[ CAS No. 5399-03-1 ] {[proInfo.proName]}

Name: 5399-03-1|2-Iodo-1-methoxy-4-nitrobenzene|95%
Brand: Ambeed
SKU: A112188
Rating: 93 (40 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 5399-03-1

Structure of 5399-03-1 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 5399-03-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 5399-03-1 ]

SDS Specification

Alternatived Products of [ 5399-03-1 ]

Product Details of [ 5399-03-1 ]

CAS No. :	5399-03-1	MDL No. :	MFCD00024328
Formula :	C₇H₆INO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KBQBNJHOTNIGDD-UHFFFAOYSA-N
M.W :	279.03	Pubchem ID :	94806
Synonyms :

Calculated chemistry of [ 5399-03-1 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	54.47
TPSA :	55.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.32 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.71
Log Po/w (XLOGP3) :	2.37
Log Po/w (WLOGP) :	2.21
Log Po/w (MLOGP) :	1.53
Log Po/w (SILICOS-IT) :	0.64
Consensus Log Po/w :	1.69

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.3
Solubility :	0.139 mg/ml ; 0.0005 mol/l
Class :	Soluble
Log S (Ali) :	-3.17
Solubility :	0.19 mg/ml ; 0.000681 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.85
Solubility :	0.391 mg/ml ; 0.0014 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.18

Safety of [ 5399-03-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 5399-03-1 ]

* 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 [ 5399-03-1 ]
Downstream synthetic route of [ 5399-03-1 ]

[ 5399-03-1 ] Synthesis Path-Upstream 1~24

1
[ 5399-03-1 ]
[ 6639-36-7 ]

Reference： [1] European Journal of Organic Chemistry, 2011, # 1, p. 53 - 57

2
[ 100-17-4 ]
[ 5399-03-1 ]

Reference： [1] Molecules, 2005, vol. 10, # 10, p. 1307 - 1317
[2] Bulletin of the Chemical Society of Japan, 1997, vol. 70, # 7, p. 1665 - 1669
[3] Tetrahedron, 2004, vol. 60, # 41, p. 9113 - 9119
[4] Molecules, 2005, vol. 10, # 2, p. 394 - 400
[5] Synthesis, 2006, # 7, p. 1195 - 1199
[6] Synthesis, 2004, # 3, p. 441 - 445
[7] Asian Journal of Chemistry, 2011, vol. 23, # 1, p. 41 - 43
[8] Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3552 - 3555
[9] Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 4, p. 951 - 956
[10] Journal of the American Chemical Society, 1930, vol. 52, p. 1570
[11] Journal of the Chemical Society, 1916, vol. 109, p. 1087
[12] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834

3
[ 99-59-2 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: With sulfuric acid; sodium nitrite In water at 5℃; Stage #2: With potassium iodide In water at 90℃; for 1 h;	Step A. 2-Iodo-1-methoxy-4-nitrobenzene 2-Methoxy-5-nitroaniline (10.0 g, 0.060 mol) was stirred in water (150 mL) and concentrated (conc.) sulfuric acid (12 mL, 0.22 mol). The solution was cooled below 5° C. with an ice-salt bath, and a solution of sodium nitrite (4.8 g, 0.070 mol) in water (40 mL) was added dropwise while maintaining the temperature below 5° C. A solution of potassium iodide (16.8 g, 0.101 mol) was added and the mixture was heated to 90° C. for 1 hour. Cooling to 0° C. gave dark red crystals which were filtered, washed with water, and dried. Purification by silica gel chromatography using ethyl acetate/hexanes gave the desired compound (13.6 g, 75percent). ¹H NMR (300 MHz, DMSO-d₆): δ 8.57 (s, 1H), 8.28 (d, 1H), 7.19 (d, 1H), 3.98 (s, 3H). LCMS for C₇H₇INO₃(M+H)⁺: m/z=280.1.

Reference： [1] Canadian Journal of Chemistry, 2005, vol. 83, # 3, p. 213 - 219
[2] Patent: US2009/286778, 2009, A1, . Location in patent: Page/Page column 79
[3] Chem. News J. Ind. Sci., 1901, vol. 83, p. 285[4] Journal of the Chemical Society, 1901, vol. 79, p. 1076,1077
[5] P. Ch. S., p. 238[6] Chem. Zentralbl., 1901, vol. 72, # II, p. 97
[7] Journal of the American Chemical Society, 1984, vol. 106, # 15, p. 4218 - 4227

4
[ 529-28-2 ]
[ 64-19-7 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
56%	at 0 - 50℃; for 1 h; Inert atmosphere	2-Iodo-l-methoxy-4-nitrobenzene (45). To a stirred solution of commercially available iodoanisole (1 mL, 7.7 mmol) in AcOH (2 mL) was added fuming nitric acid (0.8 mL, 17 mmol) dropwise at 0°C. The mixture was let to warm up to rt and then heated up to 50°C and stirred for lh under a N₂ atmosphere when the color of the mixture became dark red/orange. Solid precipitate formed on cooling which was collected by filtration. Solid was washed with a 4:1 mixture of EtOH:H₂0 (10 mL) and dried on high vacuum to give 45 (1.2g, 56percent) as a light orange solid. ^]H NMR (400 MHz, CDC1₃) δ 8.66 (s, 1H), 8.24 (d, J = 8.88 Hz, 1H), 6.85 (d, J = 8.88 Hz, 1H), 3.98 (s, 3H); ¹³C NMR (100 MHz, CDC1₃) δ 163.01, 141.88, 135.10, 125.69, 109.56, 85.13, 57.13; ESI MS: m/z 279.8 (M+H)⁺

Reference： [1] Patent: WO2013/52943, 2013, A2, . Location in patent: Page/Page column 110

5
[ 529-28-2 ]
[ 5399-03-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 10, p. 4111 - 4133
[2] Chemische Berichte, 1896, vol. 29, p. 1000,2595[3] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[4] Chemische Berichte, 1896, vol. 29, p. 1000,2595[5] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[6] Bulletin of the Chemical Society of Japan, 1994, vol. 67, # 10, p. 2639 - 2646

6
[ 28896-47-1 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

7
[ 139-02-6 ]
[ 5399-03-1 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1902, vol. 134, p. 358[2] Bulletin de la Societe Chimique de France, 1902, vol. <3> 27, p. 400

8
[ 90-04-0 ]
[ 5399-03-1 ]

Reference： [1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641

9
[ 91-23-6 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

10
[ 696-62-8 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

11
[ 52692-09-8 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

12
[ 77770-09-3 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

13
[ 696-62-8 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

Reference： [1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641

14
[ 89487-91-2 ]
[ 5399-03-1 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1902, vol. 134, p. 358[2] Bulletin de la Societe Chimique de France, 1902, vol. <3> 27, p. 400

15
[ 533-58-4 ]
[ 5399-03-1 ]

Reference： [1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1902, vol. 134, p. 358[2] Bulletin de la Societe Chimique de France, 1902, vol. <3> 27, p. 400

16
[ 529-28-2 ]
[ 7697-37-2 ]
[ 64-19-7 ]
[ 5399-03-1 ]

Reference： [1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641

17
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1946, p. 406

18
[ 28896-47-1 ]
[ 7697-37-2 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

19
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

Reference： [1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[3] Bulletin de la Societe Chimique de France, 1897, vol. <3> 17, p. 115

20
[ 100-17-4 ]
[ 7553-56-2 ]
[ 7697-37-2 ]
[ 5399-03-1 ]

Reference： [1] Journal of the Chemical Society, 1916, vol. 109, p. 1087

21
[ 696-62-8 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

Reference： [1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641

22
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

23
[ 5399-03-1 ]
[ 74587-12-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With iron; ammonium chloride In ethanol; water at 85℃; for 1 h;	Into a 250-mL round-bottom flask was placed 2-iodo-l -methoxy-4-nitrobenzene (6 g, 21 ,50 mmol, 1.00 equiv), Fe (3.61 g, 3.00 equiv), NH₄C1 (3.42 g, 63.94 nimol, 3 ,00 equiv), ethanol (50 mL), and water (10 mL). The resulting solution was stirred for 1 h at 85 °C. The solid were filtered out, and the resulting mixture was concentrated under vacuum. This resulted in 5 ,35 g (100percent) of the title compound as a brown solid. LC-MS: (ES, m/z) RT = 0.847 min, LCMS 53 : m/z = 250 [M+1].
93%	With ethanol; iron; ammonium chloride In water for 5 h; Reflux	NH₄C1 (38.3 g, 716.8 mmol) dissolved in H₂0 (-100 ml) was added to a solution of compound 49 (50g, 179.2 mmol) in ethanol (600 mmol). Iron powder (40.15 g, 716.8) was added to this mixture, and the mixture was refluxed for 5 h. The reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with water and brine, dried over Na₂S0₄, filtered and concentrated under reduced pressure to give the title compound 50. (42 g, 93percent) . ^XHNMR (400 MHz , DMSO-d δ: 7.02 (d, J = 2.4 Hz, 1H) , 6.72 (d, J= 8.8 Hz, 1H) , 6.55 (dd, J = 2.8, 8.8 Hz, 1H) , 4.81 (brs, 2H) , 3.66 (s, 3H) .
83%	With iron; ammonium chloride In methanol; water for 3 h;	To 2-iodo-1-methoxy-4-nitrobenzene (485 mg, 1.74 mmol) suspended in methanol (6 mL) a solution of NH₄CI (465 mg, 8.69 mmol) in water (4.9 mL) and powdered Fe (290 mg, 5.192 mmol) were added and the mixture was heated to reflux for 3 h. The precipitate formed was filtered off and the filtrate was evaporated until the methanol was eliminated. After diluting with water and alkalinization with sodium carbonate the mixture was extracted with EtOAc (4 x 20 mL). The combined organic extracts were washed with brine (3 x 10 mL), water (10 mL), dried over sodium sulfate and the solvent was removed under vacuum. The crude dark oil was purified by flash chromatography on silica gel (hexane/EtOAc 1/1) to afford 400 mg of solid that was crystallized from n-pentane and diethyl ether to yield the title compound (363 mg, 83percent). ¹H NMR (400 MHz, DMSO-cie) δ ppm 3.66 (s, 3 H) 4.79 (s, 2 H) 6.56 (dd, J=8.61 , 2.62 Hz, 1 H) 6.73 (d, J=8.67 Hz, 1 H) 7.02 (d, J=2.69 Hz, 1 H)

71%

With dithionite In methanol; water for 0.0833333 h;

Intermediate step 4 toward Example 1: 3-iodo-4-methoxy-aniline [00230] Dithionite (3.85 g, 22.15 mmol) as a slurry in water (20 mL) was added to mixture of 2-iodo-l-methoxy-4-nitro-benzene (1.03 g, 3.69 mmol) in MeOH (50 mL). The mixture was stirred for 5 m and then diluted with a saturated aq solution of NaHCC>3 (100 mL). The mixture was concentrated to half its volume under reduced pressure. The aq phase was extracted with EtOAc (3X50 mL), and the combined organic phases were washed with brine, dried over MgSC^, filtered, and concentrated under reduced pressure. The product was purified by flash chromatography on silica gel, eluting with mixtures of hexanes and EtOAc to provide the title compound as a solid (0.652 g, 71percent). 1H NMR (300 MHz, CDC1₃) δ 7.16 (dd, J = 0.8, 2.0 Hz, 1H), 6.68-6.64 (m, 2H), 3.79 (s, 3H), 3.42 (s, 2H).

Reference： [1] Patent: WO2018/118842, 2018, A1, . Location in patent: Paragraph 0421-0424
[2] Patent: WO2016/199943, 2016, A1, . Location in patent: Paragraph 0303
[3] Patent: WO2013/14039, 2013, A1, . Location in patent: Page/Page column 45-46
[4] Patent: WO2014/152029, 2014, A2, . Location in patent: Paragraph 00230
[5] Journal of the American Chemical Society, 1941, vol. 63, p. 2482,2484
[6] Chemische Berichte, 1896, vol. 29, p. 1000,2595[7] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[8] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834

24
[ 5399-03-1 ]
[ 1300031-49-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2963 - 2967
[2] Patent: US2012/232074, 2012, A1,
[3] Patent: WO2011/54846, 2011, A1,

[ 5399-03-1 ] Synthesis Path-Downstream 1~57

1
[ 529-28-2 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
56%	With nitric acid; acetic acid at 0 - 50℃; for 1h; Inert atmosphere;
	With nitric acid; acetic acid
	With nitric acid; acetic acid

With nitric acid; acetic acid Heating;

Reference： [1]Abulwerdi, Fardokht A.; Liao, Chenzhong; Mady, Ahmed S.; Gavin, Jordan; Shen, Chenxi; Cierpicki, Tomasz; Stuckey, Jeanne A.; Showalter, H.D. Hollis; Nikolovska-Coleska, Zaneta [Journal of Medicinal Chemistry, 2014, vol. 57, # 10, p. 4111 - 4133]
[2]Reverdin [Chemische Berichte, 1896, vol. 29, p. 1000,2595][Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641]
[3]Reverdin [Chemische Berichte, 1896, vol. 29, p. 1000,2595][Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641]
[4]Pandiarajan, Karuppiah; Kabilan, Senthamaraikannan; Sankar, Punnaivanam; Kolehmainen,Erkki; Nevalainen, Tapio; Kauppinen, Reijo [Bulletin of the Chemical Society of Japan, 1994, vol. 67, # 10, p. 2639 - 2646]

2
[ 100-17-4 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium percarbonate; sulfuric acid; iodine at 45 - 50℃; for 2h;
86%	With chromium(VI) oxide; sulfuric acid; iodine In acetic anhydride; acetic acid at 55 - 65℃; for 1.5h;
84%	With sodium iodate; iodine In sulfuric acid at 25 - 30℃; for 1h;

83%	With sulfuric acid; acetic anhydride; iodic acid In acetic acid
82%	With sodium periodate; sulfuric acid; potassium iodide at 25 - 30℃; for 0.25h;
81%	With dihydrogen peroxide; iodine; acetic anhydride; urea In acetic acid at 10 - 15℃;
81%	With sodium periodate; sulfuric acid; dihydrogen peroxide In ethanol; water at 50℃; for 0.5h;
80%	With iodine; fluorine In chloroform; trichlorofluoromethane at 25℃; for 12h;
68%	With sodium periodate; sulfuric acid; iodine In acetic anhydride; acetic acid at 20℃;
	With pyridine; iodine; nitric acid at 160 - 170℃;
	With iodine; nitric acid
	With iodine; nitric acid In water at 15℃;

Reference： [1]Zielinska, Agnieszka; Skulski, Lech [Molecules, 2005, vol. 10, # 10, p. 1307 - 1317]
[2]Lulinski, Piotr; Skulski, Lech [Bulletin of the Chemical Society of Japan, 1997, vol. 70, # 7, p. 1665 - 1669]
[3]Kraszkiewicz, Lukasz; Sosnowski, MacIej; Skulski, Lech [Tetrahedron, 2004, vol. 60, # 41, p. 9113 - 9119]
[4]Krassowska-Swiebocka, Barbara; Prokopienko, Grazyna; Skulski, Lech [Molecules, 2005, vol. 10, # 2, p. 394 - 400]
[5]Kraszkiewicz, Lukasz; Sosnowski, Maciej; Skulski, Lech [Synthesis, 2006, # 7, p. 1195 - 1199]
[6]Lulinski, Piotr; Kryska, Anna; Sosnowski, Maciej; Skulski, Lech [Synthesis, 2004, # 3, p. 441 - 445]
[7]Location in patent: experimental part Sathiyapriya [Asian Journal of Chemistry, 2011, vol. 23, # 1, p. 41 - 43]
[8]Rozen, Shlomo; Zamir, Dov [Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3552 - 3555]
[9]Lulinski, Piotr; Skulski, Lech [Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 4, p. 951 - 956]
[10]Dains; Magers; Steiner [Journal of the American Chemical Society, 1930, vol. 52, p. 1570]
[11]Robinson [Journal of the Chemical Society, 1916, vol. 109, p. 1087]
[12]Emokpae, Thomas A.; Eguavoen, Osa; Khalil-Ur-Rahman; Hirst, Jack [Journal of the Chemical Society. Perkin transactions II, 1980, p. 832 - 834]

3
[ 696-62-8 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

Reference： [1]Chemische Berichte,1896,vol. 29,p. 1000,2595
Bulletin de la Societe Chimique de France,1896,vol. <3> 15,p. 641

4
[ 5399-03-1 ]
[ 5337-09-7 ]
[ 106590-34-5 ]

Reference： [1]Journal of the American Chemical Society,1932,vol. 54,p. 4434,4441

5
[ 5399-03-1 ]
[ 74587-12-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With iron; ammonium chloride; In ethanol; water; at 85℃; for 1h;	Into a 250-mL round-bottom flask was placed 2-iodo-l -methoxy-4-nitrobenzene (6 g, 21 ,50 mmol, 1.00 equiv), Fe (3.61 g, 3.00 equiv), NH4C1 (3.42 g, 63.94 nimol, 3 ,00 equiv), ethanol (50 mL), and water (10 mL). The resulting solution was stirred for 1 h at 85 C. The solid were filtered out, and the resulting mixture was concentrated under vacuum. This resulted in 5 ,35 g (100%) of the title compound as a brown solid. LC-MS: (ES, m/z) RT = 0.847 min, LCMS 53 : m/z = 250 [M+1].
95%	With iron; ammonium chloride; In ethanol; water; at 70 - 80℃; for 1h;Inert atmosphere;	Fe (490 g, 8.78 mol, 3.5 eq.) and Xi i iC'i (684 g, 12.8 mol, 5.1 eq.) were charged into EtOH (10 L, 14 vol.) and water (4.2 L, 6 vol.) in a flask (20 L) under a ? atmosphere. The mixture was heated to 70-80 C. Nitroarene 1 (700 g, 2.51 mol, 1 ,0 eq.) was added into the mixture in portions (gas was released). The mixture was stirred at 70-80 C for 1 h. The reaction was monitored by HPLC until 1 was consumed completely. The mixture was cooled to room temperature and filtered with the aid of diatomite (210 g, 0.3 w/w). The filter cake was washed with EtOH (300 mL x4). The filtrates were combined and the majority of EtOH was removed by distillation. EtOAc (7.0 L, 10.0 vol.) and water (3,5 L, 5.0 vol.) were added to the residue. The mixture was stirred for 30 min and the organic layer was separated. The aqueous layer was extracted with EtOAc (7.0 L, 10,0 vol .) and the organic layer was separated. The organic layers were combined and dried over anhydrous Na2S04 (250 g). The mixture was filtered and the filter cake was washed with EtOAc (500 mL). The filter solutions were combined and concentrated to 56 dryness, 609 g of aniline 2 as a dark brown solid was afforded with 98.1A% HPLC purity in 95% isolated yield.
93%	With ethanol; iron; ammonium chloride; In water; for 5h;Reflux;	NH4C1 (38.3 g, 716.8 mmol) dissolved in H20 (-100 ml) was added to a solution of compound 49 (50g, 179.2 mmol) in ethanol (600 mmol). Iron powder (40.15 g, 716.8) was added to this mixture, and the mixture was refluxed for 5 h. The reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with water and brine, dried over Na2S04, filtered and concentrated under reduced pressure to give the title compound 50. (42 g, 93%) . XHNMR (400 MHz , DMSO-d delta: 7.02 (d, J = 2.4 Hz, 1H) , 6.72 (d, J= 8.8 Hz, 1H) , 6.55 (dd, J = 2.8, 8.8 Hz, 1H) , 4.81 (brs, 2H) , 3.66 (s, 3H) .

83%	With iron; ammonium chloride; In methanol; water; for 3h;	To 2-iodo-1-methoxy-4-nitrobenzene (485 mg, 1.74 mmol) suspended in methanol (6 mL) a solution of NH4CI (465 mg, 8.69 mmol) in water (4.9 mL) and powdered Fe (290 mg, 5.192 mmol) were added and the mixture was heated to reflux for 3 h. The precipitate formed was filtered off and the filtrate was evaporated until the methanol was eliminated. After diluting with water and alkalinization with sodium carbonate the mixture was extracted with EtOAc (4 x 20 mL). The combined organic extracts were washed with brine (3 x 10 mL), water (10 mL), dried over sodium sulfate and the solvent was removed under vacuum. The crude dark oil was purified by flash chromatography on silica gel (hexane/EtOAc 1/1) to afford 400 mg of solid that was crystallized from n-pentane and diethyl ether to yield the title compound (363 mg, 83%). 1H NMR (400 MHz, DMSO-cie) delta ppm 3.66 (s, 3 H) 4.79 (s, 2 H) 6.56 (dd, J=8.61 , 2.62 Hz, 1 H) 6.73 (d, J=8.67 Hz, 1 H) 7.02 (d, J=2.69 Hz, 1 H)
71%	With dithionite; In methanol; water; for 0.0833333h;	Intermediate step 4 toward Example 1: 3-iodo-4-methoxy-aniline [00230] Dithionite (3.85 g, 22.15 mmol) as a slurry in water (20 mL) was added to mixture of 2-iodo-l-methoxy-4-nitro-benzene (1.03 g, 3.69 mmol) in MeOH (50 mL). The mixture was stirred for 5 m and then diluted with a saturated aq solution of NaHCC>3 (100 mL). The mixture was concentrated to half its volume under reduced pressure. The aq phase was extracted with EtOAc (3X50 mL), and the combined organic phases were washed with brine, dried over MgSC^, filtered, and concentrated under reduced pressure. The product was purified by flash chromatography on silica gel, eluting with mixtures of hexanes and EtOAc to provide the title compound as a solid (0.652 g, 71%). 1H NMR (300 MHz, CDC13) delta 7.16 (dd, J = 0.8, 2.0 Hz, 1H), 6.68-6.64 (m, 2H), 3.79 (s, 3H), 3.42 (s, 2H).

Reference： [1]Patent: WO2018/118842,2018,A1 .Location in patent: Paragraph 0421-0424
[2]Patent: WO2019/79540,2019,A1 .Location in patent: Paragraph 01611
[3]Patent: WO2016/199943,2016,A1 .Location in patent: Paragraph 0303
[4]Patent: WO2013/14039,2013,A1 .Location in patent: Page/Page column 45-46
[5]Patent: WO2014/152029,2014,A2 .Location in patent: Paragraph 00230
[6]Journal of the American Chemical Society,1941,vol. 63,p. 2482,2484
[7]Chemische Berichte,1896,vol. 29,p. 1000,2595
Bulletin de la Societe Chimique de France,1896,vol. <3> 15,p. 641
[8]Journal of the Chemical Society. Perkin transactions II,1980,p. 832 - 834

6
[ 99-59-2 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium nitrite; hydrogen iodide; dimethyl sulfoxide In water at 35℃; for 0.166667h;
75%	Stage #1: 3-amino-4-methoxynitrobenzene With sulfuric acid; sodium nitrite In water at 5℃; Stage #2: With potassium iodide In water at 90℃; for 1h;	A9.A Step A. 2-Iodo-1-methoxy-4-nitrobenzene 2-Methoxy-5-nitroaniline (10.0 g, 0.060 mol) was stirred in water (150 mL) and concentrated (conc.) sulfuric acid (12 mL, 0.22 mol). The solution was cooled below 5° C. with an ice-salt bath, and a solution of sodium nitrite (4.8 g, 0.070 mol) in water (40 mL) was added dropwise while maintaining the temperature below 5° C. A solution of potassium iodide (16.8 g, 0.101 mol) was added and the mixture was heated to 90° C. for 1 hour. Cooling to 0° C. gave dark red crystals which were filtered, washed with water, and dried. Purification by silica gel chromatography using ethyl acetate/hexanes gave the desired compound (13.6 g, 75%). 1H NMR (300 MHz, DMSO-d6): δ 8.57 (s, 1H), 8.28 (d, 1H), 7.19 (d, 1H), 3.98 (s, 3H). LCMS for C7H7INO3 (M+H)+: m/z=280.1.
	With sulfuric acid; potassium iodide; sodium nitrite 1) water, 0 deg C, 30 min, 2) water, 5 deg C, 2.5 h; Yield given. Multistep reaction;

Reference： [1]Baik, Woonphil; Luan, Wanqiang; Lee, Hyun Joo; Yoon, Cheol Hun; Koo, Sangho; Kim, Byeong Hyo [Canadian Journal of Chemistry, 2005, vol. 83, # 3, p. 213 - 219]
[2]Current Patent Assignee: INCYTE CORP - US2009/286778, 2009, A1 Location in patent: Page/Page column 79
[3]Meldola; Eyre [Chemical news and journal of industrial science, 1901, vol. 83, p. 285][Journal of the Chemical Society, 1901, vol. 79, p. 1076,1077]
[4]Meldola; Eyre [p. 238][Chemisches Zentralblatt, 1901, vol. 72, # II, p. 97]
[5]Larock, Richard C.; Harrison, L. Wayne [Journal of the American Chemical Society, 1984, vol. 106, # 15, p. 4218 - 4227]

7
[ 19093-51-7 ]
[ 5399-03-1 ]
[ 90584-85-3 ]

Yield	Reaction Conditions	Operation in experiment
63%	In N,N-dimethyl-formamide for 20h; Heating;

Reference： [1]Larock, Richard C.; Harrison, L. Wayne [Journal of the American Chemical Society, 1984, vol. 106, # 15, p. 4218 - 4227]

8
[ 5399-03-1 ]
3-iodo-4-methoxyaniline hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With iron; acetic acid In methanol; water at 40℃; for 1h;

Reference： [1]Cable, Karl M.; Wells, Guy N.; Sutherland, Derek R. [Journal of labelled compounds and radiopharmaceuticals, 2000, vol. 43, # 1, p. 29 - 45]

9
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
[ 52692-09-8 ]

Reference： [1]Chemische Berichte,1896,vol. 29,p. 1000,2595
Bulletin de la Societe Chimique de France,1896,vol. <3> 15,p. 641

10
[ 5399-03-1 ]
[ 107-19-7 ]
3-(2-methoxy-5-nitrophenyl)prop-2-yn-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at -10 - 20℃; Schlenk technique; Inert atmosphere;
	With copper(l) iodide; triethylamine In tetrahydrofuran

Reference： [1]Ambler, Brett R.; Peddi, Santosh; Altman, Ryan A. [Organic Letters, 2015, vol. 17, # 10, p. 2506 - 2509]
[2]Serra, Stefano; Fuganti, Claudio [Synlett, 2003, # 13, p. 2005 - 2008]

11
[ 5399-03-1 ]
[ 536-74-3 ]
1-methoxy-4-nitro-2-(phenylethynyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; triethylamine at 25℃;

Reference： [1]Yue, Dawei; Yao, Tuanli; Larock, Richard C. [Journal of Organic Chemistry, 2005, vol. 70, # 25, p. 10292 - 10296]

12
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-furancarboxaldehyde [ No CAS ]
[ 5399-03-1 ]
[ 846023-57-2 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium hydrogencarbonate In 1,2-dimethoxyethane; water Heating / reflux;	46 4-(2-Methoxy-5-nitrophenyl)-2-furaldehyde EXAMPLE 46 4-(2-Methoxy-5-nitrophenyl)-2-furaldehyde To a mixture of 2-iodo-4-nitroanisole (565 mg, 2.02 mmol) and 2-formylfuran-4-boronic acid pinacol ester (670 mg, 3.03 mmol) in 20 mL of ethylene glycol dimethyl ether and 12 mL of aqueous saturated sodium bicarbonate was added 80 mg of tetrakis(triphenylphosphine)palladium (0). The reaction mixture was heated at reflux overnight then allowed to cool to room temperature and added to a biphasic mixture of 10% methanol in ethyl acetate and water. The solid was collected by filtration, washed with ethyl acetate and water to provide 259 mg (52%) of 4-(2-methoxy-5-nitrophenyl)-2-furaldehyde as a light brown solid, 1H NMR (DMSO-d6) d 4.07 (s, 3H), 7.37 (d, J=9 Hz, 1H), 1H), 8.20-8.29 (m, 2H), 8.55 (d, J=3 Hz, 1H), 8.69 (s, 1H), 9.68 (s, 1H); MS 247.1 (M-H)-.
	With sodium hydrogencarbonate In 1,2-dimethoxyethane Heating;

Reference： [1]Current Patent Assignee: PFIZER INC - US2005/43537, 2005, A1 Location in patent: Page/Page column 4; 14
[2]Boschelli, Diane H.; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M.; Lucas, Judy; Boschelli, Frank [Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7868 - 7876]

13
[ 5399-03-1 ]
[ 143-33-9 ]
C₇H₅IONCNO₂⁽²⁾H^(1-) [ No CAS ]
[ 10496-75-0 ]
[ 82504-06-1 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 2803 - 2806
[2]Organic Letters,2007,vol. 9,p. 2803 - 2806

14
[ 5399-03-1 ]
[ 846023-60-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: aq. NaHCO₃ / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / 1,2-dimethoxy-ethane / Heating 2: 18 percent / sodium triacetoxyborohydride; acetic acid / 1-methyl-pyrrolidin-2-one; CH₂Cl₂ / 0 - 20 °C 3: 100 percent / hydrogen / Pd/C / methanol

Reference： [1]Boschelli, Diane H.; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M.; Lucas, Judy; Boschelli, Frank [Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7868 - 7876]

15
[ 5399-03-1 ]
[ 846023-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: aq. NaHCO₃ / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / 1,2-dimethoxy-ethane / Heating 2: 18 percent / sodium triacetoxyborohydride; acetic acid / 1-methyl-pyrrolidin-2-one; CH₂Cl₂ / 0 - 20 °C

Reference： [1]Boschelli, Diane H.; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M.; Lucas, Judy; Boschelli, Frank [Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7868 - 7876]

16
[ 5399-03-1 ]
[ 846023-62-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: aq. NaHCO₃ / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / 1,2-dimethoxy-ethane / Heating 2.1: 18 percent / sodium triacetoxyborohydride; acetic acid / 1-methyl-pyrrolidin-2-one; CH₂Cl₂ / 0 - 20 °C 3.1: 100 percent / hydrogen / Pd/C / methanol 4.1: propan-2-ol / Heating 4.2: propan-2-ol / 25 h / Heating

Reference： [1]Boschelli, Diane H.; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M.; Lucas, Judy; Boschelli, Frank [Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7868 - 7876]

17
[ 5399-03-1 ]
SKI-758 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: aq. NaHCO₃ / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / 1,2-dimethoxy-ethane / Heating 2.1: 18 percent / sodium triacetoxyborohydride; acetic acid / 1-methyl-pyrrolidin-2-one; CH₂Cl₂ / 0 - 20 °C 3.1: 100 percent / hydrogen / Pd/C / methanol 4.1: propan-2-ol / Heating 4.2: propan-2-ol / 25 h / Heating 5.1: 24 percent / phosphorus oxychloride / 24 h / 120 °C

Reference： [1]Boschelli, Diane H.; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M.; Lucas, Judy; Boschelli, Frank [Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7868 - 7876]

18
[ 5399-03-1 ]
[ 639000-16-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Et₃N; CuI / (Ph₃P)2PdCl₂ / tetrahydrofuran 2: MnO₂ / CH₂Cl₂ / 8 h / 20 °C

Reference： [1]Serra, Stefano; Fuganti, Claudio [Synlett, 2003, # 13, p. 2005 - 2008]

19
[ 5399-03-1 ]
2-[3-(2-Methoxy-5-nitro-phenyl)-prop-2-yn-(E)-ylidene]-succinic acid 1-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Et₃N; CuI / (Ph₃P)2PdCl₂ / tetrahydrofuran 2: MnO₂ / CH₂Cl₂ / 8 h / 20 °C 3: 89 percent / toluene; CHCl₃ / 4 h / 20 °C

Reference： [1]Serra, Stefano; Fuganti, Claudio [Synlett, 2003, # 13, p. 2005 - 2008]

20
[ 5399-03-1 ]
[ 168267-11-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 90 percent / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / dimethylformamide / 20 h / 80 °C 6: 80 percent / Raney nickel; sodium hypophosphite / pyridine; acetic acid; H₂O / 63 h / 80 °C
	Multi-step reaction with 6 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 51 percent / copper(I) iodide / 1-methyl-pyrrolidin-2-one / 8 h / 150 °C 6: 80 percent / Raney nickel; sodium hypophosphite / pyridine; acetic acid; H₂O / 63 h / 80 °C

Reference： [1]Cable, Karl M.; Wells, Guy N.; Sutherland, Derek R. [Journal of labelled compounds and radiopharmaceuticals, 2000, vol. 43, # 1, p. 29 - 45]
[2]Cable, Karl M.; Wells, Guy N.; Sutherland, Derek R. [Journal of labelled compounds and radiopharmaceuticals, 2000, vol. 43, # 1, p. 29 - 45]

21
[ 5399-03-1 ]
Vofopitant dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 90 percent / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / dimethylformamide / 20 h / 80 °C 6: 80 percent / Raney nickel; sodium hypophosphite / pyridine; acetic acid; H₂O / 63 h / 80 °C 7: 80 percent / glacial acetic acid; sodium triacetoxyborohydride / CH₂Cl₂ / 17 h / 20 °C
	Multi-step reaction with 7 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 51 percent / copper(I) iodide / 1-methyl-pyrrolidin-2-one / 8 h / 150 °C 6: 80 percent / Raney nickel; sodium hypophosphite / pyridine; acetic acid; H₂O / 63 h / 80 °C 7: 80 percent / glacial acetic acid; sodium triacetoxyborohydride / CH₂Cl₂ / 17 h / 20 °C

22
[ 5399-03-1 ]
[ 261173-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 90 percent / tetrakis(triphenylphosphine)palladium⁽⁰⁾ / dimethylformamide / 20 h / 80 °C
	Multi-step reaction with 5 steps 1: 63 percent / iron; acetic acid / methanol; H₂O / 1 h / 40 °C 2: 93 percent / triethylamine / CH₂Cl₂ / 19 h / 20 °C 3: 80 percent / triphenylphosphine (polymer-bound); carbon tetrachloride / 24 h / Heating 4: 4.42 g / sodium azide / acetic acid / 4 h / 70 °C 5: 51 percent / copper(I) iodide / 1-methyl-pyrrolidin-2-one / 8 h / 150 °C

23
[ 52692-09-8 ]
[ 5399-03-1 ]

Reference： [1]Journal of the Chemical Society,1916,vol. 109,p. 1087

24
[ 77770-09-3 ]
[ 5399-03-1 ]

Reference： [1]Journal of the Chemical Society,1916,vol. 109,p. 1087

25
C₁₀H₁₇BN₂O₃ [ No CAS ]
[ 5399-03-1 ]
[ 846023-60-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,2-dimethoxyethane; water for 3h; Heating / reflux;	48 (4-Methoxy-3-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine ALTERNATIVE EXAMPLE 48 (4-Methoxy-3-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine To a solution of 1-[(4-bromo-2-furyl)methyl]-4-methylpiperazine (1.43 g, 5.52 mmol) and tri-isopropyl borate (1.76 g, 9.38 mmol) in 20 mL of tetrahydrofuran at -78° C. was added 1.6 M n-butyl lithium in hexane (5.38 mL, 8.61 mmol) over 10 minutes. After stirring at -78° C. for 10 minutes, the temperature of the reaction mixture was allowed to rise to room temperature. Water (1.0 mL) was added and the solvents were removed in vacuo. The resultant intermediate boronic acid was dissolved in 20 mL of ethylene glycol dimethyl ether and 2-iodo-4-nitroanisole (1.06 mg, 4.25 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (87 mg, 0.11 mol) were added. A solution of 2.25 g of sodium carbonate in 6.5 mL of water was added and the resulting mixture was heated at reflux for 3 hours. The mixture was cooled to room temperature and partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography, eluding with a gradient of 5% methanol in dichloromethane to 10% methanol in dichloromethane to give 900 mg (70%) of (4-methoxy-3-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine as a red oil.

Reference： [1]Current Patent Assignee: PFIZER INC - US2005/43537, 2005, A1 Location in patent: Page/Page column 4; 15

26
[ 288-47-1 ]
[ 5399-03-1 ]
[ 876343-45-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate In N,N-dimethyl-formamide at 100℃;	261 5-(2-Methoxy-5-nitrophenyl)thiazoleNU; [751] N2 was bubbled through a solution of 2-iodo-4-nitroanisole (2.8g, 10.Ommol),thiazole (2.55g, 30.0mmol), potassium acetate (1.47g, IS.Ommol), and tetrakis(triphenylphosphine)palladium(O) (O.Slg, 0.70mmol) in DMF (15mL) for lOmin. The mixture wasthen heated to 100°C and stirred overnight. Solvent was removed under reduced pressure, andthe residue was purified by silica gel chromatography (dichloromethane:MeOH = 96:4) toafford the title compound. 'H-NMR (CDC13,400 MHz): 8 = 4.08 (s, 3 H), 7.09 (d, J= 9.2Hz, 1 H), 8.25 (dd, /= 2.8,9.2 Hz, 1 H), 8.37 (s, 1 H), 8.54 (d, J= 3.2 Hz, 1 H), 8.88 (s, 1 H).MS (ES+): m/z 237.13 [MH+]. HPLC: fc = 3.07 min (ZQ2000, polar_5min).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2006/17443, 2006, A2 Location in patent: Page/Page column 166

27
[ 5399-03-1 ]
[ 636-93-1 ]
[ 89487-91-2 ]
[ 98279-45-9 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 1925 - 1934

28
[ 5399-03-1 ]
[ 143-33-9 ]
[ 1007122-96-4 ]
[ 10496-75-0 ]
[ 82504-06-1 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 1925 - 1934

29
[ 5399-03-1 ]
[ 185619-66-3 ]
[ 1192471-75-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 80℃; for 0.25h;	Step B. tert-Butyl{3-[(2-methoxy-5-nitrophenyl)ethynyl]phenyl}carbamate tert-Butyl (3-ethynylphenyl)carbamate was stirred with 2-iodo-1-methoxy-4-nitrobenzene (2.60 g, 9.31 mmol) and bis(triphenylphosphine)palladium(II) chloride (163 mg, 0.23 mmol) in N,N-dimethylformamide (15 mL), and triethylamine (2.59 mL, 18.6 mmol) was added. The reaction mixture was heated at 80 C. for 15 minutes. Purification by preparative LCMS (pH 10) gave the desired compound (1.38 g, 40%). 1H NMR (300 MHz, DMSO-d6): delta 9.53 (s, 1H), 8.25 (m, 2H), 7.71 (s, 1H), 7.42 (d, 1H), 7.25 (m, 2H), 7.18 (d, 1H), 4.00 (s, 3H), 1.42 (s, 9H). LCMS for C20H21N2O5 (M+H)+: m/z=369.1.

Reference： [1]Patent: US2009/286778,2009,A1 .Location in patent: Page/Page column 79-80

30
[ 930-36-9 ]
[ 5399-03-1 ]
[ 720702-43-2 ]

Yield	Reaction Conditions	Operation in experiment
59%		A solution of N-methylpyrazole (5.12 g, 62.4 mmol) in THF (100 mL) was cooled to -78 C. and 2.5 M n-butyllithium in hexane (27.5 mL, 68.8 mmol) was added. After stirring for 30 minutes at the same temperature, 0.5 M zinc chloride in THF (107 mL, 53.5 mmol) and 1 M zinc chloride in diethyl ether (15.3 mL, 15.2 mmol) were added. The mixture was allowed to warm to room temperature and 2-iodo-4-nitroanisole (17.4 g, 62.4 mmol) followed by tetrakis(triphenylphosphine)palladium (3.6 g, 3.1 mmol) were added. After stirring at 60 C. for 20 hours, the black solution was concentrated on a rotary evaporator, and extracted with ethyl acetate and brine. Combined organic layers were dried over magnesium sulfate, filtered, and partly concentrated until a solid started to precipitate. Hexane was added, precipitate was filtered off, and washed with a cold 3:1 mixture of hexane/ethyl acetate to give 5-(2-methoxy-5-nitro-phenyl)-<strong>[930-36-9]1-methyl-1H-pyrazole</strong> (8.6 g, 36.9 mmol, 59%) as a tan solid. LCMS m/z (%/o)=234 (M+H, 100). 1H NMR (400 MHz, CDCl3) delta: 8.34 (dd, J=2.8, 9.2 Hz, 1H), 8.19 (d, J=2.8 Hz, 1H), 7.56 ( d, J=2.0 Hz, 1H), 7.08 (d, J=9.2 Hz, 1H), 6.31 (d, J=1.6 Hz, 1H), 3.96 (s, 3H), 3.74 (s, 3H).

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4412 - 4421
[2]Patent: US2007/207994,2007,A1 .Location in patent: Page/Page column 62

31
[ 5399-03-1 ]
[ 1993-03-9 ]
[ 1264712-04-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 5h; Inert atmosphere;

Reference： [1]Jepsen, Tue Heesgaard; Larsen, Mogens; Jorgensen, Morten; Solanko, Katarzyna A.; Bond, Andrew D.; Kadziola, Anders; Nielsen, Mogens Brondsted [European Journal of Organic Chemistry, 2011, # 1, p. 53 - 57]

32
[ 16114-47-9 ]
[ 5399-03-1 ]
[ 1300031-62-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 3,5-dimethylisoxazole-4-boronic acid; 2-iodo-1-methoxy-4-nitrobenzene With caesium carbonate In 1,2-dimethoxyethane; water for 0.166667h; Inert atmosphere; Stage #2: In 1,2-dimethoxyethane; water at 90℃; for 4h; Inert atmosphere;	Intermediate 13,5-dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole3-lodo-4-(methoxy) nitrobenzene (50g, 179 mmol), (3,5-dimethyl-4-isoxazolyl)boronic acid (27.8 g, 197 mmol) and cesium carbonate (1 17 g, 358 mmol) were combined in a 500ml RBF with DME (80ml) and water (40ml) and the mixture was degassed with nitrogen for 10min, then PEPPSI catalyst (3.04 g, 4.48 mmol) was added and the mixture was heated at 90°C for 4h under a nitrogen atmosphere. The cooled reaction was diluted with EtOAc (800ml), the organic layer was separated and washed with 10% sodium sulphite solution. The solvent was dried and evaporated in vacuo to give a brown solid which was triturated with ether (200 ml) and the solid product washed with ether (100ml) to give 3,5-dimethyl- 4-[2-(methyloxy)-5-nitrophenyl]isoxazole (43.9g, 177 mmol, 99 % yield) as a beige solid LCMS (formate) Rt 0.99 min, MH+ 249
99%	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; caesium carbonate In 1,2-dimethoxyethane; water at 90℃; for 4h; Inert atmosphere;	1 3,5-dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole 3-Iodo-4-(methoxy)nitrobenzene (50 g, 179 mmol), (3,5-dimethyl-4-isoxazolyl)boronic acid (27.8 g, 197 mmol) and cesium carbonate (117 g, 358 mmol) were combined in a 500 ml RBF with DME (80 ml) and water (40 ml) and the mixture was degassed with nitrogen for 10 min, then PEPPSI catalyst (3.04 g, 4.48 mmol) was added and the mixture was heated at 90° C. for 4 h under a nitrogen atmosphere. The cooled reaction was diluted with EtOAc (800 ml), the organic layer was separated and washed with 10% sodium sulphite solution. The solvent was dried and evaporated in vacuo to give a brown solid which was triturated with ether (200 ml) and the solid product washed with ether (100 ml) to give 3,5-dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole (43.9 g, 177 mmol, 99% yield) as a beige solid LCMS (formate) Rt 0.99 min, MH+ 249
97%	With barium hydroxide octahydrate In 1,2-dimethoxyethane; water at 80℃; for 16h;	Intermediate 3 : 3,5-Dimethyl-4-[2-(methoxy)-5-nitrophenyl]isoxazole; To a solution of 2-iodo-1 -(methoxy)-4-nitrobenzene (2g, 7.17mmol, 1 eq.) and (3,5- dimethylisoxazole)boronic acid (3.03g, 21 .5 mmol, 3eq.) in DME (44ml) and water (7ml) were added tetrakis(triphenylphosphine) palladium(O) (0.415g, 0.05eq.) and Ba(OH)2.8H20 (4.52g, 14.33 mmol, 2eq.). The mixture was heated at 80°C for 16h. To complete the reaction (3,5-dimethylisoxazole)boronic acid (1 eq.) was added and the mixture was heated for 4h. The cooled mixture was filtered and extracted with DCM. The organic phase was washed with saturated aqueous Sodium hydrogen carbonate and water, dried over Na2S04 and filtered. Evaporation of the solvent in vacuo gave a crude oil which was precipitated with iPr20 to afford the title compound as a rust solid (1.735g, 97%). GC/MS m/z: 248

97%	With barium hydroxide octahydrate In 1,2-dimethoxyethane; water at 80℃; for 20h;	Intermediate 3: 3,5-Dimethyl-4-[2-(methoxy)-5-nitrophenyl]isoxazole Intermediate 3: 3,5-Dimethyl-4-[2-(methoxy)-5-nitrophenyl]isoxazole To a solution of 2-iodo-1-(methoxy)-4-nitrobenzene (2 g, 7.17 mmol, 1 eq.) and (3,5-dimethylisoxazole)boronic acid (3.03 g, 21.5 mmol, 3 eq.) in DME (44 ml) and water (7 ml) were added tetrakis(triphenylphosphine) palladium(0) (0.415 g, 0.05 eq.) and Ba(OH)2.8H2O (4.52 g, 14.33 mmol, 2 eq.). The mixture was heated at 80° C. for 16 h. To complete the reaction (3,5-dimethylisoxazole)boronic acid (1 eq.) was added and the mixture was heated for 4 h. The cooled mixture was filtered and extracted with DCM. The organic phase was washed with saturated aqueous Sodium hydrogen carbonate and water, dried over Na2SO4 and filtered. Evaporation of the solvent in vacuo gave a crude oil which was precipitated with iPr2O to afford the title compound as a rust solid (1.735 g, 97%). GC/MS m/z: 248
83%	With caesium carbonate In 1,2-dimethoxyethane; water at 90℃; for 4h; Inert atmosphere;	3,5-Dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole (2) 3-Iodo-4-(methoxy) nitrobenzene (65 g, 233 mmol, Matrix Scientific), (3,5-dimethyl- 4-isoxazolyl)boronic acid (36.1 g, 256 mmol) and cesium carbonate (152 g, 466 mmol) were combined with DME (80 mL) and water (40 mL) and the mixture was degassed with nitrogen for 10min, then PEPPSITM catalyst (3.96 g, 5.82 mmol) was added and the mixture heated at 90°C for 4h, then cooled and diluted with ethyl acetate (800 mL). The resulting suspension was filtered through Celite and the filtrate washed with water (2 x 500 mL). The solvent was dried (sodium sulphate), filtered and evaporated to give a brown solid which was triturated with ether (30 mL). The solid product was washed with ether (100 mL) to give 3,5-dimethyl-4-[2- (methyloxy)-5-nitrophenyl]isoxazole as beige solid (48.2g, 83% yield). 1H-NMR (400MHz, CDCl3): d 8.30 (1H, dd), 8.06 (1H, d), 7.07 (1H, d), 3.94 (3H, s), 2.33 (3H, s), 2.17 (3H, s). LCMS (Method Formate): MH+ 249, Rt 1.01 min.
75.43%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate In 1,2-dimethoxyethane; water at 80℃; for 16h;	1B.1 Step 1: Synthesis of 4-(2-methoxy-5-nitrophenyl)-3,5-dimethyl-l,2-oxazole Into a 500 mL flask was added 2-iodo-l-methoxy-4- nitrobenzene (7.50 g, 26.88 mmol, 1.00 equiv), DME (160.00 mL), H2O (30.00 mL), (3,5- dimethylisoxazol-4-yl)boronic acid (11.36 g, 80.636 mmol, 3.00 equiv), Ba(0H)2.8H20 (16.93 g, 53.746 mmol, 2.00 equiv), Pd(PPh3)4 (3.11 g, 2.69 mmol, 0.10 equiv). The reaction was stirred at 80 degrees C for 16 h under N2 atmosphere. The solid was filtered out, the resulting mixture was extracted with DCM (3x50 mL). The combined organic layers were combined and washed with NaHCCL solution (50 mL), water (50 mL), dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. This result in 4-(2-methoxy-5-nitrophenyl)-3,5- dimethyl-l,2-oxazole (6.50 g, 75.43%) as red solid. LC/MS: mass calcd. Lor C12H12N2O4: 248.08, found: 249.05 [M+H]+.
71%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate In 1,2-dimethoxyethane; water at 80℃; for 16h; Inert atmosphere;	Intermediate 3: 4-(2-methoxy-5-nitrophenyl)-3,5-dimethylisoxazole A dried round flask was charged with 2-iodo-1-methoxy-4-nitrobenzene (30.0 g,108 mmol), 3,5-dimethylisoxazol-4-ylboronic acid (19.7 g, 140 mmol), Pd(Ph3P)4 (6.21 g,5.38 mmol) and Ba(OH)2 H20 (40.7 g, 215 mmol) in DME (461 mL) and water (77 mL)and then evacuated and refilled with N2 gas in several times. The reaction mixture wasstirred at 80 °C for 16 hours, cooled to room temperature and quenched with water. Themixture was extracted with EtOAc twice. The combined organic layers were dried overNa2SO4, filtered and concentrated in vacuo to afford the titled compound (19.0 g, 71%) as a white solid, which was used for the next reaction without further purification.1F1-NMR (400 MHz, CDC13): ö 8.30 (dd, J= 8.8 Hz, 2.8 Hz, 1H), 8.05 (d, J2.8 Hz, 1H), 7.06 (d, J-9.6 Hz, 1H), 3.94 (s, 3H), 2.33 (s, 3H), 2.17 (s, 3H).
	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride Large scale;

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/143416, 2012, A2 Location in patent: Page/Page column 30-31
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2014/45834, 2014, A1 Location in patent: Paragraph 0178-0179
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1 Location in patent: Page/Page column 41-42
[4]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2012/232074, 2012, A1 Location in patent: Page/Page column 18
[5]Mirguet, Olivier; Lamotte, Yann; Donche, Frédéric; Toum, Jérôme; Gellibert, Franoise; Bouillot, Anne; Gosmini, Romain; Nguyen, Van-Loc; Delannée, Delphine; Seal, Jonathan; Blandel, Florence; Boullay, Anne-Bénédicte; Boursier, Eric; Martin, Sandrine; Brusq, Jean-Marie; Krysa, Gael; Riou, Alizon; Tellier, Rémi; Costaz, Agns; Huet, Pascal; Dudit, Yann; Trottet, Lionel; Kirilovsky, Jorge; Nicodeme, Edwige [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2963 - 2967]
[6]Current Patent Assignee: DESIGN THERAPEUTICS - WO2021/158707, 2021, A1 Location in patent: Paragraph 00616; 00754; 00755; 00756
[7]Current Patent Assignee: KAINOS MEDICINE INC - WO2016/186453, 2016, A1 Location in patent: Page/Page column 26; 27
[8]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2013/24104, 2013, A1 Location in patent: Page/Page column 8

33
[ 5399-03-1 ]
[ 1300737-75-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: butan-1-ol / 4 h / 110 °C
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: butan-1-ol / 4 h / 110 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2012/232074, 2012, A1
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1

34
[ 5399-03-1 ]
7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N₄-(2-thienylmethyl)-3,4-quinolinediamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: acetonitrile / 24 h / 80 °C / Sealed tube
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: acetonitrile / 24 h / 80 °C / Shlenk sealed tube

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2012/232074, 2012, A1
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1

35
[ 5399-03-1 ]
[ 1300735-15-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice 8: Heating 9: bis-[(trifluoroacetoxy)iodo]benzene / acetonitrile / 20 °C
	Multi-step reaction with 8 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: acetonitrile / 4 h / 110 °C 8.1: [bis-(trifluoroacetoxy)iodo]benzene / 12 h / 50 °C
	Multi-step reaction with 8 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: acetonitrile / 4 h / 110 °C 8.1: bis-[(trifluoroacetoxy)iodo]benzene / 12 h / 50 °C

Reference： [1]Mirguet, Olivier; Lamotte, Yann; Donche, Frédéric; Toum, Jérôme; Gellibert, Franoise; Bouillot, Anne; Gosmini, Romain; Nguyen, Van-Loc; Delannée, Delphine; Seal, Jonathan; Blandel, Florence; Boullay, Anne-Bénédicte; Boursier, Eric; Martin, Sandrine; Brusq, Jean-Marie; Krysa, Gael; Riou, Alizon; Tellier, Rémi; Costaz, Agns; Huet, Pascal; Dudit, Yann; Trottet, Lionel; Kirilovsky, Jorge; Nicodeme, Edwige [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2963 - 2967]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2012/232074, 2012, A1
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1

36
[ 5399-03-1 ]
[ 1300737-80-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice 8: Heating
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: acetonitrile / 4 h / 110 °C
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: acetonitrile / 4 h / 110 °C

37
[ 5399-03-1 ]
[ 1300031-49-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice 8: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C 9: [bis(acetoxy)iodo]benzene; potassium hydroxide / methanol / 1.33 h / Cooling with ice
	Multi-step reaction with 8 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C 8.1: [bis-(trifluoroacetoxy)iodo]benzene / acetonitrile / 20 °C
	Multi-step reaction with 8 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C 8.1: [bis(acetoxy)iodo]benzene; potassium hydroxide / methanol / Cooling with ice

Multi-step reaction with 8 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2.1: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3.1: 0.5 h / 130 °C 4.1: diphenylether / 0.25 h / 280 °C / Microwave irradiation 5.1: sodium hydroxide; ethanol / 17 h / 80 °C 6.1: trichlorophosphate / 2 h / 100 °C 6.2: 0.5 h / 0 °C 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 3 h / 150 °C 8.1: potassium hydroxide; [bis(acetoxy)iodo]benzene / methanol / 1 h / 0 °C

38
[ 5399-03-1 ]
[ 1300031-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h
	Multi-step reaction with 2 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h
	Multi-step reaction with 2 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h

	Multi-step reaction with 2 steps 1: dithionite / methanol; water / 0.08 h 2: palladium diacetate; triphenylphosphine; caesium carbonate / 1,2-dimethoxyethane / 16 h / 90 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux
	Multi-step reaction with 2 steps 1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2: iron; ammonium chloride / ethanol; water / 2 h / 80 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2012/232074, 2012, A1
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/143416, 2012, A2
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2014/45834, 2014, A1
[4]Current Patent Assignee: EPIGENETIX INC - WO2014/152029, 2014, A2
[5]Current Patent Assignee: KAINOS MEDICINE INC - WO2016/186453, 2016, A1
[6]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1
[7]Current Patent Assignee: DESIGN THERAPEUTICS - WO2021/158707, 2021, A1

39
[ 5399-03-1 ]
[ 1300031-60-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C
	Multi-step reaction with 3 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C
	Multi-step reaction with 3 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C

	Multi-step reaction with 3 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C
	Multi-step reaction with 3 steps 1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3: 1 h / 130 °C
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3: 0.5 h / 130 °C

40
[ 5399-03-1 ]
[ 1300737-71-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux
	Multi-step reaction with 4 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux
	Multi-step reaction with 4 steps 1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C

Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3: 0.5 h / 130 °C 4: diphenylether / 0.25 h / 280 °C / Microwave irradiation

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/143416, 2012, A2
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2014/45834, 2014, A1
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/54846, 2011, A1
[4]Current Patent Assignee: DESIGN THERAPEUTICS - WO2021/158707, 2021, A1

41
[ 5399-03-1 ]
[ 1300737-70-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4
	Multi-step reaction with 5 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux
	Multi-step reaction with 5 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4

42
[ 5399-03-1 ]
[ 1300031-57-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice
	Multi-step reaction with 6 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice
	Multi-step reaction with 6 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: trichlorophosphate / 4 h / 20 °C / Heating 6.2: 0.5 h / Cooling with ice

	Multi-step reaction with 7 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice
	Multi-step reaction with 6 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2.1: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3.1: 0.5 h / 130 °C 4.1: diphenylether / 0.25 h / 280 °C / Microwave irradiation 5.1: sodium hydroxide; ethanol / 17 h / 80 °C 6.1: trichlorophosphate / 2 h / 100 °C 6.2: 0.5 h / 0 °C

43
[ 5399-03-1 ]
[ 1300737-69-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux 6: trichlorophosphate / 4 h / Heating 7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice 8: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4 6.1: trichlorophosphate / 20 °C / Heating 6.2: 0.5 h / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C
	Multi-step reaction with 7 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 16 h / 80 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / ethanol / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: ethanol; sodium hydroxide / Reflux 5.2: pH 4 6.1: trichlorophosphate / N,N-dimethyl-formamide / 5 h / Reflux 6.2: 1 h / 0 - 5 °C 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C

Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2.1: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3.1: 0.5 h / 130 °C 4.1: diphenylether / 0.25 h / 280 °C / Microwave irradiation 5.1: sodium hydroxide; ethanol / 17 h / 80 °C 6.1: trichlorophosphate / 2 h / 100 °C 6.2: 0.5 h / 0 °C 7.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 3 h / 150 °C

44
[ 5399-03-1 ]
[ 1300737-70-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.75 h / 255 °C 5: sodium hydroxide / ethanol / Reflux
	Multi-step reaction with 5 steps 1.1: barium hydroxide octahydrate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 20 h / 80 °C 2.1: hydrogen / palladium 10% on activated carbon / ethanol / 4 h 2.2: 20 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.75 h / 255 °C 5.1: sodium hydroxide; water / ethanol / Reflux 5.2: 0.17 h / pH 4
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide octahydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C 2: iron; ammonium chloride / ethanol; water / 2 h / 80 °C 3: 0.5 h / 130 °C 4: diphenylether / 0.25 h / 280 °C / Microwave irradiation 5: sodium hydroxide; ethanol / 17 h / 80 °C

45
[ 5399-03-1 ]
[ 1407520-01-7 ]
[ 1407520-02-8 ]

Yield	Reaction Conditions	Operation in experiment
35.5%	With potassium phosphate In N,N-dimethyl-formamide at 120℃; Sealed tube;	2.2 Step 2: Synthesis of 11Compound 10 (908mg, 3.0mmol) and 2-iodo-4-nitroanisole (963mg, 4.15mmol) were dissolved in 25 mL anhydrous DMF in a sealed tube and was added Pd(OAc)2 (86mg, 0.38mmol), XantPhos (227mg, 0.30mmol), K3P04 (921 mg, 4.3 mmol). The content was heated at 120 °C overnight. After cooling to the room temp, EtOAc was added and the mixture was filtered through celite, washed with more EtOAc. Combined filtrate was cone in vacuo, and the residue was purified by CombiFlash(MeOH/DCM). The product (476 mg, 35.5%) was obtained as a tan solid.
35.5%	With potassium phosphate; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide at 120℃;	2.2 Compound 10 (908mg, 3.0mmol) and 2-iodo-4-nitroanisole (963mg, 4.15mmol) were dissolved in 25 mL anhydrous DMF in a sealed tube and was added Pd(OAc)2 (86mg, 0.38mmol), XantPhos (227mg, 0.30mmol), K3PO4 (921 mg, 4.3 mmol). The content was heated at 120 °C overnight. After cooling to the room temp, EtOAc was added and the mixture was filtered through celite, washed with more EtOAc. Combined filtrate was cone in vacuo, and the residue was purified by CombiFlash(MeOH/DCM). The product (476 mg, 35.5%) was obtained as a tan solid.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2012/151561, 2012, A1 Location in patent: Page/Page column 40
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/169401, 2013, A1 Location in patent: Page/Page column 44-45

46
[ 5399-03-1 ]
[ 1300031-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: diphenylether / 0.5 h / Reflux
	Multi-step reaction with 6 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: diphenylether / 0.5 h / Reflux
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux 3.1: 2 h / Reflux 3.2: 2 h / Reflux 4.1: diphenylether / 0.5 h / 260 °C

47
[ 5399-03-1 ]
[ 1300031-66-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: diphenylether / 0.5 h / Reflux 7.1: nitric acid; propionic acid / 1 h / 100 °C
	Multi-step reaction with 7 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: diphenylether / 0.5 h / Reflux 7: nitric acid; propionic acid / 1 h / 100 °C
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux 3.1: 2 h / Reflux 3.2: 2 h / Reflux 4.1: diphenylether / 0.5 h / 260 °C 5.1: nitric acid; propionic acid / 1 h / 125 °C

48
[ 5399-03-1 ]
[ 1300031-65-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: diphenylether / 0.5 h / Reflux 7.1: nitric acid; propionic acid / 1 h / 100 °C 8.1: trichlorophosphate / 3 h / 110 °C 8.2: 0.17 h
	Multi-step reaction with 8 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: diphenylether / 0.5 h / Reflux 7: nitric acid; propionic acid / 1 h / 100 °C 8: trichlorophosphate / 3 h / 110 °C
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux 3.1: 2 h / Reflux 3.2: 2 h / Reflux 4.1: diphenylether / 0.5 h / 260 °C 5.1: nitric acid; propionic acid / 1 h / 125 °C 6.1: trichlorophosphate / 2 h / Reflux

49
[ 5399-03-1 ]
[ 1300737-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: diphenylether / 0.5 h / Reflux 7.1: nitric acid; propionic acid / 1 h / 100 °C 8.1: trichlorophosphate / 3 h / 110 °C 8.2: 0.17 h 9.1: 1,4-dioxane / 5 h / 20 °C 10.1: ethanol / tin(ll) chloride / 2.5 h / 40 °C 10.2: pH 12
	Multi-step reaction with 10 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: diphenylether / 0.5 h / Reflux 7: nitric acid; propionic acid / 1 h / 100 °C 8: trichlorophosphate / 3 h / 110 °C 9: 1,4-dioxane / 20 °C 10: tin(ll) chloride; ethanol / 2.5 h / 40 °C
	Multi-step reaction with 8 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux 3.1: 2 h / Reflux 3.2: 2 h / Reflux 4.1: diphenylether / 0.5 h / 260 °C 5.1: nitric acid; propionic acid / 1 h / 125 °C 6.1: trichlorophosphate / 2 h / Reflux 7.1: acetonitrile / 1 h / 60 °C 8.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 1 h / Reflux

50
[ 5399-03-1 ]
[ 1300737-52-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: caesium carbonate / 1,2-dimethoxyethane; water / 0.17 h / Inert atmosphere 1.2: 4 h / 90 °C / Inert atmosphere 2.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate; ethanol; water / 24 h 3.1: 1 h / 130 °C 4.1: diphenylether / 0.33 h / Reflux 5.1: sodium hydroxide; water / ethanol; water / Reflux 5.2: 40 °C / pH 4 6.1: diphenylether / 0.5 h / Reflux 7.1: nitric acid; propionic acid / 1 h / 100 °C 8.1: trichlorophosphate / 3 h / 110 °C 8.2: 0.17 h 9.1: 1,4-dioxane / 5 h / 20 °C
	Multi-step reaction with 9 steps 1: caesium carbonate; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol; water; ethyl acetate / 24 h 3: 1 h / 130 °C 4: diphenylether / 0.5 h / Reflux 5: sodium hydroxide; ethanol / Reflux 6: diphenylether / 0.5 h / Reflux 7: nitric acid; propionic acid / 1 h / 100 °C 8: trichlorophosphate / 3 h / 110 °C 9: 1,4-dioxane / 20 °C
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; barium hydroxide monohydrate / water; 1,2-dimethoxyethane / 16 h / 80 °C / Inert atmosphere 2.1: iron; ammonium chloride / water; ethanol; tetrahydrofuran / 2 h / Reflux 3.1: 2 h / Reflux 3.2: 2 h / Reflux 4.1: diphenylether / 0.5 h / 260 °C 5.1: nitric acid; propionic acid / 1 h / 125 °C 6.1: trichlorophosphate / 2 h / Reflux 7.1: acetonitrile / 1 h / 60 °C

51
[ 529-28-2 ]
[ 64-19-7 ]
[ 5399-03-1 ]

Yield	Reaction Conditions	Operation in experiment
56%	With nitric acid at 0 - 50℃; for 1h; Inert atmosphere;	2-Iodo-l-methoxy-4-nitrobenzene (45) 2-Iodo-l-methoxy-4-nitrobenzene (45). To a stirred solution of commercially available iodoanisole (1 mL, 7.7 mmol) in AcOH (2 mL) was added fuming nitric acid (0.8 mL, 17 mmol) dropwise at 0°C. The mixture was let to warm up to rt and then heated up to 50°C and stirred for lh under a N2 atmosphere when the color of the mixture became dark red/orange. Solid precipitate formed on cooling which was collected by filtration. Solid was washed with a 4:1 mixture of EtOH:H20 (10 mL) and dried on high vacuum to give 45 (1.2g, 56%) as a light orange solid. ]H NMR (400 MHz, CDC13) δ 8.66 (s, 1H), 8.24 (d, J = 8.88 Hz, 1H), 6.85 (d, J = 8.88 Hz, 1H), 3.98 (s, 3H); 13C NMR (100 MHz, CDC13) δ 163.01, 141.88, 135.10, 125.69, 109.56, 85.13, 57.13; ESI MS: m/z 279.8 (M+H)+

Reference： [1]Current Patent Assignee: WAYNE STATE UNIVERSITY - WO2013/52943, 2013, A2 Location in patent: Page/Page column 110

52
[ 5399-03-1 ]
[ 2365-48-2 ]
[ 1429765-76-3 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: Methyl thioglycolate With caesium carbonate; zinc(II) chloride In tetrahydrofuran at 20℃; for 0.333333h; Inert atmosphere; Stage #2: 2-iodo-1-methoxy-4-nitrobenzene With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; lithium iodide In tetrahydrofuran at 60℃; for 6.5h; Inert atmosphere;

53
[ 5399-03-1 ]
[ 1066-54-2 ]
[2-(2-methoxy-5-nitrophenyl)ethynyl]trimethylsilane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; N-butylamine In diethyl ether at 20℃;

Reference： [1]Chen, Chin-Chau; Wu, Man-Yun; Chen, Hsing-Yin; Wu, Ming-Jung [Journal of Organic Chemistry, 2017, vol. 82, # 12, p. 6071 - 6081]

54
[ 5399-03-1 ]
[ 64099-82-7 ]
1-methoxy-4-nitro-2-(prop-1-yn-1-yl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane at 80℃; Inert atmosphere;	28.1 Step 1: Synthesis of 1-methoxy-4-nitro-2-(prop-1-yn-1-yl)benzene: Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-iodo-l-methoxy-4-nitrobenzene (2.8 g, 10,03 mmol, 1.00 equiv), tributyl(prop-l-yn-l-yl)stannane (5 g, 15.19 mmol, 1.51 equiv), Pd(PPh3)2Ch (200 mg, 0.28 mmol, 0.03 equiv), dioxane (30 mL). The resulting solution was stirred overnight at 80 °C, The solids were filtered out. The resulting solution was extracted with of ethyl acetate and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (5%). This resulted in 1.06 g (55%) of the title compound.

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2018/118842, 2018, A1 Location in patent: Paragraph 0613-0615

55
1-(2-azidophenyl)prop-2-yn-1-ol [ No CAS ]
[ 5399-03-1 ]
1-(2-azidophenyl)-3-(2-methoxy-5-nitrophenyl)prop-2-yn-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 1-(2-azidophenyl)prop-2-yn-1-ol With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 2-iodo-1-methoxy-4-nitrobenzene Inert atmosphere;

Reference： [1]Qiu, Yi-Feng; Niu, Yue-Jie; Wei, Xi; Cao, Bao-Qian; Wang, Xi-Cun; Quan, Zheng-Jun [Journal of Organic Chemistry, 2019, vol. 84, # 7, p. 4165 - 4178]

56
[ 5399-03-1 ]
[ 616-38-6 ]
[ 14804-39-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 2-iodo-1-methoxy-4-nitrobenzene With tetrabutylammomium bromide; potassium carbonate; palladium dichloride In N,N-dimethyl acetamide Schlenk technique; Inert atmosphere; Stage #2: carbonic acid dimethyl ester In N,N-dimethyl acetamide at 105℃; for 12h; Schlenk technique; Inert atmosphere; regioselective reaction;

Reference： [1]Wu, Zhuo; Wei, Feng; Wan, Bin; Zhang, Yanghui [Journal of the American Chemical Society, 2021, vol. 143, # 12, p. 4524 - 4530]

57
[ 109-69-3 ]
[ 5399-03-1 ]
C₁₅H₂₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-(4-(hydroxymethyl)phenyl)-N-methylacetamide; tetrabutylammomium bromide; palladium diacetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 85℃; for 12h; Inert atmosphere;

Reference： [1]Jiang, Hang; Wu, Zhuo; Zhang, Yanghui [Chemical Science, 2021, vol. 12, # 24, p. 8531 - 8536]

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 5399-03-1 ]

Aryls

[ 5458-84-4 ]

1-Iodo-2-methoxy-4-nitrobenzene

Similarity: 0.98

[ 52692-09-8 ]

4-Iodo-1-methoxy-2-nitrobenzene

Similarity: 0.87

[ 58755-70-7 ]

1-Iodo-4-methoxy-2-nitrobenzene

Similarity: 0.86

[ 214279-40-0 ]

2-Iodo-4-methoxy-1-nitrobenzene

Similarity: 0.85

[ 55215-55-9 ]

1,4-Diiodo-2-methoxy-5-nitrobenzene

Similarity: 0.79

Ethers

[ 5458-84-4 ]

1-Iodo-2-methoxy-4-nitrobenzene

Similarity: 0.98

[ 52692-09-8 ]

4-Iodo-1-methoxy-2-nitrobenzene

Similarity: 0.87

[ 58755-70-7 ]

1-Iodo-4-methoxy-2-nitrobenzene

Similarity: 0.86

[ 214279-40-0 ]

2-Iodo-4-methoxy-1-nitrobenzene

Similarity: 0.85

[ 55215-55-9 ]

1,4-Diiodo-2-methoxy-5-nitrobenzene

Similarity: 0.79

Nitroes

[ 5458-84-4 ]

1-Iodo-2-methoxy-4-nitrobenzene

Similarity: 0.98

[ 52692-09-8 ]

4-Iodo-1-methoxy-2-nitrobenzene

Similarity: 0.87

[ 58755-70-7 ]

1-Iodo-4-methoxy-2-nitrobenzene

Similarity: 0.86

[ 214279-40-0 ]

2-Iodo-4-methoxy-1-nitrobenzene

Similarity: 0.85

[ 55215-55-9 ]

1,4-Diiodo-2-methoxy-5-nitrobenzene

Similarity: 0.79

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
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.
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. 5399-03-1 ] {[proInfo.proName]}

Quality Control of [ 5399-03-1 ]

Related Doc. of [ 5399-03-1 ]

Product Details of [ 5399-03-1 ]

Calculated chemistry of [ 5399-03-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 5399-03-1 ]

Application In Synthesis of [ 5399-03-1 ]

[ 5399-03-1 ] Synthesis Path-Upstream 1~24

[ 5399-03-1 ] Synthesis Path-Downstream 1~57

Related Functional Groups of [ 5399-03-1 ]

Aryls

Ethers

Nitroes

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 5399-03-1 ]