Name: 5650-51-1|5,6-Dihydro-4H-cyclopenta[b]thiophen-4-one|95%
Brand: Ambeed
SKU: A612666
Rating: 91 (40 reviews)

1
[ 5650-51-1 ]
[ 298-12-4 ]
[4-Oxo-4,6-dihydro-cyclopenta[b]thiophen-(5E)-ylidene]-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sulfuric acid In 1,4-dioxane for 3h; Heating;

Reference： [1]Ravina, Enrique; Fueyo, Javier; Masaguer, Christian F.; Negreira, Jesus; Cid, Jose; Loza, Isabel; Honrubia, Angeles; Tristan, Helena; Ferreiro, Tomas G.; Fontenla, Jose A.; Rosa, Elizabeth; Calleja, Jose M.; De Ceballos, Maria L. [Chemical and Pharmaceutical Bulletin, 1996, vol. 44, # 3, p. 534 - 541]

2
[ 849769-14-8 ]
[ 5650-51-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With 2,2,6,6-tetramethyl-piperidine; bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; Tri(p-tolyl)phosphine In toluene at 90℃; for 3.5h;

Reference： [1]Yamabe, Hokuto; Mizuno, Akio; Kusama, Hiroyuki; Iwasawa, Nobuharu [Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3248 - 3249]

3
[ 188290-36-0 ]
[ 5650-51-1 ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: N,N-Dimethylacrylamide With trifluoromethylsulfonic anhydride In 1,1-dichloroethane at 0℃; for 0.416667h; Stage #2: thiophene In 1,1-dichloroethane for 7h; Heating / reflux;	23.a Over a period of 10 minutes a solution of triflic anhydride (84.7g, 0.30 mol) in DCE (300 mL) was added to a cold solution of N,N-dimethylacrylamide (29,8 g, 0.30 mol) in DCE (270OmL). The mixture was stirred for 15 minutes at O0C. A solution of thiophene (25,3 g, 0.30 mol) was added and the mixture was refluxed for seven hours. A solution of potassium carbonate (15Og in 200OmL of water) was added. The mixture was extracted two times with DCM dried over sodium sulphate and evaporated under reduced pressure. The compound was purified by silica gel chromatography with ethyl acetate/hexane. Yield: 36.8 g = 53% 1H-NMR CDCl3 7.32 (dd, IH), 7.14 (dd, IH), 3.20 (m, 2H), 3.00 (m, 2H)

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/84688, 2006, A1 Location in patent: Page/Page column 74-75

4
[ 5650-51-1 ]
[ 905842-31-1 ]

Yield	Reaction Conditions	Operation in experiment
81.6%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one With potassium hydroxide; [bis(acetoxy)iodo]benzene In methanol at 0 - 20℃; Stage #2: With hydrogenchloride In 1,4-dioxane; water at 20℃; for 2h;	23.b 5-Hydroxy-5,6-dihydro-cyclopenta[b ] thiophen-4-one (23b) 5,6-dihydro-cyclopenta[δ]thiophen-4-one (36.8 g, 0.266 mol) in MeOH (100OmL) was added at about 5°C to a solution of potassium hydroxide 85% (52.7 g, 0.798 mol) in MeOH (50OmL). Between 0°C and 5°C iodobenzene diacetate (94.4g, 0.293 mol) was added in portions and the mixture was allowed to come to room temperature. The mixture was stirred overnight at room temperature. The mixture was evaporated and a 20% solution of potassium carbonate (50OmL) was added. The mixture was extracted for times with DCM dried with sodium sulphate and evaporated under reduced pressure. The residue was dissolved in 1,4-dioxane (400 mL) and water (150 mL) and concentrated hydrochloric acid (15OmL) was added. The mixture was stirred for two hours at room temperature. The mixture was neutralized by the addition of potassium carbonate and extracted four times with dichloromethane. The organic phase was dried with sodium sulphate and evaporated under reduced pressure. The product was crystallized with ether ethyl acetate and the mother liquid was purified by silica gel chromatography with toluene and acetone. Yield: 33.5 g = 81,6%. 1H-NMR CDCl3 δ 7.36 (dd, IH), 7.18 (d, IH), 4.76 (m, IH), 3.64 (m, 2H), 3.10 (m, IH)

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/84688, 2006, A1 Location in patent: Page/Page column 75

5
[ 5650-51-1 ]
5,6-dihydrocyclopenta[b]thiophen-4-one oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride In methanol; ethyl acetate	25.i i i 5,6-Dihydrocyclopenta[b]thiophen-4-one Oxime A mixture of 5,6-dihydrocyclopenta[b]thiophen-4-one (11.7 g, 85 mmol, [Russ. J. Org. Chem. 1998, 34(7), 1019]), hydroxylamine hydrochloride (9.03 g, 0.13 mol) and methanol (150 mL) was heated at 70° C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (500 mL), washed with water, dried with sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (1:3 ethyl acetate/hexanes) to afford the title compound (10.7 g). 1H NMR (400 MHz, DMSO-d6) δ 10.42 (s, 1H), 7.56 (d, 1H), 7.00 (d, 1H), 3.12 (m, 2H), 3.02 (m, 2H); MSCI: m/z 154 (MH+).

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/114666, 2003, A1

6
[ 188290-36-0 ]
[ 2680-03-7 ]
[ 5650-51-1 ]

Yield	Reaction Conditions	Operation in experiment
39%	With trifluoromethylsulfonic anhydride In 1,2-dichloro-ethane for 15h; Heating / reflux;	R.68 Reference Example 68 5,6-dihydro-4H-cyclopenta[b]thien-4-one To a solution of N,N-dimethylacrylamide (6.6 g, 71 mmol) in dichloroethane (400 ml) was gradually added dropwise a solution of trifluoromethanesulfonic acid anhydride (20 g, 71 mmol) in dichloroethane (50 mL) under ice-cooling. A solution of thiophene (6.0 g, 71 mmol) in dichloroethane (50 mL) was added to the mixture, and the mixture was heated under reflux for 15 hrs. The reaction mixture was concentrated under reduced pressure, saturated sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9:5 to 4:1) to give the title compound (3.8 g, yield 39%) as a white powder. 1H NMR (CDCl3) δ 3.00 (2H, t, J=4.7 Hz), 3.19 (2H, t, J=4.7 Hz), 7.15 (1H, d, J=5.1 Hz), 7.31 (1H, d, J=5.1 Hz).
34%	With trifluoromethylsulfonic anhydride In 1,2-dichloro-ethane for 7h; Reflux;

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1559422, 2005, A1 Location in patent: Page/Page column 81
[2]Duan, Ya-Nan; Cui, Li-Qian; Zuo, Lin-Hong; Zhang, Chi [Chemistry - A European Journal, 2015, vol. 21, # 37, p. 13052 - 13057]

7
[ 5928-51-8 ]
[ 5650-51-1 ]

Reference： [1]Chemical Papers,2013,vol. 67,p. 59 - 65,7

8
[ 5650-51-1 ]
[ 954238-22-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;

Reference： [1]MacHara, Ales; Svoboda, Jiri [Chemical Papers, 2013, vol. 67, # 1, p. 59 - 65,7]

9
[ 614-98-2 ]
[ 5650-51-1 ]
[ 1469858-26-1 ]

Yield	Reaction Conditions	Operation in experiment
27%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	17 5,6-Dihydro-cyclopenta[b]thiophen-4-one in 40 mL of THF was treated with NaH (60 percent, 0.8 g, 36.25 mmol). After the addition of Furan-3-carboxylic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(Furan-3-carbonyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (0.9 g, 38 mmol) as brown solid in 27% yield.
27%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	17 6-furan-3-yl-4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a]5-dihydro-cyclopenta [b] thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 0.8 g, 36.25 mmol). After the addition of the furan-3-carboxylic acid ethyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (70 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. (Furan-3-carbonyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (0.9 g, 38 mmol) was recrystallized from ethanol and recrystallized from ethanol to obtain the resulting precipitate Of the brown solid in 27% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0217
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 52

10
[ 5650-51-1 ]
[ 5798-76-5 ]
[ 1469858-09-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 6h;	1 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 1.45 g, 36.3 mmol). After the addition of 4-Bromo-benzoic acid phenyl ester (6.7 g, 24.2 mmol), the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was extracted with ethyl acetate. The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(4-Bromo-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (5.4 g, 16.9 mmol) as yellow solid in 70% yield.
70%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	1 A solution of 5,6-dihydro-cyclopentadienyl [b] thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 1.45 g, 36.3 mmol).After the addition of 4-bromo-benzoate phenyl ester (6.7 g, 24.2 mmol)The reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours.The solution was cooled to room temperature and poured into water.The resulting mixture was acidified with concentrated HCl and extracted with ethyl acetate. The organic layer was collected, treated with brine, dried over MgSO4 (s), and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (4-bromo-phenyl) -5,6-dihydro-cyclopentadiene and [b] thiophen-4-one as a yellow solid 5.4 g, 16.9 mmol) in 70% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0159
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 32

11
[ 614-18-6 ]
[ 5650-51-1 ]
[ 1469858-25-0 ]

Yield	Reaction Conditions	Operation in experiment
35%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	16 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 1.45 g, 36.25 mmol). After the addition of Nicotinic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(Pyridine-3-carbonyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.23 g, 5 mmol) as red solid in 35% yield.
35%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	16 (5.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 1.45 g, 36.25 mmol) in 5 mL of 5-dihydro-cyclopenta [b] thiophen-4-one. After addition of the nicotinic acid ethyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding red solid 5- (pyridine-3-carbonyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (1.23 g , 5 mmol) in 35% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0214
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 51

12
[ 5650-51-1 ]
[ 1985-12-2 ]
[ 1469857-31-5 ]

Yield	Reaction Conditions	Operation in experiment
32%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Bromophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	20 Example 20 (4-bromophenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Bromo-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4-Bromo-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 32% yield. [0229] MS (ESI) m/z: 332.0 (M+H)+. 1H NMR (CDCl3): 7.36-7.32 (m, 3H), 7.19 (d, 1H), 6.89 (d, 2H), 3.46 (s, 2H).
32%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Bromophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	20 Example 20(4-bromo-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) amine 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-bromo-4-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4-bromo-phenyl) - (4,7-dihydro-1, Cyclopentadiene [a] cyclopentan-6-yl) -amine in 32% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0228-0229
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 55; 56

13
[ 5650-51-1 ]
[ 6590-96-1 ]
[ 1469857-32-6 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2, 4-dichlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	21 Example 21 (2,4-dichlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 2,4-Dichloro-1-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (2,4-Dichloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 33% yield. [0231] MS (ESI) m/z: 322.0 (M+H)+. 1H NMR (DMSO-d6): 7.92 (s, 1H), 7.57 (d, 1H), 7.50 (d, 1H), 7.25-7.21 (m, 2H), 3.51 (s, 2H).
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2, 4-dichlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	21 Example 21(2,4-dichloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopropan-6-yl) amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 2,4-dichloro-1-isothiocyanato (Benzene) (1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product (2,4-dichloro-phenyl) - (4,7-dihydro-1-thio-4,5 - diazo-cyclopentadienyl [a] cyclopentan-6-yl) -amine in 33% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0230-0231
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 56; 57

14
[ 5650-51-1 ]
[ 2059-76-9 ]
[ 1469857-33-7 ]

Yield	Reaction Conditions	Operation in experiment
32%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-iodophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	22 Example 22 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(4-iodophenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Iodo-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-iodo-phenyl)-amine as brown solid in 32% yield. [0233] MS (ESI) m/z: 380.0 (M+H)+. 1H NMR (DMSO-d6): 12.10 (s, 1H), 8.57 (br, 1H), 7.56-7.47 (m, 3H), 7.18 (d, 2H), 6.72 (d, 1H), 3.50 (s, 2H).
32%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-iodophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	22 Example 22(4-iodo-phenyl) -amine (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentadiene 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-iodo-4-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (4-iodo-phenyl) -amine in 32% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0232-0233
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 57

15
[ 5650-51-1 ]
[ 2284-20-0 ]
[ 1469857-34-8 ]

Yield	Reaction Conditions	Operation in experiment
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Methoxyphenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	23 Example 23 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(4-methoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-4-methoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-methoxy-phenyl)-amine as brown solid in 34% yield. [0235] MS (ESI) m/z: 284.0 (M+H)+. 1H NMR (DMSO-d6): 11.88 (s, 1H), 8.04 (s, 1H), 7.54 (d, 1H), 7.17 (d, 1H), 6.82 (d, 2H), 3.69 (s, 3H), 3.43 (s, 2H).
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Methoxyphenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	23 Example 23(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (4-methoxy-phenyl) amine 5,6-dihydro-cyclopenta [b] thien-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-isothiocyanato-4-methoxy- Benzene (1.5 g, 7.2 mmol)A solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol) was added dropwise at room temperature. The reaction mixture was stirred for 8 hours.Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture,And then heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (4-methoxy-phenyl) -amine in 34% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0234-0235
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 57; 58

16
[ 5650-51-1 ]
[ 33904-04-0 ]
[ 1469857-35-9 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-isothiocyanato-1,2-dimethoxybenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	24 Example 24 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(3,4-dimethoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 4-Isothiocyanato-1,2-dimethoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(3,4-dimethoxy-phenyl)-amine as brown solid in 30% yield. [0237] MS (ESI) m/z: 314.0 (M+H)+. 1H NMR (DMSO-d6): 11.92 (s, 1H), 8.086 (s, 1H), 7.54 (d, 1H), 7.17 (d, 1H), 6.83 (s, 1H), 6.81 (s, 1H), 3.72 (s, 3H), 3.68 (s, 3H), 3.46 (s, 2H).
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-isothiocyanato-1,2-dimethoxybenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	24 Example 24(4,7-dihydro-1-thioxo-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (3,4-dimethoxy- )-amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL)And 4-isothiocyanato-1,2-methoxy-benzene(1.5 g, 7.2 mmol)A solution of lithium hexamethyldisilane was added dropwise at room temperature(7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (3,4-dimethoxy-phenyl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0236-0237
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 58; 59

17
[ 5650-51-1 ]
[ 2392-68-9 ]
[ 627516-47-6 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-chlorophenyl-isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	25 Example 25 (3-chlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Chloro-3-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (3-Chloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 30% yield. [0239] MS (ESI) m/z: 288.0 (M+H)+. 1H NMR (DMSO-d6): 12.05 (s, 1H), 8.67 (s, 1H), 7.57 (d, 1H), 7.20 (t, 2H), 6.75 (d, 1H), 3.51 (s, 2H).
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-chlorophenyl-isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	25 Example 25(3-chloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) amine 5-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-chloro-3-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (3-chloro-phenyl) - (4,7-dihydro-1, Cyclopentadiene [a] and cyclopentadien-6-yl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0238-0239
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 59

18
[ 5650-51-1 ]
[ 3125-64-2 ]
[ 627514-81-2 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-methoxyphenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	26 Example 26 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(3-methoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-3-methoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 in L) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(3-methoxy-phenyl)-amine as brown solid in 33% yield. [0241] MS (ESI) m/z: 284.0 (M+H)+. 1H NMR (DMSO-d6): 12.06 (s, 1H), 8.351 (s, 1H), 7.55 (d, 1H), 7.19 (s, 1H), 7.09 (t, 2H), 6.32 (d, 1H), 3.70 (s, 3H), 3.49 (s, 2H).
32%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-methoxyphenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	26 Example 26(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (3-methoxy- phenyl)amine 5,6-dihydro-cyclopenta [b] thien-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-isothiocyanato-3-methoxy- Benzene (1.5 g, 7.2 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopenta-6-yl) - (3-methoxy-phenyl) -amine in 32% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0240-0241
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 59; 60

19
[ 5650-51-1 ]
[ 1840-19-3 ]
[ 1469857-40-6 ]

Yield	Reaction Conditions	Operation in experiment
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-3-trifluoromethyl-benzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	29 Example 29 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(3-trifluoromethylphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-3-trifluoromethyl-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(3-trifluoromethyl-phenyl)-amine as brown solid in 34% yield. [0247] MS (ESI) m/z: 322.0 (M+H)+.
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-3-trifluoromethyl-benzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	29 Example 29(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (3-trifluoromethyl-phenyl) amine 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-isothiocyanato-3-trifluoromethyl (Benzene) (1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopenta-6-yl) - (3-trifluoromethyl-phenyl) -amine in 34% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0246-0247
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 61

20
[ 5650-51-1 ]
[ 404-72-8 ]
[ 627515-82-6 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-fluorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	30 Example 30 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(3-fluorophenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Fluoro-3-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(3-fluoro-phenyl)-amine as brown solid in 33% yield. [0249] MS (ESI) m/z: 273.0 (M+H)+.
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-fluorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	30 Example 30(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (3-fluoro-phenyl) amine 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-fluoro-3-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (3-fluoro-phenyl) -amine in 33% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0248-0249
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 62

21
[ 5650-51-1 ]
[ 2740-81-0 ]
[ 1469857-42-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2-chlorophenylisothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	31 Example 31 (2-chlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Chloro-2-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (2-Chloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 30% yield. [0251] MS (ESI) m/z: 289.0 (M+H)+.
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2-chlorophenylisothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	31 Example 31(4-chloro-phenyl) - (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) amine THF (1.0 g, 7.4 mmol) and 1-chloro-2-isothiocyanato-benzene (1.0 g, 7.4 mmol) in THF (2.0 mL) was added to a solution of 5,6-dihydro-cyclopenta [b] 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (2-chloro-phenyl) - (4,7-dihydro-1, Cyclopentadiene [a] and cyclopentadien-6-yl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0250-0251
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 62; 63

22
[ 5650-51-1 ]
[ 2131-55-7 ]
[ 1469857-43-9 ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Chlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	32 Example 32 (4-chlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Chloro-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4-Chloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 35% yield. [0253] MS (ESI) m/z: 289.0 (M+H)+.
35%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-Chlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	32 Example 32(4-chloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) amine 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-chloro-4-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4-chloro-phenyl) - (4,7-dihydro-1, Cyclopentadiene [a] cyclopentan-6-yl) -amine in 35% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0252-0253
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 63

23
[ 5650-51-1 ]
[ 1645-65-4 ]
[ 1469857-46-2 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 4-(trifluoromethyl)phenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	35 Example 35 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(4-trifluoromethylphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-4-trifluoromethyl-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-trifluoromethyl-phenyl)-amine as brown solid in 30% yield. [0259] MS (ESI) m/z: 322.0 (M+H)+. 1H NMR (CDCl3): 7.43 (d, 2H), 7.25 (d, 1H), 7.02 (d, 1H), 6.96 (d, 2H), 3.21 (s, 2H).

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0258-0259

24
[ 5650-51-1 ]
[ 2131-59-1 ]
[ 1469857-47-3 ]

Yield	Reaction Conditions	Operation in experiment
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-bromophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	36 Example 36 (3-bromophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Bromo-3-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (3-Bromo-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 34% yield. [0261] MS (ESI) m/z: 333.0 (M+H).
34%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3-bromophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	36 Example 36(3-bromo-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) amine 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-bromo-3-isothiocyanato-benzene 1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (3-bromo-phenyl) - (4,7-dihydro-1, Cyclopentadiene [a] cyclopentan-6-yl) -amine in 34% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0260-0261
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 65

25
[ 5650-51-1 ]
[ 451-02-5 ]
5-(3-fluorobenzoyl)-5,6-dihydrocyclopenta[b]thiophen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 6h;	38 5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 4-Fluoro-benzoic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(2-Fluoro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (0.56 g, 2.15 mmol) as brown solid in 15% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0266

26
[ 5650-51-1 ]
[ 2905-65-9 ]
5-(3-chlorobenzoyl)-5,6-dihydrocyclopenta[b]thiophen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100℃; for 8h;	5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 10 mL of THF was treated with NaH (60 percent, 0.73 g, 18 mmol). After the addition of 3-Chloro-benzoic acid methyl ester, the reaction mixture was heated at 100 C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(4-Chloro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (0.9 g, 3.3 mmol) as brown solid in 45% yield.

Reference： [1]Patent: US2013/274255,2013,A1 .Location in patent: Paragraph 0269

27
[ 5650-51-1 ]
[ 451-46-7 ]
[ 1469858-32-9 ]

Yield	Reaction Conditions	Operation in experiment
14%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	40 5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 3-Fluoro-benzoic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(4-Fluoro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (0.56 g, 2.1 mmol) as brown solid in 14% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0272

28
[ 5650-51-1 ]
[ 1743-86-8 ]
[ 1469857-53-1 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2-(trifluoromethyl)phenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	42 Example 42 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(2-trifluoromethylphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-2-trifluoromethyl-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give a (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(2-trifluoromethyl-phenyl)-amine as brown solid in 33% yield. [0279] MS (ESI) m/z: 323.0 (M+H)+. 1H NMR (DMSO-d6): 12.11 (s, 1H), 7.56 (d, 2H), 7.48 (t, 2H), 7.21 (d, 1H), 6.94 (d, 1H), 3.46 (s, 2H).
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2-(trifluoromethyl)phenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	42 Example 42(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (2-trifluoromethyl-phenyl) amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-isothiocyanato-2-trifluoromethyl (Benzene) (1.5 g, 7.2 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (2-trifluoromethyl-phenyl) -amine in 33% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0278-0279
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 70; 71

29
[ 5650-51-1 ]
[ 96617-71-9 ]
[ 1469858-33-0 ]

Yield	Reaction Conditions	Operation in experiment
41%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	43 5,6-Dihydro-cyclopenta[b]thiophen-4-one in 13 mL of THY was treated with NaH (60 percent, 1.1 g, 27 mmol). After the addition of 3,5-Bis-trifluoromethyl-benzoic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(3,5-Bis-trifluoromethyl-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.07 g, 4.1 mmol) as yellow solid in 41% yield.
41%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	43 5,6-dihydro-cyclopenta [b] thiophen-4-one in 13 mL of THF was treated with NaH (60%, 1.1 g, 27 mmol). After the addition of 3,5-bis-trifluoromethyl-benzoic acid ethyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (70 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (3,5-bis-trifluoromethyl-benzoyl) -5,6-dihydro-cyclopenta [b] thiophene- 4-one (1.07 g, 4.1 mmol) as a yellow solid in 41% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0280
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 71; 72

30
[ 5650-51-1 ]
[ 1989-22-6 ]
[ 1469858-34-1 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	44 5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 2-Bromo-benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(2-Bromo-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.5 g, 8.2 mmol) as brown solid in 58% yield.
58%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	44 5,6-dihydro-cyclopenta [b] thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60%, 1.5 g, 36 mmol).After the addition of 2-bromo-benzoate phenyl ester,The reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give 5- (2-bromo-benzoyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (2.5 g, 8.2 mmol) as a yellow solid in 58% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0283
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 72

31
[ 5650-51-1 ]
[ 3288-04-8 ]
[ 1469857-56-4 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-2-methoxybenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	45 Example 45 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(2-methoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-2-methoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(2-methoxy-phenyl)-amine as brown solid in 33% yield. [0287] MS (ESI) m/z: 285.0 (M+H)+. 1H NMR (CDCl3): 7.29 (s, 1H), 7.20 (d, 1H), 7.14 (t, 1H), 6.92-6.87 (m, 3H), 3.87 (s, 3H), 3.49 (s, 2H).
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-2-methoxybenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	45 Example 45(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (2-methoxy-phenyl)amine Example 45(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (2-methoxy-phenyl)5-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1-isothiocyanato-2-methoxy- Benzene (1.5 g, 7.2 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (2-trifluoromethyl-phenyl) Amine, yield 33%.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0286-0287
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 73

32
[ 5650-51-1 ]
[ 64285-95-6 ]
[ 1469857-57-5 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-4-(trifluoromethoxy)benzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	46 Example 46 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(4-trifluoromethoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-4-trifluoromethoxy-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-trifluoromethoxy-phenyl)-amine as brown solid in 33% yield. [0289] MS (ESI) m/z: 339.0 (M+H)+. 1H NMR (CDCl3): 7.23 (d, 1H), 7.07 (d, 2H), 7.02 (d, 1H), 6.93 (d, 2H), 3.19 (s, 2H).
33%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-4-(trifluoromethoxy)benzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	46 Example 46(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (4-trifluoromethoxy-phenyl)amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL)And 1-isothiocyanato-4-trifluoromethoxy-benzene(1.5 g, 7.2 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (4-trifluoromethoxy-phenyl) -amine in 33% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0288-0289
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 73; 74

33
[ 5650-51-1 ]
[ 82723-17-9 ]
[ 1469858-35-2 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	47 5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 3-Bromo-benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(3-Bromo-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.5 g, 8.2 mmol) as brown solid in 58% yield.
58%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	47 5,6-dihydro-cyclopenta [b] thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60%, 1.5 g, 36 mmol).After the addition of 3-bromo-benzoate phenyl ester,The reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (3-bromo-benzoyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one as a brown solid (2.5 g, 8.2 mmol) in 58% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0290
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 74

34
[ 175205-33-1 ]
[ 5650-51-1 ]
[ 1469857-59-7 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 1-isothiocyanato-2-trifluoromethoxybenzene; 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	48 Example 48 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)(2-trifluoromethoxyphenyl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Isothiocyanato-2-trifluoromethoxy-benzene (1.6 g, 7.4 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(2-trifluoromethoxy-phenyl)-amine as brown solid in 33% yield. [0294] MS (ESI) m/z: 339.0 (M+H)+.
33%	Stage #1: 1-isothiocyanato-2-trifluoromethoxybenzene; 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	48 Example 48(4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (2-trifluoromethoxy- -amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL)And 1-isothiocyanato-2-trifluoromethoxy-benzene(1.6 g, 7.4 mmol) was added dropwise at room temperature to a solution of lithium hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The resulting mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (2-trifluoromethoxy-phenyl) -amine in 33% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0293-0294
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 75

35
[ 5650-51-1 ]
[ 6590-93-8 ]
[ 1469857-60-0 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3,5-dichlorophenylisothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	49 Example 49 (3,5-dichlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1,3-Dichloro-5-isothiocyanato-benzene (1.2 g, 7.4 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (3,5-Dichloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 30% yield. [0296] MS (ESI) m/z: 323.0 (M+H)+. 1H NMR (CDCl3): 7.28 (d, 1H), 7.04 (d, 1H), 6.89 (s, 3H), 3.02 (s, 2H).
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3,5-dichlorophenylisothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	49 Example 49(3,5-dichloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentadien-6-yl)amine Example 49(4,5-dichloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 1,3-dichloro-5-isothiocyanato -benzene (1.2 g, 7.4 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (3,5-dichloro-phenyl) - (4,7-dihydro-1, Diazo-cyclopentadienyl [a] cyclopentan-6-yl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0295-0296
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 75; 76

36
[ 5650-51-1 ]
[ 10268-71-0 ]
[ 1469858-36-3 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100.0℃; for 8.0h;	5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 2-Methoxy-benzoic acid phenyl ester, the reaction mixture was heated at 100 C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(2-Methoxy-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.53 g, 8.3 mmol) as yellow solid in 59% yield.
59%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100.0℃; for 8.0h;	5,6-dihydro-cyclopenta [b] thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60%, 1.5 g, 36 mmol).To the addition of 2-methoxy-benzeneAcid phenyl ester,The reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (70 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (2-methoxy-benzoyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (2.53 G, 8.3 mmol) as a yellow solid in 59% yield

Reference： [1]Patent: US2013/274255,2013,A1 .Location in patent: Paragraph 0299
[2]Patent: TWI553010,2016,B .Location in patent: Page/Page column 77

37
[ 5650-51-1 ]
[ 10268-71-0 ]
[ 1469857-62-2 ]

Reference： [1]Patent: US2013/274255,2013,A1
[2]Patent: TWI553010,2016,B

38
[ 5650-51-1 ]
[ 6590-94-9 ]
[ 1469857-63-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3,4-dichlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	53 Example 53 (3,4-dichlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 3,4-Dichloro-1-isothiocyanato-benzene (1.2 g, 7.4 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (0.4 mL, 7.9 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (3,4-Dichloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 30% yield. [0305] MS (ESI) m/z: 323.0 (M+H)+. 1H NMR (CDCl3): 7.31 (d, 1H), 7.25 (d, 1H), 7.11 (d, 1H), 7.08 (d, 1H), 6.77 (d, 1H), 6.16 (brs, 1H), 3.44 (s, 2H).
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 3,4-dichlorophenyl isothiocyanate With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	53 Example 53(3,4-dichloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 3,4-dichloro-5-isothiocyanato -benzene (1.2 g, 7.4 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (3,4-dichloro-phenyl) - (4,7-dihydro-1, Diazo-cyclopentadienyl [a] cyclopentan-6-yl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0304-0305
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 78; 79

39
[ 5650-51-1 ]
[ 6590-97-2 ]
[ 1469857-64-4 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2,3-dichloro-1-isothiocyanatobenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	54 Example 54 (2,3-dichlorophenyl)(4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 2,3-Dichloro-1-isothiocyanato-benzene (1.2 g, 7.4 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (2,3-Dichloro-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 30% yield. [0307] MS (ESI) m/z: 322.0 (M+H)+. 1H NMR (CDCl3): 7.32 (d, 1H), 7.26 (d, 1H), 7.18 (d, 2H), 7.07 (d, 1H), 6.51 (brs, 1H), 3.48 (s, 2H).
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 2,3-dichloro-1-isothiocyanatobenzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	54 Example 54(2,3-dichloro-phenyl) - (4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL) and 2,3-dichloro-5-isothiocyanato -benzene (1.2 g, 7.4 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the desired product as a brown solid (2,3-dichloro-phenyl) - (4,7-dihydro-1, Diazo-cyclopentadienyl [a] cyclopentan-6-yl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0306-0307
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 79

40
[ 5650-51-1 ]
[ 7356-55-0 ]
[ 1469857-65-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-(4-isothiocyanatobenzenesulfonyl)piperidine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran for 24h; Reflux;	55 Example 55 (4,7-dihydro-1-thia-4,5-diazacyclopenta[a]pentalen-6-yl)[4-(piperidine-1-sulfonyl)phenyl]amine A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-(4-Isothiocyanato-benzenesulfonyl)-piperidine (2.0 g, 7.4 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-[4-(piperidine-1-sulfonyl)-phenyl]-amine as brown solid in 29% yield. [0309] MS (ESI) m/z: 401.0 (M+H)+. 1H NMR (CDCl3): 7.63 (d, 2H), 7.31 (d, 1H), 7.11 (t, 3H), 5.30 (s, 2H), 2.98-2.95 (m, 4H), 1.66-1.62 (m, 4H), 1.43-1.41 (m, 2H).
29%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-(4-isothiocyanatobenzenesulfonyl)piperidine With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	55 Example 55(4,7-dihydro-1-thi-4,5-diazo-cyclopentadiene [a] and cyclopentadien-6-yl) - [4- (piperidine-1-sulfonyl ) -phenyl] -amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in THF (2.0 mL)And 1- (4-isothiocyanato-benzenesulfonyl) -piperidine(2.0 g, 7.4 mmol)A solution of lithium hexamethyldisilane was added dropwise at room temperature(7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours.Will monohydrated amine(0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - [4- (piperidine-l-sulfonyl) -phenyl] -amine in 29% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0308-0309
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 79; 80

41
[ 5650-51-1 ]
[ 91085-56-2 ]
[ 1469858-38-5 ]

Yield	Reaction Conditions	Operation in experiment
34%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100℃; for 8h;	5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 ml of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 3,5-Dichloro-benzoic acid ethyl ester, the reaction mixture was heated at 100 C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(3,5-Dichloro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.5 g, 4.8 mmol) as brown solid in 34% yield.
34%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100℃; for 8h;	5,6-dihydro-cyclopenta [b] thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60%, 1.5 g, 36 mmol).Adding 3,5-dichloro-benzoic acidEthyl ester,The reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (70 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (3,5-dichloro-benzoyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one 1.5 g, 4.8 mmol) as a brown solid in 34% yield.

Reference： [1]Patent: US2013/274255,2013,A1 .Location in patent: Paragraph 0312
[2]Patent: TWI553010,2016,B .Location in patent: Page/Page column 77

42
[ 5650-51-1 ]
[ 91085-56-2 ]
[ 1469857-67-7 ]

Reference： [1]Patent: US2013/274255,2013,A1
[2]Patent: TWI553010,2016,B

43
[ 1570-45-2 ]
[ 5650-51-1 ]
[ 1469858-42-1 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	60 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.66 g, 12 mmol) in 40 mL of THF was treated with NaH (60 percent, 0.7 g, 17 mmol). After the addition of Isonicotinic acid ethyl ester (0.3 g, 20 mmol), the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(Pyridine-4-carbonyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.78 g, 7.3 mmol) as red solid in 61% yield.
61%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	60 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.66 g, 12 mmol) in 40 mL of THF was treated with NaH (60%, 0.7 g, 17 mmol). After addition of isonicotinic acid ethyl ester (0.3 g, 20 mmol), the reaction mixture was heated to 100 ° C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. Collecting organic layer,Treated with brine, dried over MgSO4 (s), and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (pyridine-4-carbonyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (1.78 g, 7.3 mmol) The red solid,Yield 61%.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0322
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 84

44
[ 5650-51-1 ]
ethyl 6-bromopyridine-3-carboxylate [ No CAS ]
[ 1469858-45-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	64 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.38 g, 10 mmol) in 30 mL of THF was treated with NaH (60 percent, 0.6 g, 15 mmol). After the addition of 6-Bromo-nicotinic acid ethyl ester (2.3 g, 10 mmol), the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(6-Bromo-pyridine-3-carbonyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.28 g, 7.1 mmol) as red solid in 71% yield.
71%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	64 A solution of 5,6-dihydro-cyclopentadienyl [b] thiophen-4-one (1.38 g, 10 mmol) in 30 mL of THF was treated with NaH (60%, 0.6 g, 15 mmol). After the addition of 6-bromo-nicotinic acid ethyl ester (2.3 g, 10 mmol), the reaction mixture was heated to 100 ° C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and extracted with ethyl acetate. The organic solution was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give a corresponding red solid5- (6-bromo-pyridyl-3-carbonyl) -5,6-dihydro-cyclopentadiene and [b] thiophen-4-one as 2.28 g, 7.1 mmol) in 71% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0333
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 87; 88

45
[ 5650-51-1 ]
[ 4181-97-9 ]
C₁₅H₁₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	3 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 0.5 g, 12.4 mmol). After the addition of 4-Methoxy-benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 6-(4-Methoxy-phenyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene (3.4 g, 12.5 mmol) as lemon yellow solid in 89% yield.
89%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	3 Will be in 40 mL of THF(6,34 g, 24.2 mmol) was treated with NaH (60%, 0.5 g, 12.4 mmol) in the presence of 5,6-dihydro-cyclopenta [b] thiophen-4-one After the addition of 4-methoxy-benzoate phenyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water.The product mixture was acidified with concentrated hydrochloric acid,Ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 6- (4-methoxy-phenyl) -4,7-dihydro-1-thia-4,5-diazo-cyclopenta [ A] cyclopentadiene (3.4 g, 12.5 mmol) of lemon yellow solid in 89% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0166
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 34; 35

46
[ 5650-51-1 ]
[ 883789-09-1 ]
[ 1469858-13-6 ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	4 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 1.45 g, 12.4 mmol). After the addition of 2,4-Dimethoxy-benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(2,4-Dimethoxy-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.0 g, 6.6 mmol) as brown solid in 47% yield.
47%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	4 5,6-dihydro-cyclopenta [b] thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 1.45 g, 12.4 mmol). After the addition of 2,4-dimethoxy-benzoate phenyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (2,4-dimethoxy-phenyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one 2.0 g, 6.6 mmol) as a brown solid in 47% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0169
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 35; 36

47
[ 5650-51-1 ]
[ 93-99-2 ]
[ 1469858-15-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	6 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 1.45 g, 36.25 mmol). After the addition of Benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-Benzoyl-5,6-dihydro-cyclopenta[b]thiophen-4-one (4.3 g, 17.7 mmol) as white solid in 73% yield.
73%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	6 (5.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 1.45 g, 36.25 mmol) in 5 mL of 5-dihydro-cyclopenta [b] thiophen-4-one. After addition of phenyl benzoate, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give a white solid corresponding to 5-benzoyl-5,6-dihydro-cyclopenta [b] thiophen-4-one (4.3 g, 17.7 mmol) , Yield 73%.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0175
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 37

48
[ 5650-51-1 ]
[ 1429-05-6 ]
[ 1469858-14-7 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	555 5,6-Dihydro-cyclopenta[b]thiophen-4-one (3.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60 percent, 1.45 g, 36.25 mmol). After the addition of 2,4-Dimethoxy-benzoic acid phenyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(4-Nitro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (2.8 g, 9.7 mmol) as brown solid in 69% yield.
69%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	5 (5.34 g, 24.2 mmol) in 40 mL of THF was treated with NaH (60%, 1.45 g, 36.25 mmol) in 5 mL of 5,6-dihydro-cyclopenta [b] thiophen-4-one.After the addition of 2,4-dimethoxy-benzoate, phenyl esterThe reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours.The solution was cooled to room temperature and poured into water.The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (4-nitro-phenyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (2.8 g, 9.7 Mmol) as a brown solid in 69% yield

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0172
[2]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 36; 37

49
[ 5650-51-1 ]
[ 443-26-5 ]
[ 1469858-30-7 ]

Yield	Reaction Conditions	Operation in experiment
14%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100℃; for 8h;	5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 mL of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 3-Fluoro-benzoic acid ethyl ester, the reaction mixture was heated at 100 C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(2-Fluoro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (0.56 g, 2.1 mmol) as brown solid in 14% yield.

Reference： [1]Patent: US2013/274255,2013,A1 .Location in patent: Paragraph 0275

50
[ 5650-51-1 ]
[ 443-26-5 ]
[ 1469857-52-0 ]

Reference： [1]Patent: US2013/274255,2013,A1

51
[ 2524-52-9 ]
[ 5650-51-1 ]
[ 1469858-39-6 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium hydride In tetrahydrofuran; mineral oil at 100℃; for 8h;	58 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.66 g, 12 mmol) in 40 mL of THF was treated with NaH (60 percent, 2.4 g, 17 mmol). After the addition of Nicotinic acid ethyl ester (0.3 g, 20 mmol), the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (80 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(Pyridine-2-carbonyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.23 g, 8 mmol) as red solid in 55% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - US2013/274255, 2013, A1 Location in patent: Paragraph 0315

52
[ 5650-51-1 ]
[ 5176-27-2 ]
tert-butyl 4-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one With sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: N-tert-butyloxycarbonyl-pyrrole In tetrahydrofuran Reflux;

Reference： [1]Duan, Ya-Nan; Cui, Li-Qian; Zuo, Lin-Hong; Zhang, Chi [Chemistry - A European Journal, 2015, vol. 21, # 37, p. 13052 - 13057]

53
[ 5650-51-1 ]
[ 64285-95-6 ]
[ 1469857-46-2 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 5,6-dihydro-<6H>-cyclopenta-<b>-thiophene-4-one; 1-isothiocyanato-4-(trifluoromethoxy)benzene With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 8h; Stage #2: With hydrazine hydrate; acetic acid In tetrahydrofuran; water for 24h; Reflux;	35 Example 35(4,7-dihydro-1-thia-4,5-diazo-cyclopentadienyl [a] cyclopentan-6-yl) - (4-trifluoromethyl-phenyl) amine A solution of 5,6-dihydro-cyclopenta [b] thiophen-4-one (1.0 g, 7.4 mmol) in 2.0 mL of THF and 1-isothiocyanato-4-trifluoromethoxy- Benzene (1.5 g, 7.2 mmol) was added dropwise at room temperature hexamethyldisilane (7.0 mL, 7.2 mmol). The reaction mixture was stirred for 8 hours. Aqueous monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture and heated at reflux temperature for 24 hours. The product mixture was added to water (30 mL) and extracted with ethyl acetate. Purification by gravity column chromatography (50% EtOAc in hexanes) afforded the title product as a brown solid (4,7-dihydro-1-thi-4,5-diazo-cyclopentadienyl [a] Cyclopentadien-6-yl) - (4-trifluoromethyl-phenyl) -amine in 30% yield.

Reference： [1]Current Patent Assignee: DEVELOPMENT CENTER FOR BIOTECHNOLOGY - TWI553010, 2016, B Location in patent: Page/Page column 64; 65

54
[ 5650-51-1 ]
[ 2905-65-9 ]
[ 1469858-09-0 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium hydride; In tetrahydrofuran; mineral oil; at 100℃; for 8h;	5,6-dihydro-cyclopenta [b] thiophen-4-one (2.1 g, 15.0 mmol) in 10 mL of THF was treated with NaH (60%, 0.73 g, 18 mmol).After the addition of 3-chloro-benzoic acid methyl ester, the reaction mixture was heated to 100 & lt; 0 & gt; C and maintained for 8 hours. The solution was cooled to room temperature and poured into water. The product mixture was acidified with concentrated hydrochloric acid and ethyl acetate (80 mL) was added. The organic layer was collected, treated with brine, dried over MgSO4 (s) and concentrated under reduced pressure. The resulting precipitate was collected and recrystallized from ethanol to give the corresponding 5- (4-chloro-benzoyl) -5,6-dihydro-cyclopenta [b] thiophen-4-one (0.9 g, 3.3 mmol) as a brown solid in 45% yield.

Reference： [1]Patent: TWI553010,2016,B .Location in patent: Page/Page column 68

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	5650-51-1	MDL No. :	MFCD00757271
Formula :	C₇H₆OS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KOBLGOHFGYWCRC-UHFFFAOYSA-N
M.W :	138.19	Pubchem ID :	1958632
Synonyms :

Num. heavy atoms :	9
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.29
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	37.37
TPSA :	45.31 Å²

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) :	-6.16 cm/s

Log Po/w (iLOGP) :	1.69
Log Po/w (XLOGP3) :	1.38
Log Po/w (WLOGP) :	1.88
Log Po/w (MLOGP) :	1.1
Log Po/w (SILICOS-IT) :	3.5
Consensus Log Po/w :	1.91

[ CAS No. 5650-51-1 ] {[proInfo.proName]}

Quality Control of [ 5650-51-1 ]

Related Doc. of [ 5650-51-1 ]

Product Details of [ 5650-51-1 ]

Calculated chemistry of [ 5650-51-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 5650-51-1 ]

Application In Synthesis of [ 5650-51-1 ]

[ 5650-51-1 ] Synthesis Path-Downstream 1~54

Related Functional Groups of
[ 5650-51-1 ]

Ketones

Related Parent Nucleus of
[ 5650-51-1 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-1.98
Solubility :	1.46 mg/ml ; 0.0105 mol/l
Class :	Very soluble
Log S (Ali) :	-1.93
Solubility :	1.61 mg/ml ; 0.0116 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.36
Solubility :	0.609 mg/ml ; 0.00441 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.19

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:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling