[ CAS No. 533-37-9 ] {[proInfo.proName]}

Name: 533-37-9|6,7-Dihydro-5H-cyclopenta[b]pyridine|95%
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Quality Control of [ 533-37-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 533-37-9 ]

CAS No. :	533-37-9	MDL No. :	MFCD00005933
Formula :	C₈H₉N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KRNSYSYRLQDHDK-UHFFFAOYSA-N
M.W :	119.16	Pubchem ID :	68292
Synonyms :

Calculated chemistry of [ 533-37-9 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.38
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	36.86
TPSA :	12.89 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.7
Log Po/w (XLOGP3) :	1.54
Log Po/w (WLOGP) :	1.57
Log Po/w (MLOGP) :	1.48
Log Po/w (SILICOS-IT) :	2.69
Consensus Log Po/w :	1.8

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.04
Solubility :	1.08 mg/ml ; 0.00907 mol/l
Class :	Soluble
Log S (Ali) :	-1.42
Solubility :	4.53 mg/ml ; 0.038 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.8
Solubility :	0.187 mg/ml ; 0.00157 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.72

Safety of [ 533-37-9 ]

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

Application In Synthesis of [ 533-37-9 ]

* 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 [ 533-37-9 ]
Downstream synthetic route of [ 533-37-9 ]

[ 533-37-9 ] Synthesis Path-Upstream 1~7

1
[ 533-37-9 ]
[ 253-69-0 ]

Reference： [1] Journal of the Chemical Society, Chemical Communications, 1984, # 5, p. 265 - 266

2
[ 533-37-9 ]
[ 253-72-5 ]

Reference： [1] Journal of the Chemical Society, Chemical Communications, 1984, # 5, p. 265 - 266

3
[ 533-37-9 ]
[ 41598-71-4 ]

Reference： [1] Organic Letters, 2006, vol. 8, # 9, p. 1879 - 1882
[2] Synlett, 2013, vol. 24, # 7, p. 837 - 838
[3] RSC Advances, 2015, vol. 5, # 126, p. 104509 - 104515

4
[ 533-37-9 ]
[ 31170-78-2 ]

Reference： [1] Journal of Organic Chemistry, 1984, vol. 49, # 12, p. 2208 - 2212
[2] Chemische Berichte, 1991, vol. 124, # 3, p. 571 - 576
[3] Synlett, 2013, vol. 24, # 7, p. 837 - 838

5
[ 533-37-9 ]
[ 28566-14-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tert.-butylhydroperoxide; manganese(II) triflate In water at 20℃; for 24 h;	A solution of 0.883 mg of Mn (OTf) 2 (0.5 molpercent), 60 mg of 2,3-cyclopentenopyridine, 0.35 g of 65percent aqueous TBHP and 2.5 ml of water was added successively to a 25 mL round bottom flask, in the air at room temperature for 24 hours, the reaction solution was extracted with 3 x 5 mL of ethyl acetate, the ethyl acetate layer was collected, dried over anhydrous sodium sulfate, filtered and the ethyl acetate was distilled off, using petroleum ether and ethyl acetate in a volume ratio of 5: 1 as eluent, the product of 6,7-dihydro-5H-cyclopenta [b] pyridin-5-one 60.5 mg was obtained as a pale yellow solid in a yield of 91percent by silica gel column chromatography.
63%	With tert.-butylhydroperoxide In water at 60℃; for 12 h;	General procedure: A 15‐mL RBF was charged with substrate (0.5 mmol),MnOx‐N(at)C catalyst (1 mg, pyrolysis at 600 °C) and TBHP (1.5mmol, 65percent in H2O). The flask was then sealed, and the mixturewas heated at 60 °C for 12 h. The reaction was cooled to roomtemperature and diluted with ethyl acetate (4 mL), before beingcentrifuged at 10000 r/min for 1 min to separate the catalyst.The supernatant was removed and the catalyst waswashed with ethyl acetate (5 × 4 mL). The supernatant wassubsequently combined the ethyl acetate wash solutions andevaporated to dryness to give a residue, which was purified byflash column chromatography over silica gel (ethyl acetate/n‐hexane = 1:10, v/v).
35%	With chromium(VI) oxide; sulfuric acid; acetic acid In water at 10℃;	To a stirring solution of 6,7-dihydro-5H-cyclopenta[b]pyridine SM1 (3.83 g, 32 mmol) in HOAc (20 mL) and conc.H2S04 (3.5 ml) was added a solution of Cr03 (6.7 g, 67.2mmol) in 10 mlof HOAc and 2 mL of H20. The temperature was kept below 10 °C during the addition. Afteraddition completed the resultant mixture was stirred at room temperature overnight. The mixture was then poured into crushed ice and treated with NH4OH to pH 11 and extracted with DCM. The organic phase was worked up and purified by silica gel column chromatography eluting with 50percent EtOAc/Hexane to afford compound 1(1.1 g, 35percent). LC-MS: m/z = 134.0[M+H]

18.6%	Stage #1: With chromium(VI) oxide; sulfuric acid; acetic acid In water at 0℃; Stage #2: With ammonia In water at 0℃;	6,7-Dihydro-[1]pyrindin-5-one^xxxi: To a solution of 6,7-dihydro-5H-[1]pyrindine (11.00 g, 92.30 mmol) in 50 mL HOAc and 10 mL H₂SO₄at 0° C. was added CrO₃(18.50 g, 0.19 mol) dissolved in 6 mL H₂O and 30 mL HOAc. The resulting mixture was stirred overnight, cooled on ice and basified with NH₄OH to pH 11. The mixture was extracted with CHCl₃(3.x.250 mL), and the combined organic extracts were washed with H₂O (3.x.100 mL), brine (1.x.200 mL), dried over MgSO₄and concentrated. Purification by column chromatography using hexane:EtOAc (2:3) as the eluant gave 2.29 g (18.6percent) of the title compound. Spectroscopic data: ¹H NMR (300 MHz, CDCl₃) δ 2.77-2.83 (m, 2H), 3.27-3.33 (m, 2H), 7.34 (dd, J=7.62 Hz, 1H), 8.03 (dd, J=7.62 Hz, 1H), 8.82 (dd, J=4.69 Hz, 1H).
5 g	at 15 - 25℃;	Step A 6,7-dihydro-5H-cyclopenta[b]pyridin-5-one (24a) To a solution of 6,7-dihydro-5H-cyclopenta[b]pyridine (10 g, 83.99 mmol)[comercially available from Sigma-Aldrich, St. Louis, MO, USA] in a mixture of acetic acid and sulfuric acid (5: 1, 60 mL), was added CrO₃(16.7 g, 167.1 mmol) dissolved in acetic acid (30 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was cooled to 0°C and the pH was adjusted to ~ (approximately) 11 using ammonium hydroxide and then extracted with dichloro-methane. The combined organic layers were washed with water and brine, and dried over anhydrous Na₂SO₄. The solvent was evaporated under reduced pressure and the crude mass was purified by column chromatography using 50percent ethyl acetate in petroleum ether (v/v) to afford 24a (5 g). Molecular Formula: C₈H₇NO; LC-MS purity: 94.1percent; Expected: 133; Observed: 134.2 (M+1).

Reference： [1] Patent: CN105669548, 2016, A, . Location in patent: Paragraph 0027; 0028
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 15, p. 4078 - 4082[3] Angew. Chem., 2018, vol. 130, # 15, p. 4142 - 4146,5
[4] Chinese Journal of Catalysis, 2016, vol. 37, # 8, p. 1216 - 1221
[5] Organic Letters, 2018, vol. 20, # 7, p. 1987 - 1990
[6] Patent: WO2016/44770, 2016, A1, . Location in patent: Page/Page column 571
[7] Patent: US2008/255239, 2008, A1, . Location in patent: Page/Page column 33
[8] Journal of Medicinal Chemistry, 1991, vol. 34, # 9, p. 2736 - 2746
[9] Patent: WO2015/50798, 2015, A1, . Location in patent: Page/Page column 69

6
[ 533-37-9 ]
[ 54664-55-0 ]

Reference： [1] Patent: US2014/200216, 2014, A1,
[2] Patent: US2014/200227, 2014, A1,
[3] Patent: WO2016/168098, 2016, A1,
[4] Patent: WO2016/196244, 2016, A1,

7
[ 533-37-9 ]
[ 80756-85-0 ]
[ 957-68-6 ]
[ 98753-19-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	for 0.0666667 h; Microwave irradiation	The method for synthesizing cefpirome sulfuric acid by microwave method according to the present invention,Comprising the steps of:(1) 7-aminocephalosporanic acid (2.72 g, 7-ACA, Compound I, MW272, 0.01 mol) and AE-activity(AEMA, Compound VII, MW 350, 0.011 mol) was mixed and homogeneously ground.(Compound IV, MW 119, 0.011 mol) and concentrated sulfuric acid (10.88 g, 98percent by weight) were added to the solution, followed by the addition of 2,30 g of 2,3-cyclopentenopyridine.(2) 300W microwave reaction for 1 minute,450W microwave reaction for 1 minute,750W microwave reaction for 2 minutes;(3) After completion of the reaction,The reaction residue was added to 29.92 g of deionized water,Mixing and filtering,Take filtrate,The solvent was removed,A white solid,50 & lt; 0 & gt; C for 4 hours under vacuum,That is to get the cefpirome sulfuric acid 5.09g (MW514),Yield 99.0percentPurity 99.9percent or more.

Reference： [1] Patent: CN105646542, 2016, A, . Location in patent: Paragraph 0027; 0040; 0041; 0042; 0043; 0044; 0045

[ 533-37-9 ] Synthesis Path-Downstream 1~47

1
[ 533-37-9 ]
[ 90685-58-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With dihydrogen peroxide; acetic acid; In water; at 70℃;	Example 9: 4-({(5R,6R)-6-[(3R)-3-aminopiperidin-1-yl]-6,7-dihydro-5H- cyclopenta[b]pyridin-5-yl}oxy)-3-chlorobenzonitrile (compound 137); 9.1 6,7-dihydro-5H-cyclopenta[ib]pyridine 1 -oxide; To a solution of 6,7-dihydro-5H-cyclopenta[ifc>]pyridine (5g, 1 eq.) in acetic acid (25 ml) is added H202 (2.51 g, 50% in water, 0.88 eq.). The solution is warmed to 70 C. After 3 hours, further H202 (2.51 g, 50% in water, 0.88 eq.) is added and the mixture is stirred at 70 ^ over night. After cooling down, the solvent is evaporated under reduced pressure and water (20 ml) is added to the residue. Solid K2C03 is then added to have pH=9. The aqueous layer is separated and extracted three times with CH2CI2. The combined organic layers are dried over anhydrous Na2S04, filtered and evaporated under reduced pressure to yield 5.55g (97%) of the desired compound, used in the next step without further purification.
97%		9.1 <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> 1-oxide To a solution of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (5g, 1 eq.) in acetic acid (25 ml) is added H2O2 (2.51g, 50% in water, 0.88 eq.). The solution is warmed to 70C. After 3 hours, further H2O2 (2.51 g, 50% in water, 0.88 eq.) is added and the mixture is stirred at 70C over night. After cooling down, the solvent is evaporated under reduced pressure and water (20 ml) is added to the residue. Solid K2CO3 is then added to have pH=9. The aqueous layer is separated and extracted three times with CH2Cl2. The combined organic layers are dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to yield 5.55g (97%) of the desired compound, used in the next step without further purification.
89%		Example 49; Synthesis of Compound (II-7); Step (1): Compound 7a ? Compound 7b; Compound 7a (8.34 g, 70 mmol) was dissolved in methylene chloride (80 mL), and then m-chloroperbenzoic acid (18.58 g, 70 mmol) was added thereto, subsequently stirring at 0C for 45 minutes. To the reaction solution was added an aqueous solution of sodium hydrogen sulfite (8.01 g, 77 mmol), and then adjusted to pH 10 with aqueous 2 N sodium hydroxide solution. After extraction from the aqueous layer with chloroform and tetrahydrofuran, the organic layer was dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and then the solvent was evaporated under reduced pressure to yield Compound 7b as a gray solid (8.46 g, 89% yield). 1H-NMR (CDCl3) delta(delta) : 8.05 (1H, d, J = 6.3 Hz), 7.14-7.05 (2H, m), 3.18 (2H, t, J = 7.6 Hz), 3.03 (2H, t, J = 7.6 Hz), 2.28-2.10 (2H, m).

87.3%		<strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (1.4g, 11.7mmol) was added to a dichloromethane (40 mL), and added with stirring 3-chloroperbenzoic acid (77% mass fraction , 5.25g, 23.4mmol), the reaction was heated to reflux for 2 hours, cooled to room temperature, calcium hydroxide (3.47g, 46.8mmol), stirred for 16 hours, suction filtered, the filter cake washed with dichloromethane, and the combined organic phases, concentrated in vacuo to give the title compound (1.38g, yield 87.3%).
79%	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃; for 2h;	m-Chloroperbenzoic acid (10.0 g, 44.6 mmol) was added slowly to a mixture of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (5.0 g, 42 mmol DCM (50 mL). The reaction mixture was stirred at room temperature for 2 h. The resulting solution was washed with aq. Na2S2O3 (50 mL) and aq. 1 M NaOH (50 mL). The aqueous layer was extracted with DCM (70 mL*5). The combined organic extracts were dried, filtered and concentrated under reduced pressure to give the sub-title compound (4.5 g, 79%). LCMS calc. for C8H10NO (M+H)+: m/z=136.3. Found: 136.2
79%	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20 - 30℃; for 2h;	mCPBA (10.0 g, 44.6 mmol) was added slowly to a mixture of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (from Aldrich, 5.0 g, 42 mmol) in DCM (50 mL). The reaction mixture was stirred at room temperature for 2 h. The solution was then washed with aq. Na2S2O3 (50 mL) and 1 M NaOH (50 mL). The aqueous layer was extracted with DCM (5×70 mL). The combined organic layers were dried, filtered and concentrated under reduced pressure to give the sub-title compound (4.5 g, 79%). LCMS calc. for C8H10NO (M+H)+: m/z=136.1. Found: 136.2.
79%	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃; for 2h;	mCPBA (10.0 g, 44.6 mmol) was added slowly to a mixture of 6,7-dihydro-5H- cyclopenta[Z>]pyridine (from Aldrich, 5.0 g, 42 mmol) in DCM (50 mL). The reaction mixture was stirred at room temperature for 2 h. The solution was then washed with aqueous Na2S203 (50 mL) and 1 M NaOH (50 mL). The aqueous layer was extracted with DCM (5 x 70 mL). The combined organic layers were dried, filtered and concentrated under reduced pressure to give the sub-title compound (4.5 g, 79%). LCMS calc. for CsHioNO (M+H)+: m/z = 136.1. Found: 136.2.
57%		Intermediate 3 can also be prepared as follows : 174g 3-chloroperoxybenzoic acid (mCPBA) (1.6eq) was added to IL ethyl acetate (EtOAc) (6mL/g mCPBA). The reaction mixture (mixture A) was stirred for 10 minutesat ambient temperature. 76g (0.641mol) was dissolved in 375ml EtOAc (5mL/g). This solution was added dropwise to reaction mixture A over 20 minutes keeping the temperature constant at 1O0C. The mixture was stirred overnight at ambient temperature. The reaction mixture was washed two times with a solution of 27g NaHSO3 (0.25mols/mol mCPBA) in 30OmL H2O (1 lmL/g NaHSO3) and the water layers were combined. The organic layer (+ intermediate layer) was extracted with 30OmL H2O (4mL/g). The two layers were separated. The 2 water layers were joined (pH: +/- 5) and neutralized with Na2CO3 until pH: 8. The product was extracted from the water layer by continuous extraction with dichloromethane for one night. The two layers were separated. The organic layer was dried with MgSO4. The MgSO4 was filtered off and the filtrate was concentrated under reduced pressure. Yield: 49.5g (57%) of intermediate a (off-white product)
		To a solution of 25.0 g (209.8 mmol) of the pyridine compound 1 in200 mL of dichloromethane (DCM) at 0 0C was added m-chloroperbenzoic acid (m- CPBA) portionwise. The resulting mixture was stirred at 0 C for 2 hours, warmed to room temperature and stirred for an additional 7 hours. After this period, a saturated solution of 50 mL of aqueous Na2S2O3 was added and the mixture was stirred for 0.5 hour. A saturated solution of 50 mL of aqueous NaHCO3 was added slowly to this mixture. The layers were separated, and the aqueous layer was extracted with 500 mL of DCM. The organic layers were combined and washed with 100 mL of brine solution and dried with anhydrous Na2SO4. The organic layer was then concentrated to give 21.3 g of the N-oxide 2 as a white solid.
	With dihydrogen peroxide; methyltrioxorhenium(VII); In dichloromethane; at 20℃; for 16h;	Step 1 : 6,7-dihydro-5H-cyclopenta[blpyridine-l -oxide To a solution of 6,7-dihydro-5H- cyclopenta[b]pyridine (50 g, 420 mmol) and methyl trioxorhenium(VII) (0.3 g, 1.204 mmol) in DCM (400 mL) was added hydrogen peroxide (86 mL, 839 mmol, 30%wt). After addition, the mixture was stirred at 20C for 16h. TLC showed SM was consumed. The mixture was quenched with sodium sulfite (about 75 g solid) portion-wise at ice bath and extracted with CHC13 (500 mL x 3). The combined organic phases were dried over Na2S04, filtered and concentrated to give the title compound which was used for the next step without further purification.
1610 mg	With 3-chloro-benzenecarboperoxoic acid; In ethyl acetate; for 4h;	3-Chloroperbenzoic acid, technical grade ~ 70 % (6740 mg; 27.34 mmol) was dissolved in EA (40 mL) and the solution was treated dropwise with a solution of <strong>[533-37-9]2,3-cyclopentenopyridine</strong> (2036 mg; 17.09 mmol) in EA (10 mL) over 10 min. The reaction solution was stirred for 4 h. The reaction solution was successively washed with a solution of NaHSC>3 (700 mg) in H20 (10 mL) twice and with H20 (10 mL). The aqueous layers were combined and then neutralized with Na2C03 until pH about 8. The product was finally extracted with DCM (5 x 20 mL). The combined organic layers were dried over MgSO i, filtered and concentrated to dryness to afford <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong>-l-oxide (1610 mg) as an off- white solid. (0723) MS m/z (+ESI): 136.2 [M+H]+.

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 3266 - 3267
[2]Synlett,2013,vol. 24,p. 837 - 838
[3]RSC Advances,2015,vol. 5,p. 104509 - 104515
[4]Patent: WO2011/107474,2011,A1 .Location in patent: Page/Page column 45
[5]Patent: EP2368876,2011,A1 .Location in patent: Page/Page column 24
[6]Advanced Synthesis and Catalysis,2007,vol. 349,p. 2345 - 2352
[7]Journal of the Chemical Society. Chemical communications,1984,p. 265 - 266
[8]Patent: EP2341053,2011,A1 .Location in patent: Page/Page column 99-101
[9]Journal of Organic Chemistry,1998,vol. 63,p. 1740 - 1741
[10]Patent: CN105884752,2016,A .Location in patent: Paragraph 0155; 0156; 0157
[11]Chemical Communications,2015,vol. 51,p. 11293 - 11296
[12]Patent: US2014/200216,2014,A1 .Location in patent: Paragraph 0530; 0531
[13]Patent: US2014/200227,2014,A1 .Location in patent: Paragraph 0639; 0640
[14]Patent: WO2016/196244,2016,A1 .Location in patent: Page/Page column 195
[15]Angewandte Chemie - International Edition,2006,vol. 45,p. 5194 - 5197
[16]Patent: WO2009/19274,2009,A1 .Location in patent: Page/Page column 32
[17]Journal of the American Chemical Society,1958,vol. 80,p. 6254,6255
[18]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 453 - 458
[19]Organic Letters,2006,vol. 8,p. 1879 - 1882
[20]Patent: WO2007/28638,2007,A1 .Location in patent: Page/Page column 73
[21]Patent: WO2016/168098,2016,A1 .Location in patent: Page/Page column 38
[22]Journal of Organic Chemistry,2017,vol. 82,p. 2059 - 2066
[23]Patent: WO2019/72978,2019,A1 .Location in patent: Page/Page column 75
[24]Angewandte Chemie - International Edition,2020,vol. 59,p. 281 - 285
Angew. Chem.,2020,vol. 132,p. 287 - 291,5

2
[ 56946-65-7 ]
[ 533-37-9 ]

Reference： [1]Journal of the American Chemical Society,1958,vol. 80,p. 6254,6255
[2]Helvetica Chimica Acta,1945,vol. 28,p. 1684,1690

3
[ 7148-07-4 ]
[ 289-96-3 ]
[ 533-37-9 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2492 - 2494
[2]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292
[3]Liebigs Annalen der Chemie,1985,p. 1732 - 1751

4
[ 533-37-9 ]
[ 100-52-7 ]
[ 74701-35-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	With acetic anhydride; for 24h;Heating / reflux;	15 g (0.125 mol) of <strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong>, 20.1 g (0.19 mol) of freshly destilled benzaldehyde and 24.5 g (0.24 mol) of acetic acid anhydride were heated under reflux for 24 h. The reaction mixture was evaporated, the residual oil dissolved in methylene chloride, the solution extracted with 1N NaOH solution, and the organic phase dried and evaporated. The residue was destilled under reduced pressure to give 19.3 g (75%) of the title compound. Boiling point (0.013 mbar): 150C. Melting point: 72C.

Reference： [1]Chemische Berichte,1991,vol. 124,p. 571 - 576
[2]Patent: EP1388342,2004,A1 .Location in patent: Page/Page column 21

5
[ 533-37-9 ]
[ 100-52-7 ]
[ 74701-35-2 ]

Yield	Reaction Conditions	Operation in experiment
67.7%	With acetic anhydride; at 140℃;	Synthesis of 1-(6,7-dihydro-5H-[1]pyrindin-7-yl)-3-(2-fluoro-ethyl)-urea The title compound was generated from commercially available <strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong> according to the chemistry described in the scheme above. The intermediates 5-benzylidene-<strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong>, 5,6-dihydro-[1]pyrindin-7-one, 4-nitro-indan-1-one, 5,6-dihydro-[1]pyrindin-7-one O-methyl-oxime and 6,7-dihydro-5H-[1]pyrindin-7-ylamine were isolated and characterized.5-Benzylidene-6,7-dihydro-5H-[1]pyindinexxx: A sample of <strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong> (14.51 g, 0.12 mol), benzaldehyde (13.6 mL, 0.13 mol) and acetic anhydride (22.0 mL, 0.23 mol) was heated at 140 C. overnight. After cooling down to room temperature, the resulting mixture was extracted with CH2Cl2 (3×300 mL). The combined organic extracts were washed with brine (1×200 mL), dried over MgSO4 and concentrated. Purification by column chromatography using hex: Et2O (4:1) as eluant afforded 12.18 g (67.7% yield) of the title compound. Spectroscopic data: 1H NMR (300 MHz, CDCl3) delta 3.06-3.21 (m, 4H), 7.06-7.15 (m, 1H), 7.22-7.30 (m, 1H), 7.34-7.43 (m, 2H), 7.51-7.60 (m, 4H), 8.45-8.50 (m, 1H).

Reference： [1]Tetrahedron,2007,vol. 63,p. 2426 - 2431
[2]Journal of Organic Chemistry,1984,vol. 49,p. 2208 - 2212
[3]Patent: US2008/255239,2008,A1 .Location in patent: Page/Page column 32
[4]Journal of Materials Chemistry,2007,vol. 17,p. 841 - 849
[5]Archiv der Pharmazie,1980,vol. 313,p. 375 - 377
[6]Journal of Medicinal Chemistry,2008,vol. 51,p. 392 - 395

6
[ 533-37-9 ]
[ 74-88-4 ]
[ 54664-57-2 ]

Reference： [1]Journal of the American Chemical Society,1981,vol. 103,p. 1525 - 1533
[2]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 453 - 458

7
[ 533-37-9 ]
[ 28566-14-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tert.-butylhydroperoxide; manganese(II) triflate; In water; at 20℃; for 24h;	A solution of 0.883 mg of Mn (OTf) 2 (0.5 mol%), 60 mg of 2,3-cyclopentenopyridine, 0.35 g of 65% aqueous TBHP and 2.5 ml of water was added successively to a 25 mL round bottom flask, in the air at room temperature for 24 hours, the reaction solution was extracted with 3 x 5 mL of ethyl acetate, the ethyl acetate layer was collected, dried over anhydrous sodium sulfate, filtered and the ethyl acetate was distilled off, using petroleum ether and ethyl acetate in a volume ratio of 5: 1 as eluent, the product of 6,7-dihydro-5H-cyclopenta [b] pyridin-5-one 60.5 mg was obtained as a pale yellow solid in a yield of 91% by silica gel column chromatography.
63%	With tert.-butylhydroperoxide; In water; at 60℃; for 12h;	General procedure: A 15-mL RBF was charged with substrate (0.5 mmol),MnOx-N(at)C catalyst (1 mg, pyrolysis at 600 C) and TBHP (1.5mmol, 65% in H2O). The flask was then sealed, and the mixturewas heated at 60 C for 12 h. The reaction was cooled to roomtemperature and diluted with ethyl acetate (4 mL), before beingcentrifuged at 10000 r/min for 1 min to separate the catalyst.The supernatant was removed and the catalyst waswashed with ethyl acetate (5 × 4 mL). The supernatant wassubsequently combined the ethyl acetate wash solutions andevaporated to dryness to give a residue, which was purified byflash column chromatography over silica gel (ethyl acetate/n-hexane = 1:10, v/v).
35%	With chromium(VI) oxide; sulfuric acid; acetic acid; In water; at 10℃;	To a stirring solution of 6,7-dihydro-5H-cyclopenta[b]pyridine SM1 (3.83 g, 32 mmol) in HOAc (20 mL) and conc.H2S04 (3.5 ml) was added a solution of Cr03 (6.7 g, 67.2mmol) in 10 mlof HOAc and 2 mL of H20. The temperature was kept below 10 C during the addition. Afteraddition completed the resultant mixture was stirred at room temperature overnight. The mixture was then poured into crushed ice and treated with NH4OH to pH 11 and extracted with DCM. The organic phase was worked up and purified by silica gel column chromatography eluting with 50% EtOAc/Hexane to afford compound 1(1.1 g, 35%). LC-MS: m/z = 134.0[M+H]

34%	With potassium permanganate; magnesium sulfate; In water; tert-butyl alcohol; at 20 - 30℃; for 5h;	A 50 L glass reactor was charged KMn04 (1857 g, 11748.0 mmol). Water (35 L) was charged to the reaction mass. The reaction mass was stirred for 30 min (Note: KMn04 completely soluble in water). Another 100 L reactor was charged 6,7-dihydro-5H-cyclopenta[b]pyridine (700 g, 5874 mmol) in /<? /7-butanol (17.5 L) at 25 °C. MgS04 (1414 g, 11748 mmol) was charged to the above reaction mixture. The reaction mixture was cooled to 20-25 °C with ice water. KMn04 solution was added dropwise for 2 h (Note: Slight exothermic was observed and temperature maintained below 30 °C with ice water). The reaction mixture was maintained at 30 °C for 3 h. Progress of the reaction was monitored by TLC/LCMS (50percent EtOAc in pet ether, Rf value of the product is 0.3). After completion of the reaction, EtOAc was added to the above reaction mixture and the resulting mixture stirred at 25 °C for 10 min. The aqueous and EtOAc layers were separated. The aqueous layer was again extracted with EtOAc. The combined organic layers were washed with DM water and the organic layer was separated. The combined organic layers were washed with sodium chloride solution. The EtOAc layer was dried over anhydrous Na2S04 and filtered.EtOAc was evaporated below 40-45 °C under vacuum. After completion of evaporation, the brown color liquid was subjected to drying by rotary evaporation at 40-45 °C for 1.0 h. Drying was terminated and a brown color gum was obtained (600 g). A chromatography column was packed with silica gel (4.0 kg, 100-200 mesh). The crude compound was dissolved in DCM and adsorbed onto silica gel (1.0 kg) and loaded onto the column. The mobile phase was run with n- hexane (25 L) followed by increasing the polarity from 2-10percent EtOAc in hexane (100 L). All pure fractions (TLC) were collected and concentrated under reduced pressure at 40-45 °C to give 6,7-dihydro-5H-cyclopenta[b]pyridin-5-one as a brown thick gum (270 g, yield 34percent). 1 H NMR (400 MHz, CDCE) d 8.45 (dd, / = 1.5, 4.5 Hz, 1H), 8.02 (dd, / = 2.0, 8.0 Hz, 1H), 7.46-7.44 (m, 1H), 3.19-3.16 (m, 2H), 2.73-2.71 (m, 2H). LCMS (ES) m/z 134.07 [M+H]+.
18.6%		6,7-Dihydro-[1]pyrindin-5-onexxxi: To a solution of 6,7-dihydro-5H-[1]pyrindine (11.00 g, 92.30 mmol) in 50 mL HOAc and 10 mL H2SO4 at 0 C. was added CrO3 (18.50 g, 0.19 mol) dissolved in 6 mL H2O and 30 mL HOAc. The resulting mixture was stirred overnight, cooled on ice and basified with NH4OH to pH 11. The mixture was extracted with CHCl3 (3×250 mL), and the combined organic extracts were washed with H2O (3×100 mL), brine (1×200 mL), dried over MgSO4 and concentrated. Purification by column chromatography using hexane:EtOAc (2:3) as the eluant gave 2.29 g (18.6%) of the title compound. Spectroscopic data: 1H NMR (300 MHz, CDCl3) delta 2.77-2.83 (m, 2H), 3.27-3.33 (m, 2H), 7.34 (dd, J=7.62 Hz, 1H), 8.03 (dd, J=7.62 Hz, 1H), 8.82 (dd, J=4.69 Hz, 1H).
5 g	With chromium(VI) oxide; sulfuric acid; acetic acid; at 15 - 25℃;	Step A 6,7-dihydro-5H-cyclopenta[b]pyridin-5-one (24a)To a solution of 6,7-dihydro-5H-cyclopenta[b]pyridine (10 g, 83.99 mmol)[comercially available from Sigma-Aldrich, St. Louis, MO, USA] in a mixture of acetic acid and sulfuric acid (5: 1, 60 mL), was added CrO3(16.7 g, 167.1 mmol) dissolved in acetic acid (30 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was cooled to 0C and the pH was adjusted to ~ (approximately) 11 using ammonium hydroxide and then extracted with dichloro-methane. The combined organic layers were washed with water and brine, and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure and the crude mass was purified by column chromatography using 50% ethyl acetate in petroleum ether (v/v) to afford 24a (5 g). Molecular Formula: C8H7NO; LC-MS purity: 94.1%; Expected: 133; Observed: 134.2 (M+1).

Reference： [1]Patent: CN105669548,2016,A .Location in patent: Paragraph 0027; 0028
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 4078 - 4082
Angew. Chem.,2018,vol. 130,p. 4142 - 4146,5
[3]Cuihua Xuebao/Chinese Journal of Catalysis,2016,vol. 37,p. 1216 - 1221
[4]Organic Letters,2018,vol. 20,p. 1987 - 1990
[5]Chemical Communications,2019,vol. 55,p. 937 - 940
[6]Chemical Communications,2019,vol. 55,p. 7840 - 7843
[7]Patent: WO2016/44770,2016,A1 .Location in patent: Page/Page column 571
[8]Patent: WO2019/149959,2019,A1 .Location in patent: Page/Page column 63; 83; 84
[9]Patent: US2008/255239,2008,A1 .Location in patent: Page/Page column 33
[10]Journal of Medicinal Chemistry,1991,vol. 34,p. 2736 - 2746
[11]Patent: WO2015/50798,2015,A1 .Location in patent: Page/Page column 69

8
[ 98-03-3 ]
[ 533-37-9 ]
5,7-dihydro-7-(2-thienylmethylene)-5H-1-pyrindine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In acetic anhydride;	EXAMPLE XIII 5,7 -Dihydro-7-(2-thienylmethylene)-5H-1-pyrindine A solution of <strong>[533-37-9]2,3-cyclopentenopyridine</strong> (5.96 g) in acetic anhydride (20 ml) is treated with 2-thiophenecarboxaldehyde (6.06 g) and heated at gentle reflux temperature for 24 hours. Acetic anhydride is evaporated, the residue is digested with 5 percent sodium bicarbonate and the residual oil is extracted into ethyl acetate. Purification on silica gel (9:1 Skelly B:ethyl acetate) gives pure 5,7-dihydro-7-(2-thienylmethylene)-5H-1-pyrindine (2.85 g). Crystallization from hexane provides the analytical sample, m.p. 60 C.-61 C. IR (mull) 1620, 1560, 1405, 1240, 1215, 1195, 1155, 1095, 880, 855, 820, and 780 cm-1. NMR (CDCl3)delta 2.97 (s, 4, CH2), 6.87-7.57 (m, 5, ArH), 7.73 (s, 1, CH=), 8.43 (d, J=5 Hz, 1, ArH4). MS m/e 213 (M+), 212 (base peak), 211, 210, 178, 167, 105, 69, and 32. Anal. Calcd. for C13 H11 NS: C 73.20; H, 5.20; N, 6.57; S, 15.04. Found: C, 72.98; H, 5.19; N, 6.60; S, 14.56.

Reference： [1]Patent: US4576949,1986,A

9
[ 120-92-3 ]
[ 2450-71-7 ]
[ 533-37-9 ]

Reference： [1]Journal of Organic Chemistry,2003,vol. 68,p. 6959 - 6966

10
[ 533-37-9 ]
[ 13671-00-6 ]
7-fluorobenzo[c]cyclopentano[i,j]quinolizin-6-one [ No CAS ]
7-fluoro-6-hydroxy-4,5-dihydro-10b-azonia-acephenanthrylene; chloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 962 - 972

11
[ 533-37-9 ]
[ 912277-45-3 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 5194 - 5197
[2]RSC Advances,2015,vol. 5,p. 104509 - 104515
[3]RSC Advances,2015,vol. 5,p. 104509 - 104515
[4]RSC Advances,2015,vol. 5,p. 104509 - 104515
[5]RSC Advances,2015,vol. 5,p. 104509 - 104515

12
[ 533-37-9 ]
(S)-6,7-dihydro-5H-[1]pyrindin-7-ol [ No CAS ]

13
[ 533-37-9 ]
[ 41598-71-4 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 1879 - 1882
[2]Synlett,2013,vol. 24,p. 837 - 838
[3]RSC Advances,2015,vol. 5,p. 104509 - 104515

14
[ 533-37-9 ]
[ 253-72-5 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 265 - 266

15
[ 533-37-9 ]
[ 270-92-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 94 percent / 30percent H₂O₂ / acetic acid / 12 h / 75 °C 2: 77 percent / 3.5 h / 100 °C 3: conc. H₂SO₄ / 2 h / 125 °C

Reference： [1]Giam, C. S.; Ambrozich, Deborah [Journal of the Chemical Society. Chemical communications, 1984, # 5, p. 265 - 266]

16
[ 533-37-9 ]
[ 90685-59-9 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 265 - 266
[2]Journal of the American Chemical Society,1958,vol. 80,p. 6254,6255
[3]Patent: WO2011/107474,2011,A1
[4]Patent: EP2368876,2011,A1
[5]Synlett,2013,vol. 24,p. 837 - 838
[6]Chemical Communications,2015,vol. 51,p. 11293 - 11296
[7]RSC Advances,2015,vol. 5,p. 104509 - 104515
[8]Patent: CN105884752,2016,A

17
[ 533-37-9 ]
[ 31170-78-2 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 2208 - 2212
[2]Chemische Berichte,1991,vol. 124,p. 571 - 576
[3]Synlett,2013,vol. 24,p. 837 - 838

19
[ 533-37-9 ]
[ 23808-43-7 ]
[ 214612-77-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In tetrahydrofuran; hexane; water;	Example 255 Synthesis of 7-[4-hydroxy-1-(4-fluorophenethyl)piperidin-4-yl]-5.6-dihydro-7H-pyrindine 6,7-Dihydro-5H-cyclopenta[B]pyridine (1.00 g, CAS Registry No. 533-37-9) was dissolved in tetrahydrofuran (15 ml). Under a stream of nitrogen, a 1.6 M solution (5.8 ml) of n-butyllithium in hexane was added dropwise into the resultant solution while cooling to -55 C. or below. After stirring for 5 min, a solution of 1-(4-fluorophenethyl)-4-piperidone (2.04 g) in tetrahydrofuran (10 ml) was added dropwise thereinto at the same temperature over 20 min. After stirring for 30 min, the reaction solution was allowed to warm to room temperature again and water was added thereto. Then it was extracted with ethyl acetate and the organic layer was washed with brine and dried over magnesium sulfate. After evaporating the solvent, the resulting residue (3.17 g) was purified by silica gel column chromatography (methanol/methylene chloride system) to give the title compound (600 mg) as a slight brown oil. 1H-NMR (400 MHz, CDCl3): delta(ppm) 1.72-2.08(4H, m), 2.22-3.10(12H, m), 3.37(1H, d, J=9.5Hz), 5.81(1H, br-s), 6.93-7.01(2H, m), 7.08(1H, dd, J=8.0, 5.5Hz), 7.12-7.20(2H, m), 7.33(1H, d, J=8.0Hz), 8.28(1H, d, J=5.5Hz). FAB-Mass: 341(MH+).

Reference： [1]Patent: US2002/19531,2002,A1

20
[ 533-37-9 ]
3-bromo-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bromine;AlCl3;	A. 3-Bromo-<strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong> To a solution of <strong>[533-37-9]6,7-dihydro-5H-[1]pyrindine</strong> (20 gm) and AlCl3 (56 gm) at 100 C. was added 10 mL of bromine over 2 hours, stirred an additional 15 minutes, cooled to room temperature, and poured over ice. The pH of the reaction was adjusted until it was basic with NaOH and then celite and ether were added and the mixture filtered. The filter cake was washed well with additional ether and the filtrate was extracted from the aqueous layer. The ether layer was washed with saturated aqueous NaCl solution, dried over MgSO4, filtered, and concentrated to dryness. The residue was chromatographed on silica gel using 10:1 hexane/ethyl acetate as the eluant to yield 4 gm of compound. 1 H NMR (CDCl3): d 8.35 (s, 1 H), 7.60 (s, 1 H), 2.90 (m, 4 H), 2.10 (m, 2 H).

Reference： [1]Patent: US5338740,1994,A

21
[ 533-37-9 ]
[ 936103-42-3 ]

Yield	Reaction Conditions	Operation in experiment
		400 ml of water and 123 g (1.032 mol) <strong>[533-37-9]2,3-cyclopentenopyridine</strong> was put in a 1000-ml three-necked flask equipped with a bubbler, a thermometer and a mechanical stirrer. 46.6 g (0.413 mol) of hydroxylamine-o-sulphonic acid was then added in small portions, and the mixture was refluxed for 18 hours. The reaction mixture was cooled to room temperature and 74.2 g (0.537 mol) of potassium carbonate was gently added. The resultant mixture was stirred for 30 minutes. The aqueous phase was washed with 4×200 ml of ethyl acetate, and the aqueous phase was co-evaporated with 2-propanol to obtain a chestnut-brown solid, which was taken up in 400 ml of ethanol to remove the salts. The brown ethanol solution was put in a 2-liter three-necked flask equipped with an isobaric funnel; while stirring, at -70 C. 67.5 ml (0.516 mol) of hydriodic acid was added dropwise. At the end of discharge, the temperature was allowed to return to zero degrees and the insoluble beige product was drained on a No. 3 frit. This solid was washed with 3×150 ml of isopropyl ether and dried under vacuum in the presence of P2O5 for 12 hours. 27.7 g of a beige solid corresponding to the expected compound was recovered. NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and mass spectrometry were consistent with the expected structure. The expected cation [C8H11N2]+ was mainly detected at m/z,ESP+=135. Detection of I- ions in electrospray was negative.
	With potassium carbonate; hydroxylamine-O-sulfonic acid; In water; at 20℃; for 18.5h;Heating / reflux;	400 ml of water and 123 g (1.032 mol) of <strong>[533-37-9]2,3-cyclopentenopyridine</strong> were put in a 1000 ml three-necked flask equipped with a bulb condenser, a thermometer and a mechanical stirrer, then 46.6 g (0.413 mol) of hydroxylamine-o-sulphonic acid was added in small portions and reflux was carried out for 18 hours. The reaction mixture was cooled to room temperature and 74.2 g (0.537 mol) of potassium carbonate was gently added, then stirred for 30 minutes. The aqueous phase was washed with 4×200 ml of ethyl acetate, then co-evaporated with 2-propanol to obtain a chestnut-brown solid; this was taken up in 400 ml of ethanol to remove the salts. The brown ethanol solution was put in a 2-litre three-necked flask equipped with an isobaric funnel and cooled to -50 C. with stirring. Then added, dropwise, were 67.5 ml (0.516 mol) of hydriodic acid. At the end of addition, the temperature was returned to zero degrees and the beige insoluble matter was drained on a frit. This solid was washed with 3×150 ml of isopropyl ether. After drying under vacuum in the presence of P2O5 for 12 hours, 27.7 g of a beige solid corresponding to the expected compound was recovered. NMR analyses (1H 400 MHz and 13C 100.61 MHz DMSO d6) and mass spectrometry were consistent with the expected structure. The expected cation [C8H11N2]+ was mainly detected at m/z, ESP+=135. Detection of I- ions in electrospray was negative.

Reference： [1]Patent: US2007/136959,2007,A1 .Location in patent: Page/Page column 26
[2]Patent: US2007/143935,2007,A1 .Location in patent: Page/Page column 44

22
[ 533-37-9 ]
[ 124-38-9 ]
[ 76-05-1 ]
[ 1356932-89-2 ]

Yield	Reaction Conditions	Operation in experiment
50%		To a cooled (0 C.) solution of 16 mL (25 mmol) of a 1.6 M n-butyl lithium solution in hexane was added 3.9 mL (25 mmol) of N,N,N',N'-tetramethylethylenediamine followed by a solution of 3.0 mL (25 mmol) of <strong>[533-37-9]2,3-cyclopentenopyridine</strong> in 5 mL of anhydrous tetrahydrofuran. The resulting mixture was allowed to warm to ambient temperature over 15 min and then anhydrous carbon dioxide gas was bubbled through the reaction mixture for 1 h. The solid precipitate was next filtered and the crude solid purified by reverse phase HPLC (TMC Pro-Pac C18; 0-40% 0.01% trifluoroacetic acid in acetonitrile/0.01% trifluoroacetic acid in water gradient) to give the title compound as a yellow solid (2.0 g, 50%). LC-MS: m/z (ES) 164.1 (MH)+.
		To a cooled (0C) solution of 16 mL (25 mmol) of a 1.6 M «-butyl lithium solution in hexanes was added 3.9 mL (25 mmol) of N, N, N', N'-teitauamethylethylenediamine followed by a solution of 3.0 mL (25 mmol) of 2,3,-cyclopentenopyridine in 5 mL of anhydrous tetrahydrofuran. The resulting mixture was allowed to warm to ambient temperature over 15 min and then anhydrous carbon dioxide gas was bubbled through the reaction mixture for 1 h. The solid precipitate was next filtered and the crude solid purified by reverse phase HPLC (TMC Pro-Pac C 18; 0-40% 0.1% trifluoroacetic acid in acetonitrile/ 0.1% trifluoroacetic acid in water gradient) to give the title compound as a yellow solid. LC-MS: m/z (ES) 164.1 (MH)+.

Reference： [1]Patent: US2009/253705,2009,A1 .Location in patent: Page/Page column 47
[2]Patent: WO2009/123870,2009,A1 .Location in patent: Page/Page column 35

23
[ 533-37-9 ]
[ 64-19-7 ]
[ 90685-59-9 ]

Reference： [1]Chemical Communications,2010,vol. 46,p. 7259 - 7261

24
[ 533-37-9 ]
[ 270-91-7 ]
[ 270-92-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: dihydrogen peroxide; acetic acid / water / 70 °C 2.1: water / 4 h / 20 - 100 °C 3.1: sulfuric acid / 20 - 130 °C 3.2: Cooling with ice
	Multi-step reaction with 3 steps 1.1: dihydrogen peroxide / water; acetic acid / 70 °C 1.2: pH 9 2.1: water / 20 - 100 °C 3.1: sulfuric acid / 20 - 130 °C

Reference： [1]Current Patent Assignee: SANOFI - WO2011/107474, 2011, A1
[2]Current Patent Assignee: SANOFI - EP2368876, 2011, A1

25
[ 533-37-9 ]
[ 623-49-4 ]
[ 1350468-67-5 ]

Yield	Reaction Conditions	Operation in experiment
74%		Preparation 8: Ethyl 7-(Hvdroxymethyl)-6,7-dihvdro-5H-cvclopenta[blpyridine-7- carboxylate; Step A: Diethyl 5,6-Dihvdro-7H-cvclopentarblpyridine-7,7-dicarboxylate To a solution of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (1 .49 mL, 12.7 mmol) in 2-MeTHF (32 mL), cooled in a dry ice/acetone bath, was added TMEDA (2.87 mL, 19.1 mmol) and ferf-butyllithium (1 1 .3 mL, 19.1 mmol, 1.7 M in pentane), affording a dark brown solution. This solution was transferred to a separate flask, which contained a solution of ethyl cyanoformate (3.92 mL, 39.5 mmol) in 2-MeTHF (32 mL), also cooled in a dry ice/acetone bath. The reaction mixture was allowed to warm to room temperature, slowly. After 20 min., the reaction was quenched with water and then extracted with EtOAc. Brine was added to mitigate the formation of an emulsion. The organic layer was isolated, washed with 1 .0 M aq. HCI and brine, dried over Na2S04, andconcentrated to dryness. The residue was purified by MPLC (gradient from pure heptane to 7:3 EtOAc/heptane) to give the title compound (2.49 g, 74 % yield). LCMS (ESI) m/z: 264.3 [M+H] (75 %). 1H NMR (400 MHz, CDCI3) delta 1 .27 (t, J=7.1 Hz, 6 H), 2.78-2.84 (m, 2 H), 2.98-3.04 (m, 2 H), 4.20-4.33 (m, 4 H), 7.16 (dd, J=7.7, 4.8 Hz, 1 H), 7.53-7.58 (m, 1 H), 8.51 (m, J=4.9, 1 .6, 0.9, 0.9 Hz, 1 H).

Reference： [1]Patent: WO2011/145022,2011,A1 .Location in patent: Page/Page column 57

26
[ 533-37-9 ]
[ 74-85-1 ]
[ 30564-54-6 ]

Reference： [1]Journal of the American Chemical Society,2011,vol. 133,p. 18086 - 18089

27
[ 533-37-9 ]
(anti)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol [ No CAS ]
(syn)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%		Example 185 (anti)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol To a solution of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (157 mg, 1.315 mmol) in THF (10 mL) at -78 C. was added n-BuLi (0.986 mL, 1.577 mmol) carefully under N2. The mixture was stirred at -20 C. for 30 minutes. A solution of Example 179D (300 mg, 1.315 mmol) in THF (5 mL) was added slowly and the mixture was warmed up to -20 C. and stirred for 60 minutes. Saturated NH4Cl solution (60 mL) was added, then the mixture was extracted with ethyl acetate (75 mL). The organic layer was washed with brine (175 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by Prep-HPLC (Column: Hanbon Benetnach C18 10 mum, 20250 mm, eluent: water (10 mM NH4HCO3): acetonitrile, 55-85%) to afford Example 185 (32 mg, yield: 7%) and Example 186 (22 mg, yield: 5%). LC-MS: 348(M+H). 1H NMR (400 MHz, CDCl3): delta 8.33 (d, J=4.8 Hz, 1H), 7.60 (s, 1H), 7.54 (d, J=7.6 Hz, 1H), 7.41-7.48 (m, 3H), 7.00 (t, J=6.2 Hz, 1H), 4.77 (s, 1H), 3.06 (t, J=8.6 Hz, 1H), 2.60-2.75 (m, 4H), 2.34-2.43 (m, 2H), 1.87-2.12 (m, 2H), 1.52-1.67 (m, 2H). Example 186 [1832] (syn)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol [1833] The title compound was the second isomer isolated along with Example 185. LC-MS: 348(M+H). 1H NMR (400 MHz, CDCl3): delta 8.20 (s, 1H), 7.69-7.73 (m, 2H), 7.43-7.47 (m, 3H), 6.99-7.05 (m, 2H), 4.21 (d, J=9.2 Hz, 1H), 2.71-2.86 (m, 3H), 2.32-2.50 (m, 4H), 2.01-2.06 (m, 2H), 1.73-1.98 (m, 2H).

Reference： [1]Patent: US2013/131036,2013,A1 .Location in patent: Paragraph 1830; 1831; 1832; 1833

28
[ 533-37-9 ]
[ 1432492-71-1 ]
(anti)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol [ No CAS ]
(syn)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{1-[3-(trifluoromethyl)-phenyl]cyclobutyl}methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%; 5%		General procedure: (anti)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl{ l-[3-(trifluoromethyl)- phenyl]cyclobutyl}methanol[356] To a solution of <strong>[533-37-9]6,7-dihydro-5H-cyclopenta[b]pyridine</strong> (157 mg, 1.315 mmol) in THF (10 mL) at -78C was added n-BuLi (0.986 mL, 1.577 mmol) carefully under N2. The mixture was stirred at -20 C for 30 minutes. A solution of Example 179D (300 mg, 1.315 mmol) in THF (5 mL) was added slowly and the mixture was warmed up to -20 C and stirred for 60 minutes. Saturated NH4C1 solution (60 mL) was added, then the mixture was extracted with ethyl acetate (75 mL). The organic layer was washed with brine (1 x 75 mL), dried over Na2S04, filtered and concentrated. The residue was purified by Prep- HPLC (Column: Hanbon Benetnach C18 10 ???, 20x250 mm, eluent: water (10 mM NH4HC03) : acetonitrile, 55-85 %) to afford Example 185 (32 mg, yield: 7 %) and Example 186 (22 mg, yield: 5 %). LC-MS: 348(M+H). 'H NMR (400MHZ, CDC13): ? 8.33 (d, J=4.8Hz,lH), 7.60 (s, IH), 7.54 (d, J=7.6Hz, IH), 7.41-7.48 (m, 3H), 7.00 (t, J=6.2Hz, IH), 4.77 (s,lH), 3.06 (t, J=8.6Hz, IH), 2.60-2.75 (m, 4H), 2.34-2.43 (m, 2H), 1.87-2.12 (m, 2H), 1.52-1.67 (m, 2H).

Reference： [1]Patent: WO2013/62966,2013,A2 .Location in patent: Paragraph 355; 356

29
[ 96-41-3 ]
[ 156-87-6 ]
[ 533-37-9 ]

Reference： [1]ACS Catalysis,2016,vol. 6,p. 1247 - 1253
[2]Chemical Communications,2013,vol. 49,p. 6632 - 6634

30
[ 533-37-9 ]
[ 1065609-70-2 ]

Yield	Reaction Conditions	Operation in experiment
		Step A: 6,7-Dihydro-SH-cyclopenta[b]pyridin-5-ol: To a solution of6,7-dihydro-5Hcyclopenta[b]pyridine (5.0 g, 42 mmol) and MgS04 (10 g, 84 mmol) in acetone (250 mL) wasadded a solution ofKMn04 (13 g, 84 mmol) in water (500 mL) at 60 degrees. The mixture wasallowed to stir for 30 minutes at 60 C. IPA was slowly added to quench excess KMn04. Thereaction was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and pumped on a high vacuum pump to ensure complete removal of water. The residuewas dissolved in ethanol (200 mL), and cooled with an ice bath. To this solution was slowlyadded NaBH4 (3.2 g, 84 mmol). When TLC showed complete reduction, water was added toquench excess NaBH4. Ethanol was removed on a rotavapor. The crude material was dissolvedin EtOAc, washed with aq. NaHC03, dried over sodium sulfate, and purified by MPLC (MeOH - DCM: 0-7 %). The title compound was collected. LC-MS (IE, mlz): 136 [M +It.

Reference： [1]Patent: WO2013/28474,2013,A1 .Location in patent: Page/Page column 94
[2]Patent: WO2019/149959,2019,A1

31
[ 533-37-9 ]
[ 54664-55-0 ]

Reference： [1]Patent: US2014/200216,2014,A1
[2]Patent: US2014/200227,2014,A1
[3]Patent: WO2016/168098,2016,A1
[4]Patent: WO2016/196244,2016,A1

32
[ 533-37-9 ]
[ 592-41-6 ]
2-(hexan-2-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]

Reference： [1]Inorganic Chemistry,2018,vol. 57,p. 11788 - 11800
[2]Journal of the American Chemical Society,2014,vol. 136,p. 12209 - 12212

33
[ 533-37-9 ]
[ 5664-17-5 ]
C₁₇H₂₃N [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 8394 - 8398

34
[ 300-57-2 ]
[ 533-37-9 ]
C₁₇H₁₉N [ No CAS ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 17104 - 17107

35
[ 533-37-9 ]
[ 108-70-3 ]
3-(2,4,6-trichlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 375 - 379

36
[ 120-92-3 ]
[ 540-61-4 ]
[ 533-37-9 ]

Yield	Reaction Conditions	Operation in experiment
89%Chromat.	With C19H15AuClN2PS; silver trifluoromethanesulfonate; In ethanol; at 120℃; for 5h;	General procedure: In this part, the developed Au(I)-complexes of Au-L1 and Au-L2were applied as the pre-catalysts for the one-pot reaction of 1,3-diphenylacetone and propargylamine for the efficient synthesis ofpyridine derivatives (Table 3).Without the involvement of any auxiliary additive, under theselected reaction conditions, over Au-L1 (2.5 mol%) the conversionsof 1,3-diphenylacetone were steadily increased as the reaction tem-perature increased from 70 to 140C along with 100% selectivityto 2-benzyl-3-phenylpyridine (Entries 1-4). And 90% yield of 2-benzyl-3-phenylpyridine was obtained at 120C after screeningethanol as the optimal solvent (Entry 4, 95%). In contrast, underthe same reaction conditions, Au-L2 exhibited much lower activ-ity towards the reaction with the product yield of 53% (Entry10). The involvement of AgOTf (silver trifluoromethanesulfonate)in Au-L1 or Au-L2 as a scavenger of Cl-ligand for the benefi-cial formation of P-Au+species [39,40] showed negligible effecton their catalytic performance (Entries 12 and 13). While N-methylimidazole was added additionally in Au-L2, the yield of2-benzyl-3-phenylpyridine was improved up to 75%, but still muchlower than that obtained over Au-L1 (Entry 11 vs 3).As verified in Fig. 2 the coordination abilities of the phosphinefragments in L1 and L2 are very similar (L1,1J31P-77Se= 758 Hz;L2,1J31P-77Se= 761 Hz). Hence, the different catalytic performanceof Au-L1 and Au-L2 towards above reaction was not due to thechange of the coordinating ability of the involved phosphines in L1and L2. Reasonably, the presence of N-containing moiety in themode of the intramolecular incorporation in Au-L1 contributedto the high efficiency of this sequential condensation/annulationreaction (Entry 3). Au-L1 was able to act as a unique bifunctionalcatalyst in combination of the phosphine-ligated Au-complex (asthe transition metal catalyst) and the Lewis base organocatalystderived from imidazolyl group (Scheme 4). Due to the rigid andbulky backbone of thiophenylimidazolyl moiety, the incorporatedimidazolyl, which was located remotely to the phosphine frag-ment without competitive N-hemilabile ligation to Au-center, justplayed the role of Lewis base to effectively catalyze the con-densation of 1,3-diphenylacetone with propargylamine for theformation of the imino intermediate with enamino tautomer (A).Since the exclusive alkynophilicity of the Au-complex catalyst[16,17], carbon-carbon triple bond was activated by P-Au+speciesthrough the -coordination, and then attached by the carbon ofthe enamino moiety through regioselective 6-endo-dig intramolec-ular nucleophilic addition to give dehydropyridine intermediate(B). The latter undergoes auto-oxidation reaction to afford thepyridine derivatives. In contrast, Au-L2 without the incorporatedLewis base exhibited lower activity with the product yield of 53%(Entry 10). Although, the sequential reaction efficiency over themechanical mixtures of Au-L2 and N-methylimidazole could beimproved to some extent (75% yield, Entry 11), it was still lowerthan that over Au-L1. These results further confirmed that theintramolecular combination of the Au-complex unit with the imi-dazolyl ring by the stable chemical bonds in Au-L1 was not theresult of the simple mechanical mixture of the phosphine-ligatedAu-complex of Au-L2 and the Lewis base of N-methylimidazole.In the mechanical mixtures of Au-L2 and N-methylimidazole, theauxiliary N-methylimidazole as an N-containing donor with thefree mobility unavoidably competed with the alkyne substrate tocoordinate to Au-center, leading to the depressed condensation ofketone and amine over the basic imidazole catalyst and the subse-quent activation of alkyne for annulation over Au-L2 catalyst.The generality of Au-L1 as the bi-functional catalyst for the syn-theses of the pyridine derivatives was examined on the differentscope of carbonyl compounds. As shown in Table 4, under theselected reaction conditions, Au-L1 universally exhibited accept-able catalytic activities towards the sequential transformation.The steric and electronic effects of the applied ketones had theobvious influence on the reaction rate. The cycloalkanones withexposed C O groups gave rise to the formation of 2,3-fusedpyridines with the good isolated yields (Entries 1-4, 53-89%),in which cyclopentanone with the least steric hindrance corre-sponded to the best yield of cyclopentylpyridine (Entry 3, 89%).The reaction of the less activated aryl/(heteroaryl)-methyl ketoneswith propargylamine led to the formation of 2-aryl(heteroaryl)-substituted pyridines with the moderate yields (Entries 5-9), whichrepresented an alternative to the Suzuki cross-coupling protocol[41]. The involved substitutes with intensive electron withdraw-ing effect (such as -Br/-F/pyridinyl) dramatically slowed down thereaction rate (Entries 6-9). Under the prolonged reaction time(10 h), the aliphatic aldehydes in general gave 3-alkyl-substitutedpyridines with 92% yield of 3-p...

Reference： [1]Journal of Molecular Catalysis A: Chemical,2016,vol. 424,p. 323 - 330

37
[ 533-37-9 ]
[ 80756-85-0 ]
[ 957-68-6 ]
[ 98753-19-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sulfuric acid; for 0.0666667h;Microwave irradiation;	The method for synthesizing cefpirome sulfuric acid by microwave method according to the present invention,Comprising the steps of:(1) 7-aminocephalosporanic acid (2.72 g, 7-ACA, Compound I, MW272, 0.01 mol) and AE-activity(AEMA, Compound VII, MW 350, 0.011 mol) was mixed and homogeneously ground.(Compound IV, MW 119, 0.011 mol) and concentrated sulfuric acid (10.88 g, 98% by weight) were added to the solution, followed by the addition of 2,30 g of 2,3-cyclopentenopyridine.(2) 300W microwave reaction for 1 minute,450W microwave reaction for 1 minute,750W microwave reaction for 2 minutes;(3) After completion of the reaction,The reaction residue was added to 29.92 g of deionized water,Mixing and filtering,Take filtrate,The solvent was removed,A white solid,50 & lt; 0 & gt; C for 4 hours under vacuum,That is to get the cefpirome sulfuric acid 5.09g (MW514),Yield 99.0%Purity 99.9% or more.

Reference： [1]Patent: CN105646542,2016,A .Location in patent: Paragraph 0027; 0040; 0041; 0042; 0043; 0044; 0045

38
propynylamine [ No CAS ]
[ 120-92-3 ]
[ 533-37-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	at 70℃; for 5h;Autoclave; Ionic liquid; Microwave irradiation;	The specific steps are as follows: 6,7-dihydro-5H-cyclopenta [b] pyridine pyridine Synthesis: microwave sealed autoclave 42g (0.5mol) of cyclopentanone, 35.7g of propargylamine (0.65mol) , BMImBF4 / BMImZnCl3 catalyst system 181g (catalyst 18g, accounting for 10%), the reaction was stirred under microwave irradiation at 70 C for 5h. The reaction was completed, cooled to room temperature, extracted with ethyl acetate 150mL, the combined organic layer was dried over anhydrous magnesium sulfate; filtered,The solvent was distilled off, the solvent was recovered, the temperature was further increased and the fraction was collected to obtain 44 g of a 6,7-dihydro-5H-cyclopenta [b] pyridine product in an amount of 99.2%. The yield was 74%.
72%	With activated carbon supported ferric nitrate; In toluene; at 120℃; under 3750.38 Torr; for 8h;Autoclave; Inert atmosphere;	Specific steps are as follows: Catalyst synthesis: To 500mL reaction flask was added 100g ferric nitrate, added 150mL ethanol, 50g water, 50g granular activated carbon, soak 0.5h at room temperature, and then heated to reflux for 2h. Suction filtration, air-dried, and then dried in a blast oven 110 ~ 130 C 2h, 150 ~ 180 C drying 2h, get 80g activated carbon supported ferric nitrate catalyst. Synthesis of 6,7-Dihydro-5H-cyclopenta[b]pyridine: Into a 1000 mL autoclave, 101 g (1.2 mol) of cyclopentanone, 55 g (1.0 mol) of propynyl amine,16g, toluene 400mL, nitrogen replacement air 3 times, under nitrogen protection, slowly open the stirring, heated to an internal temperature of 120 C, adjust the pressure to 0.5Mpa, incubated for 8 hours. Sample detection to complete reaction of propynyl amine. After the completion of the reaction to stop heating and naturally cooled to room temperature, filtered, the filter cake as a catalyst, rinsed with solvent drying and re-use. The filtrate water 50ml, dropping ammonia to adjust the pH to 8. The organic layer was separated and the organic layer was dried over anhydrous magnesium sulfate. Filtration, the filtrate vacuum distillation, solvent recovery 320g, and then increased temperature distillation, collecting fractions, that is, the content of 99.5% of the product 86g, a yield of 72%.

Reference： [1]Patent: CN106316952,2017,A .Location in patent: Paragraph 0013; 0014; 0016; 0018; 0020
[2]Patent: CN106316951,2017,A .Location in patent: Paragraph 0014; 0015; 0016; 0017; 0018; 0019; 0020; 0021

39
[ 117890-55-8 ]
[ 533-37-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen; In ethanol;Large scale;	35 kg of ethanol was put into the hydrogenation kettle.Catalyst 1,Put the second step intermediate 19kg with stirring.Controlling the temperature to react between certain temperatures,Until the hydrogen is no longer absorbed, after the hydrogenation is completed, the material is discharged.The catalyst was recovered and the ethanol was concentrated to dryness under reduced pressure.

Reference： [1]Patent: CN108395402,2018,A .Location in patent: Paragraph 0005; 0006

40
[ 533-37-9 ]
[ 62-23-7 ]
6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl 4-nitrobenzoate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 3074 - 3082

41
[ 533-37-9 ]
[ 78183-15-0 ]

Reference： [1]Patent: WO2019/72978,2019,A1

42
[ 533-37-9 ]
C₂₂H₂₂ClN₅O₆S₂ [ No CAS ]
C₃₀H₃₁N₆O₆S₂⁽¹⁺⁾*I^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.21%		7.7 g of the activator sodium iodide was added to 380 ml of acetone and stirred until it was dissolved. Compound A was added and stirred at room temperature for 1.0 h.12.0 ml of 2,3-cyclopentenepyridine was added dropwise, and solid precipitation was carried out after completion of the dropwise addition. The reaction was further continued for 2.5 hours, and 25.8 g of Compound B was obtained by filtration, and the yield was 80.21%.

Reference： [1]Patent: CN109651400,2019,A .Location in patent: Paragraph 0035; 0038-0039; 0042; 0045-0046

43
[ 109-76-2 ]
[ 120-92-3 ]
[ 533-37-9 ]

Yield	Reaction Conditions	Operation in experiment
12%	With oxygen; copper diacetate; palladium diacetate; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 16h;	General procedure: Pd(OAc)2 (9.00 mg, 0.04 mmol) and () (14.6 mg, 0.08 mmol) were placed in a screw-top test tube, and a solution of 3,4-dihydronaphthalen-l(2H)-one (8) (58.6 mg, 0.40 mmol) in DMSO (0.08 mL) was added at room temperature. Then 1,3-diaminopropane (6) (0.10 mL, 1.20 mmol) was added to the reaction mixture. The test tube was filled with oxygen and then the resulting mixture was stirred at 120 C for 16 h. After cooling down to room temperature, the palladium residue was removed by filtering through Celite. The organic solvent was removed under reduced pressure, and then the reaction was quenched by addition of 10% aqueous NH3 solution. The solution was extracted three times with a 4:1 mixture of hexane and EtOAc. The combined organic layers were washed with saturated aqueous NaCl solution, dried over anhydrous Na2S04, and filtered through Celite. The filtrate was concentrated to afford 5,6-dihydrobenzo[h]quinoline (9) (51.1 mg, 70%) as a yellow oil.

Reference： [1]Heterocycles,2019,vol. 99,p. 1315 - 1321

44
[ 533-37-9 ]
[ 358-23-6 ]
[ 2408844-78-8 ]
[ 2378344-98-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 2,3-cyclopentenopyridine; trifluoromethylsulfonic anhydride; 5-(diphenylphosphaneyl)-2-(trifluoromethyl)pyridine In dichloromethane at -50℃; for 1h; Inert atmosphere; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -78 - 20℃; for 0.333333 - 0.5h; Inert atmosphere;

Reference： [1]Alegre-Requena, Juan V.; Levy, Jeffrey N.; Liu, Renrong; McNally, Andrew; Paton, Robert S. [Journal of the American Chemical Society, 2020, vol. 142, # 25, p. 11295 - 11305]

45
[ 533-37-9 ]
[ 912277-45-3 ]
(S)-6,7-dihydro-5H-[1]pyrindin-7-ol [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 5194 - 5197

46
[ 533-37-9 ]
[ 1379342-51-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: aluminum (III) chloride; bromine / 2.25 h / 100 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 20 °C 3: 90 °C 4: water; potassium carbonate / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - EP3782995, 2021, A1

47
[ 533-37-9 ]
[ 1336955-89-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: aluminum (III) chloride; bromine / 2.25 h / 100 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 20 °C 3: 90 °C 4: water; potassium carbonate / methanol / 2 h / 20 °C 5: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 2 h / 20 °C

Reference： [1]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - EP3782995, 2021, A1

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

[ CAS No. 533-37-9 ] {[proInfo.proName]}

Quality Control of [ 533-37-9 ]

Related Doc. of [ 533-37-9 ]

Product Details of [ 533-37-9 ]

Calculated chemistry of [ 533-37-9 ]

Physicochemical Properties

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Water Solubility

Medicinal Chemistry

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[ 533-37-9 ] Synthesis Path-Upstream 1~7

[ 533-37-9 ] Synthesis Path-Downstream 1~47

Related Parent Nucleus of [ 533-37-9 ]

Aliphatic Heterocycles

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[ 533-37-9 ]