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[ CAS No. 22996-21-0 ] {[proInfo.proName]}

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Chemical Structure| 22996-21-0

Chemical Structure| 22996-21-0

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Quality Control of [ 22996-21-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 22996-21-0 ]

Product Details of [ 22996-21-0 ]

CAS No. :	22996-21-0	MDL No. :	MFCD00024254
Formula :	C₈H₇NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KLTDQLIGNSBZPO-UHFFFAOYSA-N
M.W :	181.15	Pubchem ID :	357691
Synonyms :

Calculated chemistry of [ 22996-21-0 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	3
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.14
TPSA :	72.12 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.38 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.09
Log Po/w (XLOGP3) :	1.45
Log Po/w (WLOGP) :	1.42
Log Po/w (MLOGP) :	0.03
Log Po/w (SILICOS-IT) :	-0.17
Consensus Log Po/w :	0.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.02
Solubility :	1.73 mg/ml ; 0.00955 mol/l
Class :	Soluble
Log S (Ali) :	-2.57
Solubility :	0.487 mg/ml ; 0.00269 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.85
Solubility :	2.54 mg/ml ; 0.014 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.88

Safety of [ 22996-21-0 ]

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 [ 22996-21-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 22996-21-0 ]
Downstream synthetic route of [ 22996-21-0 ]

[ 22996-21-0 ] Synthesis Path-Upstream 1~19

1
[ 22996-21-0 ]
[ 49609-15-6 ]

Reference： [1] Patent: WO2016/130968, 2016, A1,

2
[ 22996-21-0 ]
[ 57559-52-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 18, p. 6254 - 6276

3
[ 22996-21-0 ]
[ 33844-21-2 ]
[ 141080-74-2 ]

Reference： [1] Journal of Fluorine Chemistry, 2007, vol. 128, # 12, p. 1461 - 1468

4
[ 22996-21-0 ]
[ 90151-04-5 ]

Yield	Reaction Conditions	Operation in experiment
61%	With boron tribromide In dichloromethane at 0 - 20℃; for 4.5 h;	To a stirred solution of 4-m robenzaldehyde (4.5 g, 24.84 mmol) in dichloromethane (100 mL) at 0 °C was added boron tribromide (8 mL, 84.5 mmol) dropwise. The mixture was stirred for thirty minutes at 0 °C and an additional four hours at room temperature. The reaction mixture was poured into ice water (200 mL) and stirred for two days. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water, brine, dried (Na₂SO₄) and concentrated. The resulting residue was purified via MPLC eluting with a gradient of ethyl acetate/petroleum ether (1:15-1:5) to afford 4- hydroxy-2-nitrobenzaldehyde (2.55 g, 61percent) as an orange solid.

Reference： [1] Patent: WO2015/171610, 2015, A2, . Location in patent: Paragraph 000656
[2] Patent: WO2010/48582, 2010, A1, . Location in patent: Page/Page column 170-171

5
[ 17484-36-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 4.5 h; Heating / reflux Stage #2: With silver (II) carbonate In water; acetone at 20℃;	Example 4Preparation of 3-(7-(l-Methylpiperidin-4-yloxy)quinazolin-2-ylarnino)benzenesulfonanτideStep 1. Preparation of 4-methoxy-2-nitrobenzaldehydeCompound 5 (20.43 g, 0.122 mol, 1.0 eq) was dissolved in 480 ml OfCCl₄ under Ar. NBS (48.94 g, 0.275 mol, 2.2 eq) was added to the solution as a solid in one portion followed by addition of benzoyl peroxide (0.67 g, 2.76 mmol). The reaction mixture was stirred under reflux conditions for 4.5 hours. The ¹H NMR of an aliquot showed ~ 90percent conversion of starting material to dibromo derivative.The reaction mixture was cooled to RT, and concentrated. CCI₄ was chased twice with acetone. The residue was taken into acetone (IL) and Ag₂COa (37.1 g, 0.135 mol, 1.1 eq) was added followed by addition of water (100 mL). The reaction mixture was left stirring at RT overnight. TLC ( EtOAc: Hexanes= 3:7) showed a new spot. The reaction mixture was filtered though <n="311"/>PP028218.0002celite, and the filter cake was washed with acetone and the filtrate was concentrated. 340 mL of H₂O was added to the crude and the product was extracted with EtOAc (800 mL, 400 mL). The emulsion that formed was filtered through celite and the layers were separated. The organic layer was washed with hrine, dried over Na₂SO₄, and concentrated to give 8.27 g of crude material, which was purified by column chromatography (EtOAc/Hexanes) giving 14.7 g (67percent yield) of pure compound.

Reference： [1] Patent: WO2007/117607, 2007, A2, . Location in patent: Page/Page column 309-310
[2] Journal of the Chemical Society, 1949, p. Spl. 231
[3] Chemical and Pharmaceutical Bulletin, 1962, vol. 10, p. 856 - 865
[4] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 3091 - 3095[5] Zhurnal Obshchei Khimii, 1960, vol. 30, # 9, p. 3118
[6] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 9100 - 9104
[7] Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246
[8] Patent: US2813128, 1955, ,
[9] Collection of Czechoslovak Chemical Communications, 1960, vol. 25, p. 784 - 796
[10] Patent: WO2016/112088, 2016, A1,
[11] Patent: WO2008/101979, 2008, A1,

6
[ 123-11-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	at 0 - 20℃; for 0.5 h; Inert atmosphere	General procedure: 10 mmol of the desired p-substituted benzaldehyde was dissolved in 5 mL of conc. sulfuric acid, and cooled to 0 °C, and then 1.2 equiv. of nitric acid was dissolved in 1 mL of conc. sulfuric acid, and then slowly added to the reaction mixture. The reaction was allowed to warmgradually to room temperature and stirred for 30 min at room temperature. It was then poured into 50 mL of ice-cold water. The produced precipitate was filtered and washed with cold water. The product was purified on reverse phase column chromatography with gradient increase of methanol in water containing 0.1percent of formic acid as eluent.

Reference： [1] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 361 - 377
[2] Drug Development Research, 2016, p. 241 - 250

7
[ 38469-83-9 ]
[ 22996-21-0 ]

Reference： [1] Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056

8
[ 22996-23-2 ]
[ 22996-21-0 ]

Reference： [1] Journal of Natural Products, 2008, vol. 71, # 3, p. 313 - 320
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6412 - 6415

9
[ 1335101-95-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
5 g	With sodium periodate In tetrahydrofuran; water at 35℃; for 16 h;	To a mixture of (E)-l-(4-methoxy-2- nitrostyryl)pyrrolidine (7.4 g, 30 mmol) in THF (80 mL) was added a solution of NalC (16 g, 75 mmol) in H2O (240 mL). The reaction mixture was stirred at 35 °C for 16 hr then extracted with DCM (100 mL). The organic layer was separated, dried over anhydrous Na2SC>4, and concentrated under reduced pressure.[0229] The residue was purified by flash column chromatography to afford 4-methoxy-2- nitrobenzaldehyde (5 g, 92percent yield). LC-MS: m/z 182 (M+H)+.

Reference： [1] Patent: WO2016/112088, 2016, A1, . Location in patent: Paragraph 0228-0229

10
[ 57559-52-1 ]
[ 22996-21-0 ]

Reference： [1] Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246
[2] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 9100 - 9104
[3] Patent: US2813128, 1955, ,
[4] Organic and Biomolecular Chemistry, 2008, vol. 6, # 18, p. 3284 - 3291

11
[ 5344-78-5 ]
[ 22996-21-0 ]

Reference： [1] Journal of Fluorine Chemistry, 2007, vol. 128, # 12, p. 1461 - 1468

12
[ 75-17-2 ]
[ 96-96-8 ]
[ 22996-21-0 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 9, p. 2397 - 2407

13
[ 33844-21-2 ]
[ 22996-21-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6412 - 6415
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7834 - 7847

14
[ 123-11-5 ]
[ 22996-21-0 ]
[ 31680-08-7 ]

Reference： [1] Journal of Organic Chemistry, 2011, vol. 76, # 19, p. 8088 - 8094

15
[ 100193-41-7 ]
[ 22996-21-0 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 1960, vol. 25, p. 784 - 796

16
[ 2042-14-0 ]
[ 22996-21-0 ]

Reference： [1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 3091 - 3095[2] Zhurnal Obshchei Khimii, 1960, vol. 30, # 9, p. 3118

17
[ 50-00-0 ]
[ 96-96-8 ]
[ 22996-21-0 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1969, vol. 5, p. 938 - 941[2] Zhurnal Organicheskoi Khimii, 1969, vol. 5, # 5, p. 953 - 956

18
[ 22996-21-0 ]
[ 99532-52-2 ]

Reference： [1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 32, p. 6702 - 6705

19
[ 22996-21-0 ]
[ 187731-65-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7834 - 7847

[ 22996-21-0 ] Synthesis Path-Downstream 1~88

1
[ 141-82-2 ]
[ 22996-21-0 ]
[ 90945-66-7 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: malonic acid; 4-methoxy-2-nitro-benzaldehyde With pyridine at 125℃; for 12h; Stage #2: With hydrogenchloride	55 Iiiterm^di^; To a mixture of 4-methoxy-2-nitrobenzaldchydc (20 g, 0.11 mol) and malonic acid (28.8 g, 0.28 mol) in pyridine (200 mL) is added piperidine (1 mL, catalytic amount) and the mixture is refluxed at 125°C under nitrogen for 12 h. After cooling to room temperature, the solvent is removed under reduced pressure and the residue is acidified with 1.5 N HCl. The product is extracted with EtOAc and the organic layer is washed with water and brine then dried over Na2SO4 The solvent is removed under reduced pressure to afford 16 g (65%) of the title compound as a pale brown solid. 1H NMR (DMSO-dβ, 400MHz) δ 12.59 (bs, IH), 7.91-7.93 (m, IH), 7.68-7.72 (m, IH), 7.56 (s, IH), 7.31-7.33 (m, IH), 7.46-7.50 (m, I H), 3.87 (s, 3H).
64%	Stage #1: malonic acid; 4-methoxy-2-nitro-benzaldehyde With pyridine for 3h; Reflux; Stage #2: With hydrogenchloride In water; ethyl acetate at 20℃;	(E)-3-(4-Methoxy-2-nitro-phenyl)-acrylic acid 4-Methoxy-2-nitro-benzaldehyde (320 mmol) was dissolved in pyridine (500 rnL) and malonic acid (320 mmol) was added. Refluxed for 3h, then the mixture was cooled to room temperature. Ethyl acetate was added and the mixture was rendered acidic with HCl (2M). The phases were separated, the organic phase was washed with HCl (2M), then washed with water and then brine. Dried on MgSO4 and filtered, the solvent was removed by evaporation.Yield = 64%1H NMR (D6-DMSO): 3.89 (s, 3H); 6.49 (d, IH); 7.33 (dd, IH); 7.58 (d, IH); 7.72 (d, IH);7.93 (d, IH); 12.57 (br s, IH).
	With piperidine; pyridine

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2008/101979, 2008, A1 Location in patent: Page/Page column 75
[2]Current Patent Assignee: H. LUNDBECK A/S - WO2009/106534, 2009, A1 Location in patent: Page/Page column 63
[3]Sidhu et al. [Justus Liebigs Annalen der Chemie, 1959, vol. 627, p. 224,225]

2
[ 57559-52-1 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetra(n-butyl)ammonium dichromate(VI) In chloroform for 0.166667h; Heating;
75%	With tetra(n-butyl)ammonium dichromate(VI) In chloroform for 8h; Heating;
	With hexamethylenetetramine; acetic acid anschliessendes Erhitzen mit wss.HCl;

With tetra(n-butyl)ammonium dichromate(VI)

Reference： [1]Mohan, Raju; Katzenellenbogen, John A. [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246]
[2]Katritzky, Alan R.; Xu, Yong-Jiang; Vakulenko, Anatoliy V.; Wilcox, Allan L.; Bley, Keith R. [Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 9100 - 9104]
[3]Current Patent Assignee: PFIZER INC - US2813128, 1955, A
[4]Serafinowski, Pawel J.; Garland, Peter B. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 18, p. 3284 - 3291]

3
[ 17484-36-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
67%		Example 4Preparation of 3-(7-(l-Methylpiperidin-4-yloxy)quinazolin-2-ylarnino)benzenesulfonantauideStep 1. Preparation of 4-methoxy-2-nitrobenzaldehydeCompound 5 (20.43 g, 0.122 mol, 1.0 eq) was dissolved in 480 ml OfCCl4 under Ar. NBS (48.94 g, 0.275 mol, 2.2 eq) was added to the solution as a solid in one portion followed by addition of benzoyl peroxide (0.67 g, 2.76 mmol). The reaction mixture was stirred under reflux conditions for 4.5 hours. The 1H NMR of an aliquot showed ~ 90% conversion of starting material to dibromo derivative.The reaction mixture was cooled to RT, and concentrated. CCI4 was chased twice with acetone. The residue was taken into acetone (IL) and Ag2COa (37.1 g, 0.135 mol, 1.1 eq) was added followed by addition of water (100 mL). The reaction mixture was left stirring at RT overnight. TLC ( EtOAc: Hexanes= 3:7) showed a new spot. The reaction mixture was filtered though <n="311"/>PP028218.0002celite, and the filter cake was washed with acetone and the filtrate was concentrated. 340 mL of H2O was added to the crude and the product was extracted with EtOAc (800 mL, 400 mL). The emulsion that formed was filtered through celite and the layers were separated. The organic layer was washed with hrine, dried over Na2SO4, and concentrated to give 8.27 g of crude material, which was purified by column chromatography (EtOAc/Hexanes) giving 14.7 g (67% yield) of pure compound.

Reference： [1]Patent: WO2007/117607,2007,A2 .Location in patent: Page/Page column 309-310
[2]Journal of the Chemical Society,1949,p. Spl. 231
[3]Chemical and pharmaceutical bulletin,1962,vol. 10,p. 856 - 865
[4]Journal of general chemistry of the USSR,1960,vol. 30,p. 3091 - 3095
Zhurnal Obshchei Khimii,1960,vol. 30,p. 3118
[5]Journal of Organic Chemistry,2003,vol. 68,p. 9100 - 9104
[6]Journal of Organic Chemistry,1984,vol. 49,p. 1238 - 1246
[7]Patent: US2813128,1955,
[8]Collection of Czechoslovak Chemical Communications,1960,vol. 25,p. 784 - 796
[9]Patent: WO2016/112088,2016,A1
[10]Patent: WO2008/101979,2008,A1

4
[ 141-82-2 ]
[ 22996-21-0 ]
[ 109300-72-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	In acetic acid at 60℃; for 24h;

Reference： [1]Yoshida; Nagai; Oda; Sakakibara [Synthesis, 1986, vol. No. 12, # 12, p. 1026 - 1027]

5
[ 22996-21-0 ]
[ 126-81-8 ]
[ 55579-84-5 ]

Yield	Reaction Conditions	Operation in experiment
45%	With hydrogenchloride; hydroquinone In acetic acid at 80℃;

Reference： [1]Duerckheimer; Raether; Seliger; Seidenath [Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 7, p. 1041 - 1046]

6
[ 22996-21-0 ]
[ 107-91-5 ]
[ 55149-63-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With piperidine In methanol for 2h; Heating;

Reference： [1]Althuis, T. H.; Kadin, S. B.; Czuba, L. J.; Moore, P. F.; Hess, H.-J. [Journal of Medicinal Chemistry, 1980, vol. 23, # 3, p. 262 - 269]

7
[ 22996-21-0 ]
[ 22996-23-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium tetrahydroborate In methanol at 0 - 5℃; for 1h; Inert atmosphere;
72%	With sodium tetrahydroborate In methanol at 0 - 5℃; for 1h;
	With sodium hydroxide

Reference： [1]Location in patent: experimental part Reddy, M. V. Ramana; Venkatapuram, Padmavathi; Mallireddigari, Muralidhar R.; Pallela, Venkat R.; Cosenza, Stephen C.; Robell, Kimberly A.; Akula, Balaiah; Hoffman, Benjamin S.; Reddy, E. Premkumar [Journal of Medicinal Chemistry, 2011, vol. 54, # 18, p. 6254 - 6276]
[2]Katritzky, Alan R.; Xu, Yong-Jiang; Vakulenko, Anatoliy V.; Wilcox, Allan L.; Bley, Keith R. [Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 9100 - 9104]
[3]Gal'bershtam,M.A.; Budarina,Z.N. [Journal of Organic Chemistry USSR (English Translation), 1969, vol. 5, p. 938 - 941][Zhurnal Organicheskoi Khimii, 1969, vol. 5, # 5, p. 953 - 956]

8
[ 75-15-0 ]
[ 17484-36-5 ]
CrO₂Cl₂ [ No CAS ]
[ 22996-21-0 ]

Reference： [1]Journal of the Chemical Society,1949,p. Spl. 231

9
[ 22996-21-0 ]
[ 141080-74-2 ]

Yield	Reaction Conditions	Operation in experiment
86.9%	With [¹⁸F]-potassium fluoride; [2.2.2]cryptande In dimethyl sulfoxide at 180℃; for 0.0833333h;	A2 Herstellung von [2-(18)F-fluor-4-methoxy-benzaldehyd 1 2-(18)F-FLUOR-4-METHOXY-BENZALDEHYD 1 wird durch nukleophile Substitution aus 4-Methoxy-2-nitro-benzaldehyd 2 in Gegen- wart eines Kronenethers als [IONENFäNGER] hergestellt. Die Herstellung von 4-Methoxy-2-nitro-benzaldehyd 2 ist bekannt (siehe C. Lemaire et al., Synthesis of fluorine-18 Substi- tuted Aromatic Aldehydes and Benzyl Bromides, New Intermedi- ates for n. c. a. [[L8F]] Fluorination. Applied Radiation and Iso- topes, Bd. 43, Nr. 4, S. 485-494,1992). [ 2 1]. Der in Schritt AI erhaltene Rückstand wurde mit einer Lösung aus 15 mg Verbindung 1 in 1 ml DMSO behandelt. Das Reakti- onsgemisch wurde anschließend 5 min auf 180 [°C] erwärmt. Nach dem Abkühlen wurde das Reaktionsgemisch mit [8, 5] ml Wasser verdünnt. Eine Probe des Reaktionsproduktes wurde durch Radio- Dünnschichtchromatographie (Radio-TLC) unter Verwendung ei- ner Silikagelplatte und Methylenchlorid analysiert. Die Re- tentionszeit (Rf) für [L8F-FLUORID] war 0, für Verbindung 1 0,45. Basierend auf den Radio-TLC-Werten wurde eine Einbau- rate von [18F-FLUOR] in die Aldehydstruktur von durchschnitt- lich 86,9 [%] 0,9 [%] (Zahl der Versuche [(N) = 4)] errechnet. Um Verbindung 2 von [NICHT-UMGESETZTENM L8F-FLUORID] zu tren- nen, wurde das verdünnte Reaktionsgemisch über einer C18- Supelco-Säule (600 mg C18, gepackt in eine 6-ml-Säule) ge- führt, die zuvor mit 10 ml Methanol und 15 ml Wasser kondi- tioniert worden war. Die C18-Säule wurde zweimal mit 5 ml Wasser gereinigt.
	With [2.2.2]18F In dimethyl sulfoxide at 180℃; for 0.0833333h;
	With [¹⁸F]-potassium fluoride; K 2.2.2; potassium carbonate In dimethyl sulfoxide at 180℃; for 0.0833333h;

	With K[18F]F-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane complex In N,N-dimethyl-formamide at 140℃;
	With K[18F]F-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane complex In dimethyl sulfoxide at 180℃; for 0.0833333h;
	With K[18F]F-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane complex In N,N-dimethyl-formamide at 140℃; for 0.116667h; Sealed vial;
	With K[18F]-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]-hexacosane complex In water; dimethyl sulfoxide at 140℃; for 0.25h;	4.3.1. Labeling step General procedure: 600-800 mL of the ammonium substrate or nitro precursor inMe2SO (water content 3000 ppm, 15-20 mg/mL) were added tothe dry KryptofixK222/[18F]fluoride complex (111-370 MBq),prepared as previously described [30]. The mixture was thenallowed to react at 140 °C for 2.5 min. The nitro starting precursorwas labeled at the same temperature but for 15 min. After labeling,the Me2SO solution was diluted with water (20-30 mL) and thewhole solution passed through a previously activated tC18 Sep-Pak1 cartridge. An environmental tC18 cartridge (1 g) was used forthe trapping of aldehydes 2, 3, 7-9 (Table 1). For compounds 4-6 acartridge containing 400 mg of phase material was more suitable.The [18F]fluorobenzaldehyde trapped on the support was thenwashed with 10 mL of water. For analytical purposes, the activityretained on the cartridge was eluted with 2 mL of CH3CN and wasanalyzed by TLC and HPLC (see above). Radiolabeling yields aresummarized in Table 1.

Reference： [1]Current Patent Assignee: ABX GMBH - WO2003/99746, 2003, A1 Location in patent: Page 13, 14
[2]Fedorova, O. S.; Zaitsev, V. V.; Mosevich, I. K.; Kuznetsova, O. F.; Gomzina, N. A.; Westera, G.; Ametamey, S. M.; Schubiger, P. A.; Krasikova, R. N. [Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S852 - S854]
[3]Gomzina, N. A.; Zaitsev, V. V.; Krasikova, R. N. [Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S895 - S897]
[4]Location in patent: experimental part Shen, Bin; Löffler, Dirk; Reischl, Gerald; Machulla, Hans-Jürgen; Zeller, Klaus-Peter [Journal of Fluorine Chemistry, 2009, vol. 130, # 2, p. 216 - 224]
[5]Location in patent: experimental part Fedorova; Kuznetsova; Shatik; Stepanova; Belokon; Maleev; Krasikova [Russian Journal of Bioorganic Chemistry, 2009, vol. 35, # 3, p. 306 - 314]
[6]Location in patent: experimental part Shen, Bin; Loeffler, Dirk; Reischl, Gerald; Machulla, Hans-Juergen; Zeller, Klaus-Peter [Journal of labelled compounds and radiopharmaceuticals, 2010, vol. 53, # 3, p. 113 - 119]
[7]Location in patent: experimental part Lemaire, Christian; Libert, Lionel; Plenevaux, Alain; Aerts, Joël; Franci, Xavier; Luxen, André [Journal of Fluorine Chemistry, 2012, vol. 138, p. 48 - 55]

10
[ 2675-79-8 ]
[ 22996-21-0 ]
[ 1027298-73-2 ]

Yield	Reaction Conditions	Operation in experiment
37%	Stage #1: 1-bromo-3,4,5-trimethoxybenzene With iodine; magnesium In tetrahydrofuran at 25℃; for 1h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran at 0 - 25℃; for 12h; Stage #3: With ammonium chloride In tetrahydrofuran; water at 0℃; for 0.166667h;
	Stage #1: 1-bromo-3,4,5-trimethoxybenzene With magnesium In tetrahydrofuran at 25℃; for 1h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran at 25℃; for 0.333333h; Further stages.;

Reference： [1]Galli, Ubaldina; Travelli, Cristina; Aprile, Silvio; Arrigoni, Elena; Torretta, Simone; Grosa, Giorgio; Massarotti, Alberto; Sorba, Giovanni; Canonico, Pier Luigi; Genazzani, Armando A.; Tron, Gian Cesare [Journal of Medicinal Chemistry, 2015, vol. 58, # 3, p. 1345 - 1357]
[2]Liou, Jing-Ping; Chang, Chun-Wei; Song, Jeng-Shin; Yang, Yung-Ning; Yeh, Ching-Fang; Tseng, Huan-Yi; Lo, Yu-Kang; Chang, Yi-Ling; Chang, Chung-Ming; Hsieh, Hsing-Pang [Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2556 - 2562]

11
[ 22996-21-0 ]
[ 117968-39-5 ]
[ 714229-76-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	With piperidine In benzene Heating;

Reference： [1]Kataoka, Tadashi; Watanabe, Shin-Ichi; Mori, Eiji; Kadomoto, Ryoji; Tanimura, Susumu; Kohno, Michiaki [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 9, p. 2397 - 2407]

12
[ 75-17-2 ]
[ 96-96-8 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
27%	Stage #1: 4-methoxy-2-nitroaniline With hydrogenchloride; sodium nitrite In water for 0.25h; Stage #2: formaldoxime With sodium acetate; copper(II) sulfate; sodium sulfite In water at 20℃; for 2h;

Reference： [1]Kataoka, Tadashi; Watanabe, Shin-Ichi; Mori, Eiji; Kadomoto, Ryoji; Tanimura, Susumu; Kohno, Michiaki [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 9, p. 2397 - 2407]

13
[ 38469-83-9 ]
[ 22996-21-0 ]

Reference： [1]Organic Letters,2001,vol. 3,p. 2053 - 2056

14
methyl 2-acetylamino-2-(dimethoxyphosphinyl)-acetate [ No CAS ]
[ 22996-21-0 ]
(E)-2-N-acetylamino-3-(4-methoxy-2-nitrophenyl)acrylic acid methyl ester [ No CAS ]
[ 353242-37-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl 2-acetylamino-2-(dimethoxyphosphinyl)-acetate With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane for 0.166667h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In dichloromethane at 20℃; for 2h; Further stages.;

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

15
[ 22996-21-0 ]
[ 404-90-0 ]
[ 908583-98-2 ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 7191 - 7193

16
[ 22996-21-0 ]
[ 104-47-2 ]
[ 908583-89-1 ]

Yield	Reaction Conditions	Operation in experiment
76.9%	With sodium In ethanol for 5h;
	With sodium In ethanol for 5h;

Reference： [1]Chen, Wuhong; Lin, Zhaohu; Ning, Mengmeng; Yang, Chunhao; Yan, Xueming; Xie, Yuyuan; Shen, Xu; Wang, Ming-Wei [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 17, p. 5828 - 5836]
[2]Chen, Wuhong; Liu, Bo; Yang, Chunhao; Xie, Yuyuan [Tetrahedron Letters, 2006, vol. 47, # 40, p. 7191 - 7193]

17
[ 22996-21-0 ]
[ 108683-61-0 ]
C₁₈H₁₉NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: triphenyl(3,4,5-trimethoxybenzyl)phosphonium chloride With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1.5h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; for 19h;

Reference： [1]Chang, Jang-Yang; Yang, Ming-Fang; Chang, Chi-Yen; Chen, Chi-Ming; Kuo, Ching-Chuan; Liou, Jing-Ping [Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6412 - 6415]

18
[ 22996-23-2 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With Celite; water; pyridinium chlorochromate In dichloromethane at 20℃; for 4.5h;
	With dipyridinium dichromate; molecular sieve In dichloromethane at 20℃; for 16h;

Reference： [1]Location in patent: experimental part Siles, Rogelio; Ackley, J. Freeland; Hadimani, Mallinath B.; Hall, John J.; Mugabe, Benon E.; Guddneppanavar, Rajsekhar; Monk, Keith A.; Chapuis, Jean-Charles; Pettit, George R.; Chaplin, David J.; Edvardsen, Klaus; Trawick, Mary Lynn; Garner, Charles M.; Pinney, Kevin G. [Journal of Natural Products, 2008, vol. 71, # 3, p. 313 - 320]
[2]Chang, Jang-Yang; Yang, Ming-Fang; Chang, Chi-Yen; Chen, Chi-Ming; Kuo, Ching-Chuan; Liou, Jing-Ping [Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6412 - 6415]

19
[ 22996-21-0 ]
[ 59236-36-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride; iron⁽⁰⁾; glacial acetic acid In ethanol; lithium hydroxide monohydrate at 60 - 65℃; for 1h;	4.2 Step 2. Preparation of 2-Formyl-5-methoxyanilineA flask was charged with 4-methoxy-2-nitrobenzaldehyde (14.7 g, 81.2 mmol, l.Oeq), EtOH (270 mL), glacial AcOH (270 mL), H2O (135 mL), degassed and filled with argon. Then Fe powder (325 mesh) (27.2 g, 0.49 mol, 6.0 eq) was added followed by addition of concentrated HCl (12.24 mL, 0.148 mol, 1.8 eq). After stirring the reaction mixture for 1 hour at 60-650C (oil bath) TLC (EtO Ac/Hex = 4:6) showed that no starting material was left. The reaction mixture was cooled down to RT5 diluted with 200 mL of H2O and neutralized with Na2CO3 to pH= 7-8. The product was extracted into CH2Cl2. The emulsion that formed was filtered through celite, organic layer was washed with brine, dried over Na2SO^ concentrated giving 12.0 g (98% yield) of the title compound.
95%	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 24h;	11.C [0230] Step C. 2-amino-4-methoxybenzaldehyde. To a mixture of 4-methoxy-2- nitrobenzaldehyde (4.6 g, 25.4 mmol) in MeOH (80 mL) was added 10% Pd/C (460 mg). The reaction mixture was stirred at r.t. for 24 hr under 1 atmosphere of . The resulting mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash columnchromatography to afford 2-amino-4-methoxybenzaldehyde (3.7 g, 95% yield). LC-MS: m/z 152 (M+H)+.
87%	With iron sulphate heptahydrate; ammonium hydroxide In methanol; lithium hydroxide monohydrate at 90℃; for 1h;

	With iron⁽⁰⁾; ammonia hydrochloride In ethanol; lithium hydroxide monohydrate at 60℃; for 1h;
	With hydrogenchloride; iron⁽⁰⁾ Inert atmosphere; Schlenk technique;
	With hydrogenchloride; iron⁽⁰⁾ In ethanol; lithium hydroxide monohydrate at 80℃; for 1h;
	With hydrogenchloride; iron⁽⁰⁾ In ethanol; lithium hydroxide monohydrate at 78℃; for 4h; Inert atmosphere;
	With hydrogenchloride; iron⁽⁰⁾; glacial acetic acid In ethanol; lithium hydroxide monohydrate for 0.666667h;
	With hydrogenchloride; iron⁽⁰⁾ In ethanol; lithium hydroxide monohydrate at 85℃; for 0.666667h;

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2007/117607, 2007, A2 Location in patent: Page/Page column 310
[2]Current Patent Assignee: SPERO THERAPEUTICS INC - WO2016/112088, 2016, A1 Location in patent: Paragraph 0230
[3]Fackler, Philipp; Huber, Stefan M.; Bach, Thorsten [Journal of the American Chemical Society, 2012, vol. 134, # 30, p. 12869 - 12878]
[4]Nakamura, Akira; Tanaka, Satoshi; Imamiya, Akira; Takane, Reo; Ohta, Chiaki; Fujimura, Kazuma; Maegawa, Tomohiro; Miki, Yasuyoshi [Organic and Biomolecular Chemistry, 2017, vol. 15, # 32, p. 6702 - 6705]
[5]Liu, Xianghui; Wang, Kai; Guo, Wengang; Liu, Yan; Li, Can [Chemical Communications, 2019, vol. 55, # 18, p. 2668 - 2671]
[6]Fansher, Douglas J.; Granger, Richard; Kaur, Satinderpal; Palmer, David R. J. [ACS Catalysis, 2021, vol. 11, # 12, p. 6939 - 6943]
[7]Laraia, Luca; Olsen, Asger Hegelund; Whitmarsh-Everiss, Thomas [Angewandte Chemie - International Edition, 2021, vol. 60, # 51, p. 26755 - 26761][Angew. Chem., 2021, vol. 133, # 51, p. 26959 - 26965]
[8]Mao, Wenhui; Zhao, He; Zhang, Min [Chemical Communications, 2022, vol. 58, # 27, p. 4380 - 4383]
[9]Fan, Lijia; Fu, Junkai; Huang, Yangfei; Wang, Tao; Yang, Lingyun; Yu, Weijie [Journal of Organic Chemistry, 2022, vol. 87, # 8, p. 5136 - 5148]

20
[ 22996-21-0 ]
[ 95-54-5 ]
[ 942614-32-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 4-methoxy-2-nitro-benzaldehyde; 1,2-diamino-benzene In ethanol for 1.5h; Heating; Stage #2: With p-benzoquinone In ethanol Heating; Further stages.;

Reference： [1]Henary, Maged M.; Wu, Yonggang; Cody, John; Sumalekshmy; Li, Jing; Mandal, Subrata; Fahrni, Christoph J. [Journal of Organic Chemistry, 2007, vol. 72, # 13, p. 4784 - 4797]

21
[ 22996-21-0 ]
[ 942614-36-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: ethanol / 1.5 h / Heating 1.2: 82 percent / 1,4-benzoquinone / ethanol / Heating 2.1: 99 percent / H₂ / Pd/C / methanol / 20 °C / atmospheric pressure

Reference： [1]Henary, Maged M.; Wu, Yonggang; Cody, John; Sumalekshmy; Li, Jing; Mandal, Subrata; Fahrni, Christoph J. [Journal of Organic Chemistry, 2007, vol. 72, # 13, p. 4784 - 4797]

22
[ 22996-21-0 ]
[ 942519-28-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: ethanol / 1.5 h / Heating 1.2: 82 percent / 1,4-benzoquinone / ethanol / Heating 2.1: 99 percent / H₂ / Pd/C / methanol / 20 °C / atmospheric pressure 3.1: 36 percent / pyridine / 18 h / 20 °C

Reference： [1]Henary, Maged M.; Wu, Yonggang; Cody, John; Sumalekshmy; Li, Jing; Mandal, Subrata; Fahrni, Christoph J. [Journal of Organic Chemistry, 2007, vol. 72, # 13, p. 4784 - 4797]

23
[ 22996-21-0 ]
(4-(2-(1H-benzimidazol-2-yl)-5-methoxyphenylsulfamoyl)phenoxy)acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: ethanol / 1.5 h / Heating 1.2: 82 percent / 1,4-benzoquinone / ethanol / Heating 2.1: 99 percent / H₂ / Pd/C / methanol / 20 °C / atmospheric pressure 3.1: 36 percent / pyridine / 18 h / 20 °C 4.1: 88 percent / LiOH*H₂O / methanol; H₂O; tetrahydrofuran / 3 h / Heating

Reference： [1]Henary, Maged M.; Wu, Yonggang; Cody, John; Sumalekshmy; Li, Jing; Mandal, Subrata; Fahrni, Christoph J. [Journal of Organic Chemistry, 2007, vol. 72, # 13, p. 4784 - 4797]

24
[ 33844-21-2 ]
[ 22996-21-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6412 - 6415
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 7834 - 7847

25
[ 22996-21-0 ]
(S)-3-tert-butoxycarbonyl-7-methoxy-1-(4-toluenesulfonyl)-1,2,3,4-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C 5.1: H₂ / Pd/C / tetrahydrofuran / 1 h / 20 °C / 2327.23 Torr 6.1: triethylamine / CH₂Cl₂ / 20 °C 7.1: DMAP / tetrahydrofuran / 4 h / Heating 7.2: 26 percent / hydrazine / tetrahydrofuran; methanol / 4 h / 20 °C

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

26
[ 22996-21-0 ]
[ 1025803-35-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C 5.1: H₂ / Pd/C / tetrahydrofuran / 1 h / 20 °C / 2327.23 Torr

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

27
[ 22996-21-0 ]
(S)-3-acetamido-7-methoxy-1-ethoxy-1,2,3,4-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C 5.1: 9 mg / H₂ / Pd/C / 2 h / 20 °C / 2327.23 Torr

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

28
[ 22996-21-0 ]
[ 353242-42-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

29
[ 22996-21-0 ]
(S)-2-N-acetylamino-3-(4-methoxy-2-aminophenyl)propionic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: H₂ / Pd/C / tetrahydrofuran; methanol / 0.67 h / 20 °C / 2068.65 Torr

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

30
[ 22996-21-0 ]
[ 353242-39-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

31
[ 22996-21-0 ]
(R)-2-N-acetylamino-3-(4-methoxy-2-nitrophenyl)propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 99 percent / H₂ / [C₅₅H₆₀O₈P₂)Rh(COD)]⁽¹⁺⁾SbF₆^(1-) / tetrahydrofuran / 20 °C / 2068.65 Torr

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

32
[ 22996-21-0 ]
[ 353242-43-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

33
[ 22996-21-0 ]
[ 353242-45-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C 5.1: H₂ / Pd/C / tetrahydrofuran / 1 h / 20 °C / 2327.23 Torr 6.1: triethylamine / CH₂Cl₂ / 20 °C

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

34
[ 22996-21-0 ]
<i>N</i>-acetyl-<i>N</i>-[7-methoxy-1-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-quinolin-3-yl]-4-methyl-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: DBU / CH₂Cl₂ / 0.17 h 1.2: CH₂Cl₂ / 2 h / 20 °C 2.1: 98 percent / H₂ / Rh⁺[L₁^*][COD]SbF₆^- / tetrahydrofuran / 2327.23 Torr 3.1: 87 percent / super hydride(R) / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / CH₂Cl₂ / 0.5 h / 0 °C 5.1: H₂ / Pd/C / tetrahydrofuran / 1 h / 20 °C / 2327.23 Torr 6.1: triethylamine / CH₂Cl₂ / 20 °C

Reference： [1]Gallou-Dagommer, Isabelle; Gastaud, Philippe; RajanBabu [Organic Letters, 2001, vol. 3, # 13, p. 2053 - 2056]

35
[ 22996-21-0 ]
[ 88932-45-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1) n-Butyllithium / 1) a) -78 deg C, b) room temperature, 1.5 h, 2) THF, a) - 78 deg C, 0.5 h, b) room temperature, 16 h 2: TiCl₄ / CH₂Cl₂ / 1 h / -78 °C 3: 95 percent / H₂ / tris(triphenylphosphine)rhodium chloride / benzene / 3 h / 25 °C 4: 90 percent / iodotrimethylsilane / 1) CHCl₃, 25 deg C, 9 h, 2) CHCl₃/methanol, 25 deg C, 12 h

Reference： [1]Mohan, Raju; Katzenellenbogen, John A. [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246]

36
[ 22996-21-0 ]
[ 88932-46-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1) n-Butyllithium / 1) a) -78 deg C, b) room temperature, 1.5 h, 2) THF, a) - 78 deg C, 0.5 h, b) room temperature, 16 h 2: TiCl₄ / CH₂Cl₂ / 1 h / -78 °C 3: 95 percent / H₂ / tris(triphenylphosphine)rhodium chloride / benzene / 3 h / 25 °C 4: 90 percent / iodotrimethylsilane / 1) CHCl₃, 25 deg C, 9 h, 2) CHCl₃/methanol, 25 deg C, 12 h

Reference： [1]Mohan, Raju; Katzenellenbogen, John A. [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246]

37
[ 22996-21-0 ]
[ 88932-54-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1) n-Butyllithium / 1) a) -78 deg C, b) room temperature, 1.5 h, 2) THF, a) - 78 deg C, 0.5 h, b) room temperature, 16 h 2: TiCl₄ / CH₂Cl₂ / 1 h / -78 °C 3: 95 percent / H₂ / tris(triphenylphosphine)rhodium chloride / benzene / 3 h / 25 °C

Reference： [1]Mohan, Raju; Katzenellenbogen, John A. [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246]

38
[ 22996-21-0 ]
[ 88932-55-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1) n-Butyllithium / 1) a) -78 deg C, b) room temperature, 1.5 h, 2) THF, a) - 78 deg C, 0.5 h, b) room temperature, 16 h 2: TiCl₄ / CH₂Cl₂ / 1 h / -78 °C 3: 95 percent / H₂ / tris(triphenylphosphine)rhodium chloride / benzene / 3 h / 25 °C

Reference： [1]Mohan, Raju; Katzenellenbogen, John A. [Journal of Organic Chemistry, 1984, vol. 49, # 7, p. 1238 - 1246]

39
[ 50541-93-0 ]
[ 1634-04-4 ]
[ 22996-21-0 ]
[ 338801-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium borohydrid In methanol; (2S)-N-methyl-1-phenylpropan-2-amine hydrate	A.12 4-methoxy-2-nitro-N-(1-phenylmethyl-4-piperidinyl)benzylamine EXAMPLE A12 4-methoxy-2-nitro-N-(1-phenylmethyl-4-piperidinyl)benzylamine A mixture of 3.0 g (16.561 mmol) of 4-methoxy-2-nitrobenzaldehyde, 3.2 g (16.817 mmol) of 1-phenylmethyl-4-piperidinamine and 30 mL of methanol was stirred for 2 hours at ambient temperature. Then 681 mg (18.0 mmol) of sodium borohydride was added and stirring was continued for one hour at ambient temperature. The mixture was stirred into 500 mL of ice water and carefully acidified with 10% hydrochloric acid. The solution obtained was washed twice with 50 mL of tert-butylmethylether, then made alkaline with 20% sodium hydroxide solution and extracted exhaustively with tert-butylmethylether. The final extracts obtained were combined, washed twice with 20 mL of water, dried over magnesium sulfate and evaporated down in vacuo. The colorless oil remaining was used in the next step without any further purification. Yield: 3.2 g (54% of theoretical). IR (KBr): no C=O; MS: M+=355.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2003/139417, 2003, A1

40
[ 110-89-4 ]
[ 22996-21-0 ]
[ 108-59-8 ]
dimethyl (4-methoxy-2-nitrophenyl)methylidenemalonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In methanol	R.81 Dimethyl (4-Methoxy-2-nitrophenyl)methylidenemalonate REFERENCE EXAMPLE 81 Dimethyl (4-Methoxy-2-nitrophenyl)methylidenemalonate A mixture of 4-methoxy-2-nitrobenzaldehyde (21.3 g, Org. Synth., Vol. V, p-139, 1973), dimethyl malonate (16.5 g), piperidine (2.5 ml), and acetic acid (0.25 ml) in methanol (125 ml) was heated under reflux for 24 hr. The reaction mixture was concentrated, diluted with 1 N aqueous hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with 10% aqueous potassium carbonate and saturated aqueous sodium chloride, dried, and concentrated. The residue was purified by silica gel column chromatography (eluent: ethyl acetate:hexane=1:2) to obtain the titled compound (25 g). 1H NMR δ: 3.67 (3H, s), 3.88 (3H, s), 3.92 (3H, s), 7.16 (1H, dd, J=8.8, 2.6 Hz), 7.36 (1H, d, J=8.8 Hz), 7.70 (1H, d, J=2.6 Hz), 8.14 (1H, s).
	With acetic acid In methanol	R.55 Dimethyl (4-methoxy-2-nitrophenyl)methylidenemalonate Reference Example 55 Dimethyl (4-methoxy-2-nitrophenyl)methylidenemalonate A methanol (125 ml) solution of 4-methoxy-2-nitrobenzaldehyde (21.3 g, described in Org. Synth., volume V, p-139, 1973), dimethyl malonate (16.5 g), piperidine (2.5 ml) and acetic acid (0.25 ml) was heated under reflux for 24 hours. The reaction mixture was concentrated, to which was added 1N hydrochloride, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous potassium carbonate solution and a saturated aqueous sodium chloride solution, then dried and concentrated. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/2) to obtain the entitled compound (25 g). 1H-NMR δ: 3.67(3H, s), 3.88(3H, s), 3.92(3H, s), 7.16(1H, dd), 7.36(1H, d), 7.70(1H, d), 8.14(1H, s).

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF TOKYO - US6310107, 2001, B1
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US6329389, 2001, B1

41
[ 5340-78-3 ]
[ 22996-21-0 ]
C₁₆H₂₃NO₆ [ No CAS ]
C₁₆H₂₃NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl 3,3-dimethylbutanoate; 4-methoxy-2-nitro-benzaldehyde With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78 - 20℃; for 2h; Stage #2: With water In tetrahydrofuran; n-heptane; ethylbenzene	1.C A 2 M solution of LDA in heptane/THF/ethylbenzene (15.2 mL) was added to a mixture of 4.0 g ethyl 3,3-dimethyIbutanoate in 100 mL anhydrous THF at -78 0C. 4-methoxy-2-nitrobenzaldehyde (5.0 g) from the step above was added to the reaction mixture. The resulting mixture was stirred for 2 hours and was allowed to warm to room temperature. The reaction was quenched by addition of 2 mL water. Solvents were removed under reduced pressure and the residue was partitioned between EtOAc and water. The organic extract was washed with 1 N HCl and NaHCO3. The resulting crude product was purified on silica gel using 100:15 hexanes and EtOAc to give two diastereomeric isomers of the title compound. 1H NMR in CDCl3 at 500 MHz of the less polar pair of isomers: 7.56 (d, 9 Hz, IH), 7.52 (d, 2.5 Hz, IH), 7.16 ( dd, 9 Hz, 2.5 Hz, IH), 5.73 ( d, 8.5 Hz, IH), 4,84 (d, 9.5 Hz, IH), 4.10-3.95 ( m, 2H), 3.88 ( s, 3H), 2.64 (d, 2 Hz, IH), 1.20 (s, 9H), 1.09 (t, 7 Hz, 3H)

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2007/108968, 2007, A2 Location in patent: Page/Page column 26

42
[ 5344-78-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: 4-bromo-3-nitroanizole With phenyllithium In tetrahydrofuran at -90 - -70℃; for 2h; Stage #2: With N,N-dimethyl-formamide In tetrahydrofuran at -90 - 0℃; for 2h; Further stages.;

Reference： [1]Shen, Bin; Löffler, Dirk; Zeller, Klaus-Peter; Übele, Michael; Reischl, Gerald; Machulla, Hans-Jürgen [Journal of Fluorine Chemistry, 2007, vol. 128, # 12, p. 1461 - 1468]

43
[ 22996-21-0 ]
[ 33844-21-2 ]
[ 141080-74-2 ]

Reference： [1]Journal of Fluorine Chemistry,2007,vol. 128,p. 1461 - 1468

44
[ 22996-21-0 ]
[ 24131-30-4 ]
[ 1072121-79-9 ]
C₁₇H₁₇NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: (3,5-dimethoxybenzyl)triphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran at 20℃; for 6h;	1.1.i (Z)-1-[2-(3,5-Dimethoxy-phenyl)-vinyl]-4-methoxy-2-nitrobenzene (3b) (Z)-1-[2-(3,5-Dimethoxy-phenyl)-vinyl]-4-methoxy-2-nitrobenzene (3b) The phosphonium salt 1 (3 mmol, 1.48 g) was suspended in 10 mL of anhydrous tetrahydrofuran (THF). The suspension is cooled in an ice bath and then NaH (55% in mineral suspension, (3.4 mmol, 148 mg) is added. After about 30 minutes, a solution of aldehyde 2b (2 mmol, 362 mg) in 5 mL of THF is added. The reaction is stirred at room temperature for 6 h, filtered on a Celite bed, and washed with THF. After solvent evaporation, the residue is dissolved in methylene chloride (20 mL), washed with water (5 mL) and brine (5 mL), dried and evaporated again. The residue is purified by flash chromatography on silica gel (30% Ethyl acetate/light petroleum) to afford the expected cis compound 3b (240 mg), and trans isomers. Oil; Yield 38%. 1H NMR (CDCl3): δ 3.62 (s, 6H), 3.86 (s, 3H), 6.21-6.23 (m, 2H), 6.27-6.29 (m, 1H), 6.63 (d, J=12.4, 1H), 6.83 (d, J=12.4, 1H), 6.95 (dd, J=2.6, J=8.6, 1H), 7.20 (d, J=8.6, 1H), 7.58 (d, J=2.6, 1H).

Reference： [1]Current Patent Assignee: VIRGINIA COMMONWEALTH UNIVERSITY - US2008/261982, 2008, A1 Location in patent: Page/Page column 8

45
1-(dibromomethyl)-4-methoxy-2-nitrobenzene [ No CAS ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With water; sodium hydrogencarbonate for 22h; Heating / reflux;	54 Intermediate 54 : 4-Methoxv-2-sHtrobe8izakehydg; A mixture of l-(dibromomethyl)-4-rnethoxy-2 -nitrobenzene (42 g, 0.23 mol) and NaHCO3 (3Eq) in water (400 mL) is rcfluxed for 22 h. The reaction mixture is cooled to room temperature and the product is extracted with EtOAc (2x 150 mL). The organic layer is washed with a solution of 1.5N HCl (2x100 mL), water (2x100 mL) and brine then dried over Na2SOj. The solvent is removed under reduced pressure to afford 20 g (85%) of the title compound as a brown solid. 1H NMIUDMSO-dtf, 400MHz) δ 10.03 (s, IH), 7.93-7.95 (m, IH), 7.61 (s, IH), 7.40- 7.41 (m, IH), 3.93 (s, 3H).

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2008/101979, 2008, A1 Location in patent: Page/Page column 75

46
[ 22996-21-0 ]
[ 519060-36-7 ]
[ 1017293-89-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 42% 2: 47%	With sulfuric acid; nitric acid at 0℃; for 0.166667h;
1: 46% 2: 38%	With sulfuric acid; nitric acid at 0℃; for 2h; Inert atmosphere; regioselective reaction;	2.1.1 4.1.2.1. Nitration of aldehyde16 4-Methoxy-2-nitrobenzaldehyde(1.53 g, 8.45 mmol) was dissolved in concentratedH2SO4 (25 mL). To this solution, a pre-cooled mixture of HNO3and H2SO4 (3.85 mL/2.85 mL) was added dropwise. The reactionmixture was stirred for 10 min, and then the resulting solutionwas added dropwise into ice-water (100 mL). After stirring for2 h at 0 C, the solution was filtered, and the solid containing thedesired product was rinsed with ice-water (10 mL). Purification by flash column chromatography (40% EtOAc/hexanes) yieldedregio-isomers 1 and 2. 4.1.2.1.1. 4-Methoxy-2,3-dinitrobenzaldehyde (1) 16 This compound was isolated as a yellow solid (0.879 g, 3.89 mmol, 46%). 1H NMR (500 MHz, CDCl3): δ 9.95 (1H, s), 8.15 (1H, d, J = 8.9 Hz), 7.40 (1H, d, J = 8.9 Hz), 4.09 (3H, s), 13C NMR (125 MHz, CDCl3): δ 184.05, 155.69, 133.11, 128.96, 121.04, 115.92, 114.53, 57.88.
1: 38% 2: 41%	With sulfuric acid; nitric acid at 0℃;

1: 29% 2: 20%

With nitric acid at 0 - 20℃;

Reference： [1]Location in patent: experimental part Siles, Rogelio; Ackley, J. Freeland; Hadimani, Mallinath B.; Hall, John J.; Mugabe, Benon E.; Guddneppanavar, Rajsekhar; Monk, Keith A.; Chapuis, Jean-Charles; Pettit, George R.; Chaplin, David J.; Edvardsen, Klaus; Trawick, Mary Lynn; Garner, Charles M.; Pinney, Kevin G. [Journal of Natural Products, 2008, vol. 71, # 3, p. 313 - 320]
[2]Devkota, Laxman; Lin, Chen-Ming; Strecker, Tracy E.; Wang, Yifan; Tidmore, Justin K.; Chen, Zhi; Guddneppanavar, Rajsekhar; Jelinek, Christopher J.; Lopez, Ramona; Liu, Li; Hamel, Ernest; Mason, Ralph P.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 5, p. 938 - 956]
[3]Location in patent: scheme or table Akselsen, Øyvind W.; Odlo, Kristin; Cheng, Jing-Jy; MacCari, Giorgio; Botta, Maurizio; Hansen, Trond Vidar [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 234 - 242]
[4]Serafinowski, Pawel J.; Garland, Peter B. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 18, p. 3284 - 3291]

47
[ 22996-21-0 ]
[ 100-58-3 ]
[ 179104-61-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 4-methoxy-2-nitro-benzaldehyde; phenylmagnesium bromide In tetrahydrofuran at -78 - -10℃; for 0.75h; Stage #2: With hydrogenchloride In tetrahydrofuran; water for 0.333333h;
85%	Stage #1: 4-methoxy-2-nitro-benzaldehyde; phenylmagnesium bromide In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 0℃; Inert atmosphere;
	In tetrahydrofuran at 0℃; for 3h; Inert atmosphere;

Reference： [1]Serafinowski, Pawel J.; Garland, Peter B. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 18, p. 3284 - 3291]
[2]Stokes, Benjamin J.; Vogel, Carl V.; Urnezis, Linda K.; Pan, Minjie; Driver, Tom G. [Organic Letters, 2010, vol. 12, # 12, p. 2884 - 2887]
[3]Massaro, Nicholas P.; Chatterji, Aayushi; Sharma, Indrajeet [Journal of Organic Chemistry, 2019, vol. 84, # 21, p. 13676 - 13685]

48
phosphonium bromide [ No CAS ]
[ 22996-21-0 ]
3,4-Methylenedioxy-5,4'-dimethoxy-3'-nitro-Z-stilbene [ No CAS ]
3,4-Methylenedioxy-5,4'-dimethoxy-3'-nitro-E-stilbene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	Stage #1: phosphonium bromide With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 4h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran for 18h;	3,4-Methylenedioxy-5,4'-dimethoxy-3'-nitro-stilbene, Z - and E isomers (6a and 6b) The phosphonium bromide 4 (20.1 g, 39.6 mmol) was placed in a flame dried flask under Ar and suspended in THF (300 ml). After being stirred for 45 minutes at room temperature, the solution was cooled to 0°C, and n-butyllithium (15.9 ml, 39.8 mmol) was added. This resulted in the reaction mixture turning a deep red color. Stirring continued for 4 hours at room temperature. 3-Nitro-4-methoxy-benzaldehyde (5,7. 20 g, 3.97 mmol) was dissolved in THF (100 ml), and the solution was added dropwise to the reacting mixture via an addition FUNNEL. The solution color turned from deep red to YELLOW/GREEN. After being stirred 18 hours, the reaction mixture was cooled to 0°C. The reaction was terminated with ethyl acetate, and the solution filtered and concentrated under vacuum to yield a dark green oil. The product was separated by gravity column chromatography on silica gel (4: 1, hexane: ethyl acetate) and recrystallized (hexane-acetone) to yield the Z-stilbene 6a (4.09 g, 31%) as a yellow/green solid: m. p. 109-110°C ; Rf 0.29 (4: 1, hexane: ethyl acetate) ; IH-NMR (400 MHz, CDC13) 6 3.78 (3H, s, OCH3), 3.94 (3H, s, OCH3), 5.96 (2H, S,-CH2-), 6.41 (3H, M, vinyl H, 2 x ArH), 6.54 (1H, d, J= 12.4 Hz, vinyl H), 6.94 (1H, d, J= 8.4 Hz, ArH), 7.42 (1H, dd, J= 8.8, 2.0 Hz, ArH), 7.76 (1H, d, J= 2.0 Hz, ArH); 13C-NMR (400 MHz, CDC13) 5 151.7, 148.9, 143.6, 139.6, 134.9, 134.5, 131.1, 130.7, 129.7, 126.6, 126.0, 113.2, 108.5, 102.8, 101.5, 56.5, 56.5 ; HRMS calcd for C17HL6NO6 [M+H] + 330. 0978, found 330.0947. Anal. (CL7HISNO6) C, H, N. The E-stilbene 6b was isolated from the aforementioned column and recrystallized (hexane-acetone) as an orange solid (2.90 g, 22%): m. p. 165. 5-167°C ; Rf 0.18 (4: 1, hexane: ethyl acetate) ; IH-NMR (500 MHz, CDCl3) S 3.92 (3H, s, OCH3), 3.94 (3H, s, OCH3), 5.97 (2H, S,-CH2-), 6.62 (1H, s, ArH), 6.70 (1H, s, ArH), 6.81 (1H, d, J= 16 Hz, vinyl H), 6.90 (1H, d, J= 16 Hz, vinyl H), 7.03 (1H, d, J= 9.0 Hz, ArH), 7. 58 (1H, dd, J= 9.0, 2.0 Hz, ArH), 7.92 (1H, d, J = 2.0 Hz, ArH); 13C-NMR (500 MHz, CDC13) 8 152.0, 149.3, 143.6, 139.7, 135.4, 131.7, 131.6, 130.3, 129.2, 124.4, 122.9, 113.7, 107.1, 101.6, 99.8, 56.6, 56.6 ; HRMS calcd for C17H16N06 [M+H] + 330.0978, found 330.0869. Anal. (CL7HL5NO6) C, H, N.

Reference： [1]Current Patent Assignee: ARIZONA BOARD OF REGENTS - WO2004/52875, 2004, A1 Location in patent: Page 13

49
[ 22996-21-0 ]
[ 90151-04-5 ]

Yield	Reaction Conditions	Operation in experiment
61%	With boron tribromide; In dichloromethane; at 0 - 20℃; for 4.5h;	To a stirred solution of 4-m robenzaldehyde (4.5 g, 24.84 mmol) in dichloromethane (100 mL) at 0 C was added boron tribromide (8 mL, 84.5 mmol) dropwise. The mixture was stirred for thirty minutes at 0 C and an additional four hours at room temperature. The reaction mixture was poured into ice water (200 mL) and stirred for two days. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water, brine, dried (Na2SO4) and concentrated. The resulting residue was purified via MPLC eluting with a gradient of ethyl acetate/petroleum ether (1:15-1:5) to afford 4- hydroxy-2-nitrobenzaldehyde (2.55 g, 61%) as an orange solid.
	With boron tribromide; In dichloromethane; at 20℃;Cooling with ice;	To 4-methoxy-2-nitrobenzaldehyde (CarboCore, CO-Ol 19, 5.5g) and 200 mL DCM in a 500 mL round-bottom flask was added borontribromide (24g) dropwise with cooling in an ice bath. The reaction was stirred at the same temperature for 30 minutes and then at ambient temperature for 3 hours. The reaction mixture was carefully poured into ice water and let stand at ambient temperature for 3 days. The aqueous mixture was extracted with EtOAc, washed with sat. aq. NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by a SiO2 gel flash chromatography using a linear gradient of 20 to 60% EtOAc in hexanes (Rf. 0.32, 50% EtOAc in hexanes), affording TU3627-002 as orange crystals. MS (ESI+): calcd. 168.02, found 168.10 (MH+). H-NMR (400MHz, DMSO-d6): delta 7.211 (IH, dd, J= 2.4, 8.4Hz), 7.362 (IH, d, J= 2.4Hz), 7.866 (IH, d, 8.8Hz), 9.998 (IH, s), 11.466 (IH, s). C-NMR (100MHz, DMSO-d6): delta 110.726, 119.683, 120.770, 132.616, 151.225, 162.650, 187.885.

Reference： [1]Patent: WO2015/171610,2015,A2 .Location in patent: Paragraph 000656
[2]Patent: WO2010/48582,2010,A1 .Location in patent: Page/Page column 170-171

50
[ 5348-42-5 ]
[ 22996-21-0 ]
[ 1224878-11-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 4,5-Dichloro-1,2-phenylenediamine; 4-methoxy-2-nitro-benzaldehyde In acetonitrile for 1h; Reflux; Stage #2: With iron(III) chloride hexahydrate; oxygen In acetonitrile for 6h; Heating;

Reference： [1]Location in patent: experimental part Tonelli, Michele; Simone, Matteo; Tasso, Bruno; Novelli, Federica; Boido, Vito; Sparatore, Fabio; Paglietti, Giuseppe; Pricl, Sabrina; Giliberti, Gabriele; Blois, Sylvain; Ibba, Cristina; Sanna, Giuseppina; Loddo, Roberta; La Colla, Paolo [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 8, p. 2937 - 2953]

51
[ 22996-21-0 ]
2-azido-4-methoxybenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium azide In N,N,N,N,N,N-hexamethylphosphoric triamide at 20℃; Inert atmosphere;
98%	With sodium azide In N,N,N,N,N,N-hexamethylphosphoric triamide at 0 - 20℃; Inert atmosphere;
92%	With sodium azide In N,N,N,N,N,N-hexamethylphosphoric triamide at 50℃; Inert atmosphere;

	With N,N,N,N,N,N-hexamethylphosphoric triamide; sodium azide at 50℃; for 72h;
	With sodium azide at 25℃; for 24h;

Reference： [1]Stokes, Benjamin J.; Vogel, Carl V.; Urnezis, Linda K.; Pan, Minjie; Driver, Tom G. [Organic Letters, 2010, vol. 12, # 12, p. 2884 - 2887]
[2]Stokes, Benjamin J.; Liu, Sheng; Driver, Tom G. [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4702 - 4705]
[3]Sun, Ke; Liu, Sheng; Bec, Patryk M.; Driver, Tom G. [Angewandte Chemie - International Edition, 2011, vol. 50, # 7, p. 1702 - 1706]
[4]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]
[5]Muthengi, Alex; Erickson, Jon; Muriph, Rachel E.; Zhang, Wei [Journal of Organic Chemistry, 2019, vol. 84, # 9, p. 5927 - 5935]

52
[ 558-13-4 ]
[ 22996-21-0 ]
[ 1312450-64-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine In dichloromethane at 0℃;	2.1.1 General procedure for the synthesis of (2,2-dibromovinyl)-nitroaryls 1-(2,2-dibromovinyl)-2-nitrobenzene: 2-nitrobenzaldehyde (10.00 g, 66.2 mmol) was dissolved in DCM (350 mL). CBr4 (23.04 g, 69.5 mmol) was added and the solution cooled to 0 °C in an ice bath. PPh3 (36.4 g, 139 mmol) was added in several portions, and the solution stirred at 0 °C until the reaction was complete by TLC (30 minutes). Hexanes (350 mL) were added to precipitate P(O)Ph3 and P(O)Br2Ph3, and the solution was vacuum filtered over a pad of silica gel, rinsing with 10% EtOAc (hexanes). The filtrate was collected and solvent removed to yield pure 1-(2,2-dibromovinyl)-2-nitrobenzene (19.80 g, 97%).
	With triphenylphosphine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;

Reference： [1]Kunzer, Aaron R.; Wendt, Michael D. [Tetrahedron Letters, 2011, vol. 52, # 15, p. 1815 - 1818]
[2]Zeidan, Nicolas; Bognar, Sabine; Lee, Sophia; Lautens, Mark [Organic Letters, 2017, vol. 19, # 19, p. 5058 - 5061]

53
[ 22996-21-0 ]
[ 187731-65-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7834 - 7847

54
[ 53-43-0 ]
[ 22996-21-0 ]
[ 1414852-28-0 ]

Yield	Reaction Conditions	Operation in experiment
63.8%	With potassium hydroxide In methanol at 20℃; for 2h;	3 General method for the preparation of compounds 1-5 General procedure: A mixture of dehydroepiandrosterone (2.60 mmol), the appropriate aldehyde (4-pyridine carboxaldehyde/3,4,5-trimethoxybenzaldehyde/ 4-methoxy-2-nitrobenzaldehyde/benzo-[1,3]dioxol-5-carboxaldehyde/imidazole-2-carboxaldehyde) and potassium hydroxide (1 g) in methanol (20 ml) was stirred at room temperature for 2 h until the reaction was completed (monitored by TLC). Cold water was added to the reaction mixture and the precipitate obtained was filtered, washed with water, dried and crystallized from methanol to give the corresponding 16-arylideno steroid 1-5.

Reference： [1]Bansal, Ranju; Thota, Sridhar; Karkra, Nalin; Minu, Maninder; Zimmer, Christina; Hartmann, Rolf W. [Bioorganic Chemistry, 2012, vol. 45, p. 36 - 40]

55
[ 22996-21-0 ]
[ 543-24-8 ]
4-(4-methoxy-2-nitrobenzylidene)-2-methyloxazol-5(4H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium acetate In acetic anhydride for 4h; Inert atmosphere; Reflux;	4.3. General procedure-2: synthesis of the oxazoles 2, or acrylic acids, 3 General procedure: 5 mmol of the substituted benzaldehyde was dissolved in 20 mL of acetic anhydride then 1.2 equiv. of N-acetyl glycine and 5 equiv. of sodium acetate were added and the reaction was stirred under reflux for 4 h. Then solvent was partially evaporated then was poured into 50 mL of crushed ice and stirred vigorously for 30 min. A precipitate was obtained which was separated and washed with cold water and dried under vacuum to get the oxazolyl product 2, or its hydrolyzed acrylic acid, 3.

Reference： [1]Takrouri, Khuloud; Chen, Ting; Papadopoulos, Evangelos; Sahoo, Rupam; Kabha, Eihab; Chen, Han; Cantel, Sonia; Wagner, Gerhard; Halperin, Jose A.; Aktas, Bertal H.; Chorev, Michael [European Journal of Medicinal Chemistry, 2014, vol. 77, p. 361 - 377]

56
[ 123-11-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sulfuric acid; nitric acid at 0 - 20℃; for 0.5h; Inert atmosphere;	Method B. General procedure: 10 mmol of the desired p-substituted benzaldehyde was dissolved in 5 mL of conc. sulfuric acid, and cooled to 0 °C, and then 1.2 equiv. of nitric acid was dissolved in 1 mL of conc. sulfuric acid, and then slowly added to the reaction mixture. The reaction was allowed to warmgradually to room temperature and stirred for 30 min at room temperature. It was then poured into 50 mL of ice-cold water. The produced precipitate was filtered and washed with cold water. The product was purified on reverse phase column chromatography with gradient increase of methanol in water containing 0.1% of formic acid as eluent.
74%	With sulfuric acid; nitric acid at 20℃; Cooling with ice;

Reference： [1]Takrouri, Khuloud; Chen, Ting; Papadopoulos, Evangelos; Sahoo, Rupam; Kabha, Eihab; Chen, Han; Cantel, Sonia; Wagner, Gerhard; Halperin, Jose A.; Aktas, Bertal H.; Chorev, Michael [European Journal of Medicinal Chemistry, 2014, vol. 77, p. 361 - 377]
[2]Bansal, Ranju; Kumar, Gulshan; Rohilla, Suman; Klotz, Karl-Norbert; Kachler, Sonja; Young, Louise C.; Harvey, Alan L. [Drug Development Research, 2016, p. 241 - 250]

57
[ 22996-21-0 ]
[ 1601474-96-7 ]
C₁₉H₂₃NO₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-3,4,5-trimethoxy-2-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In tetrahydrofuran; hexane at 0℃; for 1h;	6 4.1.8 General procedure C for synthesis of 2-(methoxymethoxy)-3,4,5-trimethoxy benzophenone (24a-c, 24e-f and 10) General procedure: A stirred solution of 1-bromo-3,4,5-trimethoxy-2-(methoxymethoxy)benzene (1.2equiv) in THF (0.13M) was cooled to-78°C and n-BuLi (1.2equiv, 1.6M in hexane) was added dropwise. The resulting solution was stirred at-78°C for 1h. The previous solution was added slowly to a solution of the substituted benzaldehyde (1equiv) in THF (0.3M) at 0°C. The solution was stirred at 0°C for 1h and then was quenched with water. The mixture was extracted with EtOAc and the organic layer was collected. The crude product was purified through chromatography to afford (EtOAc/hexane) the substituted benzhydrol. To a solution of the substituted benzhydrol (0.1M) in CH2Cl2, pyridinium dichromate (2equiv) and 4 molecular sieves (0.3g) was added at room temperature. The resulting mixture was stirred at room temperature for 6h. The mixture was diluted with EtOAc and filtered through a pad of Celite. The organic layer was collected and the crude product was purified by flash chromatography (EtOAc/hexane) to yield the substituted benzophenone.

Reference： [1]Chang, Chih-Yi; Chuang, Hsun-Yueh; Lee, Hsueh-Yun; Yeh, Teng-Kuang; Kuo, Ching-Chuan; Chang, Chi-Yen; Chang, Jang-Yang; Liou, Jing-Ping [European Journal of Medicinal Chemistry, 2014, vol. 77, p. 306 - 314]

58
[ 540-88-5 ]
[ 22996-21-0 ]
[ 1166240-97-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With titanium tetrachloride; triethylamine In dichloromethane at 0 - 25℃; Inert atmosphere; stereoselective reaction;	General procedure for the TiCl4-mediated synthesis of alkyl (E)-α,β-unsaturated carboxylates (2a-m): General procedure: To a mixture of an aldehyde (0.1 mol) and alkyl acetate (0.1 mol) in dichloromethane (15 mL) was added Et3N (0.3 mol). The resulting reaction mixture was cooled to 0 °C under nitrogen atmosphere. To this was added TiCl4 (0.12 mol) dropwise over a period of 15 min and the mixture was stirred for further 2-4 h at room temperature. When the reaction was complete as confirmed by TLC, the mixture was diluted with water (25 mL) and the dichloromethane layer was separated. The organic phase was washed with 0.5 M aqueous HCl, water and brine. It was then dried over anhydrous Na2SO4 and evaporated under reduced pressure to afford the corresponding alkyl (E)-α,β-unsaturated carboxylate (2) in excellent yield and purity.

Reference： [1]Augustine, John Kallikat; Boodappa, Chandrakantha; Venkatachaliah, Srinivasa; Mariappan, Ayyampillai [Tetrahedron Letters, 2014, vol. 55, # 24, p. 3503 - 3506]

59
[ 22996-21-0 ]
[ 5717-37-3 ]
(E)-ethyl 3-(4-methoxy-2-nitrophenyl)-2-methylacrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With sodium hydride In tetrahydrofuran at 0 - 20℃; for 4h;	a Step-a: Synthesis of (E)-ethyl 3-(4-methoxy-2-nitrophenyl)-2-methylacrylate To a stirred suspension of sodium hydride (0.44 g, i i.04 mmol) in THF (20 mL) at 0°C were added 4-methoxy-2-nitrobenzaldehyde (i.0 g, 5.52 mmol) and ethyl-2-(triphenyl phosphoranylidene)propanoate (2.0 g, 5.52 mmol), allowed to stir at RT for 4 h. After completion of the reaction, the reaction mixture diluted with water and extracted with EtOAc (200 mL X 2). The combined organic layers were washed with water (200 mL), brine (iOO mL),dried over sodium sulphate and concentrated. The residue was purified on silica gel (iOO-200 mesh) to afford the title product as a brown solid (0.33 g, 22%). 1H NMR (400 MHz, CDC13): ö 7.83 (s, 1H), 7.63 (d, J=2.4 Hz, 1H), 7.26 (s, 1H), 7.20-7. 17 (m, 1H), 4.28 (q, J=7.3 Hz, 2H),3.90 (s, 3H), 1.91 (s, 3H), 1.35 (t, J=7.4 Hz, 3H).
22%	With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 4h;	a Step-a Synthesis of (E)-ethyl 3-(4-methoxy-2-nitrophenyl)-2-methylacrylate Step-a Synthesis of (E)-ethyl 3-(4-methoxy-2-nitrophenyl)-2-methylacrylate To a stirred suspension of sodium hydride (0.44 g, 11.04 mmol) in THF (20 mL) at 0° C. were added 4-methoxy-2-nitrobenzaldehyde (1.0 g, 5.52 mmol) and ethyl-2-(triphenyl phosphoranylidene)propanoate (2.0 g, 5.52 mmol), allowed to stir at RT for 4 h. After completion of the reaction, the reaction mixture diluted with water and extracted with EtOAc (200 mL*2). The combined organic layers were washed with water (200 mL), brine (100 mL), dried over sodium sulphate and concentrated. The residue was purified on silica gel (100-200 mesh) to afford the title product as a brown solid (0.33 g, 22%). 1H NMR (400 MHz, CDCl3): δ 7.83 (s, 1H), 7.63 (d, J=2.4 Hz, 1H), 7.26 (s, 1H), 7.20-7.17 (m, 1H), 4.28 (q, J=7.3 Hz, 2H), 3.90 (s, 3H), 1.91 (s, 3H), 1.35 (t, J=7.4 Hz, 3H).

Reference： [1]Current Patent Assignee: ORION OYJ - WO2015/104653, 2015, A1 Location in patent: Page/Page column 33; 34
[2]Current Patent Assignee: ORION OYJ - US2016/368906, 2016, A1 Location in patent: Paragraph 0160

60
[ 22996-21-0 ]
[ 105-53-3 ]
diethyl 2-(4-methoxy-2-nitrobenzylidene)malonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With piperidine; acetic acid In ethanol Reflux;	12.I Part I -- Synthesis of Diethyl 2-(4-methoxy-2-nitrobenzylidene)malonate j00370j 4-Methoxy-2-nitrobenzaldehyde (10 g, 55.20 mmol) was dissolved in ethanol (110 mL), and diethyl malonate (9.73 g, 60.72 mmol) was added followed by piperidine (0.94 g, 11.04 mmol) and acetic acid (0.663 g, 11.04 mmol). The reaction mixture was then heated at reflux overnight. Next, the reaction mixture was concentrated, and the resulting residue was partitioned between iN HC1 and ethyl acetate. The organic phase was washed with 10% sodium carbonate solution, washed with brine, dried (Na2SO4), and concentrated to provide a residue. The residue was purified by MPLC eluting with a gradient of 5-15% ethyl acetate in hexanes to afford diethyl 2-(4-methoxy-2-nitrobenzylidene)malonate as an oil (10.01 g, 56%).
56%	With piperidine; acetic acid In ethanol Reflux;	8.I Synthesis of Diethyl 2-(4-methoxy-2-nitrobenzylidene)malonate 4-Methoxy-2-nitro , 55.20 mmol) was dissolved in ethanol (110 mL), and diethyl malonate (9.73 g, 60.72 mmol) was added followed by piperidine (0.94 g, 11.04 mmol) and acetic acid (0.663 g, 11.04 mmol). The reaction mixture was then heated at reflux overnight. Next, the reaction mixture was concentrated, and the resulting residue was partitioned between 1N HCl and ethyl acetate. The organic phase was washed with 10% sodium carbonate solution, washed with brine, dried (Na2SO4), and concentrated to provide a residue. The residue was purified by MPLC eluting with a gradient of 5-15% ethyl acetate in hexanes to afford diethyl 2-(4-methoxy-2-nitrobenzylidene)malonate as an oil (10.01 g, 56%).

Reference： [1]Current Patent Assignee: LYCERA CORPORATION - WO2015/131035, 2015, A1 Location in patent: Paragraph 00370
[2]Current Patent Assignee: LYCERA CORPORATION - WO2015/171610, 2015, A2 Location in patent: Paragraph 000346

61
[ 22996-21-0 ]
[ 61240-20-8 ]
[ 519060-25-4 ]
1,2,3-trimethoxy-5-((E)-4-methoxy-2-nitrostyryl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 72% 2: 25%	Stage #1: triphenyl-(3,4,5-trimethoxybenzyl)phosphonium bromide With sodium hydride In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; Stage #2: 4-methoxy-2-nitro-benzaldehyde In dichloromethane for 5h; Inert atmosphere;	1 4.1.2.3. Procedure for the synthesis of Z- and E-stilbenes (5a and5b) At 0 C, a NaH suspension (0.478 g, 19.9 mmol) in dryCH2Cl2 (50 mL) was stirred for 10 min. The previously preparedsolution of 3,4,5-trimethoxybenzylphosphonium bromide (1.73 g,3.30 mmol) was added dropwise. After stirring for 20 min, 4-methoxy-2-nitrobenzaldehyde (0.501 g, 2.76 mmol) was added. Theresulting mixture was stirred for 5 h. At this point, ice-water wasadded carefully until H2 evolution stopped. Workup of the reactionmixture was carried out by extraction with CH2Cl2 (2 25 mL), followedby washing the combined organic layers with water (twice)and brine and finally drying over Na2SO4. The Z- and E-isomerswere isolated after flash column chromatography (40% EtOAc/hexanes)and re-crystallization of the Z and E-isomer mixture fromEtOAc and hexanes. 4.1.2.3.1 (Z)-2-(4'-Methoxy-2'-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)ethene (5a) This compound was isolated as a yellow solid (0.690 g, 1.99 mmol, 72%). 1H NMR (500 MHz, CDCl3): δ 7.59 (1H, d, J = 2.7 Hz), 7.24 (1H, d, J = 8.6 Hz), 7.01 (1H, dd, J = 8.6, 2.6 Hz), 6.80 (1H, d, J = 11.9 Hz), 6.62 (1H, d, J = 11.9 Hz), 6.29 (2H, s), 3.87 (3H, s), 3.81 (3H, s), 3.62 (6H, s). 13C NMR (125 MHz, CDCl3): δ 159.0, 152.9, 148.6, 137.4, 133.4, 131.5, 131.2, 125.9, 125.7, 120.0, 108.7, 106.3, 60.9, 55.9, 55.8.

Reference： [1]Devkota, Laxman; Lin, Chen-Ming; Strecker, Tracy E.; Wang, Yifan; Tidmore, Justin K.; Chen, Zhi; Guddneppanavar, Rajsekhar; Jelinek, Christopher J.; Lopez, Ramona; Liu, Li; Hamel, Ernest; Mason, Ralph P.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 5, p. 938 - 956]

62
[ 22996-21-0 ]
benzyl 2-(pentafluoro-λ⁶-sulfanyl)acetate [ No CAS ]
benzyl 3-hydroxy-3-(4-methoxy-2-nitrophenyl)-2-(pentafluorosulfanyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: benzyl 2-(pentafluoro-λ⁶-sulfanyl)acetate With di-n-butylboryl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - -20℃; for 1h; Stage #2: 4-methoxy-2-nitro-benzaldehyde In dichloromethane at -45℃; for 1h;

Reference： [1]Joliton, Adrien; Plancher, Jean-Marc; Carreira, Erick M. [Angewandte Chemie - International Edition, 2016, vol. 55, # 6, p. 2113 - 2117]

63
[ 5440-00-6 ]
[ 22996-21-0 ]
C₁₄H₁₅N₅O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63.07%	With acetic acid In methanol at 20℃; for 18h;

Reference： [1]Bansal, Ranju; Kumar, Gulshan; Rohilla, Suman; Klotz, Karl-Norbert; Kachler, Sonja; Young, Louise C.; Harvey, Alan L. [Drug Development Research, 2016, p. 241 - 250]

64
[ 22996-21-0 ]
[ 623-51-8 ]
[ 187753-62-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In N,N-dimethyl-formamide at 0 - 60℃; for 8.5h;	36 Example 36(diethylphosphoryl)methyl6-methoxybenzothiophene-2-carboxylate (Compound 36) Under ice-cooling, 2-nitro-4-methoxybenzaldehyde(3.62g, 20mmol) and anhydrous K2CO3 (3.31g, 24mmol) was dissolved (50ml) atDMF, was slowly added dropwise ethyl thioglycolate (2.40g, 20mmol). Completionof the dropwise addition, 0 ° C was stirred for 30min, then at 60 ° C in an oilbath, the reaction 8h. The reaction solution was poured into ice water, overFiltered, the solid was dissolved in chloroform, dried over anhydrous Na2SO4,filtered, and spin dry the solvent, by silica gel column chromatography After ayellow solid 3.72g(79% yield), which was dissolved in dioxane (30ml) was added 1N Sodiumhydroxide solution (16ml), stirred at room temperature 2h, the dioxane wasevaporated to dryness, the residual liquid was poured into ice-water, Washedwith dichloromethane, adjusting the PH value to 2, the solid was collected byfiltration 3.05g (93% yield), which was dissolved in dichloromethane (40ml),was added DIC (2.14g, 16.98mmol), after stirring at room temperature 1h, wasadded DMAP (0.53g, 4.34mmol) and hydroxymethyl phosphonic acid diethylester (2.71g, 16.16mmol), was heatedunder reflux for 5h, washed with water and saturated The reaction solution waswashed with brine, dried over anhydrous magnesium sulfate, filtered, evaporatedto dryness, ethyl acetate - petroleum ether recrystallization System Crystal,to give the product 6 - methoxy -2-thiophene carboxylic acid (2 '- phosphonicacid diethyl ester), methyl 2.23g (81%)

Reference： [1]Current Patent Assignee: ZHEJIANG MEDICINE CO., LTD.; CHINESE ACADEMY OF MEDICAL SCIENCES - CN103130705, 2016, B Location in patent: Paragraph 0279-0281

65
[ 1335101-95-5 ]
[ 22996-21-0 ]

Yield	Reaction Conditions	Operation in experiment
5 g	With sodium periodate In tetrahydrofuran; water at 35℃; for 16h;	11.B [0228] Step B. 4-methoxy-2-nitrobenzaldehyde. To a mixture of (E)-l-(4-methoxy-2- nitrostyryl)pyrrolidine (7.4 g, 30 mmol) in THF (80 mL) was added a solution of NalC (16 g, 75 mmol) in H2O (240 mL). The reaction mixture was stirred at 35 °C for 16 hr then extracted with DCM (100 mL). The organic layer was separated, dried over anhydrous Na2SC>4, and concentrated under reduced pressure.[0229] The residue was purified by flash column chromatography to afford 4-methoxy-2- nitrobenzaldehyde (5 g, 92% yield). LC-MS: m/z 182 (M+H)+.

Reference： [1]Current Patent Assignee: SPERO THERAPEUTICS INC - WO2016/112088, 2016, A1 Location in patent: Paragraph 0228-0229

66
[ 22996-21-0 ]
[ 1099-45-2 ]
[ 105905-82-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	In toluene for 2h; Inert atmosphere; Reflux;	29.1 Step 1. (E)-Ethyl 3-(4-methoxy-2-nitro hen l acr late To a solution of 4-methoxy-2-nitrobenzaldehyde (500 mg, 2.8 mmol) in anhydrous toluene (36 mL) under N2 atmosphere, ethyl 2-(triphenyl-λ5-phosphanylidene)acetate (1.2 g, 3.6 mmol) was added and stirred at reflux for 2 hours. After solvent evaporation, compound (E)- ethyl 3-(4-methoxy-2-nitrophenyl)acrylate was purified by flash chromatography using hexanes:ethyl acetate as solvent. Yield 90%.1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 15.8 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.49 (d, J = 2.6 Hz, 1H), 7.15 (dd, J = 8.7, 2.6 Hz, 1H), 6.29 (d, J = 15.8 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.90 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H).
88%	In toluene at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: YALE UNIVERSITY - WO2016/130968, 2016, A1 Location in patent: Page/Page column 183
[2]Chaabouni, Slim; Simonet, Florent; François, Alison; Abid, Souhir; Galaup, Chantal; Chassaing, Stefan [European Journal of Organic Chemistry, 2017, vol. 2017, # 2, p. 271 - 277]

67
[ 22996-21-0 ]
[ 2213-43-6 ]
C₁₃H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 90℃; for 2h; Sealed tube;	General procedure for preparation of N-substituted-2H-indazol-2-amine derivatives 8 General procedure: To a solution of 2-nitrobenzaldehyde (0.5 mmol) in 4 mL of anhydrous toluene was added phenyl hydrazine (0.55 mmol) at room temperature in a sealed tube. The reaction mixture was heated at 90 °C for 2 hours and then cooled down to room temperature to add tri(N-butyl)phosphine (375 L, 1.5 mmol). The reaction mixture was further heated at 90 °C for 18 hours. After completion of the reaction (monitored by LC/MS), the reaction mixture was cooled down to room temperature, CH2Cl2 (15 mL) and water (15 mL) were added. The phases were separated and the organic layer was washed two times with water (10 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash chromatography (hexane/EtOAc 9:1) to provide the N-substituted-2H-indazol-2-amine derivative 8.

Reference： [1]Schoene, Jens; Bel Abed, Hassen; Christmann, Mathias; Nazaré, Marc [Tetrahedron Letters, 2017, vol. 58, # 16, p. 1633 - 1635]

68
[ 109-97-7 ]
[ 22996-21-0 ]
C₁₆H₁₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.50g	With trifluoroacetic acid for 0.5h; Inert atmosphere;	5 In a (100 mL) dry round bottom flask,4-Methoxy-2-nitrobenzaldehyde (1 g, 5.5 mmol) was added,Under nitrogen protection,Pyrrole (779 [mu] L, 11 mmol) was added,Trifluoroacetic acid (80 [mu] L, 1.1 mmol) was added dropwise slowly,After completion of the dropwise addition, the reaction was maintained for 0.5 hour.Followed by direct distillation under reduced pressure and the pyrrole was distilled off to give a tan yellow oil which was purified by silica gel column chromatography (80% methylene chloride / petroleum ether)To give the imine product as a tan solid 1.50g.
	With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Inert atmosphere;

Reference： [1]Current Patent Assignee: HANGZHOU B P BIOTECHNOLOGY - CN106478702, 2017, A Location in patent: Paragraph 0066
[2]Wu, Yanping; Mack, John; Xiao, Xuqiong; Li, Zhifang; Shen, Zhen; Lu, Hua [Chemistry - An Asian Journal, 2017, vol. 12, # 17, p. 2216 - 2220]

69
[ 22996-21-0 ]
[ 99-93-4 ]
C₁₆H₁₃NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water for 4h;	General procedure: A suspension of aromatic aldehyde 1 (40 mmol) and aromaticketone 2 (40 mmol) in mixture of 10 ml saturatedNaOH solution in water and 10 ml ethanol was stirred for 4 hat 20 °C to obtain pure chalcone 3 (Ozdemir et al. 2007;Chimenti et al. 2010). Further, mixture of chalcone 3 (10mmol) and thiosemicarbazide (20 mmol) was refluxed understirring with KOH (20 mmol) in 70mL EtOH for approximately6 h to get N-thiocarbamoyl pyrazole derivative 4(Scheme 1). This N-thiocarbamoyl pyrazole derivative 4 (10mmol) was added in appropriate quantity of EtOAc and wasrefluxed with ethyl bromoacetate (30 mmol) for 1.5 h (EISabbaghet al. 2009; Seebacher et al. 2003). After completionof reaction, the reaction mixture was mixed with CHCl3and allowed to evaporate to obtain pyrazol-1-yl-1,3-thaizol-4(5H)-one derivative (5a-5m, Fig. 2). The refined compoundwas obtained by subsequent purification withrecrystallization by using ethanol-acetone (1:1).

Reference： [1]Jagdale, Deepali M.; Ramaa [Medicinal Chemistry Research, 2017, vol. 26, # 9, p. 2127 - 2140]

70
[ 22996-21-0 ]
[ 99532-52-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 6702 - 6705

71
[ 22996-21-0 ]
[ 47522-13-4 ]
C₁₅H₁₂ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran for 4h; Reflux;	3 4.1.1.3 4-Fluoro-2-nitro-4′-fluoro stilbene (5a) General procedure: 4-Fluoro-2-nitrobenzaldehyde (2a) (1.0g, 5.91mmol) and (4-Flurobenzyl) triphenylphosphonium bromide (4a) (2.94g, 6.51mmol) were dissolved in 20ml of 66 THF. 57 DBU (1.08g, 7.10mmol) was added to the solution. The resulting reaction mixture was refluxed for 4h. Then the solvent was evaporated and the residue was dissolved in 30ml of 74 ethyl acetate. The organic layer was washed by brine, then dried by anhydrous sodium sulfate and concentrated under reduced pressure to provide crude 56 4-fluoro-2-nitro-4′-fluoro stilbene (5a) (1.45g, 5.55mmol, 94%) as a brown oil [24].

Reference： [1]Kang, Hongjun; Xiao, Xingqing; Huang, Chao; Yuan, Yan; Tang, Dongyan; Dai, Xiaochang; Zeng, Xianghui [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 426 - 437]

72
[ 22996-21-0 ]
(4-fluorobenzyl)(triphenyl)phosphonium bromide [ No CAS ]
C₁₅H₁₂FNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran for 4h; Reflux;	3 4.1.1.3 4-Fluoro-2-nitro-4′-fluoro stilbene (5a) General procedure: 4-Fluoro-2-nitrobenzaldehyde (2a) (1.0g, 5.91mmol) and (4-Flurobenzyl) triphenylphosphonium bromide (4a) (2.94g, 6.51mmol) were dissolved in 20ml of 66 THF. 57 DBU (1.08g, 7.10mmol) was added to the solution. The resulting reaction mixture was refluxed for 4h. Then the solvent was evaporated and the residue was dissolved in 30ml of 74 ethyl acetate. The organic layer was washed by brine, then dried by anhydrous sodium sulfate and concentrated under reduced pressure to provide crude 56 4-fluoro-2-nitro-4′-fluoro stilbene (5a) (1.45g, 5.55mmol, 94%) as a brown oil [24].

Reference： [1]Kang, Hongjun; Xiao, Xingqing; Huang, Chao; Yuan, Yan; Tang, Dongyan; Dai, Xiaochang; Zeng, Xianghui [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 426 - 437]

73
[ 22996-21-0 ]
2-Hydroxy-4-methoxy-6-nitro-benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With palladium diacetate; toluene-4-sulfonic acid; 1-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate; acetic acid; 2-Amino-4-chlorobenzoic acid at 90℃; for 24h; Sealed tube;

Reference： [1]Chen, Xiao-Yang; Ozturk, Seyma; Sorensen, Erik J. [Organic Letters, 2017, vol. 19, # 23, p. 6280 - 6283]

74
[ 22996-21-0 ]
6-methoxybenzo[c]isoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With stannous chloride hydrate In methanol; ethyl acetate at 20℃; for 24h;
	With tin(II) chloride dihdyrate In methanol; ethyl acetate at 20℃; for 24h; Inert atmosphere;

Reference： [1]Wang, Fei; Xu, Pei; Wang, Shun-Yi; Ji, Shun-Jun [Organic Letters, 2018, vol. 20, # 8, p. 2204 - 2207]
[2]Huang, Yan-Xia; Huang, Zhuo-Jun; Jiang, Chun-Yong; Liang, Jing-Yi; Liang, Qiu-Ping; Shu, Bing; Xie, Hui; Zeng, Jun-Yi; Zhang, Shang-Shi; Zhou, Binhua [Organic and Biomolecular Chemistry, 2021, vol. 19, # 39, p. 8487 - 8491]

75
[ 4795-29-3 ]
[ 22996-21-0 ]
6-methoxy-2-((tetrahydrofuran-2-yl)methyl)-2H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With diphenylsilane; 3-Methyl-1-phenyl-2-phospholene 1-oxide In toluene at 20 - 110℃; for 24h; Sealed tube; regioselective reaction;

Reference： [1]Schoene, Jens; Bel Abed, Hassen; Schmieder, Peter; Christmann, Mathias; Nazaré, Marc [Chemistry - A European Journal, 2018, vol. 24, # 36, p. 9090 - 9100]

76
[ 22996-21-0 ]
[ 22246-17-9 ]

Reference： [1]Patent: WO2009/106534,2009,A1

77
[ 22996-21-0 ]
[ 39720-65-5 ]
methyl 3-(4-methoxy-2-nitrophenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In tetrahydrofuran at 60℃; for 20h; Schlenk technique; Inert atmosphere;	5.1 (1) Synthesis of methyl 3-(4-methoxy-2-nitrophenyl)acrylate Add phosphine ylide (2.54g) to a Schleck bottle containing 200mL of tetrahydrofuran under nitrogen atmosphere, add 1.03g of potassium carbonate under stirring, add, stir at room temperature for 2 hours, then add 0.9g4-Methoxy-2-nitrobenzaldehyde was stirred at 60 ° C for 20 hours.After the reaction was completed, it was filtered, and the filtrate was evaporated under reduced pressure to give a yellow oil.Column chromatography gave 1.19 g of methyl 3-(4-methoxy-2-nitrophenyl)acrylate in 100% yield.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN108863899, 2018, A Location in patent: Paragraph 0092-0095

78
[ 22996-21-0 ]
[ 1779-49-3 ]
[ 126759-34-0 ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: Methyltriphenylphosphonium bromide With potassium carbonate In 1,4-dioxane at 20℃; for 4h; Inert atmosphere; Stage #2: 4-methoxy-2-nitro-benzaldehyde at 100℃; for 24h; Inert atmosphere;	1.2.2. Method B: Wittig olefination General procedure: To a 2-necked round bottom flask (previously dried) equipped with a magnetic stirrer, a solution of 1.2 mmol of methyl triphenylphosphonium bromide and 1.6 mmol of previously grinded potassium carbonate in 30 mL of 1,4-dioxane were added. The system was purged with nitrogen and stirred at room temperature for 4 hours. Then, 1.0 mmol of the corresponding aldehyde was added dropwise. The reaction was then stirred at 100 °C for 24 hours. After reaction completion, the flask was cooled to room temperature and 50 mL of water were poured. The crude product was extracted with dichloromethane (3 x 20 mL). The combined organic layers were dried over anhydrous MgSO4 and the solvent removed in vacuo. The styrene product was then purified by flash chromatography employing SiO2 and n-hexane as eluent.

Reference： [1]Acelas, Mauricio; Sierra, Andrés Felipe; Sierra, César A. [Synthetic Communications, 2020, vol. 50, # 9, p. 1335 - 1352]

79
[ 2033-24-1 ]
[ 22996-21-0 ]
[ 2917-02-4 ]
2-propylmercapto-5-(4-methoxy-2-nitrophenyl)-5,8-dihydropyridino[2,3-d]pyrimidine-4,7(3H,6H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12.8%	In ethylene glycol at 200℃; for 2h;	40 Preparation of 2-Propylmercapto-5-(4-methoxy-2-nitrophenyl)-5,8-dihydropyridine[2,3-d]pyrimidine-4,7(3H,6H)- Diketone (LSL-9-41) The 2-propanemercapto-6-aminopyrimidine-4(3H)-one (185mg, 1.0mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (173mg, 1.2mmol) and 4-Methoxy-2-nitrobenzaldehyde (181mg, 1.0mmol) was dissolved in about 5mL of ethylene glycol, heated in an oil bath at 200°C for about 2 hours, TLC (petroleum ether/ethyl acetate = 1/ 2) The point of detecting raw material disappears. Pour the reaction liquid into an appropriate amount of ice water, flocculent precipitation is formed, filtered to obtain a crude product. After separation and purification by a flash column (dichloromethane/methanol: 1.3%), 50 mg of pure product was obtained, and the yield was 12.8%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - CN111925368, 2020, A Location in patent: Paragraph 0452-0458

80
[ 22996-21-0 ]
[ 98-86-2 ]
(E)-3-(4-methoxy-2-nitrophenyl)-1-phenylprop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; sodium hydroxide In neat (no solvent) at 20℃; for 0.166667h; Schlenk technique;

Reference： [1]Zhang, Guan; Yang, Kai; Wang, Shihui; Feng, Qiang; Song, Qiuling [Organic Letters, 2021, vol. 23, # 2, p. 595 - 600]

81
[ 22996-21-0 ]
[ 81290-20-2 ]
2,2,2-trifluoro-1-(4-methoxy-2-nitrophenyl)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrabutyl ammonium fluoride In tetrahydrofuran at -20 - 20℃; for 3h;	General Procedure G for Synthesis of Compounds 30a-30d General procedure: The appropriate benzaldehyde (1 eq.) was dissolved in anhydrous THF (0.3 M) and cooled to -20 oC. Tothis, TMSCF3 (1.2 eq.) and TBAF (0.2 eq.) were added, slowly. The reaction was allowed to attain roomtemperature and stirred for 3 h followed by the addition of 1 mL of 1M HCl solution. The mixture was thendiluted with EtOAc/H2O and the layers were separated. The organic layer was dried over Na2SO4, filtered,solvent removed under reduced pressure. Column chromatography gave the desired compounds 30a-30d(53-88%).
	Stage #1: 4-methoxy-2-nitro-benzaldehyde; (trifluoromethyl)trimethylsilane With cesium fluoride In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 20 - 24℃; for 0.5h;	6.1 Step 1- Preparation of 2, 2, 2-trifluoro-1-(4-methoxy-2-nitrophenyl)ethan-1-ol (C7): To 4-methoxy-2-nitrobenzaldehyde (10 g, 55.2 mmol) in THF (100 mL) were added trimethyl(trifluoromethyl)silane (13 mL, 82.8 mmol) and cesium fluoride (CsF; 1.67 g, 11.0 mmol) and the reaction mixture was stirred at 0 °Cunder nitrogenfor 3 h. After 3 h, concentrated hydrochloric acid (10 mL, 155 mmol) was added, and the reaction mixture was stirred at rt for 30 min. The reaction mixture was diluted with water (100 mL) and was extracted with DCM (2 x 100 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the unpurified title compound as yellow oil which was used in the next step without any purification (16 g):1H NMR (400 MHz, CDCl3) d 7.83 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 2.8 Hz, 1H), 7.24- 7.21 (m, 1H), 6.05- 6.03 (m, 1H), 3.90 (s, 3H), 3.76 - 3.72 (m, 1H).
	With sodium acetate In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 1h;

Reference： [1]Wang, Zhiyu; Wang, Yanfei; Pasangulapati, Jagadeesh Prasad; Stover, Kurt R.; Liu, Xiaojing; Schier, Stephanie (Wohnig); Weaver, Donald F. [European Journal of Medicinal Chemistry, 2021, vol. 222]
[2]Current Patent Assignee: CORTEVA INC - WO2021/11722, 2021, A1 Location in patent: Page/Page column 74; 77
[3]Bao, Lan; Liu, Yu; Peng, Jinghan; Wang, Yuan; Dong, Jinhuan; Xu, Xianxiu [Organic Letters, 2022, vol. 24, # 1, p. 105 - 109]

82
[ 22996-21-0 ]
[ 15827-84-6 ]
(E)-4-((4-methoxy-2-nitrobenzylidene)amino)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With titanium tetrachloride; triethylamine In tetrahydrofuran; toluene at -78 - -5℃; for 6.75h;

Reference： [1]Prime, Michael E.; Liu, Longbin; Lee, Matt R.; Khetarpal, Vinod; Brown, Christopher J.; Johnson, Peter D.; Miranda-Azpiazu, Patricia; Chen, Xuemei; Clark-Frew, Daniel; Coe, Samuel; Davis, Randall; Dickie, Anthony; Ebneth, Andreas; Esposito, Simone; Gadouleau, Elise; Gai, Xinjie; Galan, Sebastien; Green, Samantha; Greenaway, Catherine; Giles, Paul; Halldin, Christer; Hayes, Sarah; Herbst, Todd; Herrmann, Frank; Heßmann, Manuela; Jia, Zhisheng; Kiselyov, Alexander; Kotey, Adrian; Krulle, Thomas; Mangette, John E.; Marston, Richard W.; Menta, Sergio; Mills, Matthew R.; Monteagudo, Edith; Nag, Sangram; Nibbio, Martina; Orsatti, Laura; Schaertl, Sabine; Scheich, Christoph; Sproston, Joanne; Stepanov, Vladimir; Svedberg, Marie; Takano, Akihiro; Taylor, Malcolm; Thomas, Wayne; Toth, Miklós; Vaidya, Darshan; Vanräs, Katarina; Weddell, Derek; Wigginton, Ian; Wityak, John; Mrzljak, Ladislav; Munoz-Sanjuan, Ignacio; Bard, Jonathan A.; Dominguez, Celia [Journal of Medicinal Chemistry, 2020, vol. 63, # 15, p. 8608 - 8633]

83
[ 22996-21-0 ]
[ 852402-71-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: iron; hydrogenchloride / ethanol; water / 1 h / 80 °C 2: Pseudomonas putida trans-o-hydroxybenzylidenepyruvate hydratase-aldolase / dimethyl sulfoxide; aq. phosphate buffer / 16 h / 20 °C / pH 6.5 / Enzymatic reaction

Reference： [1]Fansher, Douglas J.; Granger, Richard; Kaur, Satinderpal; Palmer, David R. J. [ACS Catalysis, 2021, vol. 11, # 12, p. 6939 - 6943]

84
[ 22996-21-0 ]
[ 1895-39-2 ]
1-(2,2-difluorovinyl)-4-methoxy-2-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With triphenylphosphine In N,N-dimethyl-formamide at 110℃; for 0.5h; Inert atmosphere;

Reference： [1]Liu, Jun; Yu, Longhui; Zhao, Gang; Zheng, Changwu [Angewandte Chemie - International Edition, 2021, vol. 60, # 44, p. 23641 - 23645][Angew. Chem., 2021, vol. 133, # 44, p. 23833 - 23837]

85
[ 22996-21-0 ]
(3S*,4aS*,12bS*)-10-methoxy-12b-methyl-1,2,3,4,4a,5,6,12b-octahydrobenzo[c]acridin-3-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogenchloride; iron / water; ethanol / 4 h / 78 °C / Inert atmosphere 2: potassium hydroxide / 20 h / 70 °C / Inert atmosphere

Reference： [1]Laraia, Luca; Olsen, Asger Hegelund; Whitmarsh-Everiss, Thomas [Angewandte Chemie - International Edition, 2021, vol. 60, # 51, p. 26755 - 26761][Angew. Chem., 2021, vol. 133, # 51, p. 26959 - 26965]

86
[ 22996-21-0 ]
2-bromo-4-methoxy-6-nitrobenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-Bromosuccinimide; 4-chloro-2-(trifluoromethyl)aniline; palladium diacetate; trifluoroacetic acid In 1,2-dichloro-ethane at 60℃; for 24h;

Reference： [1]Altenbach, Robert J.; Buchman, Marek; Farney, Elliot P.; Gfesser, Gregory A.; Greszler, Stephen N.; Voight, Eric A. [Journal of Organic Chemistry, 2022, vol. 87, # 1, p. 776 - 789]

87
[ 22996-21-0 ]
3,11-dioxo-18β-olean-12-en-30-oic acid [ No CAS ]
(2S,4aS,6aS,6bR,8aR,12aS,12bR,14bR)-11-((Z)-4-methoxy-2-nitrobenzylidene)-2,4a,6a,6b,9,9,12a-heptamethyl-10,13-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.5%	With potassium hydroxide In ethanol at 20℃; for 3h;	General procedures for the preparation of compounds series 1 and series 2. General procedure: To a solution of different substituted benzaldehyde (0.48mmol) and GA-O or GA-O-Bn (0.32mmol) in 10mL of EtOH was added potassium hydroxide (0.64mmol). The mixture was stirred at room temperature for 3h. At the end of the reaction, the mixture was dried in vacuo and the pH was adjusted between 4 and 6 with hydrochloric acid (5%). The residue was poured into 100mL of water and extracted with ethyl acetate (3×40mL). The organic layer was combined, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ ethyl acetate, 6:1, V: V, containing 5‰ formic acid and petroleum ether/ ethyl acetate, 10:1, V: V) to afford compounds series 1 and series 2, respectively.
72.5%	With potassium hydroxide In ethanol at 20℃; for 3h;	General procedures for the preparation of compounds series 1 and series 2. General procedure: To a solution of different substituted benzaldehyde (0.48mmol) and GA-O or GA-O-Bn (0.32mmol) in 10mL of EtOH was added potassium hydroxide (0.64mmol). The mixture was stirred at room temperature for 3h. At the end of the reaction, the mixture was dried in vacuo and the pH was adjusted between 4 and 6 with hydrochloric acid (5%). The residue was poured into 100mL of water and extracted with ethyl acetate (3×40mL). The organic layer was combined, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ ethyl acetate, 6:1, V: V, containing 5‰ formic acid and petroleum ether/ ethyl acetate, 10:1, V: V) to afford compounds series 1 and series 2, respectively.

Reference： [1]David Hong, Weiqian; Gan, Lishe; Jin, Jingwei; Li, Dongli; Liang, Jinfeng; Lu, Yujing; Ou, Yi; Tu, Borong; Wong, Wing-Leung; Wu, Jiaqiang; Wu, Panpan; Wu, Rihui; Zhang, Kun; Zhang, Xinyue; Zheng, Wende [Bioorganic Chemistry, 2022, vol. 122]
[2]David Hong, Weiqian; Gan, Lishe; Jin, Jingwei; Li, Dongli; Liang, Jinfeng; Lu, Yujing; Ou, Yi; Tu, Borong; Wong, Wing-Leung; Wu, Jiaqiang; Wu, Panpan; Wu, Rihui; Zhang, Kun; Zhang, Xinyue; Zheng, Wende [Bioorganic Chemistry, 2022, vol. 122]

88
[ 1321990-56-0 ]
[ 22996-21-0 ]
benzyl (2S,4aS,6aS,6bR,8aR,12aS,12bR,14bR)-11-((Z)-4-methoxy-2-nitrobenzylidene)-2,4a,6a,6b,9,9,12a-heptamethyl-10,13-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.2%	With potassium hydroxide In ethanol at 20℃; for 3h;	General procedures for the preparation of compounds series 1 and series 2. General procedure: To a solution of different substituted benzaldehyde (0.48mmol) and GA-O or GA-O-Bn (0.32mmol) in 10mL of EtOH was added potassium hydroxide (0.64mmol). The mixture was stirred at room temperature for 3h. At the end of the reaction, the mixture was dried in vacuo and the pH was adjusted between 4 and 6 with hydrochloric acid (5%). The residue was poured into 100mL of water and extracted with ethyl acetate (3×40mL). The organic layer was combined, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ ethyl acetate, 6:1, V: V, containing 5‰ formic acid and petroleum ether/ ethyl acetate, 10:1, V: V) to afford compounds series 1 and series 2, respectively.
50.2%	With potassium hydroxide In ethanol at 20℃; for 3h;	General procedures for the preparation of compounds series 1 and series 2. General procedure: To a solution of different substituted benzaldehyde (0.48mmol) and GA-O or GA-O-Bn (0.32mmol) in 10mL of EtOH was added potassium hydroxide (0.64mmol). The mixture was stirred at room temperature for 3h. At the end of the reaction, the mixture was dried in vacuo and the pH was adjusted between 4 and 6 with hydrochloric acid (5%). The residue was poured into 100mL of water and extracted with ethyl acetate (3×40mL). The organic layer was combined, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ ethyl acetate, 6:1, V: V, containing 5‰ formic acid and petroleum ether/ ethyl acetate, 10:1, V: V) to afford compounds series 1 and series 2, respectively.

Reference： [1]David Hong, Weiqian; Gan, Lishe; Jin, Jingwei; Li, Dongli; Liang, Jinfeng; Lu, Yujing; Ou, Yi; Tu, Borong; Wong, Wing-Leung; Wu, Jiaqiang; Wu, Panpan; Wu, Rihui; Zhang, Kun; Zhang, Xinyue; Zheng, Wende [Bioorganic Chemistry, 2022, vol. 122]
[2]David Hong, Weiqian; Gan, Lishe; Jin, Jingwei; Li, Dongli; Liang, Jinfeng; Lu, Yujing; Ou, Yi; Tu, Borong; Wong, Wing-Leung; Wu, Jiaqiang; Wu, Panpan; Wu, Rihui; Zhang, Kun; Zhang, Xinyue; Zheng, Wende [Bioorganic Chemistry, 2022, vol. 122]

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Code	Phrase
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H200	Unstable explosive
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H202	Explosive; severe projection hazard
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Code	Phrase
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