[ CAS No. 6294-17-3 ] {[proInfo.proName]}

Name: 6294-17-3|1-Bromo-6-chlorohexane|95%
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Quality Control of [ 6294-17-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 6294-17-3 ]

SDS Specification

Alternatived Products of [ 6294-17-3 ]

Product Details of [ 6294-17-3 ]

CAS No. :	6294-17-3	MDL No. :	MFCD00001019
Formula :	C₆H₁₂BrCl	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JTYUIAOHIYZBPB-UHFFFAOYSA-N
M.W :	199.52	Pubchem ID :	80516
Synonyms :

Calculated chemistry of [ 6294-17-3 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	5
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	43.62
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.38 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.53
Log Po/w (XLOGP3) :	3.01
Log Po/w (WLOGP) :	3.18
Log Po/w (MLOGP) :	3.45
Log Po/w (SILICOS-IT) :	3.05
Consensus Log Po/w :	3.04

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.64
Solubility :	0.454 mg/ml ; 0.00227 mol/l
Class :	Soluble
Log S (Ali) :	-2.67
Solubility :	0.422 mg/ml ; 0.00212 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.78
Solubility :	0.033 mg/ml ; 0.000166 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.04

Safety of [ 6294-17-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 6294-17-3 ]

* 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 [ 6294-17-3 ]
Downstream synthetic route of [ 6294-17-3 ]

[ 6294-17-3 ] Synthesis Path-Upstream 1~10

1
[ 2009-83-8 ]
[ 6294-17-3 ]

Reference： [1] Chemical Communications, 2003, # 2, p. 260 - 261
[2] Journal of the American Oil Chemists' Society, 1951, vol. 28, p. 417[3] Chem.Abstr., 1952, p. 3493
[4] Justus Liebigs Annalen der Chemie, 1964, vol. 673, p. 26 - 36
[5] Synthesis, 1987, # 5, p. 511 - 512
[6] Patent: US3953499, 1976, A,

2
[ 629-11-8 ]
[ 6294-17-3 ]
[ 2009-83-8 ]

Reference： [1] Patent: US5880318, 1999, A,

3
[ 4286-55-9 ]
[ 6294-17-3 ]

Reference： [1] Journal of Organic Chemistry, 1994, vol. 59, # 9, p. 2616 - 2619

4
[ 629-11-8 ]
[ 6294-17-3 ]

Reference： [1] Journal of Organic Chemistry, 1994, vol. 59, # 9, p. 2616 - 2619

5
[ 544-10-5 ]
[ 6294-17-3 ]
[ 66538-73-6 ]

Reference： [1] Chemical Communications (London), 1967, p. 903 - 904

6
[ 544-10-5 ]
[ 6294-17-3 ]
[ 66538-73-6 ]

Reference： [1] Chemical Communications (London), 1967, p. 903 - 904

7
[ 629-11-8 ]
[ 6294-17-3 ]
[ 2009-83-8 ]

Reference： [1] Patent: US5880318, 1999, A,

8
[ 6294-17-3 ]
[ 75-01-4 ]
[ 871-90-9 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: With magnesium In tetrahydrofuran at 0℃; for 4 h; Inert atmosphere Stage #2: With iron(III) chloride In tetrahydrofuran at 0℃; for 3 h; Inert atmosphere	2.55 g (105 mmol) of metallic magnesium (20 to 50 mesh) and 75 g of tetrahydrofuran (THF) were charged in a 200 mL flask replaced with a nitrogen atmosphere, and the reaction solution was cooled to 0 ° C. with stirring. After cooling, 19.95 g (100 mmol) of 1-bromo-6-chlorohexane (solvent / dihaloalkane weight ratio 3.76) was added over about 2 hours and aged at the same temperature for 2 hours to obtain a Grignard reagent It was. Analysis of this reaction solution by gas chromatography (GC) revealed that the yield of the Grignard reagent was 86 areapercent and the selectivity was 86percent.In the case of0.16 g (1.0 mmol) of ferric chloride was added to the solution of the Grignard reagent obtained by the above operation, 6.25 g (100 mmol) of vinyl chloride was bubbled in over 2 hours while maintaining the temperature at 0 ° C., And aged at a temperature for 1 hour. After completion of the reaction, a 10percent ammonium chloride aqueous solution and methylene chloride were added, and the resultant salt was dissolved and separated. After fractionation of the organic layer, this was quantitatively analyzed by gas chromatography (GC). As a result, 8-chloro-1-octene as a target product was produced with a yield of 72percent. The results are shown in Table 4.

Reference： [1] Patent: JP5885213, 2016, B2, . Location in patent: Paragraph 0041; 0042; 0043

9
[ 6294-17-3 ]
[ 872-06-0 ]

Reference： [1] Organic Letters, 2015, vol. 17, # 15, p. 3682 - 3685
[2] Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1969, vol. 268, p. 1152 - 1154

10
[ 6294-17-3 ]
[ 106-95-6 ]
[ 872-06-0 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1981, vol. 30, # 12, p. 2215 - 2219[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1981, # 12, p. 2663 - 2668

[ 6294-17-3 ] Synthesis Path-Downstream 1~88

1
[ 2009-83-8 ]
[ 6294-17-3 ]

Yield	Reaction Conditions	Operation in experiment
		A. 1-Bromo-6-chlorohexane Following the procedure of Cloke, et al., J. Am. Chem. Soc. 53, 2794 (1931), hexamethylene chlorohydrin was converted to 1-bromo-6-chlorohexane, b.p. 66°-68°C./1mm., N25 =1.4795. Anal. Calc'd. for C6 H12 BrCl: C, 36.11, H, 6.06. Found: C, 37.11; H, 6.05.

Reference： [1]Chemical Communications,2003,p. 260 - 261
[2]Journal of the American Oil Chemists' Society,1951,vol. 28,p. 417
Chem.Abstr.,1952,p. 3493
[3]Justus Liebigs Annalen der Chemie,1964,vol. 673,p. 26 - 36
[4]Synthesis,1987,p. 511 - 512
[5]Patent: US3953499,1976,A

2
[ 6294-17-3 ]
[ 74-86-2 ]
[ 24088-97-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; sodium; In water;	B. 8-Chloro-1-octyne To about 450 ml. of liquid ammonia saturated with acetylene was added slowly 15.5 g. of sodium with continued addition of acetylene so that the solution remained colorless. After all the sodium had dissolved addition of acetylene was ended and the acetylene delivery tube was removed, then a dry-ice acetone condensor was fitted and 135 g. of <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> was added dropwise. The ammonia refluxed vigorously during the addition of the <strong>[6294-17-3]1-bromo-6-chlorohexane</strong>. After the addition was completed the mixture was stirred for 2 hours, then 200 ml. water was added slowly and the mixture was allowed to warm to room temperature and extracted with ether. The ether extract was washed with water, 3N hydrochloric acid, and aqueous sodium bicarbonate, then was dried over sodium sulfate and evaporated to leave a residue which was distilled under reduced pressure. The major fraction collected, 84 g., comprised 8-chloro-1-octyne boiling at 60°-65°C./10 mm. and showing infrared absorption maxima at 3270, 2120 and 735 cm-1. Anal. Calc'd. for C8 H13 Cl: C, 66.43; H, 9.06; Cl, 24.52. Found: C, 65.53; H, 8.60; Cl, 25.07.

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1972,vol. 8,p. 2523 - 2527
Zhurnal Organicheskoi Khimii,1972,vol. 8,p. 2474 - 2479
[2]Bulletin de la Societe Chimique de France,1964,p. 2477 - 2480
[3]Patent: US3953499,1976,A

3
[ 6294-17-3 ]
[ 5418-86-0 ]
[ 153556-99-1 ]

Reference： [1]Journal of Fluorine Chemistry,2005,vol. 126,p. 1239 - 1245
[2]Journal of the Chemical Society. Perkin transactions I,1993,p. 2075 - 2080

4
[ 6294-17-3 ]
[ 6665-86-7 ]
7-(6-Chloro-hexyloxy)-2-phenyl-chromen-4-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 1526 - 1535

5
[ 6294-17-3 ]
[ 106-95-6 ]
[ 872-06-0 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1981,vol. 30,p. 2215 - 2219
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1981,p. 2663 - 2668

6
[ 109-06-8 ]
[ 6294-17-3 ]
[ 237763-54-1 ]

Reference： [1]Monatshefte fur Chemie,1999,vol. 130,p. 783 - 794
[2]Journal of the American Chemical Society,2003,vol. 125,p. 12527 - 12530

7
[ 6294-17-3 ]
[ 83598-55-4 ]
1-(5,6-dimethoxy-indan-2-yl)-azepane [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4716 - 4732
[2]Journal of Medicinal Chemistry,2001,vol. 44,p. 4716 - 4732

8
[ 591-50-4 ]
[ 6294-17-3 ]
[ 56644-06-5 ]

Reference： [1]Organic Letters,2003,vol. 5,p. 423 - 425

9
[ 6294-17-3 ]
[ 92273-73-9 ]
[ 629-59-4 ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 12527 - 12530

10
[ 6294-17-3 ]
[ 108-98-5 ]
[ 64740-56-3 ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 14611 - 14626
[2]Journal of the American Chemical Society,2017,vol. 139,p. 6823 - 6826
[3]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4225 - 4234
[4]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 3295 - 3308

11
[ 109-97-7 ]
[ 6294-17-3 ]
[ 144366-95-0 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 510 - 511

12
[ 6294-17-3 ]
(5-cyano-5-methylhexyl)zinc(II) bromide [ No CAS ]
12-chloro-2,2-dimethyldodecanitrile [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 9723 - 9735
[2]Journal of Organic Chemistry,2005,vol. 70,p. 8503 - 8507

13
[ 6294-17-3 ]
[ 146796-02-3 ]
[ 376643-44-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	With 18-crown-6 ether; sodium hydride; In tetrahydrofuran; at 0℃;Heating / reflux;	Example 5; EDOT-Cl (Ib-Cl). A solution of EDOT-OH (688 mg, 4.00 mmole) and 18-crown-6 (52.8 mg, 0.200 mmole) in anhydrous THF (10 mL) was added dropwise at O0C to another air-free flask containing a suspension of sodium hydride (95percent, 505 mg, 20.0 mmole) in anhydrous THF (60 mL). The mixture was then introduced to bromochlorohexane (1.60 g, 8.00 mmole) and was refluxed under N2 overnight. After quenching the excess sodium hydride with water, THF was removed in vacuo. The reaction mixture was then washed with brine, and extracted three times with ethyl acetate. The combined organic phase was dried with MgSO4, and purified by flash chromatography (hexane/ethyl acetate = 9:1) to yield Ib-Cl (680 mg, 2.34 mmole, 59percent) as colorless crystals. 1H NMR (400 MHz, CDCl3): delta 6.34 (d, IH, J = 4 Hz), 6.32 (d, IH, J = 3.6 Hz),4.33^.27 (m, IH), 4.24 (dd, IH5 J= 11.6, 2.4 Hz), 4.06 (dd, IH, J= 11.6, 7.6 Hz), 3.68 (dd, IH,J= 10.4, 5.2 Hz), 3.60 (dd, IH, J= 10.4, 5.6 Hz), 3.53 (t, 2H, 6.8 Hz), 3.50 (t, 2H, J= 6.8 Hz), 1.82-1.73 (m, 2H), 1.64-1.55 (m, 2H), 1.50-1.31 (m, 4H).

Reference： [1]Chemistry - A European Journal,2004,vol. 10,p. 6497 - 6509
[2]Patent: WO2008/57054,2008,A1 .Location in patent: Page/Page column 23; 27

14
[ 6294-17-3 ]
[ 89-95-2 ]
2-(6'-chlorohexyloxy)benzaldehyde [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 5969 - 5979

15
[ 6294-17-3 ]
[ 854158-90-0 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 8169 - 8172
[2]Journal of Organic Chemistry,2006,vol. 71,p. 4585 - 4589

16
[ 6294-17-3 ]
[ 32316-92-0 ]
2-(6-chlorohexyl)naphthalene [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 5360 - 5361

17
[ 6294-17-3 ]
[ 100-52-7 ]
1,8-diphenyloctane-1,8-diol [ No CAS ]

Reference： [1]Tetrahedron,2006,vol. 62,p. 10417 - 10424

18
[ 106-41-2 ]
[ 6294-17-3 ]
[ 947604-73-1 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide; In water; at 100℃; for 6h;	A 1L flask provided with a stirrer was charged with 173.0 g (1.0 mol) of p-bromophenol (available from Tokyo Chemical Industry Co., Ltd.), 84.2 g (1.5 mols) of sodium hydroxide (available from Wako Pure Chemical Industries Ltd.), 399.0 g (2.0 mols) of l-chloro-6-bromohexane (available from Wako Pure Chemical Industries Ltd.) and 200 g of water. The content was maintained at 100°C for 6 hours. Then the reaction liquid was cooled to room temperature, and deposited KBr, produced by side reaction, was filtered off. The organic phase was separated and subjected to distillation under reduced pressure to give 236.9 g of the target p-(6-chlorohexyloxy)bromobenzene (yield: 78percent, purity: 96percent). Analysis of p-(6-chlorohexyloxy)bromobenzene Mass spectroscopy (m/z): 291 (m+)

Reference： [1]Patent: EP1829857,2007,A1 .Location in patent: Page/Page column 17

19
[ 6294-17-3 ]
[ 677-22-5 ]
[ 693-04-9 ]
[ 49598-54-1 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 2086 - 2089

20
[ 6294-17-3 ]
1-chloro-6-nitro-hexane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium nitrite; In dimethyl sulfoxide; at 20 - 25℃;	General procedure: To a solution of dry sodium nitrite (1.24 g, 18 mmol) in DMSO (100 mL), a solution of-bromochloroalkane 6 (15 mmol) in DMSO (20 mL) was added dropwise while keeping the temperature at 20?25 °C. After 2?5 h, the reaction was quenched by adding ice-water (400 mL)and was repeatedly extracted with diethyl ether. The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether?Et2O 5:1) to afford -chloronitroalkanes 11 as colourless oils. 1-Chloro-3-nitropropane [16694-52-3] 11a. Colourless oil (0.8 g, 42percent yield) 1H-NMR (CDCl3) delta 2.45 (qt,2H, H-2), 3.65 (t, 2H, Jvic = 6.3, H-1), 4.58 (t, 2H, Jvic = 6.3, H-3). 13C-NMR delta 29.6 (C-2), 40.7 (C-1),72.1 (C-3) [44].

Reference： [1]Molecules,2018,vol. 23
[2]Journal of Organic Chemistry,2006,vol. 71,p. 4585 - 4589

21
[ 6294-17-3 ]
[ 872-06-0 ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3682 - 3685
[2]Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques,1969,vol. 268,p. 1152 - 1154

22
[ 6294-17-3 ]
[ 141-90-2 ]
C₁₀H₁₅ClN₂OS [ No CAS ]

Reference： [1]Patent: US6342604,2002,B1 .Location in patent: Example 24

23
[ 7226-23-5 ]
[ 204138-31-8 ]
[ 6294-17-3 ]
[ 204138-95-4 ]

Yield	Reaction Conditions	Operation in experiment
	With chloro-trimethyl-silane; lithium bromide; magnesium;copper(I) iodide; In tetrahydrofuran; water; acetic acid;	a 7alpha-(6-Chlorohexyl)-11beta-fluor-estr-4-ene-3,17-dione First 30 ml of a solution of 41 ml of <strong>[6294-17-3]1-bromo-6-chloro-hexane</strong> in 270 ml of THF is added under nitrogen to a suspension of 6.8 g of magnesium chips in 100 ml of THF. After the reaction has started, the residual solution is added in drops in such a way that the internal temperature does not exceed 35° C. In a second flask, 48.1 g of lithium bromide is added to a suspension of 26.4 g of copper(I) iodide in 120 ml of THF at 0° C., whereby the internal temperature climbs to 40° C. Without cooling, 46.4 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one is now added and stirred for 30 minutes at 40° C. A clear solution is obtained, which is added in drops to the Grignard solution that is cooled to -40° C. Then, it is stirred for 30 more minutes at -30° C. and mixed drop by drop at -50° C. with a solution of 23.5 g of 11beta-fluor-estra-4,6-diene-3,17-dione in 230 ml of THF, 24.6 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one and 55 ml of trimethylchlorosilane in such a way that the internal temperature does not exceed -40° C. It is stirred for 1 hour under cold conditions, then 32 ml of glacial acetic acid is added in drops, the cooling bath is removed and stirred for 1 more hour at room temperature. For working-up, the reaction mixture is added to 1.5 l of water, diluted with the same amount of ethyl acetate, the precipitate is separated overnight on Celite, rewashed with ethyl acetate, the aqueous phase is extracted 3 times with ethyl acetate, washed with sodium bicarbonate and common salt solution, dried on magnesium sulfate and concentrated by evaporation in a vacuum. After the crude product is chromatographed on silica gel with a hexane-ethyl acetate gradient, 25.2 g of 7alpha-(6-chlorohexyl)-11beta-fluor-estr-4-ene-3,17-dione is obtained.

Reference： [1]Patent: US2003/69434,2003,A1

24
[ 7226-23-5 ]
[ 204138-31-8 ]
[ 75-77-4 ]
[ 6294-17-3 ]
[ 204138-95-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium bromide; magnesium;copper(I) iodide; In tetrahydrofuran; acetic acid;	a 7alpha-(6-Chlorohexyl)-11beta-fluoro-estr-4-ene-3,17-dione First 30 ml of a solution that consists of 41 ml of <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> in 270 ml of THF is added to a suspension of 6.8 g of magnesium chips in 100 ml of THF. After the reaction starts, the remaining solution is added in drops in such a way that the internal temperature does not exceed 35° C. In a second flask, 48.1 g of lithium bromide is added to a suspension of 26.4 g of copper(I) iodide in 120 ml of THF at 0° C., whereby the internal temperature climbs to 40° C. Without cooling, 46.4 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one is now added and stirred for 30 minutes at 40° C. A clear solution is obtained, which is added in drops to the Grignard solution that is cooled to -40° C. Then, it is stirred for 30 more minutes at -30° C. and mixed drop by drop at -50° C. with a solution of 23.5 g of 11beta-fluoro-estra-4,6-diene-3,17-dione in 230 ml of THF, 24.6 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one and 55 ml of trimethyl-chlorosilane in such a way that the internal temperature does not exceed -40° C. It is stirred for 1 hour cold, then 32 ml of glacial acetic acid is added in drops, the cooling bath is removed and stirred for 1 more hour at room temperature. For working-up, the reaction mixture is added to 1.51 of water, diluted with the same amount of ethyl acetate, the precipitate is separated on Celite, rewashed with ethyl acetate, the aqueous phase is extracted 3 times with ethyl acetate, washed with sodium bicarbonate and common salt solution, dried on magnesium sulfate and concentrated by evaporation in a vacuum. After the crude product is chromatographed on silica gel with a hexane-ethyl acetate gradient, 25.2 g of 7alpha-(6-chlorohexyl)-11beta-fluoro-estr-4-ene-3,17-dione is obtained.

Reference： [1]Patent: US5866560,1999,A

25
[ 629-11-8 ]
[ 6294-17-3 ]
[ 2009-83-8 ]

Yield	Reaction Conditions	Operation in experiment
34%	With hydrogenchloride; sodium hydroxide;zinc(II) chloride;	COMPARATIVE EXAMPLE 2 Synthesis of 1-bromo-6-chlorohexane In a reactor, 240 g (2 mole) of 1,6-hexanediol, 156 g of 35percent hydrochloric acid and 1 g of ZnCl2 were charged, followed by stirring at 98° C. for 8 hours. After the reaction mixture was extracted with 200 ml of toluene, the toluene layer was washed with 200 ml of a 5percent aqueous solution of sodium hydroxide, followed by fractionation, whereby 93.5 g (yield: 34percent, purity: 98percent) of 6-chloro-1-hexanol were obtained.

Reference： [1]Patent: US5880318,1999,A

26
[ 5382-16-1 ]
[ 6294-17-3 ]
[ 6665-86-7 ]
[ 139652-60-1 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 37 7-[6-(4-Hydroxypiperidinyl)hexoxy]-2-phenyl-4H-1-benzopyran-4-one The compound was prepared by a method similar to Example 3 from <strong>[6665-86-7]7-hydroxyflavone</strong>, 1-bromo-6-chlorohexane, and 4-hydroxypiperidine: mp 130-131 C.

Reference： [1]Patent: US5278174,1994,A

27
[ 6294-17-3 ]
[ 1074-82-4 ]
[ 91-60-1 ]
[ 149600-15-7 ]

Yield	Reaction Conditions	Operation in experiment
95.3%	With potassium carbonate; In N,N-dimethyl-formamide;	Reference Example 11 Potassium carbonate (8.29 g) was added to a solution of 2-naphthalenethiol (8.01 g) and <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (9.98 g) in N,N-dimethylformamide (65 ml). The mixture was stirred at room temperature for 3 hours. Then potassium phthalimide (9.26 g) was added to the mixture, and the resulting mixture was stirred at 100° C. for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), and the solvent was distilled off under reduced pressure to obtain N-[6-(2-naphthylthio)hexyl]phthalimide (18.56 g, 95.3percent), which was then recrystallized from ethyl acetate-hexane. Colorless plate, mp: 109°-110° C.

Reference： [1]Patent: US5624917,1997,A

28
[ 6294-17-3 ]
[ 134296-23-4 ]
[ 1012041-80-3 ]
C₁₅H₂₉Cl [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 2756 - 2757
[2]Journal of the American Chemical Society,2008,vol. 130,p. 2756 - 2757

29
[ 6294-17-3 ]
[ 74631-92-8 ]
[ 952230-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate;sodium iodide; In 4-methyl-2-pentanone; tert-butyl alcohol; for 10h;Heating / reflux;	Example 1: Preparation of 2,2-dichloro-12-(4-chlorophenyl)-10-hydroxydodecanoic acid; (1) Preparation of 10-chloro-1-(4-chlorophenyl)decan-3-one Under a nitrogen atmosphere, a mixed solution of ethyl 5-(4-chlorophenyl)-3-oxopentanoate (3.02 kg, purity: 85.3 wt percent), sodium iodide (0.3 kg), potassium tert-butoxide (1.25 kg), tert-butanol (10.25 kg) and methyl isobutyl ketone (5.19 kg) was warmed, and added dropwise with a mixed solution of <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (2.22 kg) and methyl isobutyl ketone (5.19 kg) over 1 hour under reflux, and the mixture was stirred for 9 hours under reflux. The mixture was cooled to 33 to 37°C, and added dropwise with a mixture of sodium hydroxide (0.81 kg) and water (2.58 kg), and the mixture was stirred at 33 to 37°C for 5 hours. Then, the mixture was added dropwise with 35percent hydrochloric acid (4.22 kg), and the mixture was stirred at 33 to 37°C for 4 hours. The mixture was added with water (12.81 kg), and the layers were separated. The organic layer was washed successively with a mixture of sodium hydrogencarbonate (0.9 kg) and water (12 kg), a mixture of sodium thiosulfate (0.646 kg) and water (12.81 kg), and a mixture of sodium chloride (3.23 kg) and water (9.71 kg), the solvent was evaporated, then the residue was subjected to thin film distillation, and the first fraction was removed (100°C, 2 mmHg) to obtain 10-chloro-1-(4-chlorophenyl)decan-3-one (2.99 kg, purity: 65.1 wt percent) as brown oil (yield: 64percent). A part of the brown oil obtained was collected, and purified by column chromatography, and appearance and analytical data of 10-chloro-1-(4-chlorophenyl)decan-3-one were determined. Appearance: White crystal Melting point: 23.9-25.1°C NMR (400MHz, CDCl3) delta 1.20-1.34 (m, 4H), 1.36-1.46 (m, 2H), 1.50-1.60 (m, 2H), 1.70-1.80 (m, 2H), 2.37 (t, 2H, J = 7.6Hz), 2.70 (t, 2H, J = 7.6Hz), 2.86 (t, 2H, J = 7.6Hz), 3.52 (t, 2H, J = 7.6Hz), 7.09-7.13 (m, 2H), 7.21-7.26 (m, 2H) It was able to isolate the intermediate obtained in the aforementioned reaction step, 10-chloro-1-(4-chlorophenyl)-4-ethoxycarbonyldecan-3-one, and the crude product was purified by column chromatography to obtain the compound as colorless oil. NMR (400MHz, CDCl3) delta 1.22 (t, 3H, J = 7.1Hz), 1.24-1.44 (m, 6H), 1.70-1.88 (m, 4H), 2.68-2.93 (m, 4H), 3.37 (t, 1H, J = 7.3Hz), 3.51 (t, 2H, J = 6.6Hz), 4.13 (q, 2H, J = 7.1Hz), 7.11 (d, 2H, J = 8.3Hz), 7.23 (d, 2H, J = 8.3Hz)

Reference： [1]Patent: EP2003112,2008,A1 .Location in patent: Page/Page column 11

30
[ 120-72-9 ]
[ 6294-17-3 ]
[ 61205-56-9 ]

Yield	Reaction Conditions	Operation in experiment
76%		1-(6-CHLOROHEXYL)-1H-INDOLE: To a mixture of NaH (0.249 g, 10.0 mmol) in DMF (5 mL) at 0° C. was added a solution of 1-H-indole (0.585 g, 5.00 mmol) in DMF (2 mL). The reaction mixture was stirred for 30 minutes and warmed up to room temperature. Then <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (0.998 g, 5.00 mmol) was added dropwise by syringe and the reaction mixture was stirred overnight. The reaction mixture was diluted with EtOAc (30 mL), washed with water (3.x.10 mL), dried over MgSO4, concentrated in vacuo and purified by chromatography using hexane/EtOAc (97.5:2.5) to give the desired product (0.900 g, 76percent) 1H NMR (CDCl3) delta 7.76-7.54 (m, 1H), 7.47-6.96 (m, 4H), 6.60-6.34 (m, 1H), 4.13 (t, 2H, J=6.8 Hz), 3.50 (t, 2H, J=5.6 Hz), 1.98-1.79 (m, 2H), 1.79-1.64 (m, 2H), 1.54-1.17 (m, 4H).; 1-(6-CHLOROHEXYL)-1H-INDOLE: To a mixture of NaH (0.249 g, 10.0 mmol) in DMF (5.00 mL) was added a solution of 1-H-indole (0.585 g, 5.00 mmol) in DMF (2.00 mL) at 0° C. The reaction mixture was stirred for 30 minutes at 0° C. and warmed up to room temperature. To the reaction mixture <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (0.998 g, 5.00 mmol) was added dropwise via syringe and the reaction mixture was stirred overnight. The reaction mixture was diluted with EtOAc (30 mL), washed with water (3.x.10 mL), brine (10 mL), dried over MgSO4, concentrated in vacuo and purified by chromatography using hexane:EtOAc (97.5:2.5) to give the desired product (0.900 g, 76.0percent): 1H NMR (400 MHz, CDCl3) delta 7.76-7.54 (m, 1H), 7.47-6.96 (m, 4H), 6.60-6.34 (m, 1H), 4.13 (t, 2H, J=6.8 Hz), 3.50 (t, 2H, J=5.6 Hz), 1.98-1.79 (m, 2H), 1.79-1.64 (m, 2H) 1.54-1.17 (m, 4H).

Reference： [1]Patent: US6727264,2004,B1 .Location in patent: Page column 114; 115; 154; 155
[2]Angewandte Chemie - International Edition,2012,vol. 51,p. 528 - 532

31
[ 6294-17-3 ]
[ 6089-04-9 ]
[ 20334-67-2 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 11970 - 11978

32
[ 6294-17-3 ]
[ 1781-22-2 ]
[ 866595-18-8 ]

Yield	Reaction Conditions	Operation in experiment
90%		To a suspension of NaH (60percent suspension in oil) (0.72 g, 30 mM) in 20 ml dry DMF was added 6,7-dihydro-12H-benzothiepino [5, 4-b] indole (5.02 g, 20 mM, dissolved in 30 ml dry DMF) at 0°C under nitrogen atmosphere with stirring. After 15 min, 1- bromo-6-chloro hexane (4. 0g, 24 mM, dissolved in 20 ml DMF) was added dropwise and continued stirring at room temperature for 1.5 hr. On completion, the reaction mixture was poured into water, extracted with ethyl acetate and dried over sodium sulphate. The concentrate was chromatographed on silica gel using ethyl acetate/hexane (1: 20) to yield an oil, 6. 61g (90 percent).'H NMR (CDCI3) 6 : 1.07 (m, 2H), 1.64 (m, 6H), 2.99 (bs, 2H), 3.36 (t, 2H), 3. 55 (bs, 2H), 4.29 (t, 2H), 7.15 (m, 1H), 7.15 (m, 2H), 7.41 (m, 3H), 7.58 (d, J = 7. 6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H). FABMS: m/z 370 (M+1).

Reference： [1]Patent: WO2005/94833,2005,A1 .Location in patent: Page/Page column 27-28

33
[ 33177-02-5 ]
[ 6294-17-3 ]
12-(6-chlorohexyl)-6,7-dihydro-12H-benzoxepino[5,4-b]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%		To a suspension of NaH (60percent suspension in oil, 0. 048 g, 2 mM) in 5 ml dry DMF was added 6,7-dihydro-12H-benzoxepino [5, 4-b] indole (0.235 g, 1 mM, dissolved in 5 ml dry DMF) at 0°C under nitrogen atmosphere with stirring. After 15 min, 1-brom-6- chloro hexane (0.4 g, 2 mM, dissolved in 5 ml DMF) was added dropwise and continued stirring at room temperature for 1.5 hr. The reaction mixture was poured into water and extracted with ethyl acetate, dried over sodium sulphate and concentrated. The concentrate was chromatographed on silica gel using ethyl acetate/hexane (1: 20) to yield an oil, 0.34 g (95 percent).'H NMR (CDC13) 8 : 1.33 (m, 4H), 1.64 (m, 2H), 1.76 (m, 2H), 3.07 (t, 2H), 3.42 (t, 2H), 4.31 (t, 2H), 4.61 (t, 2H), 7.15-7. 22 (m, 5H), 7.44 (d, J = 7.6 Hz, 1H), 7.62 (m, 2H). FABMS: m/z 354 (M+1).

Reference： [1]Patent: WO2005/94833,2005,A1 .Location in patent: Page/Page column 41

34
[ 866268-32-8 ]
[ 6294-17-3 ]
[ 1207628-50-9 ]

Yield	Reaction Conditions	Operation in experiment
		Intermediate 16: 2-(Butyloxy)-9-(5-chlorohexyl)-8-(methyloxy)-9H-purin-6-amineTo a solution of 2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine trifuoroacetate salt (3g, 8.54mmol) in DMF (30ml) was added potassium carbonate (2.95g, 21.35mmol) and the mixture stirred at 6O0C for 1 hour under an atmosphere of nitrogen. The mixture was then cooled to room temperature and <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (1.27ml, 8.54mmol) was added and the reaction heated to 5O0C and stirred overnight under an atmosphere of nitrogen. The reaction mixture was diluted with water (ca. 50ml) and extracted with ethyl acetate (2 x 70 ml). The combined organic extracts were dried (MgSO4), filtered and the filtrate concentrated to give an orange oil (ca.3.5g). This material was dissolved in dichloromethane and purified on a Flashmaster Il (7Og aminopropyl cartridge) using a 0-100percent ethyl acetate in cyclohexane gradient over 60 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow oil which solidified to a pale yellow solid (1.2g). LCMS (System D): tRET = 3.59min; MH+ = 356, 358
		Intermediate 18: 2-(Butyloxy)-9-(5-chlorohexyl)-8-(methyloxy)-9H-purin-6-amine; To a solution of 2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine trifuoroacetate salt (3g, 8.54mmol) in DMF (30ml) was added potassium carbonate (2.95g, 21.35mmol) and the mixture stirred at 6O0C for 1 hour under an atmosphere of nitrogen. The mixture was then cooled to room temperature and <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (1.27ml, 8.54mmol) was added and the reaction heated to 5O0C and stirred overnight under an atmosphere of nitrogen. The reaction mixture was diluted with water (ca.50ml) and extracted with ethyl acetate (2 x 70 ml). The combined organic extracts were dried (MgSO4), filtered and the filtrate concentrated to give an orange oil (ca.3.5g). This material was dissolved in dichloromethane and purified on a Flashmaster Il (7Og aminopropyl cartridge) using a 0-100percent ethyl acetate in cyclohexane gradient over 60 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow oil which solidified to a pale yellow solid (1.2g). LCMS (System D): tRET = 3.59min; MH+ = 356/358

Reference： [1]Patent: WO2010/18133,2010,A1 .Location in patent: Page/Page column 51-52
[2]Patent: WO2010/18131,2010,A1 .Location in patent: Page/Page column 52-53

35
[ 6294-17-3 ]
[ 609-65-4 ]
[ 898768-20-2 ]

Reference： [1]Chemical Communications,2010,vol. 46,p. 4082 - 4084

36
potassium benzo[d][1,3]dioxol-5-yltrifluoroborate [ No CAS ]
[ 6294-17-3 ]
[ 1258063-94-3 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 5783 - 5785

37
[ 6294-17-3 ]
potassium (pyridin-4-yl)trifluoroborate [ No CAS ]
[ 154939-06-7 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 5783 - 5785

38
[ 6294-17-3 ]
[ 1298055-74-9 ]
[ 1298055-77-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate; In acetone; for 8h;Reflux;	General procedure: Compound 11 (0.5 g, 1.5 mmol) was dissolved in acetone (30 mL) and anhydrous K2CO3 (0.2 g, 1.5 mmol) and 1-bromo-3-chloropropane (0.15 mL, 1.5 mmol) were added. After refluxing for 8 h, the mixture was hot filtered, the solvent was removed under reduced pressure and the crude was purified by flash column chromatography using CH2Cl2/CH3OH (97.5:2.5) as eluant, to afford 12 as an oil (0.5 g, 82percent);

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1682 - 1693

39
[ 6294-17-3 ]
[ 145881-74-9 ]
[ 1334953-41-1 ]

Yield	Reaction Conditions	Operation in experiment
60%		CBZ Protected Haloalkane (S2) [0096] CBZ-protected amino-ethoxyethanol (1.505 g, 6.3 mmol) was stirred vigorously with 40% KOH in water (4.67 mL, 31.5 mmol) and 100 muL tertbutlyammonium hydroxide 40% in water for 1 hour. 1-bromo-6-chlorohexane (4.41 mL, 31.5 mmol) was added all at once and the reaction was allowed to proceed overnight. The product was extracted into ethyl acetate, washed with water and brine, and purified by silica column chromatography (40% ethyl acetate in hexanes). (60% yield) [0097] M/Z calculated: 357.17, observed: 380.0 [M+Na]+ [0098] 1H NMR (500 MHz, CDCl3) 1.34 (p, 2H), 1.41 (p, 2H), 1.58 (p, 2H), 1.74 (p 2H), 3.39 (q, 2H), 3.44 (t, 2H), 3.49 (t, 2H), 3.55 (m, 4H), 3.59 (m, 2H), 5.09 (s, 2H), 5.43 (bs, 1H), 7.34 (m, 5H) 13C NMR (125 MHz, CDCl3) 25.25, 26.61, 29.36, 40.79, 45.02, 66.56, 69.96, 70.22, 71.22, 128.02, 128.03, 128.44, 136.58, 156.45

Reference： [1]Journal of the American Chemical Society,2011,vol. 133,p. 16346 - 16349
[2]Patent: US2013/302258,2013,A1 .Location in patent: Paragraph 0095; 0096; 0097; 0098

40
[ 6294-17-3 ]
[ 73183-34-3 ]
[ 1361022-62-9 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 528 - 532
[2]Angewandte Chemie - International Edition,2012,vol. 51,p. 528 - 532
[3]Advanced Synthesis and Catalysis,2012,vol. 354,p. 1685 - 1691
[4]Organic Letters,2020,vol. 22,p. 1431 - 1436
[5]Journal of the American Chemical Society,2016,vol. 138,p. 6139 - 6142
[6]RSC Advances,2015,vol. 5,p. 46672 - 46676
[7]Journal of the American Chemical Society,2014,vol. 136,p. 9521 - 9523

41
[ 6294-17-3 ]
[ 73183-34-3 ]
[ 1361022-63-0 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 528 - 532
[2]Angewandte Chemie - International Edition,2012,vol. 51,p. 528 - 532
[3]Journal of the American Chemical Society,2016,vol. 138,p. 6139 - 6142
[4]Journal of the American Chemical Society,2014,vol. 136,p. 9521 - 9523
[5]ACS Catalysis,2016,vol. 6

42
[ 78-82-0 ]
[ 6294-17-3 ]
[ 1569981-01-6 ]

Yield	Reaction Conditions	Operation in experiment
76%	With lithium diisopropyl amide; In tetrahydrofuran; at -80℃; for 90h;	The solution of isobutyronitrile (0.7 g, 10 mmol) in THF (20 mL) was cooled to ?80 °C and LDA (Lithium diisopropylamide) solution (2.0 M in hexane, 6 mL, 12 mmol) was added over 10 min. The solution was stirred 30 min, and then a solution of 1-bromo-5-chloropentane (1.8 g, 10 mmol) in THF (10 mL) was added over 5 min. After stirring for 90 min, 6 N HCl (6 mL) was added slowly and the temperature allowed to rise to rt. The residue was concentrated under reduced pressure and EtOAc (20 mL) was added. The separated organic layer was washed with water (10 mL). The organic solvent was dried with Na2SO4 and concentrated in vacuo to give the crude product. Purification by column chromatography (petroleum ether (60?90 °C)/EtOAc) gave 1.5 g of 2,2-dimethyl-7-chloroheptanenitrile (88percent) as a colorless oil. 1H NMR (400 MHz, CDCl3) delta 3.57 (t, J = 6.6 Hz, 2H), 1.92?1.72 (m, 2H), 1.58?1.44 (m, 6H), 1.36 (s, 6H).

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 7504 - 7507
[2]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1596 - 1607

43
[ 6294-17-3 ]
[ 1137-42-4 ]
[ 1572037-61-6 ]

Yield	Reaction Conditions	Operation in experiment
76.8%	With potassium carbonate; In acetonitrile; for 24h;Reflux;	According to the general procedure for the halide alkylation of 4-hydroxybenzopheonone, 1- bromo-6-chlorohexane (13.9 mmol, 2.77 mL), potassium carbonate (25.2 mmol, 3.49 g) and 4- hydroxybenzophenone (12.6 mmol, 2.50 g) were stirred in acetonitrile (20.0 mL) under reflux for 24 hours to give a crude product of 4-<9-(6-chlorohexyl)benzophenone which was recrystallized in toluene/hexanes to yield compound 3b (3.07 g, 76.8percent yield). C\|9H2]C102; off white powder, mp 64-67°C; NMR (CDC13, 400 MHz) 5= 1.55 (m,-CH2-, 4H), 1.85 (m, -CH2- , 4Eta), 3.51 (m, -C1-CH2, 2Eta), 4.06 (m, -0-CH2, 2Eta), 6.95 (m, -Ax, 2Eta), 7.49 (m, -Ar, 2H),7.52 (m, -Ar, 1H), 7.77 (m, -Ar, 4H) ppm; l3C NMR (CDCI3, 100 MHz) delta 195.54 (C5), 162.74 (C9), 138.34 (C4), 132.57 (C3), 129.72 (CI), 128.18 (C2), 114.00 (C8), 67.99 (CIO), 30.32 (C15), 30.20 (C14), 28.92 (CI 1), 25.02 (C13) ppm. HRMS-DART (m/z): [M+] calcd. for C19H2\|C102, 317.1308; found, 317.131 1.

Reference： [1]Journal of Materials Chemistry B,2014,vol. 2,p. 1509 - 1520
[2]Patent: WO2014/89680,2014,A1 .Location in patent: Page/Page column 23

44
[ 30089-00-0 ]
[ 6294-17-3 ]
[ 2425-54-9 ]

Yield	Reaction Conditions	Operation in experiment
67 mg	With [((Me)NN2)NiCl]; isopropyl alcohol; sodium iodide; sodium hydroxide; In 1,4-dioxane; isopropyl alcohol; at 80℃; for 24h;Inert atmosphere;	General procedure: To a solution of NaOH (32 mg, 0.8 mmol, 1.6 equiv), catalyst 1 (8.4mg, 0.025 mmol, 5 molpercent), NaI (37 mg, 0.25 mmol, 0.5 equiv), and i-PrOH (76 muL, 1 mmol, 2 equiv) in dry 1,4-dioxane (2.4 mL), were added alkyl halide (0.5 mmol) and the alkyl-(9-BBN) (1.6 mL, 0.8mmol, 1.6 equiv) under a N2 atmosphere. The mixture was stirred at 80 °C for 24 h. The solution was diluted in Et2O (10 mL), filtered on a short pad of silica, washed with Et2O (3 × 10 mL), and concentrated to dryness under reduced pressure. The residue was purified with a flash purification system to give the coupling product (Tables 1 and 2).

Reference： [1]Synthesis,2013,vol. 45,p. 2949 - 2958

45
[ 23418-91-9 ]
[ 6294-17-3 ]
[ 56644-06-5 ]

Yield	Reaction Conditions	Operation in experiment
80 mg	With tert-Amyl alcohol; [((Me)NN2)NiCl]; sodium iodide; sodium hydroxide; In 1,4-dioxane; at 80℃; for 24h;Inert atmosphere;	General procedure: To a solution of NaOH (32 mg, 0.8 mmol, 1.6 equiv), catalyst 1 (8.4mg, 0.025 mmol, 5 mol%), NaI (37 mg, 0.25 mmol, 0.5 equiv), and i-PrOH (76 muL, 1 mmol, 2 equiv) in dry 1,4-dioxane (4 mL), were added alkyl halide (0.5 mmol) and phenyl-(9-BBN) (1.6 mL, 0.8 mmol, 1.6 equiv) under a N2 atmosphere. The mixture was stirred at 80 C for 24 h. The solution was diluted in Et2O (10 mL), filtered on a short pad of silica, washed with Et2O (3 × 10 mL), and concentrated to dryness under reduced pressure. The residue was purified with a flash purification system to give the coupling product (Tables 5 and 6).

Reference： [1]Synthesis,2013,vol. 45,p. 2949 - 2958

46
[ 6294-17-3 ]
[ 201852-49-5 ]
[ 1580471-18-6 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 1904 - 1907

47
[ 6294-17-3 ]
[ 123325-10-0 ]
[ 1604039-84-0 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 2566 - 2569

48
[ 6294-17-3 ]
[ 693-04-9 ]
[ 1002-69-3 ]

Yield	Reaction Conditions	Operation in experiment
44%	With dicarbonyl(cyclopentadienyl)iron(II) chloride; buta-1,3-diene; In tetrahydrofuran; at 0 - 20℃; for 24h;Inert atmosphere; Schlenk technique;	General procedure: To a flame-dried Schlenk tube containing CpFe(CO)2Cl (6) (10.3 mg, 0.05 mmol),3-bromopropyl phenyl ether (1j) (223 mg, 1.04 mmol), THF (0.25 mL), n-BuMgCl (2a)(2M in THF, 0.75 mL, 1.5 mmol), and 1,3-butadiene (90 mL as gas, 4.0 mmol) wereadded successively at ?78 C followed by stirring at 0 °C for 2 h and rt for 22 h. Thereaction was quenched by the addition of sat NH4Cl aq., extracted with Et2O (10 mL x3), concentrated, and purified by PTLC (eluent: hexane/Et2O = 99/1) to obtain heptylphenyl etherS2 (3ja) as yellow oil (79.5 mg, 40percent).

Reference： [1]Chemistry Letters,2018,vol. 47,p. 763 - 766
[2]Journal of Organic Chemistry,2014,vol. 79,p. 8522 - 8532

49
[ 6294-17-3 ]
[ 825-90-1 ]
C₁₂H₁₆ClO₄S^(1-)*Na⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: NaH(60percent in mineral oil, 80 mg, 2.00 mmol) was added to a solution of 4-hydroxybenzenesulfonic acid sodium salt dihydrate (464 mg, 2.00 mmol) in N,N-dimethylformamide (DMF) (5.00 mL) at 0 °C under N2. After stirring for 1 h at 0 °C, 1-bromo-4-chlorobutane (0.230 mL, 2.00 mmol) was added to the solution. The mixture was stirred for 12 h at 100 °C.The solvent was removed under reduced pressure and AcOEt (15.0 mL) was added to the residue. The resulting precipitate was collected by filtration. The precipitate was dried under reduced pressure. A mixture of the precipitate and SOCl2 (7.0 mL, 80 mmol) was heated at 90 °C for 13 h. The reaction mixture was poured into ice water. After stirring for 5 min, the product was extracted with CHCl3 (20 mL×3). The organic layer was dried over Na2SO4, filtered and evaporated. The crude product was purified by column chromatography (AcOEt : n-hexane=1 : 5) to give compound 5. Yield: 338 mg (60percent).

Reference： [1]Chemical and Pharmaceutical Bulletin,2015,vol. 63,p. 200 - 209

50
[ 5625-52-5 ]
[ 6294-17-3 ]
1-(6-chlorohexyl)-4-methylpiperazin-2,5-dione [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10881 - 10887

51
[ 6294-17-3 ]
[ 111-46-6 ]
2-(2-((6-chlorohexyl)oxy)ethoxy)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With potassium hydroxide In water; dimethyl sulfoxide at 0 - 25℃; for 12h;
15%	With potassium hydroxide In water; dimethyl sulfoxide at 0 - 20℃;	47.1 Step 1: Step 1: Based on Scheme 16, Preparation of 2-(2-((6-chlorohexyl)oxy)ethoxy)ethan-1-ol (SIAIS180112) In 250 mL of round-bottom flask, to a stirred solution of 2,2'-oxybis(ethan-1-ol) (5.3 g, 50.12 mmol) and 1-bromo-6-chlorohexane (10 g, 50.12 mmol) in DMSO (100 mL) was dropwise added 15% KOH aqueous solution (50 mL) at 0° C. After addition, the mixture was stirred overnight at room temperature. The mixture was extracted with EtOAc (150 mL3), and the combined organic layer was washed with water (100 mL3) and brine (100 mL), dried over Na2SO4, concentrated to dryness in vacuum. The residue was subjected to flash column chromatography with PE/EtOAc (3:1) to afford desired product (SIAIS1801112) as a light yellow oil (1.7 g, 15% yield). 1H NMR (500 MHz, CDCl3) δ 3.76-3.71 (m, 2H), 3.69-3.67 (m, 2H), 3.64-3.61 (m, 2H), 3.59 (dd, J=5.7, 3.6 Hz, 2H), 3.53 (t, J=6.7 Hz, 2H), 3.47 (t, J=6.6 Hz, 2H), 2.49 (s, 1H), 1.84-1.73 (m, 2H), 1.71-1.53 (m, 4H), 1.49-1.43 (m, 2H), 1.41-1.35 (m, 2H). HRMS (ESI) m/z: calcd C10H22ClO3+ [M+H]+, 225.1252; found, 225.0804.
	With potassium hydroxide In water; dimethyl sulfoxide at 0 - 25℃; Inert atmosphere;

Reference： [1]Zhao, Quanju; Ren, Chaowei; Liu, Linyi; Chen, Jinju; Shao, Yubao; Sun, Ning; Sun, Renhong; Kong, Ying; Ding, Xinyu; Zhang, Xianfang; Xu, Youwei; Yang, Bei; Yin, Qianqian; Yang, Xiaobao; Jiang, Biao [Journal of Medicinal Chemistry, 2019, vol. 62, # 20, p. 9281 - 9298]
[2]Current Patent Assignee: SHANGHAITECH UNIVERSITY - US2020/407342, 2020, A1 Location in patent: Paragraph 0224-0225
[3]Lai, Ashton C.; Toure, Momar; Hellerschmied, Doris; Salami, Jemilat; Jaime-Figueroa, Saul; Ko, Eunhwa; Hines, John; Crews, Craig M. [Angewandte Chemie - International Edition, 2016, vol. 55, # 2, p. 807 - 810][Angew. Chem., 2016, vol. 128, # 2, p. 818 - 821,4]

52
[ 6294-17-3 ]
[ 123-08-0 ]
4-((6-chlorohexyl)oxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; for 12h;Reflux;	General procedure: To a 250 mL round flask was added p-hydroxybenzaldehyde (30.0 mmol, 3.66 g), 1-bromo-4-chlorobutane (60.0 mmol, 11.04 g), potassium carbonate (15.0 g) and acetonitrile (50.0 mL). The mixture was refluxed for twelve hours. The solid was removed by filtration and the solvent was remove by rotatory evaporation at reduced pressure. The resulting solid was recrystallized in alcohol to give the desired p-(4-chlorobutoxy)benzaldehyde.

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 7504 - 7507
[2]Chinese Chemical Letters,2020,vol. 31,p. 1550 - 1553

53
[ 108-89-4 ]
[ 6294-17-3 ]
C₁₂H₁₉ClN⁽¹⁺⁾*Br^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In 1,1,1-trichloroethane; at 40℃; for 8h;Schlenk technique;	Schlenk tube (Schlenk tube) to 4-methylpyridine 8 (4- methyl pyridine, 9.3g, 100.0mmol), 1, 6-dibromohexane 9 (1, 6- dibromohexane, 24.4g, 100.0 mmol) and 1, 1, 1 -trichloroethane (1,1,1- trichloroethane, 50 mL) was placed and stirred for 8 hours at 40 ° C.. After the reaction, the compound 10 nerd by washing the product with ethyl acetate (ethyl acetate). Yield: 14.7g, 44percent.

Reference： [1]Patent: JP2016/3182,2016,A .Location in patent: Paragraph 0067; 0068

54
[ 6294-17-3 ]
[ 6825-20-3 ]
C₁₈H₁₈Br₂ClN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%		Potassium hydroxide (1.71g, 0.031 mol) was added in dibromo carbazole (5.0 g, 0.015 mol) dissolved in 20 ml of DMSO. The solutionwas heated for 3 hours at 50 ~ 60 oC. 1- bromo -6- chloro hexa (3.7g, 0.018 mol) was slowly added and it was heated for 2 hours at 50 ~ 60 o C.After confirming that the reaction was complete, the salt which had beenproduced during the reaction and potassium hydroxide were removed by using waterand chloroform. Then, the solvent was removed through adistillation under reduced pressure. Using methylene chloride and hexane (1:5), it was also separated by achromatography to obtain a white solid (4.8 g, 0.0108 mol, 72percent).

Reference： [1]Patent: KR101587829,2016,B1 .Location in patent: Paragraph 0064; 0065; 0066; 0067

55
[ 92-84-2 ]
[ 6294-17-3 ]
C₁₈H₂₀ClNS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		Potassium hydroxide (5.13 g, 0.0913 mol) was added tophenothiazine (9.1 g, 0.0457 mol) dissolved in 20ml of DMSO. After the solutionwas heated for 30 minutes at 50 ~ 60 oC, 1- bromo -6- chloro hexan(10.2 g, 0.0502 mol) was slowly added and it was heated for 2 hours at 50 ~ 60 oC.After confirming that the reaction was complete, the salt which had beenproduced during the reaction and potassium hydroxide were removed by usingwater and chloroform. Then, the solvent was removed through a distillationunder reduced pressure. Using methylene chloride and hexane (1:5), it was alsoseparated by a chromatography to obtain a white solid (6.95g , 0.0219 mol, 48percent)

Reference： [1]Patent: KR101587829,2016,B1 .Location in patent: Paragraph 0079; 0080; 0081; 0082

56
[ 6294-17-3 ]
[ 121-33-5 ]
4-((6-chlorohexyl)oxy)-3-methoxybenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: vanillin With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.25h; Schlenk technique; Inert atmosphere; Stage #2: 1-bromo-6-chlorohexane In N,N-dimethyl-formamide at 25℃; Inert atmosphere; Schlenk technique;
84.2%	With potassium carbonate In N,N-dimethyl-formamide at 70 - 80℃; for 3h;	Synthesis of 4-((6-chlorohexyl)oxy)-3-methoxybenzaldehyde (III) Synthesis of 2,6-bis(4-(3-bromopropoxy)-3-methoxybenzylidene)cyclohexanone(IV)In a round-bottom flask, a solution of compound IIb (0.2 g, 0.73 mmol) in THF(2 ml) was mixed with cyclohexanone (0.04 ml, 0.37 mmol) and stirred till the mixturebecame clear. Then, one drop of conc. HCl was added. The mixture was stirredfor 90 h. at r.t. Then, it was poured onto crushed ice with gentle stirring and keptovernight to allow the gummy product to become solid precipitate, which was filteredand thoroughly washed with cold water. The obtained green to yellow productwas dried in the oven overnight at 60 °C. Purification of the crude product onsilica gel column chromatography using (8:2) PtEt: EtAcO as the eluent afforded thepure product (0.21 g, 94% Yield). Rf = 0.42 (PtEt: EtAcO, 6:4), m.p. = 123-125 °C;ATR-FTIR (cm-1): C-H aliphatic: 2931, 2850, C=O: 1678, C=C: 1594, C=C:1552, C-O: 1250, C-Br: 729; 1H·NMR (850 MHz, CDCl3) δ (ppm) = 1.75 (2H, p,J = 6.8 Hz, CH2),2.33 (4H, p, J = 6.8 Hz, 2CH2),2.87 (4H, t, J = 5.95 Hz, 2CH2),3.57 (4H, t, J = 7.65 Hz, 2BrCH2),3.81 (6H, s, OCH3),4.14 (4H, t, J = 6.8 Hz,2OCH2),6.87 (2H, d, J = 13.5 Hz, 2Ar-H), 6.96 (2H, s, 2Ar-H), 7.03 (2H, d,J = 11.6 Hz, 2ArH), 7.68 (2H, s, 2CH =); 13C·NMR (CDCl3, 213 MHz) δ (ppm):23.04, 28.54, 30.09, 32.21, 56.09, 66.56, 112.78, 114.31, 123.92, 129.40, 134.68,136.81, 148.78, 149.07, 190.13. C28H32O5Br2 (g/mol), ESI-MS m/z [M + 1]+: calculated:608.36; found: 609.1.

Reference： [1]Cueto Diaz, Eduardo; Picard, Sébastien; Klausen, Maxime; Hugues, Vincent; Pagano, Paolo; Genin, Emilie; Blanchard-Desce, Mireille [Chemistry - A European Journal, 2016, vol. 22, # 31, p. 10848 - 10859]
[2]Noureddin, Sawsan A.; El-Shishtawy, Reda M.; Al-Footy, Khalid O. [Research on Chemical Intermediates, 2020, vol. 46, # 12, p. 5307 - 5323]

57
[ 20928-63-6 ]
[ 6294-17-3 ]
1-(6-chlorohexyl)-3-methoxypyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		In a 100 mL round bottom flask was added cesium carbonate (7.3 g, 22 mmol) in DMF (10 mL) and temperature was maintained at 0°C followed by the addition of 3-methoxypyridin-2(1H)-one 31 (2 g, 16 mmol dissolved in DMF (10 mL) and the reaction was allowed to stir for 10 min. To this was added <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> 32 (3.8 g, 19 mmol) diluted with DMF (5 mL) drop wise at room temperature and further stirred for 2 h. The reaction mixture was extracted with ice cold water and ethyl acetate (75X3mL). Organic layer was washed with brine solution, dried over anhydrous sodium sulfate, evaporated under vacuum to get the crude mass which was purified by flash chromatography to afford 1.5 g of 33.LCMS: 244 (M+1)+

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5222 - 5228

58
[ 6294-17-3 ]
[ 15992-10-6 ]
C₁₈H₂₅ClN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of 5 in anhydrous DMF was cooled to 0°C. 60percent NaH (1.1 eq.) was added and stirred for 30 min. Haloalkane(2.0 eq.) was added dropwise. The mixture was stirred at room temperature for 2 h., and then water was added and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was chromatographed by silicagel column (EtOAc/petroleum ether = 1/1) to afford 6a-6c.

Reference： [1]Letters in drug design and discovery,2016,vol. 13,p. 1025 - 1032

59
[ 6294-17-3 ]
[ 75-01-4 ]
[ 871-90-9 ]

Yield	Reaction Conditions	Operation in experiment
72%		2.55 g (105 mmol) of metallic magnesium (20 to 50 mesh) and 75 g of tetrahydrofuran (THF) were charged in a 200 mL flask replaced with a nitrogen atmosphere, and the reaction solution was cooled to 0 ° C. with stirring. After cooling, 19.95 g (100 mmol) of <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (solvent / dihaloalkane weight ratio 3.76) was added over about 2 hours and aged at the same temperature for 2 hours to obtain a Grignard reagent It was. Analysis of this reaction solution by gas chromatography (GC) revealed that the yield of the Grignard reagent was 86 areapercent and the selectivity was 86percent.In the case of0.16 g (1.0 mmol) of ferric chloride was added to the solution of the Grignard reagent obtained by the above operation, 6.25 g (100 mmol) of vinyl chloride was bubbled in over 2 hours while maintaining the temperature at 0 ° C., And aged at a temperature for 1 hour. After completion of the reaction, a 10percent ammonium chloride aqueous solution and methylene chloride were added, and the resultant salt was dissolved and separated. After fractionation of the organic layer, this was quantitatively analyzed by gas chromatography (GC). As a result, 8-chloro-1-octene as a target product was produced with a yield of 72percent. The results are shown in Table 4.

Reference： [1]Patent: JP5885213,2016,B2 .Location in patent: Paragraph 0041; 0042; 0043

60
[ 6294-17-3 ]
[ 16492-75-4 ]
C₂₄H₃₈BrCl₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium carbonate In acetonitrile at 80℃; for 12h; Inert atmosphere;
80%	With potassium carbonate In propan-2-one for 24h; Inert atmosphere; Reflux;
	With potassium carbonate In propan-2-one at 90℃; for 24h; Inert atmosphere;	2 Example 2: Preparation of Intermediate 2 Potassium carbonate (4.0 g, 6.0 eq) and intermediate 1 were dissolved in 100 mL of acetone, and nitrogen was bubbled under vacuum, 5-bromo-1,2,3-phloroglucinol (1.0 g, 1.0 eq) was added, heated to reflux at 90°C and stirred for 24 h. After the reaction was completed, it was extracted with dichloromethane and separated and purified by silica gel column chromatography (petroleum ether:ethyl acetate=10:1) to obtain Intermediate 2.

Reference： [1]Chen, Huan; Li, Shengliang; Wu, Min; Kenry; Huang, Zhongming; Lee, Chun-Sing; Liu, Bin [Angewandte Chemie - International Edition, 2020, vol. 59, # 2, p. 632 - 636][Angew. Chem., 2020, vol. 132, # 2, p. 642 - 646,5]
[2]Wang, Bing; Wang, Ming; Mikhailovsky, Alexander; Wang, Shu; Bazan, Guillermo C. [Angewandte Chemie - International Edition, 2017, vol. 56, # 18, p. 5031 - 5034][Angew. Chem., 2017, vol. 129, # 18, p. 5113 - 5116,4]
[3]Current Patent Assignee: UNIV NANJING POSTS and TELECOMMUNICATIONS - CN114409679, 2022, A Location in patent: Paragraph 0031-0033

61
[ 6294-17-3 ]
[ 91-56-5 ]
1-(6-chlorohexyl)-1H-indole-2,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: A solution of 1.47 g (10 mmol) of isatin (1) in 15 mL of DMF was cooled to 10°C, and 0.44 g (10 mmol) of sodium hydride (a 60percent suspension in mineral oil) was slowly added with stirring. The mixture was stirred for 30 min, 0.99 mL (10 mmol) of 1-bromo-3-chloropropane was added to the resulting violet solution, and the mixture was stirred for 2 h at room temperature. The mixture was poured onto 100 g of crushed ice, and the bright orange solid was filtered off, washed with water and petroleum ether, and dried under reduced pressure (18 mm).

Reference： [1]Russian Journal of Organic Chemistry,2017,vol. 53,p. 626 - 627
Zh. Org. Khim.,2017,vol. 53,p. 618 - 619,2

62
[ 6294-17-3 ]
(S)-6-(4-chlorophenyl)-1,4-dimethyl-8-(1H-pyrazol-4-yl)-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine [ No CAS ]
(S)-8-(1-(6-azidohexyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1,4-dimethyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%		Brought (S)-6-(4-chlorophenyl)-1,4-dimethyl-8-(1H-pyrazol-4-yl)-4H- benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (64-1) (0.045 g, 0.1157 mmol) up in DMF (1.0 mL) and cooled to 0°C. Added potassium 2-methylpropan-2-olate (12.9 mg, 0.1157 mmol) and stirred at reduced temp for 10 minutes and room temp for 20 minutes. Then added 1-bromo-6- chlorohexane (18.9 muL, 0.1272 mmol) dropwise at r.t. Stirred for ~ 1 hours at.r.t complete by lcms. Added sodium azide (9.77 mg, 0.1504 mmol) and stirred at r.t. for 3 hours. Very slow progress. Heated to 50 °C O/N over half complete. Added another 5 mg sodium azide and continued heating. After ~ 4 hours more complete. concnetrated onto celite and purified by isco 0-10percent MeOH/DCM to give (S)-8-(1-(6-azidohexyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1,4-dimethyl-4H- benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (99-1) (41.0 mg, 0.07976 mmol, 69.0 percent) as an oil. LCMS (ES+): m/z= 515 [M + H]+

Reference： [1]Patent: WO2017/197056,2017,A1 .Location in patent: Page/Page column 418-419

63
[ 6294-17-3 ]
6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4-yl)spiro[benzo[f] [1,2,4]triazolo[4,3-a][1,4]diazepine-4,1’-cyclopropane] [ No CAS ]
8-(1-(6-chlorohexyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1-methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1’-cyclopropane] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In acetonitrile; at 20℃; for 24h;	Brought -(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4- yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1 (59-2) (108.0 mg, 0.2694 mmol) and cesium carbonate ( 87.7 mg, 0.2694 mmol) up in Acetonitrile (2.69 mL) and stirred at r.t for 24 hours. Concentrated solution and purified by isco 0-10percent MeOH/DCM to give 8-(1-(6- chlorohexyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1-methylspiro[benzo[f][1,2,4]triazolo[4,3- a][1,4]diazepine-4,1?-cyclopropane] (78-1) (110 mg, 0.2117 mmol, 79.1 percent) as an oil. LCMS (ES+): m/z 521 [M + H]+

Reference： [1]Patent: WO2017/197056,2017,A1 .Location in patent: Page/Page column 405

64
[ 6294-17-3 ]
6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4-yl)spiro[benzo[f] [1,2,4]triazolo[4,3-a][1,4]diazepine-4,1’-cyclopropane] [ No CAS ]
8-(1-(6-azidohexyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1-methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1‘-cyclopropane] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%		Brought 6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4- yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1'-cyclopropane] (0.053 g, 0.1322 mmol) up in DMF (1.32 mL ) at 0°C. Added potassium 2-methylpropan-2-olate (16.3 mg, 0.1454 mmol) and let warm to r.t. Added <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (21.6 muL, 0.1454 mmol) 15 minutes later. Added sodium azide (8.59 mg, 0.1322 mmol) and heated to 50°C O/N. Concentrated from toluene onto celite and purified by isco 0-10percent MeOH/DCM to give 8-(1-(6-azidohexyl)-1H-pyrazol-4- yl)-6-(4-chlorophenyl)-1-methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1 (64.0 mg, 0.122 mmol, 92.0percent) as an oil. LCMS (ES+): m/z= 527 [M + H]+

Reference： [1]Patent: WO2017/197056,2017,A1 .Location in patent: Page/Page column 418

65
[ 6294-17-3 ]
1-methyl-8-(1-methyl-1H-pyrazol-4-yl)-6-(4-(piperazin-1-yl)phenyl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1'-cyclopropane] hydrochloride [ No CAS ]
6-(4-(4-(6-chlorohexyl)piperazin-1-yl)phenyl)-1-methyl-8-(1-methyl-1H-pyrazol-4-yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1'-cyclopropane] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19.5%	With caesium carbonate In N,N-dimethyl-formamide for 12h;	Intermediate 186-1. Preparation of 6-(4-(4-(6-chlorohexyl)piperazin-1-yl)phenyl)-1- methyl-8-(1-methyl-1H-pyrazol-4-yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1'-cyclopropane] 1-Methyl-8-(1-methyl-1H-pyrazol-4-yl)-6-(4-(piperazin-1-yl)phenyl)-4H- benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine hydrochloride (182-1) (0.150 g, 315 µmol) was taken up in DMF ( 0.640 mL). cesium carbonate (215 mg, 661 µmol) was added followed by 1-bromo- 6-chlorohexane (51.6 µL, 346 µmol) and the reaction stirred for 12 hours. The reaction was concentrated and the residue purified by column chromatography (silica 0-10% MeOH in DCM) to give 6-(4-(4-(6-chlorohexyl)piperazin-1-yl)phenyl)-1-methyl-8-(1-methyl-1H-pyrazol-4- yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1'-cyclopropane] (186-2) (0.034 mg, 19.5%). LC/MS (ES+): m/z 583.6 [M + H]+

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197056, 2017, A1 Location in patent: Page/Page column 481-482

66
[ 6294-17-3 ]
[ 143612-79-7 ]

Reference： [1]Patent: CN106928119,2017,A

67
[ 6294-17-3 ]
[ 135579-83-8 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; zinc; In N,N-dimethyl acetamide; at 60℃; for 5h;Inert atmosphere;	In a dry round bottom flask was added zinc powder 13g (0.2mol), vacuum was heated to 70 °C after the vacuum After 3 hours, nitrogen was introduced and then 0.95 g (0.04 mol) of iodine and 150 mL of tetrahydrofuran or N, N-dimethylacetamide andThe solution should be stirred until the red color of the iodine faded, then freshly distilled 29.9 g (0.15 mol) of 6-chloro-bromohexane was added and the resulting mixtureThe reaction mixture was heated at 60 °C for 5h. The sample was analyzed until the reaction of 6-chloro-1-bromohexane was complete. The resulting gray solution is straightThen used for the next reaction, the zinc reagent is stable, stored at room temperature under a nitrogen atmosphere for several weeks did not find decomposition, the reaction solution with noDiluted with water tetrahydrofuran or anhydrous N, N-dimethylacetamide to give a concentration of 2.0M zinc reagent solution.

Reference： [1]Patent: CN106928119,2017,A .Location in patent: Paragraph 0029-0034

68
[ 6294-17-3 ]
[ 112-29-8 ]
[ 100-46-9 ]
C₂₃H₄₀ClN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.14 g	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Benzylamine (3) (4 g), <strong>[6294-17-3]1-chloro-6-bromohexane</strong> (7.4 g), 1-bromodecane (8.3 g) and DMF (40 ml) were placed in a single-necked bottle, and potassium carbonate (6 g) was added. The reaction was stirred at room temperature overnight, and then the mixture was evaporated to ethyl ether (yield: ethyl acetate: n-hexane = 1:10). After the reaction was completed, filtered and concentrated to remove most of the DMF, and then extracted with 50 mL of ethyl acetate and 50 ml of water. Dry with sodium sulfate and concentrate the solvent to give an oil.Column chromatography (eluent: ethyl acetate: n-hexane = 1 : 50) gave 3.14 g of oil.

Reference： [1]Patent: CN108569971,2018,A .Location in patent: Paragraph 0067; 0091; 0092

69
[ 6294-17-3 ]
[ 100-46-9 ]
C₁₉H₃₁Cl₂N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.16 g	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Benzylamine (3) (2.5 g), <strong>[6294-17-3]1-chloro-6-bromohexane</strong> (4) (9.3 g) and DMF (25 ml) were placed in a single-mouth bottle, potassium carbonate (3.7 g) was added, and the reaction was stirred at room temperature overnight,TLC detected the reaction (developing agent: ethyl acetate: n-hexane = 1:3), after the reaction was completed, filtered, and concentrated to remove most of the DMF, extracted by adding 50 ml of water and 50 ml of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, the solvent was concentrated to give 10.8 g of an oil,column chromatography (eluent: ethyl acetate: n-hexane = 1:8) to give 5.16 g of oil.

Reference： [1]Patent: CN108569971,2018,A .Location in patent: Paragraph 0065; 0076; 0077

70
[ 6294-17-3 ]
[ 90-01-7 ]
(2-((6-chlorohexyl)oxy)phenyl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 10h;	General procedure: To a solution of 14b (2.00 g, 16 mmol) in acetonitrile (100 ml) was added K2CO3 (5.20 g, 37.6 mmol) and 1-bromo-4-chlorobutane or 1-bromo-5-chloropentane or <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (24 mmol) and then stirred at 60 oC for 10 h. After cooling to ambient temperature, the reaction mixture was filtrated. The filtrate was condensed and the crude product was purified by flash chromatograph eluting with ethyl acetate/petroleum ether (1:15, v: v) to afford 17l-17n as light yellow oils.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 163,p. 864 - 882

71
[ 6294-17-3 ]
[ 71653-50-4 ]
N-(tert-butyl)-3-(6-chlorohexyl)picolinamide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 571 - 574

72
[ 6294-17-3 ]
[ 24088-97-9 ]
[ 71041-98-0 ]

Yield	Reaction Conditions	Operation in experiment
80%		Compound 102 B26 (1.2 g, 8 mmol) was dissolved in 15 mL of anhydrous THF, cooled to ?40° C., 44 n-butyllithium (5.2 mL, 1.6 M, 8.3 mmol) was added dropwise. After the addition, 45 HMPA (4 mL) was added and stirred for 1 h. After that, the reaction mixture was added a solution of B25 (1.6 g, 8.2 mmol) in 5 mL 8 THF, and stirred at room temperature overnight. The reaction was quenched by the addition of a saturated aqueous solution of 10 ammonium chloride. After the addition, the two phase were separated, and the separated aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried, concentrated, and then, purified using column chromatography with PE:EA (v/v)=100/1 to give the product 106 B27, 1.6 g, yield 80percent.

Reference： [1]Patent: US2019/39989,2019,A1 .Location in patent: Paragraph 0170; 0173-0174

73
[ 6294-17-3 ]
[ 1070-00-4 ]
[ 2425-54-9 ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium fluoride; benzylnixantphos; iron(II) acetate; In tetrahydrofuran; at 40℃; for 18h;Inert atmosphere;	General procedure: A THF solution of trioctylaluminum (4.50 mL, 1.00 M, 4.5 mmol) was added to a mixture of Fe(OAc)2 (26.4 mg, 0.15 mmol), Bn-Nixantphos (193 mg, 0.30 mmol), KF (262 mg, 4.5 mmol) and (6-bromohexyl)benzene (732 mg, 3.1 mmol) in THF (1.50 mL) at 0 °C. The mixture was stirred at 40 °C for 12 h. An aqueous solution of HCl (3N) was added to the reaction mixture at 0 C. The aqueous layer was extracted with ethyl acetate four times. The combined organic layer was filtered through a pad of Florisil. After removal of the solvent, the crude product was purified by column chromatography (silica gel, hexane, Rf = 0.86) and recycling GPC (toluene) to afford the titled compound (415 mg, 50percent) as a colorless oil;

Reference： [1]Chemistry Letters,2019,vol. 48,p. 238 - 241

74
[ 6294-17-3 ]
ethyl 6-tert-butyl-9-hydroxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylate [ No CAS ]
ethyl 6-tert-butyl-9-(6-chlorohexoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a] quinolizine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
299 mg		To a solution of ethyl 6-tert-butyl-9-hydroxy-l0-methoxy-2-oxo-6,7- dihydrobenzo[a]quinolizine-3-carboxylate (intermediate 1-1, 223 mg, 0.6 mmol, prepared according to US20150210682) in DMF (4 mL) was added potassium carbonate (166 mg, 1.2 mmol), the mixture was stirred at room temperature for 1 h. Then l-bromo-6-chlorohexane (359 mg, 1.8 mmol) was added and stirred at 60 C for 5 h. After cooling to room temperature, the mixture was diluted with EtOAc and water, and then extracted with EtOAc for three times. The combined organic layer was washed with brine, dried over anhydrous Na2S04, and concentrated. The residue was washed with petroleum ether to give ethyl 6-tert-butyl-9-(6-chlorohexoxy)-l0- methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylate (compound lb, 299 mg) as a dark solid, which was directly used for next step without further purification. MS obsd. (ESI+) [(M+H)+]: 490.

Reference： [1]Patent: WO2019/129681,2019,A1 .Location in patent: Page/Page column 30-32

75
[ 6294-17-3 ]
(7E,9Z)-1-chloro-7,9-tetradecadiene [ No CAS ]
(13E,15Z)-1-chloro-13,15-eicosadiene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82.2%		Example 4 Preparation of (13E,15Z)-1-chloro-13,15-eicosadiene (1-4: X=Cl) To a reactor were charged magnesium (5.53 g, 0.228 gram atom) and tetrahydrofuran (61.5 g), and the resulting mixture was stirred at 60 to 65 C. for 30 minutes. Then, (7E,9Z)-1-chloro-7,9-tetradecadiene (4-2: X1=Cl) (47.4 g, 0.207 mol) was added dropwise at 60 to 70 C., and the resulting mixture was stirred at 70 to 75 C. for 4 hours to prepare (7E,9Z)-7,9-tetradecadienyl magnesium chloride. To another reactor were charged cuprous iodide (0.42 g, 0.0021 mol), triethyl phosphite (0.83 g, 0.0050 mol), <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> (50.0 g, 0.238 mol) and tetrahydrofuran (20.5 g), and the resulting mixture was stirred at 0 to 5 C. for 30 minutes. Then, the solution of (7E,9Z)-7,9-tetradecadienyl magnesium chloride in tetrahydrofuran as prepared above was added dropwise at 5 to 15 C. After completion of the dropwise addition, the reaction mixture was stirred at 5 to 10 C. for 1 hour, and then the reaction was stopped by the addition of ammonium chloride (1.95 g), 20 wt % aqueous hydrogen chloride (3.14 g) and (54.8 g) to the reaction mixture. After removal of the aqueous layer by liquid-liquid separation, the organic layer was concentrated by evaporating the solvent under vacuum, and the resulting concentrate was subjected to distillation under vacuum to obtain (13E,15Z)-1-chloro-13,15-eicosadiene (1-4: X=Cl) (53.3 g, 0.170 mol) with a yield of 82.2%.

Reference： [1]Patent: US2019/322614,2019,A1 .Location in patent: Paragraph 0190

76
[ 6294-17-3 ]
[ 39151-19-4 ]
C₁₆H₂₅ClO₃ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2020,vol. 26,p. 1380 - 1387

77
[ 5054-59-1 ]
[ 6294-17-3 ]
4-((6-chlorohexyl)oxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.2%	With sodium hydrogencarbonate; potassium iodide; In N,N-dimethyl-formamide; at 60℃;Schlenk technique;	General procedure: To a solution of 15 (137 mg, 0.5 mmoL) in DMF (10 mL), KI (50 mg), NaHCO3 (250 mg) and 1-bromo-2-chloroethane (100.1 mg,0.70 mmoL) were added sequentially. The resulting solution washeated to 60 C and stirred overnight at the same temperature.After cooled to r.t., the solution was filtered through Celite toremove the insoluble material and concentrated under reducedpressure. The residue was purified by silica gel column chromatographywith EtOAc and PE (1/3, V/V) as an eluent to afford79.80 mg of compound 19A as a colorless solid.Yield, 46.4%;

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 189

78
[ 6294-17-3 ]
[ 357194-03-7 ]
3′,4'-O-diphenylmethane-3-(6-O-chlorohexyl)quercetin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	1.44 g (3.07 mmol) of 3?,4?-O-diphenylmethane quercetin was dissolved in 40 mL of DMF. 0.55 g (4.0 mmol) of K2CO3 was added. 0.46 mL (3.07 mmol) of <strong>[6294-17-3]1-bromo-6-chlorohexane</strong> was added (41), and the reaction was stirred at rt overnight. The mixture was then diluted with DCM and washed 6× with 1 M HCl, dried over MgSO4, and concentrated in vacuo. The material was purified by silica gel chromatography with 5% EtOAc/toluene. 0.63 g (1.07 mmol) of 13 was isolated as a yellow oil (35% yield). 1H NMR (300 MHz, acetone-d6) delta 12.76 (s, 1H), 9.72 (br, 1H), 7.72 (d, J=2.0 Hz, 1H), 7.63 (dd, J=7.4 Hz, J=1.8 Hz, 1H), 7.45 (m, 8H), 7.17 (m, 3H), 6.50 (d, J=1.9 Hz, 1H), 6.26 (d, J=1.9 Hz, 1H), 4.08 (t, 2H), 3.50 (t, 2H), 1.67 (m, 4H), 1.39 (m, 4H); 13C NMR (100 MHz, acetone-d6) delta 179.5, 164.9, 163.2, 157.8, 156.2, 149.9, 148.1, 140.8, 138.7, 130.2, 129.3, 126.9, 125.6, 124.9, 118.6, 109.6, 109.4, 104.8, 99.4, 94.5, 73.0, 45.6, 30.5, 28.7, 27.2, 26.0; ESI-MS: m/z: 585 [M+H]+, 607 [M+Na]+

Reference： [1]Patent: US2020/79810,2020,A1 .Location in patent: Paragraph 0111-0112

79
[ 6294-17-3 ]
[ 4773-75-5 ]
C₁₉H₃₀ClNO [ No CAS ]

Reference： [1]ACS Catalysis,2020,vol. 10,p. 4671 - 4676

80
[ 20461-89-6 ]
[ 6294-17-3 ]
C₁₁H₁₉ClO₂S₂ [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 4000 - 4005

81
[ 6294-17-3 ]
[ 7188-38-7 ]
N-(tert-butyl)-7-chloroheptanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); water; sodium t-butanolate In acetonitrile at 40℃; for 22h; Inert atmosphere; Sealed tube;	Synthesis of Alkyl Amides; Typical Procedure General procedure: To a 25 mL flame-dried Schlenk tube, alkyl halide (0.2 mmol), tertbutyl isocyanide (0.2 mmol), NiCl2(dppp) (10 mol%, 0.02 mmol), t BuONa (2 equiv, 0.4 mmol), acetonitrile (0.5 mL), and H2O (0.3 mL) were added sequentially under nitrogen. The tube was sealed and stirred at 40 °C for 22 h. The combined organic phase was concentrated and purified by silica gel column chromatography (petroleum ether-EtOAc, 20:1 to 5:1) to provide the product 3.

Reference： [1]Li, Qiao; Jin, Hongwei; Liu, Yunkui; Zhou, Bingwei [Synthesis, 2020, vol. 52, # 22, p. 3466 - 3472]

82
[ 6294-17-3 ]
(2-((5-chloro-2-((2-methoxy-4-(4-(piperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide [ No CAS ]
2-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione [ No CAS ]
3-(4-((6-(4-(1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: 1-bromo-6-chlorohexane; (2-((5-chloro-2-((2-methoxy-4-(4-(piperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 45℃; for 6h; Stage #2: 2-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 50℃; for 12h;	116 Preparation of 3-(4-((6-(4-(1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)hexyl)thi0)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS219098): A 15 mL sample bottle was sequentially charged with the Brigatinib derivative C (20 mg, 0.035 mmol) and DMF(2 mL), and 1-bromo-6-chlorohexane (20.9 mg, 0.105 mmol), sodium iodide (5.2 mg, 0.035 mmol) and potassiumcarbonate (9.7 mg, 0.07 mmol) under stirring. The mixture was heated at 45°C for 6h. After membrane filtration, thereaction mixture was subjected to preparative HPLC (eluent (v/v): acetonitrile/(water+0.05% HCl) = 10%-100%) forseparation. The acetonitrile was removed by rotary evaporation, and the residue was lyophilizated to obtain 18 mg ofthe intermediate, to be used in the next step directly. The obtained intermediate (10 mg, 0.0145 mmol) and DMF (2 mL)were added to a 15 mL sample bottle, followed by addition of SIAIS151014 (9.6 mg, 0.0348 mmol), potassium carbonate(6 mg, 0.0435 mmol), and sodium iodide (4.3 mg, 0.029 mmol). The reaction mixture was heated at 50°C for 12h, andsubjected to membrane filtration, and preparative HPLC (Eluent (v/v): acetonitrile/(water+0.05% HCl) = 10%-100%) forseparation. The acetonitrile was removed by rotary evaporation, and the residue was lyophilizated to obtain the targetproduct (5.8 mg, yellow solid, the total yield of the two steps is 35%). 1H NMR (500 MHz, MeOD) δ 8.24 (s, 1H), 8.17(s, 1H), 7.73 (dd, J = 13.8, 7.8 Hz, 1H), 7.69 - 7.63 (m, 3H), 7.55 (t, J = 7.7 Hz, 2H), 7.48 (t, J = 7.4 Hz, 1H), 7.19 (s,1H), 6.96 (d, J = 7.6 Hz, 1H), 5.18 (dd, J = 13.1, 4.8 Hz, 1H), 4.49 (d, J = 17.4 Hz, 1H), 4.45 - 4.40 (m, 1H), 3.95 (s, 3H),3.95 - 3.89 (m, 4H), 3.71 (s, 4H), 3.44-3.40 (m, 4H), 3.15-3.08 (m, 4H), 2.98 - 2.89 (m, 1H), 2.85- 2.77 (m, 1H), 2.59-2.53(m, 1H), 2.43 (t, J= 11.5 Hz, 4H), 2.35 - 2.16 (m, 4H), 1.91 (s, 3H), 1.87 (s, 3H), 1.72 - 1.61 (m, 4H), 1.58 - 1.50 (m,2H).HRMS (ESI) m/z: calcd for, C47H60ClN9O5PS+ [M+H]+, 928.3859; found, 928.3851.

Reference： [1]Current Patent Assignee: SHANGHAITECH UNIVERSITY - EP3778590, 2021, A1 Location in patent: Paragraph 0523-0524

83
[ 6294-17-3 ]
[ 332386-74-0 ]
(2R,3R)-6,8-bis(benzyloxy)-3-((6-chlorohexyl)oxy)-2-(3,4,5-tris(benzyloxy)phenyl)chromane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 16h;	4.28 Synthesis of (2R,3R)-6,8-bis(benzyloxy)-3-((6-chlorohexyl)oxy)-2-(3,4,5-tris(benzyloxy) phenyl)chromane (16a) Compound 15 (2.0g, 2.6mmol) was dissolved in anhydrous DMF (30mL), and then NaH (530mg, 22.1mmol) was added in batches, and finally 1-bromo-6-chlorohexane (1.0g, 5.0mmol) was introduced dropwise. The mixture was stirred for 16h at room temperature. After all the starting materials were consumed, the addition of water (10.0mL) was used to carefully quench the mixture. Ethyl acetate (100mL) was added to extract the target compound. The organic layer was washed with water and brine, and dried with anhydrous Na2SO4, and filtered, and then condensed under the diminished pressure to afford the crude residue, which was further purified by a silica-gel column chromatogram with a mixture of petrol ether and ethyl acetate (V/V=5/1) as an eluent to afford 1.8g of compound 16a as a yellow solid. Yield, 78%, 1H NMR (400MHz, CDCl3) δ 7.42-6.95 (m, 25H), 6.74 (s, 2H), 6.22-6.11 (m, 2H), 5.07-4.77 (m, 10H), 4.17-3.92 (m, 1H), 3.69 (s, 1H), 3.37-2.99 (m, 4H), 2.99-2.56 (m, 2H), 1.63-1.51 (m, 2H), 1.27-1.17 (m, 3H), 1.09-0.94 (m, 2H), 0.85-0.75 (m, 1H); 13C NMR (100MHz, CDCl3) δ 162.58, 158.65, 158.04, 155.50, 152.53, 137.94, 137.21, 137.17, 137.13, 137.02, 134.57, 129.77, 129.02, 128.79, 128.62, 128.57, 128.54, 128.52, 128.50, 128.47, 128.44, 128.41, 128.24, 128.21, 128.18, 128.15, 128.00, 127.92, 127.87, 127.84, 127.80, 127.78, 127.70, 127.60, 127.57, 127.54, 127.50, 127.46, 127.26, 106.70, 106.18, 105.57, 101.62, 78.28, 75.26, 73.90, 71.24, 70.12, 69.96, 69.66, 51.27, 29.75, 29.21, 28.56, 24.99, 23.21.
78%	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 16h;	4.28 Synthesis of (2R,3R)-6,8-bis(benzyloxy)-3-((6-chlorohexyl)oxy)-2-(3,4,5-tris(benzyloxy) phenyl)chromane (16a) Compound 15 (2.0g, 2.6mmol) was dissolved in anhydrous DMF (30mL), and then NaH (530mg, 22.1mmol) was added in batches, and finally 1-bromo-6-chlorohexane (1.0g, 5.0mmol) was introduced dropwise. The mixture was stirred for 16h at room temperature. After all the starting materials were consumed, the addition of water (10.0mL) was used to carefully quench the mixture. Ethyl acetate (100mL) was added to extract the target compound. The organic layer was washed with water and brine, and dried with anhydrous Na2SO4, and filtered, and then condensed under the diminished pressure to afford the crude residue, which was further purified by a silica-gel column chromatogram with a mixture of petrol ether and ethyl acetate (V/V=5/1) as an eluent to afford 1.8g of compound 16a as a yellow solid. Yield, 78%, 1H NMR (400MHz, CDCl3) δ 7.42-6.95 (m, 25H), 6.74 (s, 2H), 6.22-6.11 (m, 2H), 5.07-4.77 (m, 10H), 4.17-3.92 (m, 1H), 3.69 (s, 1H), 3.37-2.99 (m, 4H), 2.99-2.56 (m, 2H), 1.63-1.51 (m, 2H), 1.27-1.17 (m, 3H), 1.09-0.94 (m, 2H), 0.85-0.75 (m, 1H); 13C NMR (100MHz, CDCl3) δ 162.58, 158.65, 158.04, 155.50, 152.53, 137.94, 137.21, 137.17, 137.13, 137.02, 134.57, 129.77, 129.02, 128.79, 128.62, 128.57, 128.54, 128.52, 128.50, 128.47, 128.44, 128.41, 128.24, 128.21, 128.18, 128.15, 128.00, 127.92, 127.87, 127.84, 127.80, 127.78, 127.70, 127.60, 127.57, 127.54, 127.50, 127.46, 127.26, 106.70, 106.18, 105.57, 101.62, 78.28, 75.26, 73.90, 71.24, 70.12, 69.96, 69.66, 51.27, 29.75, 29.21, 28.56, 24.99, 23.21.

Reference： [1]Chen, Jiansheng; Chen, Wenming; Wang, Chunmei; Wang, Meizhu; Zhang, Xu; Zhou, Cui; Zhou, Fang; Zhou, Wen [Bioorganic Chemistry, 2022, vol. 119]
[2]Chen, Jiansheng; Chen, Wenming; Wang, Chunmei; Wang, Meizhu; Zhang, Xu; Zhou, Cui; Zhou, Fang; Zhou, Wen [Bioorganic Chemistry, 2022, vol. 119]

84
[ 6294-17-3 ]
C₂₅H₃₄O₁₂ [ No CAS ]
(2R,3S)-3-((6-chlorohexyl)oxy)-6,8-bis(methoxymethoxy)-2-(3,4,5-tris(methoxymethoxy)phenyl)chroman-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;	4.10 Synthesis of (2R, 3S)-3-((6-chlorohexyl)oxy)-6,8-bis(methoxymethoxy)-2-(3,4,5-tris(methoxy methoxy)phenyl)chroman-4-one (11a) Compound 9 (2.0g, 3.8mmol) was dissolved in anhydrous DMF (30mL), and NaH (750mg, 18.8mmol) was added in batches, and finally 1-bromo-6-chlorohexane (1.5g, 7.7mmol) was introduced dropwise. The mixture was stirred for 12h at the room temperature. After all the starting material was consumed, the addition of water (10mL) was used to carefully quench the mixture. Ethyl acetate was added to extract the target compound. The organic layer was washed with water (100mL) and brine (50mL), and dried with anhydrous Na2SO4, and filtered, and then condensed under the diminished pressure to afford the crude residue 11a without further purification.

Reference： [1]Chen, Jiansheng; Chen, Wenming; Wang, Chunmei; Wang, Meizhu; Zhang, Xu; Zhou, Cui; Zhou, Fang; Zhou, Wen [Bioorganic Chemistry, 2022, vol. 119]

85
[ 6294-17-3 ]
[ 144183-31-3 ]
tert-butyl (8-((6-chlorohexyl)oxy)octyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In water; benzene at 50℃;	40.2 Step 2: Preparation of tert-butyl (8-((6-chlorohexyl)oxy)octyl)carbamate To a solution of the compound prepared in step 1 (2.00 g, 8.15 mmol) and 1-bromo-6 chlorohexane (3.22 g, 16.3 mmol) in benzene (10 mL), tetrabutylammonium hydrogen sulfate (415 mg, 1.22 mmol) and 50% NaOH (aq) (3.84 mL) was added. The mixture was stirred overnight at 50 °C. The reaction was quenched with water and then extracted with EtOAc (2*25 mL). The combined organic layers were dried over Na2SO4 and the solvent was removed in vacuo. The crude mixture was purified by silica gel column chromatography using EtOAc/Hex (3/7) as eluent to give the title compound (964 mg, 2.65 mmol, 32 %) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ4.49 (s, 1H), 3.64-3.38 (m, 2H), 3.46-3.31 (m, 3H), 3..23-2.98 (m, 2H), 1.97-1.79 (m, 3H), 1.70-1.52 (m, 2H), 1.48-1.39 (m, 9H), 1.39-1.18 (m, 8H).

Reference： [1]Current Patent Assignee: KOREA RESEARCH INSTITUTE OF BIOSCIENCE AND BIOTECHNOLOGY; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY - EP3922632, 2021, A1 Location in patent: Paragraph 0443; 0446-0447

86
[ 120-72-9 ]
[ 6294-17-3 ]
3-((6-chlorohexyl)selanyl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With selenium; sodium t-butanolate In acetonitrile at 40℃; for 6h; Sealed tube;	3.1. 0.3 mmol scale General procedure: To a 8.0-mL scintillation vial equipped with a magnetic stirrer, indole 1a (0.36 mmol, 1.2 equiv.), selenium powder 2 (0.36 mmol, 1.2 equiv.), t-BuONa (0.45 mmol, 1.5 equiv.), solvent CH3CN (1.0 mL) and (3-bromopropyl)benzene 3a (0.30 mmol, 1.0 equiv.) sequentially added at room temperature. The vial was sealed with a screw-top septum cap and placed in a heating block that was preheated to 40 °C for 6h. After the indicated reaction time, an aqueous saturated NH4Cl solution and EtOAc were added and the layers were separated. The aqueous phase was extracted with EtOAc (x 3) and the combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (eluent: Petroleum ether/EtOAc) to give the target product 4aa as a Colorless oil.

Reference： [1]Cai, Zhong-Jian; Ji, Shun-Jun; Liu, Huan [Chinese Chemical Letters, 2022]

87
[ 80-05-7 ]
[ 6294-17-3 ]
[ 533-75-5 ]
C₄₁H₄₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: BPA With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 1-bromo-6-chlorohexane With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide at 70℃; for 9h; Stage #3: 2-hydroxy-2,4,6-cycloheptatrien-1-one With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide at 25 - 90℃; for 9.5h;	1 Example 1 Anti-ultraviolet aging biodegradable mulch film, is made up of following weight component: PBAT: 9.19 parts, ultraviolet absorber: 0.001 part, opening agent: 0.8 part (select erucamide). The synthesis of ultraviolet absorber: The first step: bisphenol A (5.0g, 21.9mmol) and anhydrous potassium carbonate (18.3g, 132.6mmol) are dissolved in 50ml without In water DMF, and stirred at 25 ° C for 30 min; 1-bromo-6-chlorohexane (10.8 g, 54.5 mmol) was added dropwise to the reaction In the system, the temperature was raised to 70 ° C, and the reaction was terminated after 9 h. The reaction solution was cooled to 25°C, poured into ice water to quench, and stirred thoroughly. After stirring, it was extracted with ethyl acetate; after separation, the organic phase was dried with anhydrous sodium sulfate, and concentrated to obtain the crude product of the first-step reaction product. The crude product obtained in the first step was purified by silica gel column chromatography using n-hexane and ethyl acetate to obtain the first step. pure product of the reaction. The second step: dissolve cycloheptatrienol ketone (3.95g, 32.4mmol) with anhydrous potassium carbonate (4.45g, 32.2 mmol) In 50ml of anhydrous DMF and 18-crown-6 (0.142g, 0.54mmol), and stirred at 25C for 30min; (7.14g, 15.4mmol) the pure product (6.28g, 15.5mmol) obtained in the first step was dropped into the reaction system, and the temperature was raised to 90 °C, the reaction was completed after 9h. The reaction solution was cooled to 25°C and then poured into ice water to quench, fully stirred and extracted with ethyl acetate; After separation, the organic phase was dried with anhydrous sodium sulfate, and concentrated to obtain the crude product of the second-step reaction product. The crude product obtained in the second step Purify with silica gel column chromatography, the solvent used is n-hexane and ethyl acetate to obtain ultraviolet absorber, the structural formula is as follows:

Reference： [1]Current Patent Assignee: INST OF ENVIRONMENT AND SUSTAINABLE DEVELOPMENT IN AGRICULTURE CHINESE ACADEMY OF AGRICULTURAL SCIEN - CN114163322, 2022, A Location in patent: Paragraph 0019-0026

88
[ 6294-17-3 ]
[ 99970-80-6 ]
6-(6-chlorohexoxy)-2-(pyridin-2-yl)-1,3-benzothiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With Cs₂CO₃ In acetonitrile Heating;	2.2.2.1. Alkylation of 6-hydroxy-2-(pyridin-2-yl)-1,3-benzothiazole 1 with terminal bromochloroalkanes General procedure: General procedure: Cs2CO3 was added to a solution of 6-hydroxy-2-(pyridin-2-yl)-1,3-benzothiazole 1 (1eq.) in 10ml of acetonitrile, and then the corresponding dihaloalkane (1eq.) was added. The mixture was stirred with heating for 30-35h. The progress of the reaction was monitored by TLC using a CHCl3:CH3OH (20:1) system as an eluent. After the completion of the reaction, the solvent was removed from the reaction mixture under reduced pressure. The resulting mixture was added with water and extracted with ethyl acetate (3x50 ml). The organic fraction was washed with 2% NaOH solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. To remove unreacted haloalkane, the resulting solid was recrystallized from methanol.

Reference： [1]Abramovich, Maksim S.; Barskaya, Elena S.; Beloglazkina, Elena K.; Berezina, Anna V.; Chorbu, Alexander A.; Guk, Dmitry A.; Krasnovskaya, Olga O.; Lyssenko, Konstantin A.; Moiseeva, Anna A.; Polyakova, Margarita N.; Rzheutski, Artem V.; Zyk, Nikolai V. [Polyhedron, 2022, vol. 221]

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P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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

[ CAS No. 6294-17-3 ] {[proInfo.proName]}

Quality Control of [ 6294-17-3 ]

Related Doc. of [ 6294-17-3 ]

Product Details of [ 6294-17-3 ]

Calculated chemistry of [ 6294-17-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 6294-17-3 ]

Application In Synthesis of [ 6294-17-3 ]

[ 6294-17-3 ] Synthesis Path-Upstream 1~10

[ 6294-17-3 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry