[ CAS No. 24623-24-3 ] {[proInfo.proName]}

Name: 24623-24-3|6-Nitro-2,3-dihydro-1H-inden-1-one|98%
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Quality Control of [ 24623-24-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 24623-24-3 ]

CAS No. :	24623-24-3	MDL No. :	MFCD06656903
Formula :	C₉H₇NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MLRACZPAMDFORH-UHFFFAOYSA-N
M.W :	177.16	Pubchem ID :	90562
Synonyms :

Calculated chemistry of [ 24623-24-3 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.31
TPSA :	62.89 Å²

Pharmacokinetics

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

Lipophilicity

Log Po/w (iLOGP) :	1.35
Log Po/w (XLOGP3) :	1.49
Log Po/w (WLOGP) :	1.72
Log Po/w (MLOGP) :	0.52
Log Po/w (SILICOS-IT) :	0.54
Consensus Log Po/w :	1.12

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.15
Solubility :	1.25 mg/ml ; 0.00704 mol/l
Class :	Soluble
Log S (Ali) :	-2.42
Solubility :	0.677 mg/ml ; 0.00382 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.5
Solubility :	0.567 mg/ml ; 0.0032 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.9

Safety of [ 24623-24-3 ]

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 [ 24623-24-3 ]

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

Upstream synthesis route of [ 24623-24-3 ]
Downstream synthetic route of [ 24623-24-3 ]

[ 24623-24-3 ] Synthesis Path-Upstream 1~12

1
[ 24623-24-3 ]
[ 62803-47-8 ]

Reference： [1] Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172
[2] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508
[3] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508

2
[ 24623-24-3 ]
[ 14548-38-0 ]

Reference： [1] Chemistry - A European Journal, 2015, vol. 21, # 37, p. 13052 - 13057

3
[ 83-33-0 ]
[ 24623-25-4 ]
[ 24623-24-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: With sulfuric acid; nitric acid In nitromethane at -10 - -5℃; for 0.75 h; Stage #2: With water In nitromethaneCooling with ice	To a well-stirred mixture of H₂SO₄ (13.9 mL of a 98percent solution) and HNO₃ (2.6 mL of a 65percent solution) was added at -10 °C a solution of 1-indanone (1.0 g, 7.6 mmol) in nitromethane (1.1 mL). The addition rate was carefully adjusted to raise the temperature from -10 to -5 °C during 30 min. The reaction mixture was stirred further for 15 min at this temperature (attention has to be paid to temperature and reaction time.). After ice-water hydrolysis (200 mL), the yellow precipitate was collected and extracted with CH₂Cl₂ (2 .x. 20 mL). The organic phase was washed with a KHCO₃ solution 5percent (2 .x. 15 mL) washed with saturated brine (10 mL), dried over anhydrous Na₂SO₄ and evaporated in vacuo. The residue was separated by flash chromatography using hexane-ethyl acetate (1:0.2) as eluent. Compound 25, yield: 0.94 g, 80percent, mp: 98-100 °C (mp ¹⁵ 100-101 °C) ¹H NMR (CDCl₃) δ ppm: 2.80 (m, 2H, CH₂), 3.53 (m, 2H, CH₂), 7.61 (m, 1H, H-Ar), 8.08 (d, J = 8.5 Hz, 1H, H-Ar), 8.47 (d, J = 8.3 Hz, 1H, H-Ar). Compound 26, yield: 0.23 g, 20percent, mp: 73-74 °C (mp lit.¹⁶ 72-73 °C). ¹H NMR (CDCl₃) δ ppm: 2.83 (m, 2H, CH₂), 3.28 (m, 2H, CH₂), 7.61 (d, J = 8.5 Hz, 1H, H-Ar), 8.44 (dd, J = 2.2 Hz, J = 8.5 Hz, 1H, H-Ar), 8.56 (d, J = 2.2 Hz, 1H, H-Ar).

Reference： [1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 22, p. 6818 - 6826
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408
[3] Polish Journal of Chemistry, 2008, vol. 82, # 11, p. 2133 - 2140
[4] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3337 - 3339
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 884 - 889
[6] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853
[7] Patent: US2004/167128, 2004, A1, . Location in patent: Page 39

4
[ 496-11-7 ]
[ 24623-25-4 ]
[ 24623-24-3 ]
[ 22246-24-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853

5
[ 24623-24-3 ]
[ 610-27-5 ]

Reference： [1] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508

6
[ 24623-24-3 ]
[ 3898-66-6 ]

Reference： [1] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508
[2] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508

7
[ 24623-24-3 ]
[ 24425-40-9 ]

Reference： [1] Molecules, 2017, vol. 22, # 1,

8
[ 24623-25-4 ]
[ 24623-24-3 ]
[ 51135-91-2 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With ammonium chloride In ethanol at 90℃; for 1 h;	EXAMPLE 129B 6-amino-1-indanone [0367] A solution of Example 129A (19.68 g, 111 mmol) in ethanol (111 mL) was treated sequentially with iron powder (43.0 g, 770 mmol) and solid ammonium chloride (3.70 g, 69.2 mmol). The resulting suspension was stirred at 90° C. for 1 hour, cooled to room temperature, diluted with brine, and extracted with diethyl ether (4.x.100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to provide the desired product as a 6:1 mixture of 6-amino- and 4-amino-1-indanone (14.20 g, 87percent). 1H NMR (300 MHz, DMSO-d6, 6-amino-1-indanone) δ 7.21 (d, 1H), 6.92 (dd, 1H), 6.75 (d, 1H), 5.27 (br s, 2H), 2.90 (t, 2H), 2.54 (m, 2H); 1H NMR (300 MHz, DMSO-d6), 4-amino-1-indanone) δ 7.10 (t, 1H), 6.81 (m, 2H), 2.80 (m, 2H), 2.59 (m, 2H).

Reference： [1] Patent: US2004/167128, 2004, A1, . Location in patent: Page 39

9
[ 24623-24-3 ]
[ 69975-66-2 ]

Reference： [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408

10
[ 24623-24-3 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With hydrogen In methanol at 20℃; for 3 h;	A mixture of the 6-nitroindan-1-one (10 g, 56 mmol) and 10percent Pd/C (2.Og) in MeOH (200 mL) was stirred under 30 psi of H₂ at RT for 3h. After filtration, the filtrate was concentrated to afford 6-aminoindan-1-one (7.2 g, 87percent yield).
81%	With hydrogen In methanol at 20℃; for 14 h;	6-Nitro-l-indanone (10.0 g, 56.4 mmol) was dissolved in methanol (200 mL) , a 10percent palladium-carbon powder (500 mg) was added, and the mixture was stirred at room temperature for 14 hr under a hydrogen atmosphere. To the reaction solution were added dichloromethane and ethyl acetate to dissolve the precipitated crystals, and the catalyst was filtered off. The filtrate was concentrated under reduced pressure, and the residue was washed with methanol to give the title compound (6.71 g, yield 81percent) .¹H-NMR (CDCl₃) δ: 2.62 - 2.72 (2H, m) , 2.95 - 3.05 (2H, m) , 3.79 (2H, brs), 6.92 - 6.97 (IH, m) , 6.99 (IH, d, J = 2.2 Hz), 7.25 (IH, d, J = 8.0 Hz) .

Reference： [1] Chemistry - A European Journal, 2015, vol. 21, # 37, p. 13052 - 13057
[2] Patent: WO2006/71940, 2006, A2, . Location in patent: Page/Page column 396
[3] Patent: WO2007/148808, 2007, A1, . Location in patent: Page/Page column 126-127
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5665 - 5670
[6] Polish Journal of Chemistry, 2008, vol. 82, # 11, p. 2133 - 2140
[7] Journal of the American Chemical Society, 1943, vol. 65, p. 2311,2313
[8] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508
[9] Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172
[10] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 884 - 889
[11] Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508
[12] Patent: US6083986, 2000, A,
[13] Patent: US2005/209274, 2005, A1, . Location in patent: Page/Page column 43
[14] ChemCatChem, 2017, vol. 9, # 19, p. 3743 - 3751

11
[ 24623-25-4 ]
[ 24623-24-3 ]
[ 51135-91-2 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With ammonium chloride In ethanol at 90℃; for 1 h;	EXAMPLE 129B 6-amino-1-indanone [0367] A solution of Example 129A (19.68 g, 111 mmol) in ethanol (111 mL) was treated sequentially with iron powder (43.0 g, 770 mmol) and solid ammonium chloride (3.70 g, 69.2 mmol). The resulting suspension was stirred at 90° C. for 1 hour, cooled to room temperature, diluted with brine, and extracted with diethyl ether (4.x.100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to provide the desired product as a 6:1 mixture of 6-amino- and 4-amino-1-indanone (14.20 g, 87percent). 1H NMR (300 MHz, DMSO-d6, 6-amino-1-indanone) δ 7.21 (d, 1H), 6.92 (dd, 1H), 6.75 (d, 1H), 5.27 (br s, 2H), 2.90 (t, 2H), 2.54 (m, 2H); 1H NMR (300 MHz, DMSO-d6), 4-amino-1-indanone) δ 7.10 (t, 1H), 6.81 (m, 2H), 2.80 (m, 2H), 2.59 (m, 2H).

Reference： [1] Patent: US2004/167128, 2004, A1, . Location in patent: Page 39

12
[ 24623-24-3 ]
[ 7440-44-0 ]
[ 69975-65-1 ]

Reference： [1] Patent: US5866612, 1999, A,

[ 24623-24-3 ] Synthesis Path-Downstream 1~88

1
[ 24623-24-3 ]
[ 3898-66-6 ]

Reference： [1]Journal of the Chemical Society,1923,vol. 123,p. 1482,1508
[2]Journal of the Chemical Society,1923,vol. 123,p. 1482,1508

2
[ 24623-24-3 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 14h;	To a solution of compound 19.1 (1 g, 5.6 mmol, 1.0 eq) in CH3OH (20 mL) was added Pd/C (100 mg, 10% wt). The resulting solution was stirred at room temperature for 14 hrs under H2. The mixture was filtered to get filtrate, removed in vacuo to give compound 19.2 (0.8 g, 96%) as a brown solid, which was used directly in the next step without further purification.
87%	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; under 1551.49 Torr; for 3h;	A mixture of the 6-nitroindan-1-one (10 g, 56 mmol) and 10% Pd/C (2.Og) in MeOH (200 mL) was stirred under 30 psi of H2 at RT for 3h. After filtration, the filtrate was concentrated to afford 6-aminoindan-1-one (7.2 g, 87% yield).
81%	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; for 14h;	6-Nitro-l-indanone (10.0 g, 56.4 mmol) was dissolved in methanol (200 mL) , a 10% palladium-carbon powder (500 mg) was added, and the mixture was stirred at room temperature for 14 hr under a hydrogen atmosphere. To the reaction solution were added dichloromethane and ethyl acetate to dissolve the precipitated crystals, and the catalyst was filtered off. The filtrate was concentrated under reduced pressure, and the residue was washed with methanol to give the title compound (6.71 g, yield 81%) .1H-NMR (CDCl3) delta: 2.62 - 2.72 (2H, m) , 2.95 - 3.05 (2H, m) , 3.79 (2H, brs), 6.92 - 6.97 (IH, m) , 6.99 (IH, d, J = 2.2 Hz), 7.25 (IH, d, J = 8.0 Hz) .

	With hydrogen; In ethanol;	Preparation 5 1-benzamido-6-carboxamidoindane A mixture of 6-nitroindan-1-one (1 part) and Raney-Ni in EtOH is treated with hydrogen (60 psi) for several hours. The catalyst is removed and the solvent evaporated to give 6-aminoindan-1-one.
	With iron; ammonium chloride; In ethanol; water; for 6h;Heating / reflux;	6-nitroindan-1-one (0.27 g, 1.52 mmol), iron powder (0.34 g, 6.08 mmol) and ammonium chloride (0.08 g, 1.52 mmol) were placed together in an ethanol (8 mL)/water (3 mL) mixture and heated at reflux for 6 hours. The mixture was cooled, filtered over wet celite, extracted with ethyl acetate (3×50 mL), dried (MgSO4) and used without further purification. The crude amine (0.22 g, 1.52 mmol) was placed along with acetic acid (0.1 g, 1.6 mmol), EDCI (0.37 g, 1.9 mmol), HOBt (0.26 g, 1.9 mmol) and N-methyl morpholine (0.62 g, 6.1 mmol) in DMF (10 mL) and stirred at room temperature for 12 hours. The mixture was diluted with water, extracted with ethyl acetate (3×30 mL), organics washed with water, brine, dried (MgSO4) and concentrated to a yellow power that was used without purification in the next step. N-(3-Oxo-indan-5-yl) acetamide (0.3 g, 1.59 mmol) and piperidin-4-yl-carbamic acid tert-butyl ester (0.38 g, 1.9 mmol) were placed with titanium tetraisopropoxide (1.36 g, 4.8 mmol) in THF (15 mL) and heated at reflux for 24 hours. The mixture was cooled to room temperature, sodium triacetoxyborohydride (1.2 g, 5.6 mmol) and ethanol (4 mL) added to the mixture and heated at 50 C. After 24 hours, the mixture was cooled, quenched with isopropanol (10 mL), saturated sodium bicarbonate (30 mL) and filtered over wet celite. The crude mixture was extracted with ethyl acetate (5×30 mL), organic extracts washed with water, brine, dried (MgSO4) and concentrated to a brown foam. The crude product was dissolved in dichloromethane (6 mL) and treated with a 2M solution of HCl in Et2O (2 mL) and stirred at room temperature for 6 hours. The precipitated solid was filtered and washed with ether, dried and used as is in the next step. N-[3-(4-amino-piperidin-1-yl)-indan-5-yl]-acetamide (0.8 g, 2.32 mmol) was placed along with 7-fluoro-4-oxo-4H-chromene-2-carboxylic acid (0.54 g, 2.6 mmol), EDCI (0.60 g, 3.1 mmol), HOBt (0.42 g, 3.1 mmol) and N-methyl morpholine (1.04 g, 10.4 mmol) in DMF (10 mL) and stirred at room temperature for hours: The mixture was diluted with water, extracted with ethyl acetate (6×50 mL), organics washed with saturated sodium bicarbonate, water, brine, dried (MgSO4) and concentrated to one-half the volume when thick precipitate fell out of solution. The precipitate was filtered, washed with ethyl acetate and dried to provide a racemic mixture of the target compound as a white solid. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.50-1.59 (m, 1H), 1.67-1.76 (m, 2H), 1.80-1.85 (m, 1H), 1.95-2.05 (m, 5H), 2.15-2.22 (m, 1H), 2.33-2.40 (m, 1H), 2.50-2.52 (m, 1H), 2.65-2.72 (m, 1H), 2.77-2.85 (m, 1H), 2.89-2.93 (m, 1H), 3.70-3.80 (m, 1H), 4.28 (t, 1H, J=7 Hz), 6.81 (s, 1H), 7.10 (d, 1H, J=5 Hz), 7.28 (d, 1H, J=5 Hz), 7.42 (dt, 1H, J=10, 3 Hz), 7.61 (dd, 1H, J=10, 5 Hz), 7.64 (s, 1H), 8.11 (dd, 1H, J=10, 5 Hz), 8.85 (d, 1H, J=10 Hz), 9.83 (s, 1H); MS (ESI) m/z 464 [M+H]+.
	With tin(ll) chloride; In ethanol; at 45℃; for 24h;Inert atmosphere;	Take 10g of 6-nitro-1-indanone and 50g of stannous chloride in 20 times the amount of ethanol.Under the protection of N2, the reaction was performed at 45 C for 24 hours.The solvent was distilled off under reduced pressure, and sodium carbonate solution was added to the residue, and the mixture was stirred until no more bubbles were generated.Suction filtration, filter cake and ethanol stirred, suction filtration, the filtrate was steamed,The obtained white solid is intermediate 3,

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 13052 - 13057
[2]Patent: WO2019/84452,2019,A1 .Location in patent: Paragraph 0416
[3]Patent: WO2006/71940,2006,A2 .Location in patent: Page/Page column 396
[4]Patent: WO2007/148808,2007,A1 .Location in patent: Page/Page column 126-127
[5]Journal of Medicinal Chemistry,2003,vol. 46,p. 399 - 408
[6]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5665 - 5670
[7]Polish Journal of Chemistry,2008,vol. 82,p. 2133 - 2140
[8]Journal of the American Chemical Society,1943,vol. 65,p. 2311,2313
[9]Journal of the Chemical Society,1923,vol. 123,p. 1482,1508
[10]Farmaco, Edizione Scientifica,1983,vol. 38,p. 167 - 172
[11]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 884 - 889
[12]Journal of the Chemical Society,1923,vol. 123,p. 1482,1508
[13]Patent: US6083986,2000,A
[14]Patent: US2005/209274,2005,A1 .Location in patent: Page/Page column 43
[15]ChemCatChem,2017,vol. 9,p. 3743 - 3751
[16]Patent: CN110256410,2019,A .Location in patent: Paragraph 0065; 0070; 0074

3
[ 50-00-0 ]
[ 24623-24-3 ]
[ 58161-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen
	With hydrogen In methanol; ethyl acetate

Reference： [1]Biggs; Casy; Chu; Coutts [Journal of Medicinal Chemistry, 1976, vol. 19, # 4, p. 472 - 475]
[2]Hasbun,J.A. et al. [Journal of Medicinal Chemistry, 1973, vol. 16, p. 847 - 849]

4
[ 83-33-0 ]
[ 24623-24-3 ]

Yield	Reaction Conditions	Operation in experiment
70.2%	With sulfuric acid; nitric acid	1 Step 1: 5-nitro-1-indanone 1-indanone (2.00 g, 15.23 mmol) was dissolved in a mixed acid of nitric acid and concentrated sulfuric acid (100 mL) to carry out a nitration reaction, and the residue was purified by column chromatography to yield 1.88 g (yield: 70.2%).
66%	With sulfuric acid; potassium nitrate at 0℃; for 1.66667h;	6-Nitro-2,3-dihydro-1H-inden-1-one (2) A solution of KNO3 (10.1 g, 0.1 mol) in concd H2SO4 (30 mL) wasadded dropwise to a mixture of 1-indanone (13.2 g, 0.1 mol) andconcd H2SO4 (80 mL) at 0 °C over 40 min. Following addition, themixture was stirred at 0 °C for 1 h, then poured onto ice (500 g). Theresulting precipitate was collected by filtration, washed with H2Oand dried in air. The crude product was purified by chromatographyon silica gel (PE-EtOAc, 70:30) to give a colorless solid.Yield: 11.6 g (66%);
65.4%	With sulfuric acid; potassium nitrate In sulfuric acid at 0℃; for 1.66667h;	36.1 Step 1. Step 1. 6-Nitro-1-indatone 1-Indanone (13.2 g, 0.1 mol) was added in one portion to concentrated sulfuric acid (80 mL) at 0° C. A solution of potassium nitrate (10.1 g, 0.1 mol) in concentrated sulfuric acid (30 mL) was added in small portions over a 40 min period. The mixture was stirred for 1 h at 0° C., then poured over 500 g of ice. The mixture was filtered, washed with water, and air-dried. The crude product was purified by chromatography on silica gel (PE/EtOAc 2:1) to give 11.58 g product as colorless solid (65.4%). 1H NMR (300 MHz, CDCl3) δ: 2.81-2.85 (2H, t, J=6.3 Hz), 3.26-3.29 (2H, t, J=6.3 Hz), 7.65-7.68 (1H, d, J=8.4 Hz), 8.43-8.47 (1H, dd, J=8.4 and 2.1 Hz), 8.57 (1H, s).

64%	With sulfuric acid; potassium nitrate at 0℃; for 0.5h;	6-Nitro-2,3-dihydro-lH-inden-l-one (SR5-120) To l-indanone (4.00 g, 30.266 mmol) in cone. H2S04 (29 mL) at 0 °C was added solution of KNO3 (3.060 g, 30.266 mmol) in cone. H2SC (9 mL) over 30 min. The mixture was stirred at 0 °C for 1 h and poured into ice/water mixture. The mixture was extracted with EtOAc (3 x 100 mL), dried (Na2S04) and concentrated under reduced pressure. Purification by flash column chromatography using EtO Ac/hexane (20:80-100:0) as eluent afforded SR5-120 as a pale yellow solid (3.410 g, 64 %). 1 H NMR (500 MHz, DMSO-de) d 8.49 (dd, 7 = 8.4, 2.3 Hz, 1H), 8.29 (dd, 7 = 2.3, 0.7 Hz, 1H), 7.87 (dd, 7 = 8.4, 0.8 Hz, 1H), 3.27- 3.21 (m, 2H), 2.81-2.76 (m, 2H);
62%	With sulfuric acid; potassium nitrate at -5℃; for 4h;	6-Nitro-2,3-dihydro-1H-inden-1-one (10) To a solution of 2,3-dihydro-1H-inden-1-one (9, 1.32 g,10.0 mmol) in concentrated sulfuric acid (10 mL), KNO3 (1.21 g, 12.0 mmol) in concentrated sulfuricacid (10 mL) was added dropwise at 5°C in 30 min. The mixture was stirred at 5 C for 4 h.After adding ice water slowly, the mixture was partitioned between water and CH2Cl2. The organiclayer was washed with a saturated aqueous solution of NaHCO3 and brine, dried over anhydrousNa2SO4, and concentrated under vacuum. The residue was purified by column chromatographyon silica gel (eluent: hexane/EtOAc = 7/1) to give 10 (1.10 g, 62%) as a beige solid. m.p. 71~74°C;1H-NMR: δ 8.59 (d, J = 1.9 Hz, 1H), 8.47 (dd, J = 8.4, 2.2 Hz, 1H), 7.68 (t, J = 8.4 Hz, 1H), 3.33-3.25 (m,2H), 2.89-2.78 (m, 2H); ESI-MS: m/z [M + H]+ 178.
61%	With sulfuric acid; potassium nitrate at 0℃; for 2h;	102 To a solution of 1-indanone (30 g, 0.23 mol) in cone. H2SO4 (200 mL) was added a solution of KNO3 (34 g, 0.34 mol) in cone. H2SO4 (100 mL) at 0 °C. The resulting mixture was stirred for 2h, and then poured into ice-H2O (3 L). The mixture was extracted with EtOAc (3x500 mL). The combined organic layers were washed with brine (3x500 mL), dried (Na2SO4), filtered, concentrated and purified via column chromatography to afford 6-nitro-indan-1-one (25 g, 61% yield).
60%	Stage #1: inden-1-one With sulfuric acid; potassium nitrate at 0℃; for 1h; Stage #2: With water at 20℃;	10 1-Indanone (5.00 g, 37.8 mmol) was dissolved in sulfuric acid (40 mL) , and thereto was added dropwise a solution of potassium nitrate (3.83 g, 37.8 mmol) in sulfuric acid (10 mL) under ice-cooling. The mixture was stirred for 1 hr under ice- cooling, ice was added to the reaction solution, and the mixture was stirred at room temperature overnight. The precipitated solid was collected by filtration, and purified by silica gel column chromatography (ethyl acetate/hexane=15/85->45/55) to give the title compound (4.01 g, yield 60%).1H-NMR (CDCl3) δ: 2.78 - 2.90 (2H, m) , 3.22 - 3.34 (2H, m) , 7.67 (IH, d, J = 8.5 Hz), 8.45 (IH, dd, J = 8.5, 2.3 Hz), 8.57 (IH, d, J = 2.3 Hz).
54%	With sulfuric acid; potassium nitrate In water at 0 - 15℃; for 1.5h;	3 Preparation of compound 4 A solution of potassium nitrate (50.5g, 0. 5mol) in H2SO4 (200mL) was added, via a dropping funnel, to a solution of 1-INDANONE (60g, 0. 454mol) in concentrated sulfuric acid (500mL) cooled in an ice-water bath at a speed to maintain an internal temperature below 15°C. After stirring at 0°C for LH, the reaction mixture was poured into crushed ice and stirred for 30 min. The solid was filtered, washed with water, and air-dried. Purification by flash chromatography (TOLUENE/ETOAC, 95/5) gave compound 4 (43.5g, 54%) as a pale yellow solid. 1H NMR (CDC13, 400MHZ) : 2.81-2. 85 (2H, m, CH2), 3.28 (2H, t, J 6.1, CH2), 7.67 (1H, d, J 8.4, ArH), 8.45 (1H, d, J 8.4, ArH), 8.56 (1H, s, ArH).
52%	With sulfuric acid; potassium nitrate at 0 - 5℃; for 1.5h;
	(nitration);
	With nitric acid
	With sulfuric acid; potassium nitrate for 1h;
	With sulfuric acid; potassium nitrate
	With KNO₃ In sulfuric acid	129.A 6-nitro-1-indanone EXAMPLE 129A 6-nitro-1-indanone A solution of concentrated H2SO4 at 0° C. was treated with 1-indanone (6.00 g, 45.4 mmol) then treated dropwise with KNO3 (5.00 g, 49.94 mmol) in concentrated H2SO4 while maintaining the internal temperature at no more than 15° C. The reaction was stirred for 1 hour after the addition was complete, then poured onto ice. The resulting solids were collected by filtration, washed with water, and dried under vacuum to give a 4:1 mixture of 6-nitro- and 4-nitro-1-indanone (5.04 g, 63%). MS (ESI(+) m/e 178 (M+H)+, 195 (M+NH4)+; MS (ESI(-)) m/e 176 (M-H)-; 1H NMR (300 MHz, DMSO-d6, 6-nitro-1-indanone) δ 8.49 (dd, 1H), 8.29 (d, 1H), 7.87 (d, 1H), 3.25 (m, 2H), 2.78 (m, 2H); 1H NMR (300 MHz, DMSO-d6), 4-nitro-1-indanone) δ 8.51 (dd, 1H), 8.07 (dd, 1H), 7.74 (t, 1H), 3.53 (m, 2H), 2.76 (m, 2H).
	With sulfuric acid; potassium nitrate at 0 - 5℃; for 1.5h;	14 Compound 14A: 2,3-Dihydro-1H-indene-1-one (10 g, 75.67 mmol, 9.09 mL) was dissolved in 100 mL of concentrated sulfuric acid, and KNO3 (8.03 g, 79.45 mmol) was added thereto at 0 °C. The reaction was carried out at 0-5 °C for 1.5 hours. After the reaction was completed, the reaction solution was poured into 300 mL of water. After filtration, the filter cake was dissolved in EtOAc, dried and then concentrated to give a crude product. The crude product was purified by column chromatography to give compound 14A. 1H NMR (400MHz, DMSO-d6) δ = 8.60 (d, J = 2.0 Hz, 1H), 8.48 (dd, J = 2.3, 8.5 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 3.34 -3.27 (m, 2H), 2.90-2.83 (m, 2H).

Reference： [1]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - CN107619384, 2018, A Location in patent: Page/Page column 18
[2]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[3]Current Patent Assignee: ASTAR BIOTECH - US2014/31354, 2014, A1 Location in patent: Paragraph 0298; 0441; 0442
[4]Current Patent Assignee: H. LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE - WO2020/51571, 2020, A1 Location in patent: Page/Page column 41-42
[5]Guan, Xianghong; Luo, Peihua; He, Qiaojun; Hu, Yongzhou; Ying, Huazhou [Molecules, 2017, vol. 22, # 1]
[6]Current Patent Assignee: DECIPHERA PHARMACEUTICALS LLC - WO2006/71940, 2006, A2 Location in patent: Page/Page column 396
[7]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2007/148808, 2007, A1 Location in patent: Page/Page column 126
[8]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - WO2004/87124, 2004, A1 Location in patent: Page/Page column 45
[9]Duan, Ya-Nan; Cui, Li-Qian; Zuo, Lin-Hong; Zhang, Chi [Chemistry - A European Journal, 2015, vol. 21, # 37, p. 13052 - 13057]
[10]Simchen,G.; Kraemer,W. [Chemische Berichte, 1969, vol. 102, p. 3656 - 3665] Biggs; Casy; Chu; Coutts [Journal of Medicinal Chemistry, 1976, vol. 19, # 4, p. 472 - 475]
[11]Hasbun,J.A. et al. [Journal of Medicinal Chemistry, 1973, vol. 16, p. 847 - 849]
[12]Wan, Peter; Davis, Michael J.; Teo, Mary-Anne [Journal of Organic Chemistry, 1989, vol. 54, # 6, p. 1354 - 1359]
[13]Suckling, Colin J.; Murphy, John A.; Khalaf, Abedawn I.; Zhou, Sheng-ze; Lizos, Dimitris E.; van Nhien, Albert Nguyen; Yasumatsu, Hiroshi; McVie, Allan; Young, Louise C.; McCraw, Corinna; Waterman, Peter G.; Morris, Brian J.; Pratt, Judith A.; Harvey, Alan L. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2649 - 2655]
[14]Current Patent Assignee: ABBOTT LABORATORIES INC - US2004/157836, 2004, A1
[15]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3656769, 2020, A1 Location in patent: Paragraph 0318; 0319

5
[ 24623-24-3 ]
[ 119273-81-3 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium tetrahydroborate In methanol
92%	With sodium tetrahydroborate In tetrahydrofuran; methanol at 20℃; for 1h;	6-Nitro-2,3-dihydro-1H-inden-1-ol (11) To a solution of 10 (1.77 g, 10.0 mmol) in a mixed solution ofMeOH/THF (2:1, 20 mL), NaBH4 (1.52 g, 40.0 mmol) was added in portions. The mixture was stirredat room temperature for one hour. After the addition of water (40 mL), the mixture was partitionedbetween water and EtOAc. The organic layer was washed with a saturated aqueous brine, driedMolecules 2017, 22, 32 7 of 16over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by columnchromatography on silica gel (eluent: hexane/EtOAc = 2/1) to give 11 (1.64 g, 92%) as a white solid.m.p. 74~77°C; 1H-NMR: δ 8.26 (d, J = 1.8 Hz, 1H), 8.15 (dd, J = 8.3, 2.1 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H),5.32 (t, J = 6.2 Hz, 1H), 3.14 (m, 1H), 2.98-2.85 (m, 1H), 2.64-2.58 (m, 1H), 2.09-1.97 (m, 1H); ESI-MS:m/z [M + H]+ 180.
81%	With Potassium borohydride In methanol	6-Nitroindan-1-ol 6-Nitroindan-1-ol Potassium borohydride (2.80g, 52.8mmol) was added portionwise to a solution of 6-nitroindan-1-one (9.41g, 53.2mmol) in methanol (200ml) over 0.5 hours. The solution was stirred for 2 hours then concentrated. The residue was partitioned between ethyl acetate and water, and the organics isolated, dried (MgSO4) then concentrated under reduced pressure. Chromatography on silica (1:1 ethyl acetate/hexane) yielded 6-nitroindan-1-ol (1.67g, 81%) as a cream solid which was used without further purification.

80%	With methanol; sodium tetrahydroborate at 0℃; for 2h;	6-Nitro-indan-l-ol (SR5-122) To SR5-120 (3.30 g, 18.620 mmol) in dry MeOH (50 mL) at 0 °C was added NaBH4 (0.705 g, 18.620 mmol) and stirred for 2 h. The mixture was concentrated under reduced pressure and the resulting residue dissolved in EtOAc (50 mL). The organic layer was washed with 1N HC1 (25 mL), brine (25 mL), dried (Na2S04) and concentrated under reduced pressure to afford SR5-122 as a white solid (2.662 g, 80%). 1 H NMR (500 MHz, DMSO-ifc) d 8.14 (d, 7 = 2.3 Hz, 1H), 8.10 (ddd, 7 = 8.2, 2.3, 0.5 Hz, 1H), 7.50 (d, 7 = 8.1Hz, 1H), 5.58 (d, 7 = 5.5 Hz, 1H), 5.14 (m, 7 = 6.5 Hz, 1H), 3.02 (ddd, 7 = 17.0, 8.7, 3.6 Hz, 1H), 2.84 (dtd, 7 = 17.7, 8.2, 1.1Hz, 1H), 2.44 (dddd, 7 = 12.8, 8.1, 7.1, 3.6 Hz, 1H), 1.86 (dtd, 7 = 12.7, 8.5, 6.8 Hz, 1H). HPLC-MS (ESI+): m/z 180.2[10% (M+H)+], 202.2 [100%, (M+Na)+]
	With sodium tetrahydroborate
	Stage #1: 6-nitroindan-1-one With sodium tetrahydroborate In methanol at 0 - 20℃; for 0.5h; Stage #2: With hydrogenchloride In methanol; water	3 A solution of 4 (2.7g, 15. 254MMOL) in MeOH (50mL) was cooled in an ice-water bath and sodium borohydride (580mg, 15. 254MMOL) was added in three portions. The reaction was continued at room temperature for 30 min, quenched by adding hydrochloric acid (2M, 30mL). Most of the methanol was removed by rotavapor, the residue was diluted with water, extracted with dichloromethane, the organic phase was dried over MGS04, filtered and concentrated to provide crude alcohol 5 as a brown solid. The product was used in the next reaction without further purification. 1H NMR (CDC13, 400MHZ) : 2.00-2. 08 (1H, m, CH2), 2.44 (1H, broad, OH), 2.56-2. 63 (1H, m, CH2), 2.85- 2.94 (1H, m, CH2), 3.08-3. 16 (1H, m, CH2), 5.30-5. 31 (1H, m, CHO), 7.36 (1H, d, J 8.3, ArH), 8.11 (1H, dd, J 8. 3, 2.0, ArH), 8.22 (1H, d, J 2. 0, ArH).
	With sodium tetrahydroborate In tetrahydrofuran; ethanol at -15℃; for 1.5h; Large scale reaction;

Reference： [1]Gross, Michael F.; Beaudoin, Serge; McNaughton-Smith, Grant; Amato, George S.; Castle, Neil A.; Huang, Christine; Zou, Anruo; Yu, Weifeng [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853]
[2]Guan, Xianghong; Luo, Peihua; He, Qiaojun; Hu, Yongzhou; Ying, Huazhou [Molecules, 2017, vol. 22, # 1]
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - EP321175, 1989, A1
[4]Current Patent Assignee: H. LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE - WO2020/51571, 2020, A1 Location in patent: Page/Page column 41-42
[5]Wan, Peter; Davis, Michael J.; Teo, Mary-Anne [Journal of Organic Chemistry, 1989, vol. 54, # 6, p. 1354 - 1359]
[6]Suckling, Colin J.; Murphy, John A.; Khalaf, Abedawn I.; Zhou, Sheng-ze; Lizos, Dimitris E.; van Nhien, Albert Nguyen; Yasumatsu, Hiroshi; McVie, Allan; Young, Louise C.; McCraw, Corinna; Waterman, Peter G.; Morris, Brian J.; Pratt, Judith A.; Harvey, Alan L. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2649 - 2655]
[7]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - WO2004/87124, 2004, A1 Location in patent: Page/Page column 45-46
[8]Location in patent: experimental part Hansen, Marvin M.; Borders, Sandra S.K.; Clayton, Marcella T.; Heath, Perry C.; Kolis, Stanley P.; Larsen, Samuel D.; Linder, Ryan J.; Reutzel-Edens, Susan M.; Smith, Justin C.; Tameze, Sheila L.; Ward, Jeffrey A.; Weigel, Leland O. [Organic Process Research and Development, 2009, vol. 13, # 2, p. 198 - 208]

6
[ 24623-24-3 ]
diluted Cr₂O₃-H₂SO₄ [ No CAS ]
[ 610-27-5 ]
[ 3898-66-6 ]

Reference： [1]Journal of the Chemical Society,1923,vol. 123,p. 1482,1508

7
[ 83-33-0 ]
[ 24623-25-4 ]
[ 24623-24-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 80% 2: 20%	Stage #1: inden-1-one With sulfuric acid; nitric acid In nitromethane at -10 - -5℃; for 0.75h; Stage #2: With water In nitromethane Cooling with ice;	4.1.1. 4-Nitro-indan-1-one (25) and 6-nitro-indan-1-one (26) To a well-stirred mixture of H2SO4 (13.9 mL of a 98% solution) and HNO3 (2.6 mL of a 65% solution) was added at -10 °C a solution of 1-indanone (1.0 g, 7.6 mmol) in nitromethane (1.1 mL). The addition rate was carefully adjusted to raise the temperature from -10 to -5 °C during 30 min. The reaction mixture was stirred further for 15 min at this temperature (attention has to be paid to temperature and reaction time.). After ice-water hydrolysis (200 mL), the yellow precipitate was collected and extracted with CH2Cl2 (2 × 20 mL). The organic phase was washed with a KHCO3 solution 5% (2 × 15 mL) washed with saturated brine (10 mL), dried over anhydrous Na2SO4 and evaporated in vacuo. The residue was separated by flash chromatography using hexane-ethyl acetate (1:0.2) as eluent. Compound 25, yield: 0.94 g, 80%, mp: 98-100 °C (mp 15 100-101 °C) 1H NMR (CDCl3) δ ppm: 2.80 (m, 2H, CH2), 3.53 (m, 2H, CH2), 7.61 (m, 1H, H-Ar), 8.08 (d, J = 8.5 Hz, 1H, H-Ar), 8.47 (d, J = 8.3 Hz, 1H, H-Ar). Compound 26, yield: 0.23 g, 20%, mp: 73-74 °C (mp lit.16 72-73 °C). 1H NMR (CDCl3) δ ppm: 2.83 (m, 2H, CH2), 3.28 (m, 2H, CH2), 7.61 (d, J = 8.5 Hz, 1H, H-Ar), 8.44 (dd, J = 2.2 Hz, J = 8.5 Hz, 1H, H-Ar), 8.56 (d, J = 2.2 Hz, 1H, H-Ar).
1: 65% 2: 16%	With sulfuric acid; potassium nitrate at -5 - 20℃; for 19h;
1: 65% 2: 2%	With sulfuric acid; potassium nitrate at -1 - 2℃; for 4h;

1: 57% 2: 25%	With sulfuric acid; potassium nitrate
	With nitric acid
	With sulfuric acid; potassium nitrate
	With sulfuric acid; potassium nitrate for 1h;	129.A EXAMPLE 129; 3-Oxo-5-[(phenylsulfonyl)amino]-4-indanecarboxylic acid; EXAMPLE 129A; 6-Nitro-1-indanone EXAMPLE 129 3-oxo-5-[(phenylsulfonyl)amino]-4-indanecarboxylic acid EXAMPLE 129A 6-nitro-1-indanone [0366] A solution of concentrated H2SO4 at 0° C. was treated with 1-indanone (6.00 g, 45.4 mmol) then treated dropwise with KNO3 (5.00 g, 49.94 mmol) in concentrated H2SO4 while maintaining the internal temperature at no more than 15° C. The reaction was stirred for 1 hour after the addition was complete, then poured onto ice. The resulting solids were collected by filtration, washed with water, and dried under vacuum to give a 4:1 mixture of 6-nitro- and 4-nitro-1-indanone (5.04 g, 63%). MS (ESI(+) m/e 178 (M+H)+, 195 (M+NH4)+; MS (ESI(-)) m/e 176 (M-H)-; 1H NMR (300 MHz, DMSO-d6, 6-nitro-1-indanone) δ 8.49 (dd, 1H), 8.29 (d, 1H), 7.87 (d, 1H), 3.25 (m, 2H), 2.78 (m, 2H); 1H NMR (300 MHz, DMSO-d6), 4-nitro-1-indanone) δ 8.51 (dd, 1H), 8.07 (dd, 1H), 7.74 (t, 1H), 3.53 (m, 2H), 2.76 (m, 2H).
	With sulfuric acid; potassium nitrate at 0 - 20℃; for 1.25h;	4 4.2.1 General procedure for the synthesis of indane analogues (2a, 2d, 3a-3d, 4a-4d, 5a-5i and 6a-6g) Step 1: To a solution of 2,3-dihydro-1H-inden-1-one (1.0 eq) in sulfuric acid stirred at 0 °C was added KNO3 (1.05 eq) in several portions over 15 min and the reaction mixture was stirred for 1 h at this temperature. After the reaction completed, the mixture was poured into ice-water, and extracted with AcOEt. The organic phase was washed with water and saturated NaHCO3 solution, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (silica gel, eluent: AcOEt/Pet 0-25%, v/v) to give the 6-nitro-2,3-dihydro-1H-inden-1-one intermediate 8a and 4-nitro-2,3-dihydro-1H-inden-1-one intermediate 8b.
	Stage #1: inden-1-one With sulfuric acid at -10℃; for 0.5h; Stage #2: With sulfuric acid; potassium nitrate at -10℃; for 2.5h; Overall yield = 77 percent; Overall yield = 68 g;	11 Intermediate 6-nitro-2,3-dihydro-1H-inden-1-one To cold 98% sulfuric acid (500 mL) was added 2,3-dihydro-1H-inden-1-one (66.0 g, 500 mmol) portionwise over 30 minutes at -10° C. Then, a solution of KNO3 (75.8 g, 0.75 mol) in 98% sulfuric acid (250 mL) was added dropwise to the above mixture over 2 hours at -10° C. The resulting mixture was stirred for 30 minutes at -10° C. The obtained mixture was poured into a mixture of crushed ice (2 kg) and cold water (2 L). The formed yellowish precipitate was filtered off and washed with water (5*300 mL) and ethanol (100 mL). The precipitate was air-dried overnight to give 68.0 g (77%) of a ca. 3:1 mixture of 6-nitro-2,3-dihydro-1H-inden-1-one and 4-nitro-2,3-dihydro-1H-inden-1-one as a yellow powder. 1H NMR (CDCl3): δ 8.54 (d, J=1.9 Hz, 1H), 8.43 (dd, J=8.4, 2.1 Hz, 1H), 7.65 (d, J=8.3 Hz, 1H), 3.22-3.32 (m, 2H), 2.79-2.86 (m, 2H).
	With sulfuric acid; potassium nitrate at 0℃; for 4h; Overall yield = 80 percent;
	With sulfuric acid; potassium nitrate at 0℃; for 4h; Overall yield = 80 percent;

Reference： [1]Location in patent: experimental part Caputto, María E.; Fabian, Lucas E.; Benítez, Diego; Merlino, Alicia; Ríos, Natalia; Cerecetto, Hugo; Moltrasio, Graciela Y.; Moglioni, Albertina G.; González, Mercedes; Finkielsztein, Liliana M. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 22, p. 6818 - 6826]
[2]Musso, David L.; Cochran, Felicia R.; Kelley, James L.; McLean, Ed W.; Selph, Jeffrey L.; Rigdon, Greg C.; Orr, G. Faye; Davis, Ronda G.; Cooper, Barrett R.; Styles, Virgil L.; Thompson, James B.; Hall, William R. [Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408]
[3]Location in patent: experimental part Wodnicka; Kwiecien [Polish Journal of Chemistry, 2008, vol. 82, # 11, p. 2133 - 2140]
[4]Fouad, Farid S.; Xi, Zhen; Goldberg, Irving H.; Jones, Graham B. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3337 - 3339]
[5]Souers, Andrew J.; Iyengar, Rajesh R.; Judd, Andrew S.; Beno, David W.A.; Gao, Ju; Zhao, Gang; Brune, Michael E.; Napier, James J.; Mulhern, Mathew M.; Lynch, John K.; Freeman, Jennifer C.; Wodka, Dariusz; Chen, Chong J.; Falls, H. Doug; Brodjian, Sevan; Dayton, Brian D.; Diaz, Gilbert J.; Bush, Eugene N.; Shapiro, Robin; Droz, Brian A.; Knourek-Segel, Victoria; Hernandez, Lisa E.; Marsh, Kennan C.; Reilly, Regina M.; Sham, Hing L.; Collins, Christine A.; Kym, Philip R. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 884 - 889]
[6]Gross, Michael F.; Beaudoin, Serge; McNaughton-Smith, Grant; Amato, George S.; Castle, Neil A.; Huang, Christine; Zou, Anruo; Yu, Weifeng [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853]
[7]Current Patent Assignee: ABBVIE INC - US2004/167128, 2004, A1 Location in patent: Page 39
[8]Tian, Jinlong; Sun, Nannan; Yu, Mingcheng; Gu, Xianfeng; Xie, Qiong; Shao, Liming; Liu, Jin; Liu, Li; Wang, Yonghui [European Journal of Medicinal Chemistry, 2019, vol. 167, p. 37 - 48]
[9]Current Patent Assignee: EXXON MOBIL CORP - US2020/71344, 2020, A1 Location in patent: Paragraph 0273-0274
[10]Howlader, A. Hasan; Diaz, Keili; Mebel, Alexander M.; Kaiser, Ralf I.; Wnuk, Stanislaw F. [Tetrahedron Letters, 2020, vol. 61, # 43]
[11]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - US10954178, 2021, B1 Location in patent: Page/Page column 4; 16

8
[ 24623-24-3 ]
[ 66440-71-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile)
	With bromine In acetic acid	5.a (a) (a) 2-Bromo-6-nitro-1-indanone Analogously to Example 1 (a), reaction of 12.39 g (70.0 mmoles) of 6-nitro-1-indanone in 130 ml of glacial acetic acid, containing 0.5 ml of 48% strength aqueous hydrobromic acid, and 11.2 g (70 mmoles) of bromine in 70 ml of glacial acetic acid, in accordance with the instructions indicated above, gives 2-bromo-6-nitro-1-indanone of melting point 102°-105° C. which, as the pure product after reprecipitation from ethanol/water, has a melting point of 114°-116° C.

Reference： [1]Fouad, Farid S.; Xi, Zhen; Goldberg, Irving H.; Jones, Graham B. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3337 - 3339]
[2]Current Patent Assignee: SANOFI - US4174397, 1979, A

9
[ 24623-24-3 ]
[ 62658-54-2 ]

Yield	Reaction Conditions	Operation in experiment
35%	With ammonium acetate; sodium cyanoborohydride In methanol

10
[ 24623-24-3 ]
[ 202749-08-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂

11
[ 24623-24-3 ]
C₉H₇NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂

12
[ 24623-24-3 ]
C₁₇H₁₈N₂O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂ 4: NH₄OH 5: Et₃N / CH₂Cl₂

13
[ 24623-24-3 ]
C₁₇H₂₀N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂ 4: NH₄OH 5: Et₃N / CH₂Cl₂ 6: SnCl₂*2H₂O / ethanol

14
[ 24623-24-3 ]
C₂₅H₂₆N₂O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂ 4: NH₄OH 5: Et₃N / CH₂Cl₂ 6: SnCl₂*2H₂O / ethanol 7: Et₃N / CH₂Cl₂
	Multi-step reaction with 8 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: 96 percent / m-CPBA / CH₂Cl₂ 4: 91 percent / NH₄OH 5: 83 percent / Et₃N / CH₂Cl₂ 6: 97 percent / SnCl₂*2H₂O / ethanol 7: 93 percent / Et₃N / CH₂Cl₂ 8: chiral HPLC chromatography

Reference： [1]Gross, Michael F.; Beaudoin, Serge; McNaughton-Smith, Grant; Amato, George S.; Castle, Neil A.; Huang, Christine; Zou, Anruo; Yu, Weifeng [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853]
[2]Gross, Michael F.; Beaudoin, Serge; McNaughton-Smith, Grant; Amato, George S.; Castle, Neil A.; Huang, Christine; Zou, Anruo; Yu, Weifeng [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853]

15
[ 24623-24-3 ]
[ 41734-55-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium tetrahydroborate; toluene-4-sulfonic acid In methanol; toluene Reflux;	1 Step 2: 5-nitro-1-anthracene 5-Nitro-1-indanone (1.58 g, 8.92 mmol) was dissolved in methanol (100 mL), and sodium borohydride (506.11 mg, 13.38 mmol) was added thereto.p-Toluenesulfonic acid (3.36 g, 17.84 mmol) and toluene (1.64 g, 17.84 mmol) were heated to reflux and purified by column chromatography to yield 1.25 g (yield: 87.0%).
	Multi-step reaction with 2 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene
	Multi-step reaction with 2 steps 1: NaBH₄ 2: conc. H₂SO₄ / toluene

Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; tetrahydrofuran / 1 h / 20 °C 2: toluene-4-sulfonic acid / toluene / 2 h / Reflux

Reference： [1]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - CN107619384, 2018, A Location in patent: Page/Page column 18; 19
[2]Gross, Michael F.; Beaudoin, Serge; McNaughton-Smith, Grant; Amato, George S.; Castle, Neil A.; Huang, Christine; Zou, Anruo; Yu, Weifeng [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2849 - 2853]
[3]Wan, Peter; Davis, Michael J.; Teo, Mary-Anne [Journal of Organic Chemistry, 1989, vol. 54, # 6, p. 1354 - 1359]
[4]Guan, Xianghong; Luo, Peihua; He, Qiaojun; Hu, Yongzhou; Ying, Huazhou [Molecules, 2017, vol. 22, # 1]

16
[ 24623-24-3 ]
[ 505083-08-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 99 percent / NaBH₄ / methanol 2: 100 percent / TsOH / toluene 3: PPNO; NaOCl; aq. NaH₂PO₄ / (S,S)-Mn-salen / CH₂Cl₂ 4: NH₄OH

17
[ 24623-24-3 ]
[ 85515-20-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Fe; NH₄Cl / ethanol; H₂O / 60 °C 2: EDCI
	Multi-step reaction with 2 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol

Reference： [1]Souers, Andrew J.; Iyengar, Rajesh R.; Judd, Andrew S.; Beno, David W.A.; Gao, Ju; Zhao, Gang; Brune, Michael E.; Napier, James J.; Mulhern, Mathew M.; Lynch, John K.; Freeman, Jennifer C.; Wodka, Dariusz; Chen, Chong J.; Falls, H. Doug; Brodjian, Sevan; Dayton, Brian D.; Diaz, Gilbert J.; Bush, Eugene N.; Shapiro, Robin; Droz, Brian A.; Knourek-Segel, Victoria; Hernandez, Lisa E.; Marsh, Kennan C.; Reilly, Regina M.; Sham, Hing L.; Collins, Christine A.; Kym, Philip R. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 884 - 889]
[2]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]

18
[ 24623-24-3 ]
[ 947701-67-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 6-nitro-2,3-dihydro-1H-inden-1-one With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In Carbon tetrachloride for 2.5h; Reflux; Stage #2: With triethylamine In Carbon tetrachloride at 0℃;	Representative experimental procedure for the Synthesis of benzo[c]fluorenone General procedure: NBS (195 mg, 1.1 mmol) and AIBN (2 mg, 0.01 mmol) were added to a CCl4 solution (4 ml) of the 6-methoxyindanone (162 mg, 1 mmol). The resulting mixture was stirred at reflux temperature for 2.5 h, then cooled and filtered through Celite, which was then washed with CCl4. The filtrate was cooled to 0 °C and treated with triethylamine (0.28 mL, 2.0 mmol) overnight, then concentrated in vacuuo. Chromatography of the residue (1 : 9~1 : 4 EtOAc/hexanes) afforded 97 mg (60%) of enone 1a as the pink oil which solidified as light red solid in refrigerator.
78%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In Carbon tetrachloride for 2.5h; Reflux;	General procedure: NBS (195 mg, 1.1 mmol) and AIBN (2 mg, 0.01 mmol) were added to a CCl4 solution (4 ml) of the 6-methoxyindanone (162 mg, 1 mmol).The resulting mixture was stirred at reflux temperature for 2.5 h, then cooledand filtered through Celite, which was then washed with CCl4. The filtrate was cooled to 0 °C and treated with triethylamine (0.28 mL, 2.0 mmol)overnight, then concentrated in vacuuo. Chromatography of the residue (19~14 EtOAc/hexanes) afforded 97 mg (60%) of enone 1a as the pink oil which solidified as light red solid in refrigerator.
26.3%	Stage #1: 6-nitro-2,3-dihydro-1H-inden-1-one With trimethylsilyl trifluoropmethanesulfonate; triethylamine In toluene at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: With palladium diacetate In dichloromethane; toluene; acetonitrile at 20℃; for 2h; Inert atmosphere;	Step 2. 6-Nitro-1H-inden-1-one Step 2. 6-Nitro-1H-inden-1-one [0443] 6-nitro-1-indatone (2.66 g, 15 mmol) in dry toluene (100 mL) at 0° C. under Ar was added successively Et3N (2.55 mL, 18 mmol) and TMSOTf (2.85 mL, 15 mmol). The mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was again cooled to 0° C. and diluted with ether (100 mL) and NaHCO3 solution (150 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic extracts were washed with brine then dried (Na2SO4), filtered, and evaporated under reduced pressure to afford the silyl enol ether as a light yellow oil. [0445] The silyl enol ether was dissolved in CH2Cl2 (30 mL) and added dropwise to an aluminum foil-wrapped flask containing a suspension of Pd(OAc)2 (3.3 g, 15 mmol) in dry CH3CN (80 mL) under Ar. The mixture was stirred at room temperature for 2 h, then filtered through a short column of silica gel. The filtrate was evaporated under reduced pressure, and the residue was purified by chromatography on silica gel (9%-21% EtOAc/PE) to afford 0.69 g product as yellow solid (26.3%). 1H NMR (300 MHz, CDCl3) δ: 6.23-6.25 (1H, d, J=6.3 Hz), 7.27-7.30 (1H, d, J=8.1 Hz), 7.71-7.73 (1H, d, J=6.0 Hz), 8.26 (1H, s), 8.32-8.35 (1H, dd, J=7.8 and 2.4 Hz).

	Multi-step reaction with 2 steps 1: NBS; AIBN 2: Et₃N
	Multi-step reaction with 2 steps 1: triethylamine / toluene / 0.5 h / 0 °C 2: palladium diacetate / dichloromethane; acetonitrile / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0.5 h / 0 °C 2: palladium diacetate / dichloromethane; acetonitrile / 4 h / 20 °C / Inert atmosphere

Reference： [1]Zheng, Shuyan; Tan, Hongsheng; Zhang, Xiaoguang; Yu, Chunhui; Shen, Zhengwu [Tetrahedron Letters, 2014, vol. 55, # 5, p. 975 - 978]
[2]Zheng, Shuyan; Tan, Hongsheng; Zhang, Xiaoguang; Yu, Chunhui; Shen, Zhengwu [Tetrahedron Letters, 2015, vol. 55, # 5, p. 975 - 978]
[3]Current Patent Assignee: ASTAR BIOTECH - US2014/31354, 2014, A1 Location in patent: Paragraph 02980443; 0444
[4]Fouad, Farid S.; Xi, Zhen; Goldberg, Irving H.; Jones, Graham B. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3337 - 3339]
[5]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[6]Current Patent Assignee: SANOFI - WO2022/23460, 2022, A1

19
[ 24623-24-3 ]
[ 69975-66-2 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 399 - 408

20
[ 24623-24-3 ]
[6-Cyano-indan-(1E)-ylidene]-acetyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: 78 percent / H₂ / PtO₂ / ethanol; H₂O / 0.67 h / 3102.97 Torr 2.1: NaNO₂; aq. HCl 2.2: 52 percent / H₂O; toluene / 1 h / 50 - 60 °C 3.1: Zn; I₂ / diethyl ether; toluene / 48 h / 30 - 45 °C 4.1: 1.0 N aq. NaOH / ethanol / 18 h / 20 °C 5.1: trifluoroacetic acid / CH₂Cl₂ / 0.58 h 6.1: (COCl)2; DMF / CH₂Cl₂ / 18 h / 20 °C

Reference： [1]Musso, David L.; Cochran, Felicia R.; Kelley, James L.; McLean, Ed W.; Selph, Jeffrey L.; Rigdon, Greg C.; Orr, G. Faye; Davis, Ronda G.; Cooper, Barrett R.; Styles, Virgil L.; Thompson, James B.; Hall, William R. [Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408]

21
[ 24623-24-3 ]
(E)-2-(6-Cyano-1-indanylidene)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: 78 percent / H₂ / PtO₂ / ethanol; H₂O / 0.67 h / 3102.97 Torr 2.1: NaNO₂; aq. HCl 2.2: 52 percent / H₂O; toluene / 1 h / 50 - 60 °C 3.1: Zn; I₂ / diethyl ether; toluene / 48 h / 30 - 45 °C 4.1: 1.0 N aq. NaOH / ethanol / 18 h / 20 °C 5.1: trifluoroacetic acid / CH₂Cl₂ / 0.58 h 6.1: (COCl)2; DMF / CH₂Cl₂ / 18 h / 20 °C 7.1: 30percent aq. NH₄OH / CH₂Cl₂ / 4.5 h

22
[ 24623-24-3 ]
[6-Cyano-indan-(1E)-ylidene]-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 78 percent / H₂ / PtO₂ / ethanol; H₂O / 0.67 h / 3102.97 Torr 2.1: NaNO₂; aq. HCl 2.2: 52 percent / H₂O; toluene / 1 h / 50 - 60 °C 3.1: Zn; I₂ / diethyl ether; toluene / 48 h / 30 - 45 °C 4.1: 1.0 N aq. NaOH / ethanol / 18 h / 20 °C 5.1: trifluoroacetic acid / CH₂Cl₂ / 0.58 h

23
[ 24623-24-3 ]
(6-cyano-1-hydroxy-indan-1-yl)-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 78 percent / H₂ / PtO₂ / ethanol; H₂O / 0.67 h / 3102.97 Torr 2.1: NaNO₂; aq. HCl 2.2: 52 percent / H₂O; toluene / 1 h / 50 - 60 °C 3.1: Zn; I₂ / diethyl ether; toluene / 48 h / 30 - 45 °C 4.1: 1.0 N aq. NaOH / ethanol / 18 h / 20 °C

24
[ 24623-24-3 ]
(6-cyano-1-hydroxy-indan-1-yl)-acetic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 78 percent / H₂ / PtO₂ / ethanol; H₂O / 0.67 h / 3102.97 Torr 2.1: NaNO₂; aq. HCl 2.2: 52 percent / H₂O; toluene / 1 h / 50 - 60 °C 3.1: Zn; I₂ / diethyl ether; toluene / 48 h / 30 - 45 °C

25
[ 24623-24-3 ]
[ 62803-47-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol
	Multi-step reaction with 2 steps 1: tin (II)-chloride; concentrated hydrochloric acid; alcohol 2: Diazotization_.Verkochen
	Multi-step reaction with 3 steps 1: chloroform; bromine / 0 °C 2: tin (II)-chloride; concentrated hydrochloric acid; alcohol 3: Diazotization_.Verkochen

Reference： [1]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]
[2]Ingold; Piggott [Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508]
[3]Ingold; Piggott [Journal of the Chemical Society, 1923, vol. 123, p. 1482,1508]

26
[ 24623-24-3 ]
2,3-diidro-6-(3-metilureido)-1H-indene-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol 2: 43 percent / Et₃N / dimethylformamide / 3 h / 0 °C

Reference： [1]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]

27
[ 24623-24-3 ]
[ 85515-21-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol 2: 77 percent

Reference： [1]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]

28
[ 24623-24-3 ]
[ 85515-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol 2: 77 percent 3: 1.) POCl₃ / 1.) 0 deg C, 2.) 0 deg C

Reference： [1]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]

29
[ 24623-24-3 ]
2,2-Dichloro-N-{3-chloro-2-[(5-nitro-furan-2-carbonyl)-hydrazonomethyl]-1H-inden-5-yl}-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: H₂ / Pd/CaCO₃ / aq. ethanol 2: 77 percent 3: 1.) POCl₃ / 1.) 0 deg C, 2.) 0 deg C 4: 63 percent / acetic acid; methanol / Ambient temperature

Reference： [1]Ferranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P. [Farmaco, Edizione Scientifica, 1983, vol. 38, # 3, p. 167 - 172]

30
[ 24623-24-3 ]
[ 16513-67-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: NaBH₄ 2: conc. H₂SO₄ / toluene 3: H2O / acetonitrile / 0.17 h / Irradiation; var. H2O concentration, isotope effect (Φ_OH/Φ_OD)
	Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 1 h / 20 °C 2.1: toluene-4-sulfonic acid / toluene / 2 h / Reflux 3.1: diborane; diethyl sulphide / tetrahydrofuran / 2 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Wan, Peter; Davis, Michael J.; Teo, Mary-Anne [Journal of Organic Chemistry, 1989, vol. 54, # 6, p. 1354 - 1359]
[2]Guan, Xianghong; Luo, Peihua; He, Qiaojun; Hu, Yongzhou; Ying, Huazhou [Molecules, 2017, vol. 22, # 1]

31
[ 24623-25-4 ]
[ 24623-24-3 ]
[ 51135-91-2 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With ammonium chloride;iron; In ethanol; at 90℃; for 1h;	EXAMPLE 129B 6-amino-1-indanone [0367] A solution of Example 129A (19.68 g, 111 mmol) in ethanol (111 mL) was treated sequentially with iron powder (43.0 g, 770 mmol) and solid ammonium chloride (3.70 g, 69.2 mmol). The resulting suspension was stirred at 90 C. for 1 hour, cooled to room temperature, diluted with brine, and extracted with diethyl ether (4×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to provide the desired product as a 6:1 mixture of 6-amino- and 4-amino-1-indanone (14.20 g, 87%). 1H NMR (300 MHz, DMSO-d6, 6-amino-1-indanone) delta 7.21 (d, 1H), 6.92 (dd, 1H), 6.75 (d, 1H), 5.27 (br s, 2H), 2.90 (t, 2H), 2.54 (m, 2H); 1H NMR (300 MHz, DMSO-d6), 4-amino-1-indanone) delta 7.10 (t, 1H), 6.81 (m, 2H), 2.80 (m, 2H), 2.59 (m, 2H).

Reference： [1]Patent: US2004/167128,2004,A1 .Location in patent: Page 39

32
[ 24623-24-3 ]
[ 540-63-6 ]
[ 773056-06-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With toluene-4-sulfonic acid In toluene for 12h; Reflux; Dean-Stark;	6′-Nitro-2′,3′-dihydrospiro([1,3]dithiolane-2,1'-indene) (9) A solution of 2 (8.85 g, 50 mmol), ethane-1,2-dithiol (4.6 mL, 55 mmol) and PTSA (1.72 g, 10 mmol) in toluene (100 mL) was heated at reflux temperature for 12 h using a Dean-Stark apparatus. The cooled solution was washed with 10% NaOH (100 mL), and the aqueous layer extracted with CH2Cl2 (2 × 30 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4,filtered, and purified by chromatography on silica gel (9-18% EtOAc in PE) to give a yellow oil. Yield: 12.5 g (99%).
98%	With toluene-4-sulfonic acid In toluene at 100℃; for 24h; Dean-Stark;	INTERMEDIATE 46 6'-nitrospiro[1,3-dithiolane-2,1'-indane] Ethane-1,2-dithiol (1.68 g, 17.9 mmol, 1.10 eq), 6-nitroindan-1-one (2.88 g, 16.2 mmol, 1.00 eq), p-toluene sulfonic acid (0.56 g, 3.3 mmol, 0.20 eq) and toluene (15 mL) were heated under Dean Stark conditions at 100 °C for 24 h. The reaction was then allowed to cool to rt and the toluene removed in vacuo. The residue was purified by column chromatography on silica (EtOAc/heptane, 1:9) to yield the title product (4.05 g, 98 %) as a yellow oil. UPLC (Method A) 1.71 min, 100 %, no ionisation observed.
95%	Stage #1: 6-nitroindan-1-one; ethane-1,2-dithiol With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 2h; Stage #2: With sodium hydroxide In dichloromethane; water	3 To a solution of 4 (2.40g, 13. 56MMOL) in dry DCM (20ML) under nitrogen atmosphere was added 1,2- ethanedithiol (1.915g, 20. 34MMOL, 1. 71mL) and BF3. OET2 (1.92g, 13. 56MMOL, 1.67mL). The mixture was stirred at room temperature for 2 hours and was diluted with DCM (50ML) washed with aqueous NaOH (10%), dried over MGS04, filtered and concentrated to give 18 as a yellow oil (3.26g, 95%), which was used in next reaction without purification. 1H NMR (CDCl3, 400MHZ) : 2.76 (2H, t, J 6.75, CH2), 3. 05 (2H, t, J 6.75, CH2), 3.44-3. 51 (2H, m, CH2), 3.55-3. 62 (2H, m, CH2), 7.31 (1H, d, J 8.28, ArH), 8.08 (1H, dd, J 8. 28, 2.19, ArH), 8.35 (1H, d, J 2.19, ArH).

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2020/260871, 2020, A1 Location in patent: Page/Page column 60-61
[3]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - WO2004/87124, 2004, A1 Location in patent: Page/Page column 53-54

33
[ 109-79-5 ]
[ 24623-24-3 ]
[ 773056-09-0 ]
[ 773056-08-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 77% 2: 20%	Stage #1: n-butanethiol; 6-nitroindan-1-one With chloro-trimethyl-silane In chloroform at 20℃; Stage #2: With sodium hydroxide In dichloromethane; chloroform; water	3 To a solution of 4 (1. 0g, 5. 65MMOL) in chloroform (lOmL) under nitrogen atmosphere at room temperature was added n-butanethiol (1.27g, 14. 124MMOL, 1.513mL) and chlorotrimethylsilane (1.534g, 14. 124mmol, 1.805mL). The mixture was stirred at room temperature overnight and was diluted with DCM (20mL), washed with 2N NAOH, dried over MgSO4, filtered and concentrated. Purification by column (petro-leum ether/ether 95/5) gave compound 22 (slightly yellow oil, 1.27g, 77%) and 23 (yellow solid, 290mg, 20%). 1HNMR for 22 : 1H NMR (CDCl3, 400MHZ) : 0.89 (6H, t, J 7. 28, CH3). 1. 32-1.43 (4H, m, CH2), 1.45-1. 61 (4H, m, CH2), 2.46-2. 53 (2H, m, CH2), 2.59-2. 67 (4H, m, CH2), 3.10 (2H, t, J 6. 92, CH2), 7.38 (1H, d, J 8.06, ArH), 8.11-8. 14 (2H, m, ARH). 1HNMR for 23 : 1H NMR (CDC13, 400MHZ) : 0.97 (3H, t, J 7.35, CH3). 1. 46-1.57 (2H, m, CH2), 1.71-1. 78 (2H, m, CH2), 3.00 (2H, t, J 7.33, CH2), 3.56 (2H, d, J 2. 29, CH2), 6.35 (1H, t, J 2.29, CH), 7.56 (1H, d, J 8.14, ArH), 8.14 (1H, dd, J 8.14, 2.11, ArH), 8.22 (1H, d, J 2.11, ArH).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - WO2004/87124, 2004, A1 Location in patent: Page/Page column 56

34
[ 24623-24-3 ]
[ 2450-71-7 ]
[ 863987-52-4 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 6-nitroindan-1-one; Propargylamine In 1,2-dichloro-ethane at 25℃; for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 25℃; for 50h;	1 (6-Nitro-indan-1-yl)-prop-2-ynylamine (3(s6)) 6-Nitroindanone (6.86 g, 38.72 mmol) was dissolved in 1,2 dichlorethane (220 mL), and a solution of propargylamine (2.68 g, 48.66 mmol) in dichloroethane (15 mL) was added. The mixture was stirred at 25° C. under nitrogen for 30 min and sodium triacetoxyborohydride (13.42 g, 63.32 mmol) was added neat. The mixture was then stirred at 25° C. under nitrogen for 50 h. Solvent was evaporated under reduced pressure to give a dark solid residue. The residue was treated with ethyl acetate (300 mL) and the mixture was stirred at 45° C. for 1 h and filtered. Silica gel was added to the filtrate and the mixture was evaporated to dryness under vacuum to give silica gel impregnated with the crude product. This was placed on top of a silica gel column and purified by flash column chromatography (hexane:ethyl acetate 25:75) to give 5.80 g (69%) of a brown solid, mp 37-39° C. 1H NMR δ (CDCl3) : 8.20 (s, 1H), 8.10 (dd, 1H), 7.35 (d, 1H), 4.50 (m, 1H, C1-H), 3.55, (m, 2H, CH2C≡CH), 3.1 (m, 1H, C3-H), 2.9 (m, 1H, C3-H'), 2.5 (m, 1H, C2-H), 1.9 (m, 1H, C2-H'), 2.30 (s, 1H, CH2C≡CH) ppm.
69%	Stage #1: 6-nitroindan-1-one; Propargylamine In 1,2-dichloro-ethane at 25℃; for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 25℃; for 50h;	1 Example 1 N-Boc-(6-aminoindan-1-yl)-prop-2-ynylamine (Compound 3) 6-Nitroindanone (6.86 g, 38.72 mmol) was dissolved in 1,2 dichlorethane (220 mL), and a solution of propargylamine (2.68 g, 48.66 mmol) in dichloroethane (15 mL) was added. The mixture was stirred at 25° C. under nitrogen for 30 min and sodium triacetoxyborohydride (13.42 g, 63.32 mmol) was added neat. The mixture was then stirred at 25° C. under nitrogen for 50 h. Solvent was evaporated under reduced pressure to give a dark solid residue. The residue was treated with ethyl acetate (300 mL) and the mixture was stirred at 45° C. for 1 h and filtered. Silica gel was added to the filtrate and the mixture was evaporated to dryness under vacuum to give silica gel impregnated with the crude product. This was placed on top of a silica gel column and purified by flash column chromatography (hexane:ethyl acetate 25:75) to give 5.80 g (69%) of (6-Nitro-indan-1-yl)-prop-2-ynylamine as a brown solid, mp 37-39° C.
69%	Stage #1: 6-nitroindan-1-one; Propargylamine In 1,2-dichloro-ethane at 25℃; for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 25℃; for 50h;	1 6-Nitroindanone (6.86 g, 38.72 mmol) was dissolved in 1,2 dichlorethane (220 itiL) , and a solution of propargylamine (2.68 g, 48.66 mmol) in dichloroethane (15 inL) was added. The mixture was stirred at 25°C under nitrogen for 30 min and sodium triacetoxyborohydride (13.42 g, 63.32 mmol) was added neat. The mixture was then stirred at 25°C under nitrogen for 50 h. Solvent was evaporated under reduced pressure to give a dark solid residue. The residue was treated with ethyl acetate (300 inL) and the mixture was stirred at 45°C for 1 h and filtered. Silica gel was added to the filtrate and the mixture was evaporated to dryness under vacuum to give silica gel impregnated with the crude product. This was placed on top of a silica gel column and purified by flash column chromatography (hexane:ethyl acetate 25:75) to give 5.80 g (69%) of (6-Nitro-indan-l-yl) -prop-2-ynylamine as a brown solid, mp 37-390C

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2005/197365, 2005, A1 Location in patent: Page/Page column 14
[2]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2006/25446, 2006, A1 Location in patent: Page/Page column 9-10
[3]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2006/14968, 2006, A2 Location in patent: Page/Page column 29

35
[ 24623-24-3 ]
[ 7440-44-0 ]
[ 69975-65-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen; In ethanol;	EXAMPLE 59 Preparation of N-(3-Amino-5-indanyl)acetamidine 6-Nitroindan-1-one (18.1 g, 102 mmol) was dissolved in ethanol (400 ml) and reduced using Pd (5%) on carbon (2.0 g) and 35 psi hydrogen pressure on a Parr apparatus. Filtration on celite followed by evaporation gave 6-aminoindan-1-one (13.7 g, 93 mmol). NMR (DMSO) 7.2 (d, J=7.7Hz, 1H), 6.9 (dd, Jab=7.7Hz, J ax=2.3 Hz, 1H), 6.75 (d, J=2.3Hz, 1H), 5.3 (brs, 2H), 2.9 (t, J=5.6 Hz, 2H), 2.55 (t, J=5.6 Hz, 2H).

Reference： [1]Patent: US5866612,1999,A

36
[ 24623-24-3 ]
6-(trifluoroacetamido)indan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		6.a a. a. 6-(Trifluoroacetamido)indan-1-one Using a similar procedure to that described for Example 1.a., except starting with 6-nitro-indanone (C. K. Ingold and H. A. Piggott, J. Chem. Soc., (1923) 123, 1469) and trifluoroacetic anhydride, 6-(trifluoroacetamido)indan-1-one was obtained (73%); mp 172.5°-173.5° C.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US5095038, 1992, A

37
[ 24623-24-3 ]
[ 1159845-32-5 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrazine hydrate; acetic acid In methanol at 20℃; for 168h;

Reference： [1]Location in patent: experimental part Wodnicka; Kwiecien [Polish Journal of Chemistry, 2008, vol. 82, # 11, p. 2133 - 2140]

38
[ 24623-24-3 ]
[ 141-78-6 ]
[ 1119518-66-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 6-nitroindan-1-one; ethyl acetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Stage #2: With sulfuric acid; water at 60℃;
	Stage #1: ethyl acetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 6-nitroindan-1-one at -78℃; for 1h; Inert atmosphere; Stage #3: With sulfuric acid; water at -5 - 60℃; Inert atmosphere;

Reference： [1]Location in patent: scheme or table Mesquida, Neus; Lopez-Perez, Sara; Dinares, Immaculada; Alcalde, Ermitas [Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1739 - 1744]
[2]Location in patent: experimental part Alcalde, Ermitas; Mesquida, Neus; López-Pérez, Sara; Frigola, Jordi; Mercè, Ramon [Journal of Medicinal Chemistry, 2009, vol. 52, # 3, p. 665 - 687]

39
[ 872-50-4 ]
[ 24623-24-3 ]
[ 1197191-14-2 ]

Yield	Reaction Conditions	Operation in experiment
15%	Stage #1: 1-methyl-pyrrolidin-2-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 6-nitroindan-1-one In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #3: With trifluoroacetic acid In dichloromethane at 0 - 20℃;

Reference： [1]Location in patent: experimental part Alcalde, Ermitas; Mesquida, Neus; Lopez-Perez, Sara; Frigola, Jordi; Merce, Ramon; Holenz, Joerg; Pujol, Marta; Hernandez, Enrique [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 20, p. 7387 - 7397]

40
[ 24623-24-3 ]
[ 79-19-6 ]
[ 1350638-62-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 6-nitroindan-1-one; thiosemicarbazide In ethanol for 0.5h; Reflux; Stage #2: With sulfuric acid In ethanol Heating;	4.1.4. General procedure for the synthesis of TSCs 15-18¹⁰ General procedure: A suspension of corresponding 1-indanone (1.2 mmol) and thiosemicarbazide (2.7 mmol) in absolute ethanol (20 mL) was heated under reflux for 30 min, then concentrated H2SO4 (0.10 mL) was added and the heating was continued until the 1-indanone was consumed. The conversion of 1-indanone in the corresponding TSC was monitored by TLC on silica gel 60 F254 using chloroform-ethanol (1:0.1) as eluent. The solvent was removed in vacuo and the solid was suspended in water (20 mL), filtered and washed with water (2 × 5 mL), EtOH (5 mL), CH2Cl2 (5 mL) and finally hexane (2 × 5 mL). TSCs were recrystallized from ethanol.

41
[ 4030-18-6 ]
[ 24623-24-3 ]
C₁₅H₁₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-(acetyl)pyrrolidine With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 6-nitroindan-1-one In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;

Reference： [1]Mesquida, Neus; Lopez-Perez, Sara; Dinares, Immaculada; Alcalde, Ermitas [Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1739 - 1744]

42
[ 618-42-8 ]
[ 24623-24-3 ]
C₁₆H₂₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-piperidin-1-yl-ethanone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 6-nitroindan-1-one In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;

Reference： [1]Mesquida, Neus; Lopez-Perez, Sara; Dinares, Immaculada; Alcalde, Ermitas [Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1739 - 1744]

43
[ 127-19-5 ]
[ 24623-24-3 ]
C₁₃H₁₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N,N-dimethyl acetamide With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 6-nitroindan-1-one In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;

Reference： [1]Mesquida, Neus; Lopez-Perez, Sara; Dinares, Immaculada; Alcalde, Ermitas [Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1739 - 1744]

44
[ 24623-24-3 ]
[ 1542265-64-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: trimethylsilyl trifluoromethanesulfonate; triethylamine / toluene / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 2 h / 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 12 h / 20 °C
	Multi-step reaction with 3 steps 1: triethylamine / toluene / 0.5 h / 0 °C 2: palladium diacetate / dichloromethane; acetonitrile / 2 h / 20 °C 3: tetrahydrofuran / 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTAR BIOTECH - US2014/31354, 2014, A1
[2]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]

45
[ 24623-24-3 ]
[ 1542265-65-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: trimethylsilyl trifluoromethanesulfonate; triethylamine / toluene / 1 h / 0 - 20 °C / Inert atmosphere 1.2: 2 h / 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 12 h / 20 °C 3.1: boron trifluoride diethyl etherate / dichloromethane / -15 - 20 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1: triethylamine / toluene / 0.5 h / 0 °C 2: palladium diacetate / dichloromethane; acetonitrile / 2 h / 20 °C 3: tetrahydrofuran / 18 h / 20 °C 4: boron trifluoride diethyl etherate / dichloromethane / -15 - 20 °C

Reference： [1]Current Patent Assignee: ASTAR BIOTECH - US2014/31354, 2014, A1
[2]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]

46
[ 16642-79-8 ]
[ 24623-24-3 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluorormethanesulfonic acid; In dichloromethane; at 80℃; for 6h;High pressure; Inert atmosphere; Green chemistry;	General procedure: Trifluoromethane sulfonic acid (3 eq.) was gently added to a cooled (0 C) solution of a 3-Phenylpropionic acid (0.5 mmol) in dry CH2Cl2 (1.0 mL) in a 12 mL Q-tube pressure tube, furnished by QLabtech. The temperature was raised to room temperature. A Teflon septum was placed on the top of the tube and the appropriate cap and pressure adapter were used. The mixture was heated in an oil bath at 80 C. The reaction was monitored by TLC and GC/MS until the reactant disappeared. The mixture was poured into ice and extracted three times with CH2Cl2. The organic phase collected was dried on Na2SO4, filtered and concentrated under vacuum. The desired pure product was separated from the crude by flash chromatography.

Reference： [1]Molecules,2014,vol. 19,p. 5599 - 5610

47
[ 24623-24-3 ]
[ 1619903-71-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 24 h / 100 °C / Dean-Stark 2: pyridine hydrogenfluoride; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / dichloromethane / -70 - 20 °C

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2020/260871, 2020, A1

48
[ 24623-24-3 ]
[ 1619903-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 20 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C / Inert atmosphere 4: N,N-dimethyl-formamide / 3 h / 20 °C
	Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C / Inert atmosphere 4: 2-Nitrobenzenesulfonyl chloride; hydrazine hydrate / acetonitrile / 18 h / 0 - 20 °C / Inert atmosphere 5: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 18 h / Reflux; Inert atmosphere 6: triethylamine / tetrahydrofuran / 4 h / 20 °C / Inert atmosphere; Reflux

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[3]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]

49
[ 24623-24-3 ]
[ 1619903-73-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 24 h / 100 °C / Dean-Stark 2: pyridine hydrogenfluoride; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / dichloromethane / -70 - 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2020/260871, 2020, A1

50
[ 24623-24-3 ]
[ 1619903-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C / Inert atmosphere 4: 2-Nitrobenzenesulfonyl chloride; hydrazine hydrate / acetonitrile / 18 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / toluene / 24 h / 100 °C / Dean-Stark 2: pyridine hydrogenfluoride; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / dichloromethane / -70 - 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C 4: hydrazine hydrate / acetonitrile / 72 h / 0 - 20 °C

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2020/260871, 2020, A1

51
[ 24623-24-3 ]
[ 1619903-75-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / toluene / 12 h / Reflux; Dean-Stark 2: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; pyridine hydrogenfluoride / dichloromethane / -70 - 20 °C / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C / Inert atmosphere 4: 2-Nitrobenzenesulfonyl chloride; hydrazine hydrate / acetonitrile / 18 h / 0 - 20 °C / Inert atmosphere 5: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 18 h / Reflux; Inert atmosphere
	Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / toluene / 24 h / 100 °C / Dean-Stark 2: pyridine hydrogenfluoride; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / dichloromethane / -70 - 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / 20 °C 4: hydrazine hydrate / acetonitrile / 72 h / 0 - 20 °C 5: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 90 °C

Reference： [1]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]
[2]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2020/260871, 2020, A1

52
[ 27607-77-8 ]
[ 24623-24-3 ]
[ 1598429-77-6 ]

Yield	Reaction Conditions	Operation in experiment
33%	With triethylamine In dichloromethane at 0℃; for 0.5h;	94.1 Step 1: Trimethyl-[(6-nitro-3H-inden-1-yl)oxy]silane To a solution of 6-nitroindan-1-one (3 g, 16.9 mmol, 1 eq) and TEA (3.43 g, 33.9 mmol, 4.71 ml, 2 eq) in DCM (60 ml) was added trimethylsilyl trifluoromethanesulfonate (5.65 g, 25.4 mmol, 4.59 ml, 1.5 eq) at 0 °C and the mixture was stirred at 0 °C for 0.5 h. The reaction mixture was concentrated under vacuum at 30 °C to obtain a residue which was purified by column chromatography (SiO2, Petroleum ether/AcOEt gradient 200/1 to 10/1) to obtain trimethyl-[(6-nitro-3H-inden-1-yl)oxy]silane (1.4 g, 5.61 mmol, 33 % yield) as a yellow solid.1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J = 2.0 Hz, 1H, Ar), 8.13 (dd, J =2.0, 8.0 Hz, 1H, Ar), 7.50 (d, J = 8.0 Hz, 1H, Ar), 5.59 (t, J = 2.4 Hz, 1H, CH), 3.39 (d, J =2.4 Hz, 2H, CH2), 0.35 (s, 9H, CH3).
33%	With triethylamine In dichloromethane at 0℃; for 0.5h;	94.1 Step 1: Trimethyl-[(6-nitro-3H-inden-1-yl)oxy]silane To a solution of 6-nitroindan-1-one (3 g, 16.9 mmol, 1 eq) and TEA (3.43 g, 33.9 mmol, 4.71 ml, 2 eq) in DCM (60 ml) was added trimethylsilyl trifluoromethanesulfonate (5.65 g, 25.4 mmol, 4.59 ml, 1.5 eq) at 0 °C and the mixture was stirred at 0 °C for 0.5 h. The reaction mixture was concentrated under vacuum at 30 °C to obtain a residue which was purified by column chromatography (SiO2, Petroleum ether/AcOEt gradient 200/1 to 10/1) to obtain trimethyl-[(6-nitro-3H-inden-1-yl)oxy]silane (1.4 g, 5.61 mmol, 33 % yield) as a yellow solid.1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J = 2.0 Hz, 1H, Ar), 8.13 (dd, J =2.0, 8.0 Hz, 1H, Ar), 7.50 (d, J = 8.0 Hz, 1H, Ar), 5.59 (t, J = 2.4 Hz, 1H, CH), 3.39 (d, J =2.4 Hz, 2H, CH2), 0.35 (s, 9H, CH3).
	With triethylamine In toluene at 0℃; for 0.5h;

Reference： [1]Current Patent Assignee: SANOFI - WO2022/23460, 2022, A1 Location in patent: Page/Page column 62
[2]Current Patent Assignee: SANOFI - WO2022/23460, 2022, A1 Location in patent: Page/Page column 62
[3]Zhang, Dongfeng; Li, Peng; Lin, Ziyun; Huang, Haihong [Synthesis, 2014, vol. 46, # 5, p. 613 - 620]

53
[ 24623-24-3 ]
2,2-dihydroxy-5-nitroindane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With selenium(IV) oxide; water In 1,4-dioxane at 180℃; for 0.0833333h; Sealed tube; Microwave irradiation;	General experimental procedure for the synthesis of the ninhydrins (2): General procedure: A sealed-pressurised reaction vessel (5mL) equipped with a magnetic stirrer was charged with indan-1-one (1equiv), selenium dioxide (3.1equiv) and dioxane/water (3mL/0.3mL). It was then irradiated in a Biotage Initiator Microwave synthesizer 2.0 440W with microwave heating to 180°C with a maximum of 400W for 5min. Then, the vessel was rapidly forced-air cooled to room temperature. The mixture was transferred into a round bottom flask, and the vessel washed with acetone. Silica was added to prepare a solid deposit. The volatile solvents were then evaporated in vacuo before purification by flash chromatography (ethyl acetate/cyclohexane) to afford the corresponding ninhydrin.
	With selenium(IV) oxide In 1,4-dioxane; water at 180℃; for 0.0833333h; Microwave irradiation;

Reference： [1]Marminon, Christelle; Nacereddine, Abdelhamid; Bouaziz, Zouhair; Nebois, Pascal; Jose, Joachim; Le Borgne, Marc [Tetrahedron Letters, 2015, vol. 56, # 14, p. 1840 - 1842]
[2]Bouzina, Abdeslem; Berredjem, Malika; Nocentini, Alessio; Bua, Silvia; Bouaziz, Zouhair; Jose, Joachim; Le Borgne, Marc; Marminon, Christelle; Gratteri, Paola; Supuran, Claudiu T. [European Journal of Medicinal Chemistry, 2021, vol. 209]

54
[ 24623-24-3 ]
[ 14548-38-0 ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 13052 - 13057

55
[ 24623-24-3 ]
[ 115262-01-6 ]
2-fluoro-7-nitronaphthalen-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 6-nitroindan-1-one; [bromo(difluoro)methyl]-trimethyl-silane With tetrabutylammomium bromide In toluene at 110℃; for 7h; Sealed tube; Stage #2: With tetrabutyl ammonium fluoride In toluene at 20℃; for 2h;

Reference： [1]Chang, Jian; Song, Xiaoning; Huang, Wanqiao; Zhu, Dongsheng; Wang, Mang [Chemical Communications, 2015, vol. 51, # 84, p. 15362 - 15365]

56
[ 24623-24-3 ]
2-ethoxy-5-nitro-2,3-dihydro-1H-indene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 1 h / 20 °C 2.1: toluene-4-sulfonic acid / toluene / 2 h / Reflux 3.1: diborane; diethyl sulphide / tetrahydrofuran / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium methylate / tetrahydrofuran / 12 h / 20 °C