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[ CAS No. 622-95-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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

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Chemical Structure| 622-95-7

Chemical Structure| 622-95-7

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Quality Control of [ 622-95-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 622-95-7 ]

Product Details of [ 622-95-7 ]

CAS No. :	622-95-7	MDL No. :	MFCD00040714
Formula :	C₇H₆BrCl	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KQNBRMUBPRGXSL-UHFFFAOYSA-N
M.W :	205.48	Pubchem ID :	69329
Synonyms :

Calculated chemistry of [ 622-95-7 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.29
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.17 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.32
Log Po/w (XLOGP3) :	3.35
Log Po/w (WLOGP) :	3.08
Log Po/w (MLOGP) :	3.68
Log Po/w (SILICOS-IT) :	3.49
Consensus Log Po/w :	3.18

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.65
Solubility :	0.0458 mg/ml ; 0.000223 mol/l
Class :	Soluble
Log S (Ali) :	-3.03
Solubility :	0.193 mg/ml ; 0.000939 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.28
Solubility :	0.0109 mg/ml ; 0.000053 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.52

Safety of [ 622-95-7 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	1759
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 622-95-7 ]

* 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 [ 622-95-7 ]
Downstream synthetic route of [ 622-95-7 ]

[ 622-95-7 ] Synthesis Path-Upstream 1~16

1
[ 622-95-7 ]
[ 2948-92-7 ]
[ 442-52-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 20℃; for 16 h;	Under a nitrogen atmosphere, compound 10 (0.24mmol, 49mg) was dissolved in freshly distilled THF (0.75mL), then cooled to 0°C. To this solution was added 60percent NaH in oil (0.36mmol, 14.4mg) and the mixture was stirred at 0°C for 5min. 4-Chlorobenzyl bromide (0.26mmol, 54mg) was added followed by the addition of tetrabutylammonium iodide (0.024mmol, 9mg). The mixture was stirred at rt overnight, then diluted with water (2mL) and EtOAc (5mL). The aqueous phase was separated and extracted twice with EtOAc. The combined organic phases were dried over MgSO₄, filtered and concentrated in vacuo. The crude was purified by chromatography on silica gel (eluent: EtOAc) to afford the desired target 11 in 65percent yield (m=51mg) as a colorless solid. Mp 101–102°C. ¹H NMR (300MHz, CDCl₃) δ 7.83–7.77 (m, 1H), 7.32–7.22 (m, 5H), 7.06 (d, J=8.7Hz, 2H), 5.58 (s, 2H), 3.90 (s, 2H), 2.58 (m, 4H), 1.76 (m, 4H); ¹³C NMR (75MHz, CDCl₃) δ 152.3, 142.5, 135.9, 135.3, 133.6, 129.1 (2C), 128.1 (2C), 122.9, 122.7, 120.0, 109.7, 54.8 (2C), 53.2, 46.8, 23.7 (2C); HRMS (ESI) Calcd for C₁₉H₂₁N₃Cl [M+H]⁺ 326.1424, Found 326.1427; FTIR (neat) cm⁻¹ 2958, 2927, 2875, 2810, 1488, 1463, 1403, 1294, 1088, 1034, 1014, 742, 487.
195 mg	Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.0833333 h; Inert atmosphere Stage #2: With tetrabutylammomium bromide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere	1-(4-Chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole dihydrochloride (1). Under an atmosphere of nitrogen, compound 36 (250 mg, 1.24 mmol, 1 equiv) was dissolved in freshly distilled warm tetrahydrofuran (THF) (2.5 mL), then cooled to 0 °C. To this solution was added 60percent NaH in oil (100 mg, 60 mg pure, 2.48 mmol, 2 equiv) and the mixture stirred at 0 °C for 5 min. 4-Chlorobenzyl bromide (255 mg, 1.24 mmol, 1 equiv) was added followed by the addition of tetra-n-butylammonium bromide (23 mg, 0.07 mmol, 6 mol percent). The mixture was stirred at rt overnight, then diluted with a solution of water (2 drops) in THF (5 mL). The solution was filtered through Celite, and the Celite was washed with THF (50 mL) and then EtOAc (50 mL). The filtrate was concentrated and the remaining residue purified by flash column chromatography on silica gel (EtOAc) to give the free base (195 mg) as an oil (R_f = 0.46, EtOAc). To a solution of the free base in MeOH (2 mL) was added a solution of 37percent aqueous HCl (158 mg, 1.60 mmol, 2.7 equiv) in MeOH (2 mL). The mixture was concentrated, Et₂O (5 mL) was added, and the mixture concentrated again. High-vacuum drying gave the product (242 mg, 0.61 mmol, 49percent) as a white solid; mp 232-234 °C; R_f = 0 (EtOAc); ¹H NMR (400 MHz, CD₃OD): δ 2.10-2.26 (m, 4H), 3.55-3.78 (m, 4H), 5.21 (s, 2H), 5.95 (s, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.53-7.68 (m, 3H), 7.92 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CD₃OD): δ 24.0, 48.0, 50.0, 56.5, 114.4, 117.3, 128.0, 128.1, 129.9, 130.4, 134.0, 134.3, 135.1, 135.7, 144.5; HRMS (ESI) [M-Cl]⁺ Calcd for C₁₉H₂₁N₃Cl: 326.1424. Found: 326.1433.

Reference： [1] Tetrahedron, 2015, vol. 71, # 4, p. 700 - 708
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6788 - 6795

2
[ 622-95-7 ]
[ 104-86-9 ]

Reference： [1] Journal of the Chemical Society, 1931, p. 1225,1232
[2] Organic Letters, 2014, vol. 16, # 2, p. 484 - 487
[3] Organic Letters, 2014, vol. 16, # 17, p. 4424 - 4427

3
[ 106-38-7 ]
[ 106-43-4 ]
[ 104-83-6 ]
[ 622-95-7 ]
[ 589-17-3 ]

Reference： [1] Monatshefte fur Chemie, 1999, vol. 130, # 12, p. 1493 - 1497

4
[ 622-95-7 ]
[ 74-89-5 ]
[ 104-11-0 ]

Reference： [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 1, p. 40 - 44
[2] Journal of Medicinal Chemistry, 1998, vol. 41, # 15, p. 2882 - 2891

5
[ 622-95-7 ]
[ 15184-98-2 ]
[ 104-11-0 ]

Reference： [1] Green Chemistry, 2018, vol. 20, # 14, p. 3339 - 3345

6
[ 622-95-7 ]
[ 74-89-5 ]
[ 6970-85-0 ]
[ 104-11-0 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 1206

7
[ 7677-24-9 ]
[ 622-95-7 ]
[ 140-53-4 ]

Reference： [1] Synlett, 2009, # 8, p. 1291 - 1294
[2] Organic and Biomolecular Chemistry, 2016, vol. 14, # 10, p. 2828 - 2832

8
[ 151-50-8 ]
[ 622-95-7 ]
[ 140-53-4 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 6, p. 1239 - 1242[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 6, p. 1365 - 1368
[3] American Chemical Journal, 1880, vol. 2, p. 88
[4] Scientia Pharmaceutica, 2001, vol. 69, # 4, p. 329 - 350

9
[ 143-33-9 ]
[ 622-95-7 ]
[ 140-53-4 ]

Reference： [1] Journal of Physical Organic Chemistry, 2000, vol. 13, # 10, p. 587 - 590

10
[ 106-43-4 ]
[ 57310-39-1 ]
[ 622-95-7 ]

Reference： [1] Tetrahedron Letters, 2007, vol. 48, # 18, p. 3247 - 3250

11
[ 622-95-7 ]
[ 2012-74-0 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 6, p. 1239 - 1242[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 6, p. 1365 - 1368

12
[ 622-95-7 ]
[ 14091-08-8 ]

Reference： [1] Journal of the American Chemical Society, 1989, vol. 111, # 6, p. 2353 - 2355

13
[ 84713-70-2 ]
[ 622-95-7 ]
[ 7424-00-2 ]

Reference： [1] Synthesis, 1984, # 4, p. 313 - 315

14
[ 622-95-7 ]
[ 25015-63-8 ]
[ 517920-59-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With magnesium; triethylamine In tetrahydrofuran at 65℃; for 15 h;	Example 8Preparation of pinacol ester of 4-chlorobenzylboronic acid Magnesium turnings (2.4 mg, 0.1 mmol, 10 mol percent) are introduced into a 2 necks Schlenk-type flask, provided with a magnetic stirring bar and topped by a coolant, then 10 ml of distilled THF are added. Triethylamine (59 mg, 1 mmol) and pinacolborane (0.384 g, 3 mmol) are introduced therein. 4-chlorobenzyl bromide (0.207 g, 1 mmol) dissolved into 10 ml of distilled THF is then added drop by drop in the solution using a dropping funnel. Thereafter, the reactive mixture is stirred for approximately 15 hours at THF reflux (65° C.).At the end of the reaction, the crude reaction product is hydrolyzed by 20 ml of water neutral and extracted by diethyl ether (3.x.40 ml). The joined organic phases are washed by 2.x.ml of neutral water then dried on MgSO₄. After solvent evaporation, the pinacol ester is obtained with a yield of 90percent at a total conversion of the starting bromide (yield/conversion of 90percent). The resulting boronic ester is analyzed by GC, NMR ¹H and ¹³C and GC/MS.CharacterizationsNMR ¹H: 7.2 (2H, D, 8 Hz); 6.9 (2H, D, 8 Hz); 1.9 (2H, s); 1.3 (12H, s).NMR ¹³C: 138; 131.3; 130.5; 128.8; 83.8; 33.5; 21.4.Mass spectrometry: 254-252 (M+, 1-4percent); 127 (32percent); 126 (20percent); 125 (100percent); 124 (20percent); 63 (12percent).

Reference： [1] Journal of the American Chemical Society, 2010, vol. 132, # 34, p. 11825 - 11827
[2] Journal of the American Chemical Society, 2010, vol. 132, # 34, p. 11825 - 11827
[3] Patent: US2011/282090, 2011, A1, . Location in patent: Page/Page column 8

15
[ 622-95-7 ]
[ 73183-34-3 ]
[ 517920-59-1 ]

Yield	Reaction Conditions	Operation in experiment
31%	With copper(l) iodide; lithium methanolate; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 14 h; Inert atmosphere	4-Chlorobenzyl bromide (640 mg, 3.12 mmol), boronic acid pinacol ester (1.2 mg, 10 mmol), CuI (97 mg,0.5 mmol), LiOMe (365 mg, 4.68 mmol), PPh3 (106 mg, 0.41 mmol) and DMF (15 mL) were added to a 100 mL reaction flask. After replacing three times with nitrogen, the reaction was carried out at room temperature for 14 h, and TLC was monitored until the starting material was completely reacted. The reaction solution was poured into 100 mL of water, and the CuI was removed by filtration and washed three times with EA. The filtrate was collected and separated, and the aqueous phase was extracted with EA (60 mL*3). The title compound 30b (250 mg, 31percent) was obtained.

Reference： [1] Patent: CN108341777, 2018, A, . Location in patent: Paragraph 0445-0448

16
[ 622-95-7 ]
[ 375854-57-2 ]

Reference： [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 9, p. 1463 - 1467

[ 622-95-7 ] Synthesis Path-Downstream 1~88

1
[ 636-93-1 ]
[ 622-95-7 ]
2-(4-chloro-benzyloxy)-1-methoxy-4-nitro-benzene [ No CAS ]

Reference： [1]Journal of the Chemical Society,1927,p. 2241

2
[ 874-33-9 ]
[ 622-95-7 ]
[ 857939-83-4 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1933,vol. 507,p. 1,9

3
[ 622-95-7 ]
[ 74-89-5 ]
[ 6970-85-0 ]
[ 104-11-0 ]

Reference： [1]Journal of the Chemical Society,1929,p. 1206

4
[ 19975-56-5 ]
[ 622-95-7 ]
2-(4-chloro-phenethylsulfanyl)-4,5-dihydro-thiazole [ No CAS ]

Reference： [1]Tetrahedron Letters,1971,p. 4359 - 4362

5
[ 98-88-4 ]
[ 622-95-7 ]
[ 5216-35-3 ]
[ 6332-83-8 ]

Reference： [1]Chemistry Letters,1981,p. 1135 - 1138

6
[ 119838-38-9 ]
[ 622-95-7 ]
[ 123052-81-3 ]

Reference： [1]Liebigs Annalen der Chemie,1989,p. 1215 - 1232

7
[ 622-95-7 ]
[ 116970-50-4 ]
[ 116970-58-2 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 46 - 50

8
[ 622-95-7 ]
[ 74-89-5 ]
[ 104-11-0 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 40 - 44
[2]Journal of Medicinal Chemistry,1998,vol. 41,p. 2882 - 2891

9
[ 51784-03-3 ]
[ 622-95-7 ]
2-[1-(4-Chloro-benzyl)-piperidin-4-yl]-benzooxazole [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 707 - 718

10
[ 116861-31-5 ]
[ 622-95-7 ]
[ 174310-66-8 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 715 - 721

11
[ 1873-77-4 ]
[ 622-95-7 ]
[ 402-49-3 ]
[ 6140-17-6 ]
[ 106-43-4 ]
[ 5089-31-6 ]

Reference： [1]Tetrahedron,1997,vol. 53,p. 8479 - 8490

12
[ 144978-12-1 ]
[ 622-95-7 ]
(2R,4S)-4-(4-Chloro-benzyl)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4559 - 4570

13
[ 107819-90-9 ]
[ 622-95-7 ]
1,3-bis-tert-butoxycarbonyl-1-(4'-chlorobenzyl)-2-methyl-2-thiopseudourea [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5505 - 5511

14
[ 622-95-7 ]
[ 98-80-6 ]
[ 831-81-2 ]

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 375 - 376
[2]Tetrahedron Letters,2004,vol. 45,p. 6959 - 6962
[3]Applied Organometallic Chemistry,2012,vol. 26,p. 301 - 304

15
[ 1119-72-8 ]
[ 622-95-7 ]
[ 454647-00-8 ]

Reference： [1]Synthesis,2005,p. 1479 - 1490
[2]Macromolecules,2004,vol. 37,p. 8538 - 8547
[3]Molecular Crystals and Liquid Crystals,2005,vol. 440,p. 215 - 222

16
[ 64123-77-9 ]
[ 622-95-7 ]
[ 605679-99-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 7584 - 7587

17
[ 22876-21-7 ]
[ 622-95-7 ]
2-(4-chlorobenzylthio)-5-nitrobenzo[d]oxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In chloroform; at 60.0℃; for 2h;	To a suspension of <strong>[22876-21-7]5-nitrobenzo[d]oxazole-2(3H)-thione</strong> (196.2mg, l.Ommol) in chloroform (1OmL) was added triethylamine (278 muL, 2mmol) followed by 1- (bromomethyl)-4-chlorobenzene (226mg, l.lmmol). The reaction was stirred at 6O0C for 2h. After cooling, the reaction was diluted with ethyl acetate, washed with dilute aqueous hydrochloric solution and brine. The combined organic layers were dried over anhydrous MgSO4 and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes 1:10 v/v to afford 250mg (78%) of the title compound (LCMS RT= 7.64min) <n="137"/>1H NMR (DMSO): 8.52 (IH, d, J 2.3 Hz), 8.27 (IH, dd, J 8.9 2.3 Hz), 7.92 (IH, d, J 9.0 Hz), 7.58 (2H, d, J 8.5 Hz), 7.42 (2H, d, J 8.5 Hz), 4.67 (2H, s)

Reference： [1]Patent: WO2007/91106,2007,A2 .Location in patent: Page/Page column 134-135

18
[ 106-43-4 ]
[ 57310-39-1 ]
[ 622-95-7 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 3247 - 3250

19
[ 622-95-7 ]
[ 2012-74-0 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1986,vol. 35,p. 1239 - 1242
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1986,p. 1365 - 1368

20
[ 622-95-7 ]
(+-)-2-(4-<2-(4-chloro-benzhydryloxy)-ethyl>-piperazino)-ethanol [ No CAS ]
[ 14173-39-8 ]

Reference： [1]Liebigs Annalen der Chemie,1989,p. 1215 - 1232

21
[ 104-11-0 ]
[ 622-95-7 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1926,vol. 449,p. 264

22
[ 109-07-9 ]
[ 622-95-7 ]
[ 685535-97-1 ]

Yield	Reaction Conditions	Operation in experiment
59%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	3.49 g (17.0 MMOL) 4-CHLOROBENZYLBROMIDE was added dropwise to a mixture of 2.04 G (20.4 MMOL) 2-Methyl piperazine and 2.40 ml (17 MMOL) triethylamine in 60 ml DMF at room temperature. The reaction mixture was stirred for 16 hours at room temperature, the poured onto aq. sodium bicarbonate solution and extracted with ethylacetate. Purification of the crude product by flash chromatography gave 2.26 g (10.1 mmol, 59 %) of 1- (4-chloro- benzyl)-3-methyl-piperazine as colorless oil. 1H-NMR (400 MHz, DMSO-d6): 0.91 (d, 3H), 1.56 (t, 1H), 1.90 (TD, 1H), 1.91-2. 03 (m, 1 H), 2.56-2. 74, m, 4H), 2.79 (dt, 1 H), 3.40 and 3.44 (AB-Sys., 2H), 7.33 (d, 2H), 7.40 (d, 2H). MS (ESI+) : 225 [M+H] +

Reference： [1]Patent: WO2004/37796,2004,A2 .Location in patent: Page 130

Yield	Reaction Conditions	Operation in experiment
	With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS);	EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...

Reference： [1]Patent: US2004/102629,2004,A1 .Location in patent: Page 16-18

24
[ 405-05-0 ]
[ 622-95-7 ]
[ 918524-00-2 ]

Yield	Reaction Conditions	Operation in experiment
86.0%		4-(4-Chloro-benzyloxy)-3-fluoro-benzaldehyde 46 was synthesized in one step from 3- fluoro-4-hydroxy-benzaldehyde 44 as shown in Scheme 10.Scheme 10 <n="83"/>Step I - Synthesis qf4-(4-chlorn-henzyloxy)-3-fluoro-benzaldehgammade (46):[0186] To 3-iluoro-4-hydroxy-benzaldehyde (44, 0.800 g. 5,71 mmol) in N.N-dimethylformamide (50.0 mL) was added sodium hydride (260.0 mg, 60percent in mineral oil, 6.50 mmol). After 15 minutes, 4-chlorobenzyl bromide (45, 1.29 g, 6.28 mmol) was added to the reaction mixture. The reaction was stirred at 80 0C for 5 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30percent ethyl acetate in hexane to give the compound (46, 1.3 g, 86.0percent).
86.0%		Example 5: Synthesis of aldehyde reagents for coupling to 7-azaindoles[0140] 4-(4-Chloro-benzyloxy)-3~omegauoro-benzaldehyde 46 was synthesized in one step from 3- fluoro-4-hydtauoxy-benzaldehyde 44 as shown in Scheme 14,Scheme 14Step I - Synthesis of4-(4-chloro-benzyloxy)-3-fluoro-benzaldehyde (46):[0141] To <strong>[405-05-0]3-fluoro-4-hydroxy-benzaldehyde</strong> (44, 0.800 g, 5.71 mmol) in N,N-dimethylformamide (50.0 mL) was added sodium hydride (260.0 mg, 60percent in mineral oil, 6.50 mmol). After 15 minutes, 4-chlorobenzyl bromide (22, 1.29 g, 6.28 mmol) was added to the reaction mixture. The reaction was stirred at 80 0C for 5 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30percent ethyl acetate in hcxanc to give the compound (46, 1.3 g, 86.0percent).
86%		To <strong>[405-05-0]3-fluoro-4-hydroxy-benzaldehyde</strong> (598, 0.800 g, 5.71 mmol) in N,N-dimethylformamide (50.0 mL) was added sodium hydride (260.0 mg, 60percent in mineral oil, 6.50 mmol). After 15 minutes, 4-chlorobenzyl bromide (557, 1.29 g, 6.28 mmol) was added to the reaction mixture. The reaction was stirred at 80 0C for 5 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30percent ethyl acetate in hexane to give the compound (599, 1.3 g, 86.0percent).

Reference： [1]Patent: WO2008/79909,2008,A1 .Location in patent: Page/Page column 81-82
[2]Patent: WO2008/80001,2008,A2 .Location in patent: Page/Page column 61
[3]Patent: WO2007/2325,2007,A1 .Location in patent: Page/Page column 167

25
[ 1852-17-1 ]
[ 622-95-7 ]
[ 34790-85-7 ]

Yield	Reaction Conditions	Operation in experiment
		l-(4-Chlorobenzyl)tetrahydropyrimidin-2(lH)-onePotassium tert butoxide (1.34 g) and tetrahydropyrimidine-2(lH)-one (1.2 g) in THF (15 ml) was stirred at room temperature for 45 min, cooled to 0 0C and 4-chlolorobenzyl bromide (2.46 g) was added. After 15 min at 0 0C the the reaction mixture was stirred at room temperature for 35 min, methanol (3 ml) was added and after 1 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-2% methanol in dichloromethane, 0.2% NH4OH) to give sub title compound (265 mg). 1H-NMR (CD3OD, 400 MHz): delta 7.367.24 (m, 4H); 4.48 (s, 2H); 3.22 (m, 4H); 1.85 (s, 2H). APCI-MS: m/z 224 (MH+)

Reference： [1]Patent: WO2008/136754,2008,A1 .Location in patent: Page/Page column 39

26
[ 622-95-7 ]
[ 190900-21-1 ]
[ 1076243-01-0 ]

Yield	Reaction Conditions	Operation in experiment
		4-(4-Chloro-benzyl)-5-oxo-[l,4]diazepane-l-carboxylic acid t-butyl ester5-Oxo-[l,4]diazepane-l-carboxylic acid t-butyl ester (70 mg, 0.33 mmol) was added to a solution of KHMDS (91 mg, 0.46 mmol) in dry THF (1.6 ml) at app. -70 0C. After stirring <n="39"/>for 15 min the/?-chlorobenzyl bromide (74 mg, 0.36 mmol) was added to the reaction mixture. The reaction was quenched after 6 h at -75 0C by addition OfH2O and diluted with CH2Cl2. The organic phase was washed with H2O and filtered through an Extrelut tube.(R)., which was rinsed with CH2Cl2. The resulting organic phase was evaporated and purified by flash chromatography (SiO2, CH2Cl2-EtOAc) to give 50 mg of the subtitled compound as a semisolid.1R NMR (CD3OD) delta 7.31 (m, 4H), 4.58 (s, 2H), 3.59 (m, 2H), 3.44-3.50 (m, 4H), 2.75 (m,2H), 1.45 (s, 9H).

Reference： [1]Patent: WO2008/136754,2008,A1 .Location in patent: Page/Page column 37-38

27
[ 7533-40-6 ]
[ 622-95-7 ]
[ 321329-46-8 ]

Yield	Reaction Conditions	Operation in experiment
		According to Scheme 13, a solution of (R)-leucinol (1.288 g, 11 mmol) in 5 mL of THF at RT was added dropwise to a stirred suspension of potassium hydride (0.485 g, 12.1 mmol) in 25 mL of dry THF. After overnight stirring at RT, a solution of 4-chlorobenzylbromide (2.25 g, 11 mmol) in 5 mL of THF was added dropwise . The stirring was continued for additional 3 h. The solvent was evaporated and the residue was partitioned between water and ether. The ether layer was washed with brine, dried and the solvent was removed in vacuo to provide 2.1 g of ether 101

Reference： [1]Patent: US2003/229092,2003,A1 .Location in patent: Page 23; 24

28
[ 109-09-1 ]
[ 844501-71-9 ]
[ 622-95-7 ]
[ 1190280-80-8 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 5479 - 5481

29
[ 17180-93-7 ]
[ 844501-71-9 ]
[ 622-95-7 ]
[ 1190280-76-2 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 5479 - 5481

30
[ 461-89-2 ]
[ 622-95-7 ]
[ 1207441-70-0 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 20℃; for 0.25h;Inert atmosphere;	According to Scheme 4 Step 1: To a solution of 6-Azauracyl (5 g, 44.2 mmol) and 4-chlorobenzyl bromide (9.09 g, 44.2 mmol) in DMSO (190 mL) under nitrogen atmosphere was added portionwise NaH (55%) (1.93 g, 44.2 mmol) at room temperature. The reaction mixture was stirred during 15 min. 300 mL of water was added and the aqueous layer was extracted thrice with ethyl acetate (300 mL). The combined organic layers were washed twice with water (200 mL), dried over MgSO4, filtered and concentrated under reduce pressure to afford a yellow solid. The crude solid was purified by flash chromatography with silica gel using CH2Cl2/MeOH 98/2 as eluant to afford 4-(4-chlorobenzyl)-<strong>[461-89-2]1,2,4-triazine-3,5(2H,4H)-dione</strong> 7(A) (6.4 g, 61%) as a white solid.LC1: Rt=3.48MS m/z (ES) [M-H]-=236

Reference： [1]Patent: US2010/4246,2010,A1 .Location in patent: Page/Page column 30

31
[ 932-53-6 ]
[ 622-95-7 ]
[ 1207441-71-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 20℃; for 0.25h;Inert atmosphere;	According to Scheme 4 Step 1: To a solution of Azathymine (300 mg, 2.36 mmol) and 4-chlorobenzyl bromide (485 mg, 2.36 mmol) in DMSO (10 mL) was added portionwise NaH (55%) (103 mg, 2.36 mmol) at room temperature under nitrogen atmosphere. The mixture was stirred for 15 min at room temperature. Ethyl Acetate was then added (150 mL) and the organic layer was extracted thrice with water (100 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to afford a yellow solid. The crude solid was purified by flash chromatography with silica gel using CH2Cl2/MeOH 98/2 as eluant to afford 4-(4-chlorobenzyl)-<strong>[932-53-6]6-methyl-1,2,4-triazine-3,5(2H,4H)-dione</strong> 8(A) (500 mg, 84%) as a white solid.LC1: Rt=3.66MS m/z (ES) [M-H]-=249

Reference： [1]Patent: US2010/4246,2010,A1 .Location in patent: Page/Page column 30-31

32
[ 4956-05-2 ]
[ 622-95-7 ]
[ 1207441-63-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 20℃; for 0.25h;	According to Scheme 2 Step 2: to a solution of of 4-chlorobenzyl bromide (1 g, 5.2 mmol) and 2(A) (1.1 g, 5.2 mmol) in DMSO (10 mL) was added portionwise NaH(55%) (230 mg, 5.2 mmol). After 15 min at room temperature the reaction mixture was quenched with water and extracted with ethyl acetate (×3). The combined organic layers were successively washed with water (×2), with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography, 50 gr column, (Eluant: DCM/MeOH 98/2) to obtain 0.856 g of 4-(4-chlorobenzyl)-<strong>[4956-05-2]6-bromo-1,2,4-triazine-3,5(2H,4H)-dione</strong> 2(B).LC1: Rt=3.93MS m/z (ES) [M-H]-=315.8

Reference： [1]Patent: US2010/4246,2010,A1 .Location in patent: Page/Page column 27

33
[ 93247-78-0 ]
[ 622-95-7 ]
[ 1097196-86-5 ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of <strong>[93247-78-0]methyl indole-7-carboxylate</strong> (6.0 g) and DMF (60 mL) was ice-cooled, and potassium tert-butoxide (5.38 g) was added thereto, followed by stirring at the same temperature for 30 minutes. Then, 4-chlorobenzylbromide (7.39 g) was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was ice-cooled, and water (60 mL) was added thereto, followed by extraction with ethyl acetate (80 mL). The organic layer was washed with 1 M hydrochloric acid, a saturated sodium bicarbonate solution, and saturated saline in this order, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was left to stand for 3 days for solidification, and washed with hexane-ethyl acetate (8:1, 18 mL) to obtain methyl 1-(4-chlorobenzyl)-1H-indole-7-carboxylate (4.94 g) as a pale yellow solid.

Reference： [1]Patent: EP2172447,2010,A1 .Location in patent: Page/Page column 17

34
[ 150008-24-5 ]
[ 622-95-7 ]
[ 224178-71-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2942 - 2945

35
[ 14755-02-3 ]
[ 622-95-7 ]
[ 1227290-44-9 ]

Reference： [1]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 181 - 184

36
[ 16635-23-7 ]
[ 622-95-7 ]
[ 831-81-2 ]

Reference： [1]Advanced Synthesis and Catalysis,2010,vol. 352,p. 1718 - 1727

37
[ 622-95-7 ]
[ 25015-63-8 ]
[ 517920-59-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With magnesium; triethylamine; In tetrahydrofuran; at 65℃; for 15h;	Example 8Preparation of pinacol ester of 4-chlorobenzylboronic acid Magnesium turnings (2.4 mg, 0.1 mmol, 10 mol %) are introduced into a 2 necks Schlenk-type flask, provided with a magnetic stirring bar and topped by a coolant, then 10 ml of distilled THF are added. Triethylamine (59 mg, 1 mmol) and pinacolborane (0.384 g, 3 mmol) are introduced therein. 4-chlorobenzyl bromide (0.207 g, 1 mmol) dissolved into 10 ml of distilled THF is then added drop by drop in the solution using a dropping funnel. Thereafter, the reactive mixture is stirred for approximately 15 hours at THF reflux (65 C.).At the end of the reaction, the crude reaction product is hydrolyzed by 20 ml of water neutral and extracted by diethyl ether (3×40 ml). The joined organic phases are washed by 2×ml of neutral water then dried on MgSO4. After solvent evaporation, the pinacol ester is obtained with a yield of 90% at a total conversion of the starting bromide (yield/conversion of 90%). The resulting boronic ester is analyzed by GC, NMR 1H and 13C and GC/MS.CharacterizationsNMR 1H: 7.2 (2H, D, 8 Hz); 6.9 (2H, D, 8 Hz); 1.9 (2H, s); 1.3 (12H, s).NMR 13C: 138; 131.3; 130.5; 128.8; 83.8; 33.5; 21.4.Mass spectrometry: 254-252 (M+, 1-4%); 127 (32%); 126 (20%); 125 (100%); 124 (20%); 63 (12%).

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 11825 - 11827
[2]Journal of the American Chemical Society,2010,vol. 132,p. 11825 - 11827
[3]Patent: US2011/282090,2011,A1 .Location in patent: Page/Page column 8

38
[ 152537-03-6 ]
[ 622-95-7 ]
[ 1257858-35-7 ]

Yield	Reaction Conditions	Operation in experiment
74%		Step A: 3-r2-(4-Chloro-benzyloxy)-ethyl1-azetidine-1 -carboxylic acid tert-butyl ester. To a solution consisting of 3-(2-hydroxy-ethyl)-azetidine-1 - carboxylic acid tert-butyl ester (0.250 g, 1.24 mmol) and THF (2 ml_) at 0 0C was added sodium hydride (0.0459 g, 0.124 mmol). The reaction was stirred at 0 C for 0.5 h, then treated with tetrabutylammonium iodide (0.0459 g,0.124 mmol) and 4-chlorobenzyl bromide (0.383 g, 1.86 mmol), warmed to rt and stirred for 16 h. The reaction was quenched with saturated aqueous NH4CI (1.0 ml_), diluted with ethyl acetate (40 ml_) and extracted with 1 N NaOH (40 ml_). The organic layer was dried (MgSO4) and concentrated. The residue was purified (FCC) to give the title compound as a yellow oil (0.302 g, 74%). 1H NMR (de-DMSO): 7.40 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 4.42 (s, 2H), 3.88 (t, J = 8.0 Hz, 2H), 3.53-3.44 (m, 2H), 3.40 (t, J = 6.2 Hz, 2H), 2.62-2.53 (m, 1 H), 1.84-1.74 (m, 2H), 1.36 (s, 9H).

Reference： [1]Patent: WO2010/141809,2010,A1 .Location in patent: Page/Page column 61

39
[ 71486-53-8 ]
[ 622-95-7 ]
[ 1225491-24-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h;	0.800 g of <strong>[71486-53-8]methyl 4-oxopiperidine-3-carboxylate hydrochloride</strong> (4.134 mmol), 1.44 mL (8.268 mmol) of diisopropylethylamine and 0.852 g (4.134 mmol) of 4-chloro-benzyl bromide were stirred at room temperature in 16.0 mL of anhydrous CH2C12.The reaction was monitored by HPLC and UPLC-MS. After 16 h at room temperature, brine was added to the reaction mixture.The organic phase was separated, dried over Na2SO4 and concentrated in vacuo to give pure methyl methyl 1-(4-chlorobenzyl)-4-oxopiperidine-3-carboxylate (1.164 g, 4.133 mmol, quantitative yield).The product was used for the next step without further manipulation. MS(ESI+): 282.1.
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h;	0.800 g of <strong>[71486-53-8]methyl 4-oxopiperidine-3-carboxylate hydrochloride</strong> (4.134 mmol), 1.44 mL (8.268 mmol) of diisopropylethylamine and 0.852 g (4.134 mmol) of 4-chloro-benzyl bromide were stirred at room temperature in 16.0 mL of anhydrous CH2CI2. The reaction was monitored by HPLC and UPLC-MS. After 16 h at room temperature, brine was added to the reaction mixture. The organic phase was separated, dried over Na2S04 and concentrated in vacuo to give pure methyl methyl l-(4-chlorobenzyl)-4- oxopiperidine-3-carboxylate (1.164 g, 4.133 mmol, quantitative yield). The product was used for the next step without further manipulation.

Reference： [1]Patent: EP2361911,2011,A1 .Location in patent: Page/Page column 19; 20
[2]Patent: WO2011/101804,2011,A1 .Location in patent: Page/Page column 55

40
[ 1004-40-6 ]
[ 622-95-7 ]
2-(para-chlorobenzylthio)-6-aminouracil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In ethanol; water; at 20 - 50℃; for 17h;	General procedure: In 2-dram vials (round bottom, 15x75 mm) containing substituted alkyl or benzyl bromides (0.800 mmol) was added 0.5 mL of EtOH via a syringe. The stock solution containing 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (0.500 mmol) and 3.45 M aqueous solution of NaOH (0.800 mmol) in EtOH was prepared as followed. In a 250 mL round-bottom flask was added 4.82 g of 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, 69.6 mL of EtOH, 20 mL of water, and 10.4 mL of 3.25 M aqueous solution of NaOH. This mixture was stirred at rt until a homogenous solution was formed. 2.50 mL of this stock solution was dispensed into each 2-dram vial.The vials were capped and heated to 50 C in a shaker. After 17 h, LCMSs were randomly taken from different reactions and all showed product formation cleanly. All vials were placed in a Genevac to remove the solvents and the product was purified by mass-directed high throughput purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1055 - 1060

41
[ 57473-33-3 ]
[ 622-95-7 ]
C₁₂H₇Cl₂N₃O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2230 - 2234

42
[ 622-95-7 ]
[ 92-52-4 ]
[ 831-81-2 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2754 - 2757

43
[ 622-95-7 ]
[ 208580-23-8 ]
[ 1359818-47-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate; In acetonitrile; for 7h;Reflux;	Step 1 Potassium carbonate (0.7 g, 5.1 mmol) and 4-chlorobenzyl bromide (0.76 g, 3.7 mmol) were added to mixture of 7-bromo-3-(ethoxycarbonyl)quinolin-4(1H)-one (1.0 g, 3.4 mmol) and acetonitrile (20 mL), and stirred under heating at reflux for 7 hours. The insoluble matter was removed by filtering, and the filtrate was washed by ethyl acetate and concentrated in vacuo. The resulting solid was washed by water and hexane to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinolin-4(1H)-one (1.11 g, yield: 78%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s).
61%	With potassium carbonate; In acetonitrile; at 100℃; for 5h;	[Example 44] Preparation of 1-(4-chlorobenzyl)-7-(phenylamino)-3-(ethoxycarbonyl)quinoline-4(1H)-one (I-148) To a mixture of 7-bromo-3-(ethoxycarbonyl)quinoline-4(1H)-one (250 mg, 0.844 mmol) and acetonitrile (5 mL) were added potassium carbonate (175 mg, 1.27 mmol) and 4-chlorobenzylbromide (208 mg, 1.01 mmol), and the resulting mixture was stirred at 100C for 5 hours. The insoluble were removed by filtration and washed by ethyl acetate. The mother liquor was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinoline-4(1H)-one (216 mg, Yield: 61%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s).
61%	With potassium carbonate; In acetonitrile; at 100℃; for 5h;	EXAMPLE 44 Preparation of 1-(4-chlorobenzyl)-7-(phenylamino)-3-(ethoxycarbonyl)quinoline-4(1H)-one (I-148) To a mixture of 7-promo-3-(ethoxycarbonyl)quinoline-4(1H)-one (250 mg, 0.844 mmol) and acetonitrile (5 mL) were added potassium carbonate (175 mg, 1.27 mmol) and 4-chlorobenzylbromide (208 mg, 1.01 mmol), and the resulting mixture was stirred at 100 C. for 5 hours. The insoluble were removed by filtration and washed by ethyl acetate. The mother liquor was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinoline-4(1H)-one (216 mg, Yield: 61%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s).

Reference： [1]Patent: US2016/24072,2016,A1 .Location in patent: Paragraph 0393-0394
[2]Patent: EP2604260,2013,A1 .Location in patent: Paragraph 0404; 0405
[3]Patent: US9212130,2015,B2 .Location in patent: Page/Page column 246; 247

44
[ 1193-24-4 ]
[ 622-95-7 ]
[ 1447910-90-8 ]

Yield	Reaction Conditions	Operation in experiment
500 mg	With silver carbonate; In tetrahydrofuran; for 2h;Reflux;	B) 6- ( (4-Chlorobenzyl) oxy) pyrimidin-4 (3H) -one. To a stirred solution of pyrimidine-4 , 6-diol (2.5 g) in THF (25 ml) was added silver carbonate (15.3 g) at room temperature followed by dropwise addition of 4-chlorobenzyl bromide (4.58 g) , and the resultant mixture was heated at reflux for 2 h. The reaction mixture was then cooled to room temperature, filtered through Celite, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM) to give the title compound (500 mg) as a white solid. MS (ESI+) : [M+H]+ 237.2.

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1116 - 1139
[2]Patent: WO2013/105676,2013,A1 .Location in patent: Page/Page column 114

45
[ 38427-94-0 ]
[ 622-95-7 ]
[ 1445435-47-1 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 3476 - 3479
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 16 - 20

46
[ 622-95-7 ]
[ 208580-23-8 ]
[ 1359815-92-1 ]

Reference： [1]Patent: EP2604260,2013,A1
[2]Patent: US9212130,2015,B2

47
[ 590418-08-9 ]
[ 622-95-7 ]
[ 1627143-94-5 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 4404 - 4407
Angew. Chem.,2014,vol. 126,p. 4493 - 4496,4

48
[ 442-51-3 ]
[ 622-95-7 ]
2-(4-chlorobenzyl)-7-methoxy-1-methyl-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 339 - 343

49
[ 442-51-3 ]
[ 622-95-7 ]
9-(4-chlorobenzyl)-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 339 - 343

50
[ 344-14-9 ]
[ 622-95-7 ]
C₁₂H₁₂ClFO₄ [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 972 - 975

51
[ 622-95-7 ]
[ 122-72-5 ]

Reference： [1]Organic Letters,2015,vol. 17,p. 1954 - 1957

52
[ 1078-58-6 ]
[ 622-95-7 ]
[ 831-81-2 ]

Reference： [1]Angewandte Chemie - International Edition,2015,vol. 54,p. 5688 - 5692
Angew. Chem.,2015,vol. 127,p. 5780 - 5784,5
Angewandte Chemie,2015,vol. 127,p. 5780 - 5784,5

53
[ 1303587-99-6 ]
[ 622-95-7 ]
2-chloro-8-(4-chlorobenzyl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0℃; for 1h;Inert atmosphere;	Synthesis of 2-chloro-8-(4-chlorobenzyl)-7 , 8-dihydro-6H-pyrimido [5, 4-b] [I, 4] oxazine [0450] To a stirred solution of 2-chloro-7, 8-dihydro-6H-pyrimido [5, 4-b] [1, 4] oxazine (150 mg, 0.87 mmol) in DMF (3 mL) under argon atmosphere were added sodium hydride (40 mg, 1.75 mmol) and l-(bromomethyl)-4-chlorobenzene (215 mg, 1.05 mmol) at 0 C. The reaction mixture was stirred for 1 h at 0 C. After consumption of the starting materials (monitored by TLC), the reaction was diluted with water (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with n-pentane (2 x 5 mL) to afford 2- chloro-8-(4-chlorobenzyl)-7, 8-dihydro-6H-pyrimido [5, 4-b] [1, 4] oxazine (190 mg, 73%) as an off-white solid. 1H-NMR (DMSO-<, 500 MHz): delta 7.73 (s, 1H), 7.42 (d, 2H), 7.33 (d, 2H), 4.78 (s, 2H), 4.20-4.18 (m, 2H), 3.52-3.49 (m, 2H); LCMS: 295.8 (M+); (column; X- Select CSH C-18 (50 3.0 mm, 3.5 mupiiota); RT 3.81 min. 0.05% Aq TFA: ACN; 0.80 mL/min); UPLC (purity): 91.4%; (column; Acquity UPLC BEH C-18 2.1 X 50 mm, 1.7 mupiiota); RT 2.52 min. ACN: 0.025% TFA (Aq); 0.50 mL/min; TLC: 30% EtOAc:hexanes (R 0.6).

Reference： [1]Patent: WO2015/66697,2015,A1 .Location in patent: Paragraph 0450

54
[ 622-95-7 ]
[ 288-36-8 ]
C₉H₈ClN₃ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7146 - 7148

55
[ 622-95-7 ]
[ 130403-91-7 ]
(S)-3-(tert-butyldimethylsilyloxy)-1-(4-chlorobenzyl)pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%		A 60% dispersion of sodium hydride in mineral oil (0.608 g, 13.9 mmol) was added to a stirred solution of <strong>[130403-91-7](S)-3-((tert-butyldimethylsilyl)oxy)pyrrolidin-2-one</strong> (2.0 g, 9.29 mmol, from example 114, step A) in THF (7 mL) at 0 C. After 15 min, a solution of 1-(bromomethyl)-4-chlorobenzene (1.72 g, 8.37 mmol) in THF (7 mL) was added to the reaction mixture. The resulting mixture was stirred at RT for 6 h. The reaction was quenched with pellets of ice. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The crude reaction mixture was purified using silica gel column chromatography (0-15% EtOAc/hexanes) to afford (5)-3-((tert-butyldimethylsilyl)oxy)-1-(4-chlorobenzyl)pyrrolidin-2-one (1.34 g, 42% yield): LCMS (M+H)+340.2; 1H NMR (500 MHz, chloroform-d) delta 1H NMR (500 MHz, chloroform-d) delta 7.36-7.29 (m, J=8.4 Hz, 2H), 7.23-7.16 (m, J=8.4 Hz, 2H), 4.51-4.33 (m, 3H), 3.31-3.22 (m, 1H), 3.11 (dt, J=9.7, 7.4 Hz, 1H), 2.37-2.25 (m, 1H), 1.97-1.84 (m, 1H), 0.95 (s, 9H), 0.21 (s, 3H), 0.18 (s, 3H).

Reference： [1]Patent: US2015/191452,2015,A1 .Location in patent: Paragraph 0682

56
[ 22818-40-2 ]
[ 622-95-7 ]
[4-(4-chloro)benzyloxy]-D-phenylglycine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 9354 - 9370

57
[ 622-95-7 ]
[ 208580-23-8 ]
1-(4-chlorobenzyl)-7-[4-(5-fluoro-2-pyridyloxy)phenylamino]-3-(ethoxycarbonyl)quinolin-4(1H)-one [ No CAS ]

Reference： [1]Patent: US2016/24072,2016,A1

58
[ 199174-29-3 ]
[ 622-95-7 ]
(R)-3-[(4-chloro-benzylamino)-methyl]-pyrrolidine-1-carboxylic tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine; In acetonitrile; at 20℃;	11555] (R)-3-Aminomethyl-pyrrolidine-1 -carboxylic acid tert-butyl ester (0.385 g, 1.92 mmol) and 1 -bromomethyl-4- chloro-benzene (0.395 g, 1.92 mmol) were dissolved in acetonitrile at 0 C. (10 mE) and triethyl amine (0.793 mE, 5.76 mmol) was added. The solution was allowed to warm to room temperature and stir overnight. The reaction was concentrated down and partitioned between iN NaOH and extracted with CH2C12 (3x). The organics were collected together and dried over MgSO4, filtered and evaporated in vacuo. The residue was purified by Isco flash system (20% hexane/80% ethyl acetate) to yield the product (0.35 g, 57%).

Reference： [1]Patent: US2016/31908,2016,A1 .Location in patent: Paragraph 1555

59
[ 199174-29-3 ]
[ 622-95-7 ]
3-[(4-chloro-benzyl)-ethyl-amino]-methyl}-pyrrolidine-1-carboxylic tert-butyl ester [ No CAS ]

Reference： [1]Patent: US2016/31908,2016,A1

60
[ 622-95-7 ]
[ 98619-07-9 ]
1-(2-fluoro-4-((4-chlorobenzyl)oxy)phenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In acetonitrile; for 8.0h;Reflux;	General procedure: The starting material (1.0 mmol) was suspended in acetonitrile (20 mL) containing K2CO3 (2.0 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (1.2 mmol) and heated under reflux for 8 h. The reaction progress was monitored using silica gel TLC with Petroleum ether/EtOAc as mobile phase. Upon completion, the acetonitrile was evaporated in vacuo and the mixture was then poured into water, which was extracted with 3 x 50 mL of EtOAc, washed with brine, dried over anhydrous Na2SO4 and purified by chromatography (PE/EA, 50:1, 20:1, 10:1) on silica gel.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 5929 - 5940

61
[ 80096-64-6 ]
[ 622-95-7 ]
[ 1361926-63-7 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In acetonitrile; for 8.0h;Reflux;	General procedure: The starting material (1.0 mmol) was suspended in acetonitrile (20 mL) containing K2CO3 (2.0 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (1.2 mmol) and heated under reflux for 8 h. The reaction progress was monitored using silica gel TLC with Petroleum ether/EtOAc as mobile phase. Upon completion, the acetonitrile was evaporated in vacuo and the mixture was then poured into water, which was extracted with 3 x 50 mL of EtOAc, washed with brine, dried over anhydrous Na2SO4 and purified by chromatography (PE/EA, 50:1, 20:1, 10:1) on silica gel.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 5929 - 5940

62
[ 185613-91-6 ]
[ 622-95-7 ]
4-(benzo[d][1,3]dioxol-5-yl)-N-(4-chlorobenzyl)thiazole-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17.1%		4-(Benzo[d][1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. After dropwise addition of 4chlorobenzylbromide (1.40 g, 6.82 mmol) slowly at room temperature and reacted for 10 minutes. After the reaction wasfinished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 isdissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by columnchromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1g to give. Yield 17.1%
17%		General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product.

Reference： [1]Patent: KR101651208,2016,B1 .Location in patent: Paragraph 0148-0150
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4854 - 4857

63
[ 699-51-4 ]
[ 622-95-7 ]
3-(4-chlorobenzyl)-1,3-diazaspiro[4.4]nonane-2,4-dione [ No CAS ]

Reference： [1]CrystEngComm,2017,vol. 19,p. 469 - 483

64
[ 622-95-7 ]
[ 186663-74-1 ]
tert-butyl (2-((4-chlorobenzyl)oxy)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;Inert atmosphere;	General procedure: To a solution of the corresponding N-Boc-aminophenol (1 mmol) in DMF (2 mL), K2CO3 (207 mg,1.5 mmol) and the required benzyl bromide (1 mmol) were added. The mixture was stirred at 60 Cuntil no starting material was observed by TLC. A saturated aqueous solution of ammonium chloridewas added (5 mL) and the resulting mixture extracted with EtOAc (10 mL ×3), the organic extractswashed with brine (20 mL) and dried over MgSO4. The crude product was purified by FC eluting withhexane/EtOAc (95:5 ? 9:1).

Reference： [1]Synlett,2017,vol. 28,p. 471 - 474

65
[ 91348-45-7 ]
[ 622-95-7 ]
ethyl 3-bromo-1-(4-chlorobenzyl)-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;	General procedure: To a solution of (1) (1 mmol) and K2CO3 (3 mmol) in dry dimethylformamide (DMF) (10 mL) was added benzyl bromide or 4-chlorobenzyl bromide (1 mmol). The resulting mixture was stirred at room temperature under nitrogen gas for 24 h. Crushed ice was added and the white precipitate was collected under vacuum suction, washed with cold water, dried, and re-crystallized from ethanol to get pure product.
77%	With potassium carbonate; In N,N-dimethyl-formamide; for 48h;	General procedure: To a mechanically stirred mixture of (1) (27.97 mmol),K2CO3 (83.91 mmol) and dry DMF (50 mL), benzyl bromideor 4-chlorobenzyl bromide (30.77 mmol) was addeddropwise respectively. After stirring for 48 h, the solutionwas filtered and the filtrate was extracted with ethyl acetate(3 × 20 mL). The combined organic extracts were washedwith water (50 mL) and brine (50 mL), dried over sodiumsulfate and concentrated. The crude product was purified bycolumn chromatography using a mixture of ethyl acetate/hexane (20:80) as eluent to give the title compounds (2a/b).

Reference： [1]Medicinal Chemistry Research,2017,vol. 26,p. 745 - 759
[2]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 1542 - 1552
[3]Medicinal Chemistry Research,2018,vol. 27,p. 903 - 914

66
[ 5932-27-4 ]
[ 622-95-7 ]
C₁₃H₁₃ClN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%		(<strong>[5932-27-4]ethyl 1H-pyrazole-3-carboxylate</strong>, 1.050 g, 7.49 mmol) was dissolved in ACN (20 mL)Cs2CO3 (2.4 g, 1.0 eq) was added. After stirring for 30 minutes, 4-chlorobenzyl bromide (1.7 g, 1.1 eq) was further added, and the mixture was stirred at room temperature for 5 hours.The solvent was evaporated off, extracted with MC, treated with MgSO4, filtered, and silica-columned with EA: Hex (1: 3) to give starting material 1 (836 mg, 42percent).

Reference： [1]Patent: KR2016/137199,2016,A .Location in patent: Paragraph 0049; 0050; 0051; 0052; 0053

67
[ 622-95-7 ]
[ 35344-95-7 ]
1-(4-chlorobenzyl)-1H-pyrazole-4-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
162 mg	With caesium carbonate; In acetonitrile; at 20℃; for 2h;	To a solution of <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (70 mg, 728 mumol) in MeCN (5 mL) was added 1-(bromomethyl)-4-chlorobenzene (149 mg, 728 mumol) and cesium carbonate (472 mg, 1.45 mmol). The mixture was stirred at r.t. for 2h. The mixture was concentrated, diluted with EA and water. The organic phase was washed with brine (10 mL x 2), dried over Na2SO4and concentrated to give 1-(4-chlorobenzyl)-1H- <strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (162 mg, 101 percent) as a white solid, which was used in the next step without further purification

Reference： [1]Patent: KR2017/45749,2017,A .Location in patent: Paragraph 1033; 1036-1038

68
[ 269410-08-4 ]
4-(di-tert-butylphosphino)-N,N-dimethylaniline-dichloropalladium [ No CAS ]
[ 62150-45-2 ]
[ 622-95-7 ]
4-[1-(4-chlorobenzyl)-1H-pyrazol-4-yl]pyridine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;	Step 1. 4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]pyridine-2-carbonitrile 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.60 g, 3.1 mmol, Aldrich) in DMF (16 mL) was treated with 1-(bromomethyl)-4-chlorobenzene (0.70 g, 3.4 mmol, Aldrich) and K2CO3 (1.3 g, 9.3 mmol). After stirring for 2 hours, the mixture was partitioned between water and EtOAc. The organic layer was washed with water, followed by brine, dried over Na2SO4, filtered, and concentrated. The crude product (0.90 g, 2.8 mmol) was combined with <strong>[62150-45-2]4-bromopyridine-2-carbonitrile</strong> (0.45 g, 2.4 mmol, Synthonix), CsF (1 g, 6 mmol), and 4-(di-tert-butylphosphino)-N,N-dimethylaniline-dichloropalladium (2:1) (0.15 g, 0.22 mmol, Aldrich) in 1,4-dioxane (6 mL, 70 mmol) and water (1 mL, 70 mmol). The mixture was degassed and heated to 100° C. for 10 minutes. Upon cooling to room temperature, the mixture was partitioned between water and EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-70percent EtOAc in hexanes. Yield: 0.38 g, 44percent.

Reference： [1]Patent: US2017/190689,2017,A1

69
[ 62150-45-2 ]
[ 622-95-7 ]
4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]pyridine-2-carboximidamide [ No CAS ]

Reference： [1]Patent: US2017/190689,2017,A1

70
[ 1115-70-4 ]
[ 622-95-7 ]
N’’-methyl(4-chlorophenyl)-N,N-dimethylimino dicarboanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17.13%	With potassium iodide; sodium hydroxide; In dichloromethane; at 20℃; for 19h;	To the 250 ml round bottom flask, 8 g (12 mmol) of <strong>[1115-70-4]metformin hydrochloride</strong> and 100 ml of methylene chloride were added, and 40 ml of 25% sodium hydroxide was added. After stirring and clarification, 3 pellets of potassium iodide were added and 9.92 g (48.3 mmol ), 10 minutes or so dripping, magnetic stirring, room temperature, a total reaction of 19 hours, after treatment. Reaction flask to see the solid, filtration, dichloromethane 5ml washing, drying, to be a colorless solid 5.6g. The solid was dissolved in 220 ml of acetonitrile, cooled, and crystallized to give 2.1 g of a colorless solid. Yield 17.13%

Reference： [1]Patent: CN104829497,2017,B .Location in patent: Paragraph 0131; 0132

71
[ 622-95-7 ]
[ 133831-28-4 ]
methyl (E)-1-(4-chlorobenzyl)-3-((2-(4,5-dihydro-1H-imidazol-2-yl)hydrazono)methyl)-1H-indole-6-carboxylate hydrobromide [ No CAS ]

Reference： [1]Journal of Antibiotics,2017,vol. 70,p. 832 - 844

72
[ 622-95-7 ]
[ 166272-81-7 ]
C₁₅H₁₂Cl₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 10188 - 10204

73
[ 64318-28-1 ]
[ 622-95-7 ]
2-(4-((4-chlorobenzyl)oxy)phenyl)ethan-1-aminium chloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 232 - 244

74
[ 64318-28-1 ]
[ 622-95-7 ]
tert-butyl (4-((4-chlorobenzyl)oxy)phenethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate; In acetone; for 4h;Reflux;	General procedure: To a N-Boc-tyramine dissolved in acetone was added benzyl bromide derivative and potassium carbonate. The reaction mixture was refluxed at 50-60 C for 4 h. After the reaction, the reaction mixture was filtered, and filtered solution was evaporated in vacuo. The product residue was purified by column chromatography. Using Method C, N-Boc-tyramine (0.50 g, 2.1 mmol), 4-chlorobenzyl bromide (0.41 mL, 3.2 mmol), and potassium carbonate (1.17 g, 8.4 mmol) gave 11i as a white solid (0.70 g, 96%): Rf = 0.34 (EtOAc 1: n-Hexane 3): 1H NMR (DMSO-d6, 400 MHz) d 1.36 (s, C(CH3)3), 2.58-2.66 (m, NHCH2CH2), 3.04-3.14 (m, NHCH2CH2), 5.06 (s, OCH2), 6.84 (t, J = 5.4 Hz, NH), 6.88-6.95 (m, 2 ArH), 7.07-7.13 (m, 2 ArH), 7.41-7.50 (m, 4 ArH); 13C NMR (DMSO-d6, 75 MHz) d 28.2 (C(CH3)3), 34.6 (NHCH2CH2), 41.7 (NHCH2CH2), 68.3 (OCH2), 77.4 (C(CH3)3), 114.6, 128.4, 129.3, 129.56, 131.7, 132.3 (ArC-Cl), 136.3 (10 ArC), 155.5 (C(O)), 156.5 (OArC).

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 232 - 244

75
[ 6625-96-3 ]
[ 622-95-7 ]
1-(4-chlorobenzyl)-5-nitro-1H-indole-3-carbaldehyde [ No CAS ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2018,vol. 33,p. 727 - 742

76
[ 622-95-7 ]
[ 485-71-2 ]
C₂₆H₂₈ClN₂O⁽¹⁺⁾*Br^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In tetrahydrofuran;Reflux;	General procedure: The phase-transfer catalysts (C1-C11) were synthesized according to the proceduresbelow. To a solution of cinchonidine (1.00 g, 3.4 mmol) in THF (50 mL) was addedthe aryl benzyl bromides (3.4 mmol). The mixture was heated for 6-8 h at reflux.After cooling to room temperature, the mixture was poured into MTBE (150 mL)under stirring. The precipitated solid was filtrated and recrystallized fromCH3OH/MTBE to afford C1-C11

Reference： [1]Beilstein Journal of Organic Chemistry,2018,vol. 14,p. 1421 - 1427

77
[ 85006-25-3 ]
[ 622-95-7 ]
tert-butyl (tert-butoxycarbonyl)oxy(4-chlorobenzyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; at 20℃;	A solution of tert-butyl (tert-butoxycarbonyl) oxycarbamate (2.497 g, 10.71 mmol) and 1- (bromomethyl) -4-chlorobenzene (2 g, 9.73 mmol) in DCM (25 mL) Was added NaOH (10.71 mL, 10.71 mmol) followed by tetrabutylammonium bromide (3.14 g, 9.73 mmol) and stirred overnight at room temperature. Water (100 mL) was added to the reaction mixture, and the product was extracted with ethyl acetate (3 * 100 mL), and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to give 5.4 g of crude material. The crude material was purified by Iscor using a 40 g silica gel column and the product was eluted with 10% ethyl acetate in petroleum ether to give tert-butyl (tert-butoxycarbonyl) oxy (4-chlorobenzyl) carbamate (3.1 g, 8.66 mmol, 89% yield) as a colorless sticky material.

Reference： [1]Patent: KR2018/64507,2018,A .Location in patent: Paragraph 0106; 0111-0113

78
[ 622-95-7 ]
[ 15184-98-2 ]
[ 104-11-0 ]

Reference： [1]Green Chemistry,2018,vol. 20,p. 3339 - 3345

79
[ 622-95-7 ]
[ 73183-34-3 ]
[ 517920-59-1 ]

Yield	Reaction Conditions	Operation in experiment
56%	With 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate; palladium diacetate; In 1,4-dioxane; at 65 - 100℃; for 19h;Inert atmosphere;	General procedure: Procedure1: An oven-dried three-neck round bottom flask was fitted with a condenser. Pd(OAc)2 (145.7 mg, 0.649 mmol), dppf (359.5 mg, 0.649 mmol) bis(pinacolato)diboron (4.120 g, 16.22 mmol) and potassium acetate (1.592 g, 16.22 mmol) were added to the flask. The flask was evacuated and backfilled with argon (this process was repeated a total of 3 times). Benzyl bromide (2.000 g, 11.69 mmol) was added followed by the addition of 1,4-dioxane (30 mL). The reaction mixture was heated to 100 for 4 h and 65 for 15 h and then cooled to room temperature. The reaction mixture was passed through a plug of silica gel eluting with EtOAc and washed with saturated brine (3×50 mL). The organic layers were dried over MgSO4, concentrated in vacuo, and the residue was purified by silica gel flash chromatography.
31%	With copper(l) iodide; lithium methanolate; triphenylphosphine; In N,N-dimethyl-formamide; at 20℃; for 14h;Inert atmosphere;	4-Chlorobenzyl bromide (640 mg, 3.12 mmol), boronic acid pinacol ester (1.2 mg, 10 mmol), CuI (97 mg,0.5 mmol), LiOMe (365 mg, 4.68 mmol), PPh3 (106 mg, 0.41 mmol) and DMF (15 mL) were added to a 100 mL reaction flask. After replacing three times with nitrogen, the reaction was carried out at room temperature for 14 h, and TLC was monitored until the starting material was completely reacted. The reaction solution was poured into 100 mL of water, and the CuI was removed by filtration and washed three times with EA. The filtrate was collected and separated, and the aqueous phase was extracted with EA (60 mL*3). The title compound 30b (250 mg, 31%) was obtained.

Reference： [1]Tetrahedron Letters,2019,vol. 60,p. 1321 - 1324
[2]Patent: CN108341777,2018,A .Location in patent: Paragraph 0445-0448

80
[ 23612-48-8 ]
[ 622-95-7 ]
C₁₅H₁₃ClN₂ [ No CAS ]

Reference： [1]Patent: WO2019/28309,2019,A1 .Location in patent: Page/Page column 36; 37

81
[ 622-95-7 ]
[ 57090-88-7 ]
1-(4-chlorobenzyl)-1H-imidazole-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.2%	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h;	Compound cyanoimidazole (1.00 g, 10.74 mmol), N,N-dimethylformamide (20 ml), 1-(bromomethyl)-4-chlorobenzene (2.65 g, 12.89 mmol) and cesium carbonate (7.00 g, 21.48 mmol) was sequentially added to a dry 100 ml one-neck flask at room temperature, and heated to 100°C for 16 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, poured into 200 ml of water and extracted with ethyl acetate (80 ml 3 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified through a chromatography column (petroleum ether: ethyl acetate = 1:1) give a product 1-(4-chlorobenzyl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (0.80 g, yellow oil), yield 34.2percent. 1H-NMR(CDCl3, 400 MHz):8.22(s,1H), 8.04 (s, 1H), 7.46-7.44(d,J =8.4Hz, 2H), 7.35-7.33(d,J=8.0Hz, 2H), 5.29 (s,2H).

Reference： [1]Patent: EP3434674,2019,A1 .Location in patent: Paragraph 0172; 0173

82
[ 622-95-7 ]
[ 10111-08-7 ]
1-(4-chlorobenzyl)-1H-imidazole-2-carbaldehyde [ No CAS ]

Reference： [1]Bioorganic Chemistry,2019,vol. 88

83
[ 54840-15-2 ]
[ 622-95-7 ]
[ 1416442-73-3 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of N-Boc protected 4-aminophenol (6a, 1.0 g, 4.78 mmol, 1.0 eq) in DMF (15 mL) was added K2CO3 (1.32 g, 9.56 mmol, 2.0 eq) and stirred for 15 min followed by the addition of 4-Chlorobenzyl bromide (7, 1.18 g, 5.74 mmol, 1.2 eq) over 15 min and stirred at r.t for 12 h. Water was added and the aqueous solution was extracted with EtOAc (3×25 mL) followed by brine, dried over Na2SO4 and evaporated in vacuo to leave a colorless solid. The crude compound was triturated with ether to furnish 8c which was sufficiently pure for the next step. 1H NMR (600 MHz, DMSO-d6) delta 9.13 (s, 1H), 7.49-7.40 (m, 4H), 7.33 (d, J=7.9 Hz, 2H), 6.90 (d, J=9.0 Hz, 2H), 5.03 (s, 2H), 1.45 (s, 9H).

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 4669 - 4682
[2]Patent: US2019/240244,2019,A1 .Location in patent: Paragraph 0118

84
[ 10357-68-3 ]
[ 622-95-7 ]
8-bromo-7-(4-chlorobenzyl)-3,7-dihydro-1H-purine-2,6-dione [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 5586 - 5594

85
[ 4481-62-3 ]
[ 622-95-7 ]
C₃₇H₅₁ClO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a suspension of <strong>[4481-62-3]betulonic acid</strong> (0.94 g, 2.07 mmol) and K2CO3(1.43 g, 10.35 mmol) in anhydrous DMF (10 mL) was added 4-chlorobenzylbromide (0.85 g, 4.14 mmol) at rt. The reaction mixture wasstirred for 24 h. Then the reaction mixture was poured into water andextracted with CH2Cl2 for three times. The organic layer was washedwith brine, dried over anhydrous Na2SO4, and concentrated under reducedpressure. The residue was purified by silica gel column (petroleumether/EtOAc as eluent) to give product 11 (0.90 g). White solid,yield: 76%. 1H NMR (400 MHz, CDCl3) delta: 7.38-7.31 (m, 4H, Ph), 5.11(2d, J=12 Hz, 2H, CH2Ph), 4.75 (s, 1H, C=CH, in C29), 4.63 (s, 1H,C=CH, in C29), 3.06-2.99 (m, 1H, in C19), 2.52-2.35 (m, 2H, in C2),1.70 (s, 3H, CH3), 1.08 (s, 3H, CH3), 1.04 (s, 3H, CH3), 0.97 (s, 3H,CH3), 0.93 (s, 3H, CH3), 0.80 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3)delta: 213.18 (s), 176.02 (s), 150.34 (s), 134.17 (s), 133.25 (s), 129.88 (s),128.30 (s), 109.73 (s), 62.64 (s), 56.53 (s), 53.27 (s), 51.53 (s), 50.60(s), 49.35 (s), 42.40 (s), 37.01 (s), 36.88 (s), 35.60 (s), 30.57 (s), 29.70(s), 26.64 (s), 26.36 (s), 25.39 (s), 24.17 (s), 22.83 (s), 22.62 (s), 22.35(s), 20.81 (s), 20.60 (s), 20.24 (s), 19.29 (s), 18.75 (s), 16.21 (s), 16.18(s), 14.74 (s). ESI-HRMS (m/z): calcd for C37H52ClO3 [M+H]+:579.3599, found 579.3604.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 2871 - 2882

86
[ 54840-15-2 ]
[ 622-95-7 ]
[ 34762-56-6 ]

Reference： [1]Patent: US2019/240244,2019,A1

87
[ 2034-22-2 ]
[ 622-95-7 ]
[ 31250-84-7 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;	A mixture of <strong>[2034-22-2]2,4,5-tribromo-1H-imidazole</strong> (120 g, 393.75 mmol, 1 equiv.), 1-(bromomethyl)-4-chlorobenzene (100 g, 486.67 mmol, 1.236 equiv.) and Cs2CO3 (200 g, 613.84 mmol, 1.559 equiv.) in DMF (1000 mL) was stirred at room temperature for 16 hours. To the reaction mixture was added EtOAc (500 mL) and H2O (300 mL). The organic layer was washed with H2O (2 X 300mL) and brine (300 mL), dried over anhydrous Na2SO4, filtered. The filtrate was concentrated to afford 2,4,5-tribromo-1-[(4-chlorophenyl)methyl]-1H-imidazole (170 g, crude) as a light yellow solid.

Reference： [1]Patent: WO2019/173327,2019,A1 .Location in patent: Page/Page column 34

88
[ 622-95-7 ]
[ 26364-65-8 ]
[ 94777-01-2 ]

Yield	Reaction Conditions	Operation in experiment
80.2%	With sodium hydroxide; In water; acetonitrile; at 20℃; for 8h;	General procedure: Thiazolidin-2-ylidene-cyanamide (0.317 g, 2.50 mmol) inacetonitrile (20 mL) was dropwise added to a stirred solutionof substituted benzyl bromide (2.5 mmol) and 14 mL NaOHaqueous solution (1 M). The mixture is stirred at room temperaturefor 8-10 h. The soild was collected by filtration,washed with n-hexane and dried in vacuo.

Reference： [1]Journal of Chemical Crystallography,2020

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Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
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P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
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P263	Avoid contact during pregnancy/while nursing.
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P270	Do not eat, drink or smoke when using this product.
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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.
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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.
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P312	Call a POISON CENTER or doctor/physician if you feel unwell.
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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.
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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
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Ghs Hazard Statements

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