFA added). Yield: 41 mg (40% of theory) 1H-NMR (400 MHz, DMSO-d6): delta=8.05 (br s, 2H), 7.96-7.88 (m, 4H), 7.57 (d, 2H), 6.77 (d, 1H), 4.62 (s, 2H), 4.23 (t, 2H), 3.78 (t, 2H). LC-MS (Method 1): Rt=2.05 min; MS (ESIpos): m/z=494 [M+H]+.

Reference： [1]Patent: US2011/207698,2011,A1 .Location in patent: Page/Page column 39
[2]ChemMedChem,2017,vol. 12,p. 728 - 737

46
[ 6086-21-1 ]
[ 624-76-0 ]
[ 1335280-64-2 ]

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 10453 - 10461

47
[ 624-76-0 ]
[ 34334-96-8 ]
[ 1006950-51-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; for 18h;Reflux;	A solution of 5-methyl-3-nitro-lH-pyrazole (500 mg, 3.93 mmol) and potassium carbonate (1.08 g, 7.81 mmol) in acetonitrile (20 mL) was treated dropwise with 2- iodoethanol (2.00 g, 1 1.6 mmol) and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted with ethyl acetate (100 mL) and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, heptane to 1 : 1 ethyl acetate/heptane) to afford 2-(5-methyl-3-nitro-lH-pyrazol-l-yl)ethanol as a white solid: NMR (400 MHz, DMSO-i¾d 6.82 (s, 1H), 4.97 (t, J = 5.2 Hz, 1H), 4.19 (t, J = 5.2 Hz, 2H), 3.75 (q, J= 5.2 Hz, 2H), 2.35 (s, 3H).
	With potassium carbonate; In acetonitrile; for 18h;Reflux;	Example 7 Preparation of 2-(5-methyl-3-nitro-1H-pyrazol-1-yl)ethanol A solution of <strong>[34334-96-8]5-methyl-3-nitro-1H-pyrazole</strong> (500 mg, 3.93 mmol) and potassium carbonate (1.08 g, 7.81 mmol) in acetonitrile (20 mL) was treated dropwise with 2-iodoethanol (2.00 g, 11.6 mmol) and the reaction stirred at reflux for 18 h. After this time, the reaction was cooled to room temperature, diluted with ethyl acetate (100 mL) and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the resulting residue purified by chromatography (silica, gradient, heptane to 1:1 ethyl acetate/heptane) to afford 2-(5-methyl-3-nitro-1H-pyrazol-1-yl)ethanol as a white solid: 1H NMR (400 MHz, DMSO-d6.) d 6.82 (s, 1H), 4.97 (t, J=5.2 Hz, 1H), 4.19 (t, J=5.2 Hz, 2H), 3.75 (q, J=5.2 Hz, 2H), 2.35 (s, 3H).

Reference： [1]Patent: WO2011/112995,2011,A1 .Location in patent: Page/Page column 56
[2]Patent: US2014/148430,2014,A1 .Location in patent: Paragraph 0342

48
[ 624-76-0 ]
[ 51814-19-8 ]
[ 1339961-03-3 ]

Reference： [1]Tetrahedron,2011,vol. 67,p. 8264 - 8270

49
[ 624-76-0 ]
[ 41532-84-7 ]
[ 1360817-85-1 ]

Yield	Reaction Conditions	Operation in experiment
33%	In toluene; for 2h;Inert atmosphere; Reflux;	To a 50 mL three-necked flask, 1,1,2-Trimethyl-1H-benzo[e]indole (2.0 g, 9.556 mmol) and 10 mL of anhydrous toluene were added, and heated to 80 C. under a nitrogen atmosphere. After the 1, 1,2-Trimethyl-1H-benzo[e]indole was completely dissolved in the toluene, 2-<strong>[624-76-0]Iodoethanol</strong> (1.64 g, 9.556 mmol) was added. After heating to reflux was performed for 2 hours, cooling to room temperature was performed and precipitated pale blue crystals were collected by filtration. The crystals were washed with toluene, and dried in a desiccator to obtain a compound 4 (Scheme 4). A yield of 33% (1.21 g) was achieved.

Reference： [1]Journal of Fluorescence,2012,vol. 22,p. 719 - 727
[2]Patent: US2013/149252,2013,A1 .Location in patent: Paragraph 0138
[3]Patent: EP2682131,2014,A1 .Location in patent: Paragraph 0145-0146
[4]Patent: US2013/336896,2013,A1 .Location in patent: Paragraph 0160
[5]Patent: US9370589,2016,B2 .Location in patent: Page/Page column 26

50
[ 624-76-0 ]
[ 2432-18-0 ]
[ 1421009-21-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate; In N,N-dimethyl-formamide; at 0 - 80℃; for 9.5h;	2-<strong>[624-76-0]Iodoethanol</strong> (467 muL, 6.00 mmol) was added to a solution of 2 (1.08 g, 3.00 mmol) and Cs2CO3 (3.04 g, 9.33 mmol) in DMF (10 mL) at 0 C. The reaction mixture was stirred for 9.5 h at 80 C, then the reaction was quenched with H2O, and the mixture was extracted with AcOEt. The organic layer was washed with H2O, dried over MgSO4, and concentrated. The resulting residue was purified by silica gel chromatography (hexane/AcOEt = 3/1) to give 3 (1.02 g, 2.51 mmol, 84%) as a white solid.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 608 - 617

51
[ 288-32-4 ]
[ 624-76-0 ]
[ 18162-48-6 ]
[ 101166-65-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	In dichloromethane;	(i) Preparation of (2-iodoethoxy)-tert-butyldimethylsilane To a stirred solution of 2-iodoethanol (17.2 g; 100 mmol) and imidazole (8.17 g; 120 mmol) in dichloromethane (100 mL) was added tert-butyldimethylsilyl chloride (15.83 g; 105 mmol) at such a rate that the reaction temperature did not rise above 30° C. Upon complete addition the solution was left stirring for 17 h, then washed with water (2*50 mL) and brine (50 mL) and dried over MgSO4. Evaporation of the solvent afforded the target compound (28.0 g; 97.8 mmol; 98percent) as a colourless liquid. 1H-NMR (400 MHz) (CDCl3): delta=3.83 (t, 2H, J=7.0 Hz), 3.83 (t, 2H, J=7.0 Hz), 3.20 (t, 2H, J=7 Hz), 0.90 (s, 9H), 0.08 (s, 6H) ppm.

Reference： [1]Patent: US2013/59926,2013,A1 .Location in patent: Page/Page column

52
[ 624-76-0 ]
[ 768-52-5 ]
[ 25012-16-2 ]

Yield	Reaction Conditions	Operation in experiment
59%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 30℃; for 48h;	Compound 4a (617mg, 4.6mmol) was reacted with 2-Iodoethanol (0.54mls, 6.9mmol) and diisopropylethylamine (1.2mls, 6.9mmol) in ACN (20mls) at 30oC for 48 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane and EtOAc to provide the compound (483mg, 2.7mmol, 59% yield) as a light brown oil. HRMS (ESI, positive) m/z calcd. for C11H18N1O1 [M+H]+: 180.13829, found: 180.13829. 1H NMR (400 MHz, CDCl3) delta 7.28 - 7.19 (t, J = 8.0 Hz, 2H), 6.92 - 6.85 (d, J = 8.2 Hz, 2H), 6.83 - 6.75 (t, J = 7.3 Hz, 1H), 4.03 - 3.88 (hept, J = 6.6 Hz, 1H), 3.70 - 3.62 (t, J = 6.2 Hz, 2H), 3.34 - 3.24 (m, 2H), 1.19 - 1.12 (d, J = 6.6 Hz, 6H).
59%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 30℃; for 48h;	Compound 4a (617 mg, 4.6 mmol) was reacted with 2-Iodoethanol (0.54 mls, 6.9 mmol) and diisopropylethylamine (1.2 mls, 6.9 mmol) in ACN (20 mls) at 30 C. for 48 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane and EtOAc to provide the intermediate 4b (483 mg, 2.7 mmol, 59% yield) as a light brown oil. HRMS (ESI, positive) m/z calcd. for C11H18N1O1 [M+H]+: 180.13829, found: 180.13829. 1H NMR (400 MHz, CDCl3) delta 7.28-7.19 (t, J=8.0 Hz, 2H), 6.92-6.85 (d, J=8.2 Hz, 2H), 6.83-6.75 (t, J=7.3 Hz, 1H), 4.03-3.88 (hept, J=6.6 Hz, 1H), 3.70-3.62 (t, J=6.2 Hz, 2H), 3.34-3.24 (m, 2H), 1.19-1.12 (d, J=6.6 Hz, 6H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2951 - 2954
[2]Patent: US2013/230542,2013,A1 .Location in patent: Paragraph 0128
[3]Advanced Synthesis and Catalysis,2017,vol. 359,p. 3654 - 3664

53
[ 107-21-1 ]
[ 64-19-7 ]
[ 624-76-0 ]
[ 627-10-1 ]
[ 542-59-6 ]
[ 111-55-7 ]

Yield	Reaction Conditions	Operation in experiment
	With deuterium iodide In water at 20℃; for 25h; Autoclave;

Reference： [1]Coskun, Timur; Conifer, Christopher M.; Stevenson, Laura C.; Britovsek, George J. P. [Chemistry - A European Journal, 2013, vol. 19, # 21, p. 6840 - 6844]

54
[ 624-76-0 ]
[ 54396-44-0 ]
C₁₀H₁₂F₃NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	at 90℃; for 6h;Inert atmosphere;	a) Preparation of intermediate 52 A mixture of 2-iodoethanol (0.296 mL, 3.8 mmol) and 2-methyl-3-trifluoromethyl- aniline (1 g, 5.7 mmol) was heated at 90 °C under N2 atmosphere for 6 h.The resulting solid was dissolved in EtOAc and washed with 2M aq. NaOH solution. The organic layer was dried, filtered and concentrated to dryness. The crude product was purified by flash column chromatography (silica; EtOAc/hexane 0/100 to 50/50). The desired fractions were collected and concentrated in vacuo to yield intermediate 52 as an oil (0.711 g, 85percent).

Reference： [1]Patent: WO2013/171712,2013,A1 .Location in patent: Page/Page column 96

55
[ 624-76-0 ]
[ 108-24-7 ]
[ 627-10-1 ]

Yield	Reaction Conditions	Operation in experiment
57.8%	With pyridine; dmap; In dichloromethane; at 20℃; for 3h;	Production Example 235-1 Synthesis of 2-iodoethyl acetate 2-<strong>[624-76-0]Iodoethanol</strong> (1.541 g, 8.96 mmol) was dissolved in dichloromethane (30 ml). To the solution, pyridine (1.54 ml, 17.92 mmol), N,N-dimethyl-4-aminopyridine (109 mg, 0.896 mmol), and acetic anhydride (2.54 ml, 26.88 mmol) were added, and the mixture was stirred at room temperature for 3 hours. After reaction, the organic layer was washed with 0.1M hydrochloric acid and a saturated aqueous solution of sodium bicarbonate. The organic layer was dried over magnesium sulfate, and the solvent was distilled off to obtain the title compound (1.108 g, yield: 57.8%) as a yellow oil. 1H-NMR (400 MHz, DMSO-d6) delta: 2.10 (3H, s), 3.30 (2H, t, J=6.8 Hz), 4.33 (2H, t, J=6.8 Hz).

Reference： [1]Patent: US2014/343017,2014,A1 .Location in patent: Paragraph 1401; 1402; 1403
[2]Inorganic Chemistry,2014,vol. 53,p. 4881 - 4890

56
[ 624-76-0 ]
[ 67630-01-7 ]
[ 189744-27-2 ]

Yield	Reaction Conditions	Operation in experiment
1.8 kg	With sodium carbonate; In acetonitrile; at 23 - 85℃; for 2h;Large scale;	EXAMPLE 1 Preparation of 4-(bis-(2-hydroxyethyl)-amino-N-BOC-L-phenylalanine ethyl ester Into a suitable reactor A, 2.0 kg of N-BOC-L-phenylalanine ethyl ester and acetonitrile were loaded. The suspension was let under stirring until complete dissolution, maintaining the temperature at 23C and 1 .5 kg of sodium carbonate were then added. Subsequently, 3.2 L of 2-iodoethanol were added dropwise, the solution was heated up to 85C and these conditions were maintained for 2 hours. At the end of the reaction the mixture was quickly cooled down to 20C. In another suitable reactor B, 35L of water and 4 kg of Celite were loaded and the mixture was left under stirring for at least 5 minutes. The compound obtained into reactor A was transferred into reactor B and the suspension was kept under stirring for an hour. The suspension was filtered and washed with 12L of water. The wet Celite obtained into the reactor B and 140 L of ethyl acetate were loaded into a reactor C and the mixture was kept under stirring for 30 minutes then filtered by collecting the filtrate into a reactor D and letting the phases separate. The organic phase was distilled at reduced pressure. The residue was purified by chromatography using methylene chloride/ethyl acetate about 2:1 . About 1 .8 kg of 4-(bis-(2-hydroxyethyl)-amino-N-BOC-L-phenilalanine ethyl ester were then obtained.

Reference： [1]Patent: WO2014/191426,2014,A1 .Location in patent: Page/Page column 10

57
[ 624-76-0 ]
[ 609-23-4 ]
[ 828-92-2 ]

Yield	Reaction Conditions	Operation in experiment
5.9 g	Stage #1: 2,4,6-Triiodophenol With sodium hydroxide In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: Iodoethanol In ethanol at 25℃; for 27.25h; Reflux; Inert atmosphere;	2.a Synthesis of 2-(2,4, 6-triiodophenoxy)ethanolfrom 2,4, 6-triiodophenol In a 500m1 three-necked flat-bottomed flask fitted with a thermometer, anitrogen bubbler and an overhead stirrer, lOg of phenol were dissolved in 1 OOml ofethanol, under a nitrogen blanket and vigorous stirring conditions at room temperature. 1.25 molar equivalent of sodium hydroxide pellets were added and the slurry was stirred under a nitrogen blanket for 30 minutes until complete dissolution of the pellets. Then, 1.1 molar equivalents of 2-iodoethanol were added, maintainingthe temperature at 25°C and stirring for 15 minutes. The solution was heated to reflux of ethanol. The consumption of the phenol and formation of 2-(2,4,6- triiodophenoxy)ethanol were monitored by HPLC (conditions as per Example 1). After 25 hours, an additional 0.27 molar equivalents of 2-iodoethanol was added and the solution was stirred for a further 2 hours at reflux. After cooling the solution to room temperature, 1 50m1 of deionised water were added quickly under vigorous stirring conditions. The resulting slurry was filtered under vacuum, washed with the mother liquors, three times 30m1 of deionised water and finally with 5ml of ethanol. The resulting pink cake was taken up into 1 OOml of ethyl acetate and the organiclayer extracted with copious amounts of a sodium hydroxide solution (pH 14), dried over magnesium sulphate and concentrated on a rotary evaporator to yield 5.9g of an off-pink solid, which was identified as 2-(2,4,6-triiodophenoxy)ethanol by comparative analysis with a commercial analytical standard from sigma-aldrich.
5.9 g	Stage #1: 2,4,6-Triiodophenol With sodium hydroxide In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: Iodoethanol In ethanol at 25℃; for 0.25h; Inert atmosphere;	2.a Synthesis of 2-(2,4,6-triiodophenoxy)ethanol from 2,4,6-triiodophenol In a 500ml three-necked flat-bottomed flask fitted with a thermometer, a nitrogen bubbler and an overhead stirrer, lOg of phenol were dissolved in 100ml of ethanol, under a nitrogen blanket and vigorous stirring conditions at room temperature. 1.25 molar equivalent of sodium hydroxide pellets were added and the slurry was stirred under a nitrogen blanket for 30 minutes until complete dissolution of the pellets. Then, 1.1 molar equivalents of 2-iodoethanol were added, maintaining the temperature at 25°G and stirring for 15 minutes. The solution was heated to reflux of ethanol. The consumption of the phenol and formation of 2-(2,4,6- triiodophenoxy)ethanol were monitored by HPLC (conditions as per Example 1). After 25 hours, an additional 0.27 molar equivalents of 2-iodoethanol was added and the solution was stirred for a further 2 hours at reflux. After cooling the solution to room temperature, 150ml of deionised water were added quickly under vigorous stirring conditions. The resulting slurry was filtered under vacuum, washed with the mother liquors, three times 30ml of deionised water and finally with 5ml of ethanol. The resulting pink cake was taken up into 100ml of ethyl acetate and the organic layer extracted with copious amounts of a sodium hydroxide solution (pH14), dried over magnesium sulphate and concentrated on a rotary evaporator to yield 5.9g of ah off-pink solid, which was identified as 2-(2J4,6-trii0d0phenoxy)ethan0l by comparative analysis with a commercial analytical standard from sigma-aldrich.
5.9 g	Stage #1: 2,4,6-Triiodophenol With sodium hydroxide In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: Iodoethanol In ethanol for 27h; Reflux; Inert atmosphere;	2.a Synthesis of 2-(2,4,6-triiodophenoxy)ethanol from 2,4,6-triiodophenol In a 500 ml three-necked flat-bottomed flask fitted with a thermometer, a nitrogen bubbler and an overhead stirrer, 10 g of phenol were dissolved in 100 ml of ethanol, under a nitrogen blanket and vigorous stirring conditions at room temperature. 1.25 molar equivalent of sodium hydroxide pellets were added and the slurry was stirred under a nitrogen blanket for 30 minutes until complete dissolution of the pellets. Then, 1.1 molar equivalents of 2-iodoethanol were added, maintaining the temperature at 25° C. and stirring for 15 minutes. The solution was heated to reflux of ethanol. The consumption of the phenol and formation of 2-(2,4,6-triiodophenoxy)ethanol were monitored by HPLC (conditions as per Example 1). After 25 hours, an additional 0.27 molar equivalents of 2-iodoethanol was added and the solution was stirred for a further 2 hours at reflux. After cooling the solution to room temperature, 150 ml of deionised water were added quickly under vigorous stirring conditions. The resulting slurry was filtered under vacuum, washed with the mother liquors, three times 30 ml of deionised water and finally with 5 ml of ethanol. The resulting pink cake was taken up into 100 ml of ethyl acetate and the organic layer extracted with copious amounts of a sodium hydroxide solution (pH 14), dried over magnesium sulphate and concentrated on a rotary evaporator to yield 5.9 g of an off-pink solid, which was identified as 2-(2,4,6-triiodophenoxy)ethanol by comparative analysis with a commercial analytical standard from sigma-aldrich.

Reference： [1]Current Patent Assignee: BOSTON SCIENTIFIC CORP - WO2015/33093, 2015, A1 Location in patent: Page/Page column 22
[2]Current Patent Assignee: BOSTON SCIENTIFIC CORP - WO2015/33092, 2015, A1 Location in patent: Page/Page column 20; 21
[3]Current Patent Assignee: BOSTON SCIENTIFIC CORP - US2015/110722, 2015, A1 Location in patent: Paragraph 0110; 0111

58
[ 624-76-0 ]
[ 25981-83-3 ]
1-(2-hydroxyethyl)-5-chloro-2,3,3-trimethylindoleninium iodide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 3949 - 3956

59
[ 624-76-0 ]
[ 2295-31-0 ]
3-(2-hydroxyethyl)thiazolidine-2,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In [(2)H6]acetone; at 40℃; for 10h;	Thiazolidinedione (12.8 mmol), <strong>[624-76-0]2-iodoethanol</strong> (15.1 mmol), potassium carbonate (17.4 mmol) and tetrabutylammonium iodide (1.3 mmol) were placed in acetone (25 ml), and stirred at 40C for 10 hours. The reaction mixture was cooled to room temperature, filtered through Celite, and concentrated under reduced pressure to yield brown oil. The residue thus obtained was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1, v/v) to obtain the title compound as colorless oil (yield: 54%). 1H NMR (CDCl3, 400 MHz) delta 4.00(s, 2H), 3.85(brs, 4H), 1.94(brs, 1H)
54%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In acetone; at 40℃; for 10h;	Example 396 (Z)-3-(2-Hydroxyethyl)-5-[{7-(4-methoxyphenyl)furo[3,2-c]pyridin-2-yl}methylene]thiazolidine-2,4-dione Step 1: Synthesis of 3-(2-hydroxyethyl)thiazolidine-2,4-dione Thiazolidinedione (12.8 mmol), <strong>[624-76-0]2-iodoethanol</strong> (15.1 mmol), potassium carbonate (17.4 mmol) and tetrabutylammonium iodide (1.3 mmol) were placed in acetone (25 ml), and stirred at 40 C. for 10 hours. The reaction mixture was cooled to room temperature, filtered through Celite, and concentrated under reduced pressure to yield brown oil. The residue thus obtained was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1, v/v) to obtain the title compound as colorless oil (yield: 54%). 1H NMR (CDCl3, 400 MHz) delta 4.00 (s, 2H), 3.85 (brs, 4H), 1.94 (brs, 1H)

Reference： [1]Patent: EP2876109,2015,A1 .Location in patent: Paragraph 0619-0620
[2]Patent: US2015/191478,2015,A1 .Location in patent: Paragraph 0716-0717

60
[ 624-76-0 ]
C₁₉H₁₈N₂O₂S [ No CAS ]
C₂₁H₂₂N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.35%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	Compound 5 (1.41 g, 0.0043 mol) and potassium carbonate (1.78 g, 0.0129 mol) were added into a round bottom flask. The flask was made free of water and oxygen. The mixture was dissolved with DMF (60 ml). Then 2-iodo-ethanol (0.67 ml, 0.0086 mol) was slowly added dropwise. The reaction was raised to 50 C. and stirred. After completion of the reaction, the reaction was dissolved with ethyl acetate (250 ml), and then extracted with water (3×60 ml) to remove DMF, and washed with saturated brine, dried with anhydrous magnesium sulfate, filtered, evaporated to dryness, and dried by pumping to provide a white solid 6 (1.475 g, 93.35%).

Reference： [1]Patent: US2016/102066,2016,A1 .Location in patent: Paragraph 0021; 0025; 0029

61
[ 624-76-0 ]
4,4,8-trimethyl-N-(2-(piperazin-1-yl)ethyl)-1-thia-3-azaspiro[4.5]dec-2-en-2-amine [ No CAS ]
2-(4-(2-((4,4,8-trimethyl-1-thia-3-azaspiro[4.5]dec-2-en-2-yl)amino)ethyl)piperazin-1-yl)ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In tetrahydrofuran; at 20℃; for 20h;	General procedure: To a stirred solution of compound 42 (1.0 eq) and the corresponding alkyl iodide (1.0 eq) in THF (0.1 M) was added Et3N (2.0 eq) and themixture was stirred at room temperature for 20 h. The reaction mixture was purified by preparative HPLC (direct injection of reaction mixture) and the combined HPLC fractions were concentrated. The residue was dissolved in DCM and then washed with 2M aqueous NaOH, brine, dried over anhydrous Na2SO4 and then concentrated to give the product.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 120,p. 64 - 73

62
[ 624-76-0 ]
[ 24424-99-5 ]
[ 1186226-56-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With dmap; triethylamine; In dichloromethane; at 20℃; for 0.5h;	To a solution of 2-indoethanol (860 mg, 5.0 mmol) in CH2Cl2 at 0 C is added DMAP and di-tert-butyldicarbonate (1.2 g, 5.5 mmol) followed by NEt3 (557 mg, 5.5 mmol). The mixture was stirred at r.t. for 0.5h. Then quenched by addition of dimethyl amine (40% in water, 5 mL), extracted with Et2O and dried over NaSO4. The solvent was evaporated in vacuo and residue was purified by a flash column chromatography (EtOAc:hexane = 1:5) to afford 28 (887 mg, 65%) as a yellow liquid. 1H NMR (300 MHz, CDCl3) : 4.33 - 4.29 (m, 2H), 3.32 - 3.27 (m, 2H), 1.49 (s, 9H).

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 789 - 801

63
[ 624-76-0 ]
4-(4-chloro-1,2-diphenyl-buten-1-yl)phenol [ No CAS ]
[ 128607-22-7 ]

Yield	Reaction Conditions	Operation in experiment
		Sodium hydride (4.2 g) is loaded in portions into a solution of 4-(4-chloro-1 ,2-diphenyl-buten- 1 -yl)phenol (10 g) in tetrahydrofuran (120 ml) in an inert gasenvironment, and the mixture is maintained under stirring at room temperature for 1 h. 2-lodoethanol (11 ml) is added dropwise, and the reaction mixture is refluxed for about 9 h. Water is added, and the mixture is concentrated and extracted with ethyl acetate. The organic phase is washed with sodium carbonate aqueous solution and then with water, and then concentrated under vacuum. After crystallisation of the residue from methanol-water (about 5:1), 9.9 g of crude ospemifene is obtained.

Reference： [1]Patent: WO2016/108172,2016,A1 .Location in patent: Page/Page column 6; 7

64
[ 274-47-5 ]
[ 624-76-0 ]
2-(2-hydroxyethyl)imidazo[1,5-a]pyridin-2-ium iodide [ No CAS ]

Reference： [1]Applied Organometallic Chemistry,2016,vol. 30,p. 581 - 589

65
[ 624-76-0 ]
[ 57028-27-0 ]
9-(2-iodoethoxy)-9-(4-methoxyphenyl)-9H-fluorene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%		General procedure: Conc. H2SO4 (0.3 equiv.) was added to 9-(4-methoxyphenyl)fluoren-9-ol (13) (1.0 equiv.) in toluene and warmed up to 60 C for 15 min. After cooling the solution to rt the corresponding hydroxyl alkyl halide (1.5 equiv) or the alkyldiol (2.0 equiv.) was added. The reaction mixture was stirred at rt for the given time and then partitioned between water and toluene. The organic phase was dried over MgSO4, filtered, and concentrated to dryness. The crude product was then purified by CC (iso-hexane/EtOAc = 9.5:0.5). 5.1.1.1 9-(2-Iodoethoxy)-9-(4-methoxyphenyl)-9H-fluorene (21) According to GP1: 9-(4-methoxyphenyl)fluoren-9-ol (13) [21] (1.4 g, 4.8 mmol), toluene (12 mL), conc. H2SO4 (147 mg, 1.50 mmol, 80.0 muL), <strong>[624-76-0]2-iodoethanol</strong> (14) (1.26 g, 7.35 mmol, 0.573 mL), 20 h. Yield: 2.0 g (92%); colourless solid, m.p. 96-98 C; TLC: Rf = 0.24 (iso-hexane/EtOAc = 9.5/0.5); IR (KBr): 3035, 2931, 2903, 2841, 2044, 1951, 1918, 1605, 1580, 1508, 1447, 1302, 1252, 1184, 1169, 1107, 1031, 993 cm-1; 1H NMR (CDCl3): delta = 3.15-3.20 (m, 2 H, CH2O), 3.20-3.24 (m, 2 H, ICH2), 3.75 (s, 3 H, CH3), 6.76-6.81 (m, 2 H, Har), 7.26 (td, J = 7.4/1.2 Hz, 2 H, Har), 7.29-7.32 (m, 2 H, Har), 7.33 (d, J = 7.4 Hz, 2 H, Har), 7.37 (td, J = 7.4/1.2 Hz, 2 H, Har), 7.66 (d, J = 7.4 Hz, 2 H, Har); 13C NMR (CDCl3): delta = 4.43 (t, 1 C, ICH2), 55.20 (q, 1 C, CH3), 63.93 (t, 1 C, CH2O), 88.42 (s, 1 C, CH2OC), 113.55 (d, 2 C, Car), 120.00 (d, 2 C, Car), 125.43 (d, 2 C, Car), 126.84 (d, 2 C, Car), 128.23 (d, 2 C, Car), 129.15 (d, 2 C, Car), 135.29 (s, 1 C, Car), 140.51 (s, 2 C, Car), 146.87 (s, 2 C, Car), 158.83 (s, 1 C, Car); MS (EI, 70 eV) m/z (%): 442 (30, M+), 271 (100); HRMS (EI, 70 eV): (C22H19IO2) calc. 442.0430, found 442.0475; Anal. C22H19IO2 (C, H, I, O).

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 124,p. 852 - 880

66
[ 624-76-0 ]
[ 644-32-6 ]
[ 39252-69-2 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 5584 - 5587

67
[ 624-76-0 ]
[ 86189-87-9 ]
4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-1-(2-hydroxyethyl)pyridin-1-ium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium iodide; In acetonitrile; for 6h;Sonication; Green chemistry;	General procedure: A mixture of compound 1 (1 mmol) in acetonitrile (30 mL) and functionalized alkyl halides(1.3 mmol) was irradiated by ultrasound irradiation. The reaction was processed as described above togive the same ionic liquids 2-7.

Reference： [1]Molecules,2017,vol. 22

68
[ 624-76-0 ]
[ 1200-22-2 ]
(R)-lipoic acid 2-iodoethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine; dicyclohexyl-carbodiimide; In tert-butyl methyl ether; at 50℃; for 12h;Cooling with ice;	Method A): R-lipoic acid (15.0 g, 72.7 mmol) and methyl tert-butyl ether (300 mL) were added to the reaction flask, Was dissolved, N, N'-diisopropylcarbodiimide (11.9 g, 94.5 mmol) and pyridine (1.7 g, 21.8 mmol) were added, and the mixture was cooled in an ice bath However, <strong>[624-76-0]2-iodoethanol</strong> (18.8 g, 109.1 mmol) was added dropwise and the reaction mixture was reacted at 50 C for 12 h. After treatment and purification, crude product The mixture was recrystallized from a mixed solvent of ethyl acetate and n-hexane to give 2-iodoethyl R-lipoate, a pale yellow solid (23.0 g), yield88%, the reaction is:

Reference： [1]Patent: CN107089967,2017,A .Location in patent: Paragraph 0043; 0044; 0045; 0046

69
[ 624-76-0 ]
[ 387358-39-6 ]
(R)-lipoic acid 2-iodoethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With N,N-dimethyl-aniline; In tetrahydrofuran; at 50℃; for 3h;Cooling with ice;	Method B): R-lipoyl chloride (10.0g, 44.5mmol) and tetrahydrofuran (200mL) were added to the reaction flask, stirringN, N-dimethylaniline (16.2 g, 133.5 mmol) was added to the solution. The mixture was cooled in an ice bath and <strong>[624-76-0]2-iodoethanol</strong> (17.6 g, 102.3 mmol)The reaction mixture was reacted at 50 C for 3h. After treatment and purification, the crude product was recrystallized from a mixed solvent of ethyl acetate and n-hexane,R-lipoic acid was 2-iodoethyl ester, light yellow solid (14.1 g), yield 88%, the reaction formula is:

Reference： [1]Patent: CN107089967,2017,A .Location in patent: Paragraph 0043; 0044; 0045; 0046

70
[ 624-76-0 ]
C₁₈H₁₄BrF₃N₂O₂S₂ [ No CAS ]
C₂₀H₁₈BrF₃N₂O₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	1.47 g (3 mmol) of compound (4b) and 1.24 g (9 mmol) of potassium carbonate were added to a 50 ml round-bottomed flask. 25 ml of double distilled DMF was added and 0.7 ml (9 mmol) of iodoethanol was slowly added dropwise and the mixture was stirred at 50 C. for 8-12 h .After the reaction was completed, the reaction mixture was diluted with 100 ml of ethyl acetate and washed with water (25 ml × 4) to remove DMF. The organic phase was dried over anhydrous Na 2 SO 4 for 1 h,The filtrate was spin-dried over the column to give a pale yellow colored solid (5b) 1.08g, 67% yield.

Reference： [1]Patent: CN106317050,2017,A .Location in patent: Paragraph 0052; 0054; 0056

71
[ 624-76-0 ]
C₂₆H₂₆N₄O₄S₂ [ No CAS ]
C₂₈H₃₀N₄O₅S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 12h;	1.57 g (3 mmol) of the compound (4d) and 1.24 g (9 mmol) of potassium carbonate were added to a 50 ml round bottom flask,Add 25ml double distilled DMF, slowly add iodoethanol 0.7ml (9mmol), the reaction was stirred at 50 for 12h.After the reaction was completed, the reaction mixture was diluted with 100 ml of ethyl acetate and washed with water (25 ml × 4) to remove DMF. The organic phase was dried over anhydrous Na 2 SO 4 for 1 h, filtered and the filtrateRotate the column to give a pale yellow solid (5d) 1.11g, 65% yield.

Reference： [1]Patent: CN106317050,2017,A .Location in patent: Paragraph 0068; 0070; 0072

72
[ 624-76-0 ]
[ 2475-81-2 ]
methyl 4-fluoro-2-[(2-hydroxyethyl)amino]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	at 90 - 100℃;	Heat a mixture of <strong>[2475-81-2]methyl-2-amino-4-fluorobenzoate</strong> (2.81 g, 15.9 mmol) and 2-iodoethanol (0.879 mL, 11.2 mmol) to 90 C. for six hours then cool to room temperature. Dissolve the neat mixture in EtOAc, wash three times with aqueous 1N NaOH solution, followed by brine. Dry the organic layer over anhydrous magnesium sulfate, filter and concentrate the filtrate to obtain 2.94 g of light brown oil. Add 2-iodoethanol (1.26 mL, 15.9 mmol) and heat the mixture at 100 C. overnight. Add additional 2-iodoethanol (0.314 mL, 3.99 mmol) and continue heating at 100 C. for two hours. Cool to room temperature. Dissolve the neat mixture in EtOAc, wash three times with aqueous 1N NaOH solution, followed by brine. Dry the organic layer over anhydrous magnesium sulfate, filter and concentrate the filtrate to obtain 2.50 g brown solids. Purify by silica gel column chromatography with 20-40% EtOAc in hexanes to give the title compound (1.12 g, 33%) as a white solid. ES/MS (m/z): 214.0 (M+H).

Reference： [1]Patent: US2017/354641,2017,A1 .Location in patent: Paragraph 0090

73
[ 624-76-0 ]
[ 6681-15-8 ]
3-(2-hydroxyethoxy)-2,9,10-trimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Jatrorrhizinederivatives were synthesized according to [17]. Thesynthetic pathway of 3-substituted <strong>[6681-15-8]jatrorrhizine</strong> derivativesare shown in Figure 1. The alkylation of <strong>[6681-15-8]jatrorrhizine</strong> using1,4-dibromoethane was conducted under the basic conditionin CH3CN and afforded product 2 in 69percent yield. 3a?3fwere prepared by intermediates 2 (0.1 mol) with commerciallyavailable secondary amines (0.11mol) (dimethylamine,pyrrolidine, etc.) in DMF, and additional alkaline catalyst(K2CO3, 0.2 mol) was added, giving a 41?59percent yield,respectively. Ammonolysis of <strong>[6681-15-8]jatrorrhizine</strong> (0.05mol) withammonia solution (3 mL) -NH4Cl (0.05mol) in CH3OHat r.t. gave compounds 3g. Heating the 2-iodoethanol(0.01mmol) and <strong>[6681-15-8]jatrorrhizine</strong> (0.01mmol) in DMF at 60 °C would afford the desired product 3f. These compoundswere added to reflux MeOH containing AgCl and convertedinto corresponding chlorides. All of the compounds werepurified by chromatography on an Al2O3 column withCH3OH/CH3Cl (9:1) as eluent to give the target products(Figure 1).

Reference： [1]Journal of Chemistry,2017,vol. 2017

74
[ 624-76-0 ]
6-((tert-butyldimethylsilyl)oxy)-8-iodo-2,2-dimethyl-7-(1H-pyrrol-1-yl)-4H-benzo[d][1,3]dioxin-4-one [ No CAS ]
6-(2-hydroxyethoxy)-8-iodo-2,2-dimethyl-7-(1H-pyrrol-1-yl)-4H-benzo[d][1,3]dioxin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium fluoride; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	General procedure: To a solution of protected intermediate 39 (1 eq.) in anhydrous DMF (5mL/mmol) under argon were successively added potassium fluoride (2 eq.) and the appropriate alkyl iodide (1.5 eq.). The resulting mixture was stirred at rt until full conversion of the starting material, as assessed by LCMS and TLC. The mixture was then diluted with water and extracted twice with CH2Cl2. The combined organic layers were dried (MgSO4) and concentrated. The product was obtained by purification by flash column chromatography. KF could be substituted to TBAF if necessary.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 152,p. 101 - 114

75
[ 855766-92-6 ]
[ 624-76-0 ]
C₂₂H₂₄N₄O₂⁽²⁺⁾*2I^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%		Add in a 50 mL two-neck round bottom flask10 mL of n-propanol,4,4'-diimidazole biphenyl (1 mol),Stir at 85 C for 6 h until 4,4'-diimidazole biphenyl is dissolved and addedIodoethanol (5 mmol),The reaction was carried out for 48 h at room temperature.Finally, a white product was precipitated in diethyl ether.The yield was 90%.

Reference： [1]Patent: CN108383794,2018,A .Location in patent: Paragraph 0017

76
[ 624-76-0 ]
[ 7164-98-9 ]
1-phenyl-3-hydroxyethylimidazolium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 1-phenylimidazole In toluene at 85℃; for 6h; Stage #2: Iodoethanol In toluene at 20℃; for 48h;	5 Preparation of ionic conductor 1-phenyl-3-hydroxyethylimidazolium salt Add in a 50 mL two-neck round bottom flask10 mL of toluene,1-imidazolium (1 mol),Stir at 85 ° C for 6 h1-Imidazolium benzene is dissolved and addedIodoethanol (5 mmol),The reaction was carried out for 48 h at room temperature.Finally, it was precipitated in diethyl ether to give a pale yellow product.The yield was 90%.

Reference： [1]Current Patent Assignee: FUDAN UNIVERSITY - CN108383794, 2018, A Location in patent: Paragraph 0020

77
[ 624-76-0 ]
5-(tert-butyl)-N-(8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1,3,4-oxadiazole-2-carboxamide [ No CAS ]
5-(tert-butyl)-N-(2-(2-hydroxyethyl)-8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1,3,4-oxadiazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate; In acetonitrile; at 80℃; for 4h;	General procedure: To a solution of 5-(tert-butyl)-N-(8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)- 2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1,2,4-oxadiazole-3-carboxamide (200 mg, 0.41 mmol) in CH3CN (20 mL) were added <strong>[624-76-0]2-iodoethanol</strong> (141 mg, 0.82 mmol) and K2co3(170 mg, 1.23 mmol). The mixture was stirred at 80oC for 2 h. The mixture was diluted with EtOAc (100 mL), washed with water (60 mL) and concentrated. The crude product was purified by prep- HPLC (CH3CN/H2O with 0.05% NH4Hco3as mobile phase) to give 5-(tert-butyl)-N-(2-(2- hydroxyethyl)-8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2,3,4,5-tetrahydro-1H- benzo[c]azepin-5-yl)-1,2,4-oxadiazole-3-carboxamide as a yellow solid (90 mg, yield: 32%). ESI-MS (M+H)+: 532.3.1H NMR (400 MHz, CD3OD) delta: 8.43 (d, J = 5.2 Hz, 1H), 8.04-8.00 (m, 3H), 7.64 (s, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 5.0 Hz, 1H), 5.60 (d, J = 9.6 Hz, 1H), 4.22-4.10 (m, 2H), 3.91 (s, 3H), 3.75 (t, J = 6.0 Hz, 2H), 3.28-3.21 (m, 2H), 2.69-2.65 (m, 2H), 2.31-2.27 (m, 1H), 2.00-1.97 (m, 1H), 1.53 (s, 9H).

Reference： [1]Patent: WO2018/191577,2018,A1 .Location in patent: Page/Page column 74; 101

78
[ 624-76-0 ]
2′,3′-O-di-tert-butyldimethylsilyl-4′,5′-dehydro-5′-deoxy-5-methyluridine [ No CAS ]
C₂₄H₄₅IN₂O₇Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%		Acetone (4.0 mL) and sat. NaHCO3 aq. (20 mL) were added to a solution of compound 516 (300 mg, 0.640 mmol) in CH2Cl2 (6.0 mL). Then, a solution of Oxone (787 mg, 1.28 mmol) in H2O (10 mL) was dropwise added to this solution at 0 C. The reaction mixture was stirred at room temperature for 3 h. The resulting solution was extracted with CH2Cl2. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue (310 mg) was dissolved in anhydrous CH2Cl2 (10 mL) under Ar atmosphere, then <strong>[624-76-0]2-iodoethanol</strong> (0.50 mL, 6.40 mmol) and ZnCl2 (1 M in THF, 0.64 mL, 0.64 mmol) was added to this solution at -78 C. The reaction mixture was stirred at 0 C for 1 h. After being quenched with sat. NaHCO3 aq. at 0 C, the mixture was filtered through a pad of Celite. The filtrate was diluted with EtOAc. The solution was washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The residue (488 mg) was purified by column chromatography (silica gel 10 g, n-hexane: EtOAc = 5:1 to 2:1) to give a diastereomixture of 6 as a white powder (353 mg, 84%, 2 steps from 5).

Reference： [1]Heterocycles,2017,vol. 95,p. 342 - 352

79
[ 624-76-0 ]
[ 1154758-63-0 ]
tert-butyl ((2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-4-((tert-butoxycarbonyl)amino)-6-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-3-(((2S,3R)-3-((tert-butoxycarbonyl)amino)-6-(((2-hydroxyethyl)amino)methyl)-3,4-dihydro-2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydrogencarbonate; In acetone; acetonitrile; at 29.9℃; for 54.5h;	[00396] To a jacketed glass reactor equipped with overhead stirring, was charged tert-butyl ((2R,3R,4R,5R)-2-(((l S,2S,3R,4S,6R)-3-(((2S,3R)-6-(aminomethyl)-3-((tert- butoxycarbonyl)amino)-3,4-dihydro-2H-pyran-2-yl)oxy)-4-((tert-butoxycarbonyl)amino)-6- ((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-2-hydroxycyclohexyl)oxy)-3,5- dihydroxy-5-methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate, formula (6a), (250 g, 0.263 mol, 1 equiv). Acetonitrile (1250 mL) was charged to the reactor and the temperature was stabilized between 15 and 30 C (24.3 C). The mixture was concentrated under vacuum to a final volume target of 500 mL. The solution was sampled for water content by KF which provided a result of 0.22% w/w. An additional portion of acetonitrile (750 mL) was charged to the reactor and a second azeotropic distillation was performed to a volume target of 500 mL. The mixture was sampled for KF and a result of 0.097%> w/w was obtained. The reaction temperature was stabilized at 29.9 C and acetone (1250 mL) was charged to the mixture. The reaction was heated and the temperature stabilized at 29.9 C. Sodium bicarbonate (44.25 g, 0.527, 2.0 equiv) was charged to the reaction mixture followed by <strong>[624-76-0]2-iodoethanol</strong> (44.4 g, 20.14 mL, 0.258 mol, 0.98 equiv). After 43 h an additional portion of <strong>[624-76-0]2-iodoethanol</strong> (0.25 mL) was added to the reaction mixture. After 9.5 hours a third portion of <strong>[624-76-0]2-iodoethanol</strong> (0.3 mL) was added to the reaction mixture. After an additional 2 h, the reaction was sampled and deemed complete by HPLC analysis (consumption of tert-butyl ((2R,3R,4R,5R)-2- (((l S,2S,3R,4S,6R)-3-(((2S,3R)-6-(aminomethyl)-3-((tert-butoxycarbonyl)amino)-3,4- dihydro-2H-pyran-2-yl)oxy)-4-((tert-butoxycarbonyl)amino)-6-((S)-4-((tert- butoxycarbonyl)amino)-2-hydroxybutanamido)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5- methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate, formula (6a),). The reaction was cooled to 22.7 C and l,4-diazabicyclo[2.2.2]octane (60.0 g, 0.535 mol, 2.03 equiv) was charged as a solid. The destruction of <strong>[624-76-0]2-iodoethanol</strong> was monitored by a GC method and after 10 h the quench of this reagent was deemed complete. Water (1250 mL) and isopropyl acetate (1250 mL) were charged to the reaction mixture. The reactor contents were agitated by 25 min and the layers allowed to separate. The lower aqueous layer (API) and the upper organic layer (OP1) were collected in receivers. API was returned to the reactor and a second portion of isopropyl acetate (750 mL) was charged. The reactor contents were agitated for 30 minutes and the layers allowed to separate. The lower aqueous layer (AP2) and the upper organic layer (OP2) were collected in receivers. OP1 and OP2 were combined in the reactor and extracted with two portions of saturated sodium chloride solution (750 mL, prepared by dissolving 100 g NaCl/290 mL of water). The washed organic phase (OP4) was concentrated under vacuum to a volume target of 500 mL. Acetonitrile (2550 mL) was charged to the reactor. A second azeotropic vacuum distillation was performed to a volume target of 1550 mL. Isopropyl acetate (200 mL) was charged to the mixture. Water (10.7 mL) was charged to the mixture until a KF of 0.85% was obtained. The reactor contents were heated to 75 C upon which a solution was obtained. The reaction mixture was cooled to 57 C and seeded with tert-butyl ((2R,3R,4R,5R)-2-(((l S,2S,3R,4S,6R)-4-((tert-butoxycarbonyl)amino)-6-((S)- 4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-3-(((2S,3R)-3-((tert- butoxycarbonyl)amino)-6-(((2-hydroxyethyl)amino)methyl)-3,4-dihydro-2H-pyran-2- yl)oxy)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4- yl)(methyl)carbamate, formula (7a), (5 g, 0.0050 mol, 0.02 equiv). Stirring was maintained at 57 C for 2 h during which a thick slurry formed. The mixture was cooled from 65 C to 2.5 C over a period of 12 h. The slurry was filtered and washed with acetonitrile (900 mL) and dried in a vacuum oven to afford tert-butyl ((2R,3R,4R,5R)-2-(((l S,2S,3R,4S,6R)-4-((tert- butoxycarbonyl)amino)-6-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-3- (((2S,3R)-3-((tert-butoxycarbonyl)amino)-6-(((2-hydroxyethyl)amino)methyl)-3,4-dihydro- 2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran- 4-yl)(methyl)carbamate, formula (7a), (218.1 g, 0.220 mol, 83% molar yield)

Reference： [1]Patent: WO2019/79613,2019,A1 .Location in patent: Paragraph 00394; 00396

80
[ 624-76-0 ]
[ 92278-78-9 ]
[ 159380-94-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In acetone; at 20℃;	To a solution of compound 3 (2.00g, 6.43mmol) in acetone (20mL) was added potassium carbonate (1.33g, 9.64mmol), <strong>[624-76-0]2-iodoethanol</strong> (0.60mL, 7.72mmol) and stirred overnight at room temperature. After completion of the reaction, 120 water (150mL) and ethyl acetate (150mL) were added and the mixture was extracted with ethyl acetate twice. The combined extracts were washed with water (50mL×2) and brine (50mL×2), and dried over Na2SO4. After filtration, the solvent was removed under vacuum to obtain the crude compound. The crude compound was then purified by column chromatography on silica (60% EA/PE) to give compound 24 4 as a yellow oil (2.10g, yield 92.0%). 1H NMR (400MHz, CDCl3) delta 7.35 (s, 5H), 5.51 - 5.47 (m, 1H), 5.30 - 5.26 (m, 1H), 5.24 - 5.12 (m, 2H), 4.60 - 4.54 (m, 1H), 3.69 - 3.63 (m, 2H), 3.02 - 2.90 (m, 2H), 2.68 - 2.64 (m, 2H), 1.43 (s, 9H). 13C NMR (150MHz, CDCl3) delta 170.96, 155.46, 135.12, 128.76, 128.72, 128.62, 80.45, 67.63, 60.76, 53.77, 53.56, 36.29, 34.91, 28.39. ESI-MS: [M+Na]+ m/z 378.2

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 2784 - 2800

81
[ 624-76-0 ]
[ 81-23-2 ]
2-iodoethyl (4R)-4-((5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3,7,12-trioxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019

82
[ 624-76-0 ]
[ 40621-84-9 ]
2-(3-methyl-5-nitro-1H-indazol-1-yl)ethanol [ No CAS ]
2-(3-methyl-5-nitro-2H-indazol-2-yl)ethanol [ No CAS ]

Reference： [1]Patent: WO2019/198692,2019,A1 .Location in patent: Paragraph 0563

83
[ 624-76-0 ]
[ 40621-84-9 ]
[ 107-30-2 ]
1-(2-(methoxymethoxy)ethyl)-3-methyl-5-nitro-1H-indazole [ No CAS ]

Reference： [1]Patent: WO2019/198692,2019,A1 .Location in patent: Paragraph 0150; 0563

84
[ 624-76-0 ]
[ 13623-87-5 ]
2-(3,4-dihydro-1,8-naphthyridin-1(2H)-yl)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%		Example 408 5-(2-(difluoromethyl)-6-methylpyridin-4-yl)-4-(2-(3, 4-dihydro- 1,8-naphthyridin- 1(2//)- yl)ethoxy)-6-(4-fluorophenyl)pyrimidin-2-amine [00714] Step 1: 2-(3,4-dihydro-1,8-naphthyridin-1(2//)-yl)ethan-l-ol [00715] To a stirring solution of l,2,3,4-tetrahydro-l,8-naphthyridine (60 mg, 0.45 mmol) in DMF (3.0 mL) was added NaH (90 mg, 2.25 mmol, 60% in mineral oil) at room temperature. The resulting mixture was stirred at 30 C for 30 min, 2-iodoethanol (231 mg, 1.34 mmol) then was added. The reaction mixture was heated at 60 C for 2 h, cooled and quenched with H20 (15 mL), extracted with DCM (15 mL x 2). The combined organic phases were washed with brine (15 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography on silica gel (DCM : MeOH = 20 : 1) to get 2-(3,4-dihydro-l,8-naphthyridin- l(2//)-yl)ethan-l-ol (20 mg, 25 %) as a yellow oil.

Reference： [1]Patent: WO2020/14332,2020,A1 .Location in patent: Paragraph 00714-00715

85
[ 624-76-0 ]
[ 23593-75-1 ]
C₂₄H₂₂ClN₂O⁽¹⁺⁾*I^(1-) [ No CAS ]

Reference： [1]Organometallics,2020

86
[ 624-76-0 ]
N-(2-((5-chloro-2-((2-methoxy-4-(4-(piperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide [ No CAS ]
N-(2-((5-chloro-2-((4-(4-(4-(2-hydroxyethyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃; for 0.5h;Microwave irradiation;	<Example 22> Preparation of N-(2-((5-chloro-2-((4-(4-(4-(2-hydroxyethyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphe nyl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide While DMF (1 mL) of N-(2-((5-chloro-2-((2-methoxy-4-(4-(piperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4 -yl)amino)phenyl)methanesulfonamide (30 mg, 0.05 mmol) was stirred, DIPEA (diisopropylethylamine) (0.017 mL, 0.1 mmol) and <strong>[624-76-0]2-iodoethanol</strong> (10.9 mg 0.06 mmol) were added at ambient temperature. The above reaction mixture was heated under 80 C for 30 minutes at MW (microwave). The above reaction mixture was concentrated and purified by HPLC to obtain N-(2-((5-chloro-2-((4-(4-(4-(2-hydroxyethyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl )amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide (20.1 mg, 70%) as a white solid. 1NMR (300 MHz, CD3OD) delta 8.11 (s, 1 H), 7.76 (dd, J = 7.4, 2.1 Hz, 1 H), 7.58-7.53 (m, 1 H), 7.49-7.37 (m, 3 H), 6.91 (d, J = 2.6 Hz, 1 H), 6.66 (dd, J = 8.8, 2.5 Hz, 1 H), 3.92-3.80 (m, 7 H), 3.50 (br s, 4 H), 3.31-3.25 (m, 4 H), 3.12-3.16 (m, 4 H), 2.99 (s, 3 H), 2.23 (d, J = 12.4 Hz, 2 H), 1.99-1.87 (m, 2 H); LC-MS calcd for C29H39ClN8O4S 630.25, found 629.1 (M - H+)

Reference： [1]Patent: EP3640246,2020,A1 .Location in patent: Paragraph 0151; 0152; 0160

87
[ 624-76-0 ]
[ 508233-74-7 ]
C₂₀H₂₆N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: vortioxetine With sodium hydride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: Iodoethanol In tetrahydrofuran at 20℃; for 6h;	General procedure for the synthesis of 2-11 General procedure: To a stirred solution of vortioxetine (1) (1 eq) in dry tetrahydrofuran (THF) (10 mL) sodium hydride (2 eq) at 0° Cwas added. Contents were stirred for 20 min, and then alkyl/aryl/acyl/sulfonyl halide (1.5 eq) were added drop wise. The reaction mixture was stirred at room temperature until the reaction was complete. The reactions were quenched using cold water and extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate followed by brine washing to the organic layer. Ethyl acetate layer was dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography to afford pure compounds 2-11. 1H NMR and LCMS data of the compound 2-7 matches with the reported literature.

Reference： [1]Bagchi, Angshuman; Biswas, Goutam; Chaudhari, Raju D.; Chowdhury, Nilkanta; Fresu, Luigia G.; Pin, Arianna; Quaregna, Martina; Suryavanshi, Hemant; Talmon, Maria [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 23]

88
[ 624-76-0 ]
[ 18531-99-2 ]
[ 130536-69-5 ]
C₂₆H₂₆O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 60℃;

Reference： [1]Kondo, Masaru; Nakamura, Kento; Krishnan, Chandu G.; Takizawa, Shinobu; Abe, Tsukasa; Sasai, Hiroaki [ACS Catalysis, 2021, vol. 11, # 3, p. 1863 - 1867]

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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. 624-76-0 ] {[proInfo.proName]}

Quality Control of [ 624-76-0 ]

Related Doc. of [ 624-76-0 ]

Product Details of [ 624-76-0 ]

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[ 624-76-0 ] Synthesis Path-Upstream 1~8

[ 624-76-0 ] Synthesis Path-Downstream 1~88

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