Name: 62595-74-8|3-Bromopiperidine-2,6-dione|97%
Brand: Ambeed
SKU: A875928
Price: 5.0 USD
Availability: InStock
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1
[ 7747-10-6 ]
[ 62595-74-8 ]
[ 76059-14-8 ]

Reference： [1]Archiv der Pharmazie,1980,vol. 313,p. 481 - 487

2
[ 62595-74-8 ]
[ 876-83-5 ]
[ 74972-59-1 ]

Reference： [1]Archiv der Pharmazie,1980,vol. 313,p. 481 - 487

3
[ 62595-74-8 ]
[ 27606-61-7 ]
[ 76059-12-6 ]

Reference： [1]Archiv der Pharmazie,1980,vol. 313,p. 481 - 487

4
[ 62595-74-8 ]
[ 83-12-5 ]
[ 76059-13-7 ]

Reference： [1]Archiv der Pharmazie,1980,vol. 313,p. 481 - 487

5
4-[3-(2-methylpyrrolidin-1-yl)propoxy]benzenecarbothioamide [ No CAS ]
[ 62595-74-8 ]
2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-6,7-dihydro[1,3]thiazolo[4,5-b]pyridin-5(4H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%		Trifluoroacetic acid (0.8 ml, 10.4 mmol, 2 eq) is added to a mixture of 3-bromopiperidine- 2,6-dione x55 (1.0 g, 5.2 mmol, 1 eq) and 4-[3-(2-methylpyrrolidin-1- yl)propoxy]benzenecarbothioamide x56 (1.45 g, 5.2 mmol, 1 eq) in dioxane (10 ml) and the reaction mixture is stirred overnight at 650C. An additional amount of 3- bromopiperidine-2,6-dione x55 (0.3 g, 1.56 mmol) is added. The reaction mixture is stirred for an additional 24 h at 65 0C, cooled to room temperature and evaporated to dryness. The residue is dissolved in dichloromethane (10 ml), water and an aqueous saturated solution of potassium carbonate are added. The organic layer is washed with brine, dried with sodium sulfate and evaporated in vacuo. The residue is purified by chromatography over silicagel (gradient: dichloromethane/ methanol from 1:0 to 9:1) to afford 1.08 g of 2- {4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-6,7-dihydro[1 ,3]thiazolo[4,5-b]pyridin-5(4H)- one 69 as a yellow solid. Yield: 56 %. LC-MS (MH+): 372

Reference： [1]Patent: WO2008/12010,2008,A1 .Location in patent: Page/Page column 89; 90; 136
[2]ChemMedChem,2011,vol. 6,p. 1559 - 1565

6
[ 62595-74-8 ]
[ 4237-48-3 ]
[ 477728-23-7 ]

Reference： [1]Patent: US6670358,2003,B2 .Location in patent: Page column 72

7
[ 62595-74-8 ]
[ 4403-69-4 ]
[ 870806-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran;	1st stage: 3-(2-Aminobenzylamino)piperidine-2,6-dione A solution of 9.60 g of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> [K. Fickentscher et al., Archiv der Pharmazie Weinheim, 1980, 481-487] in 120 ml of tetrahydrofuran was added dropwise over the course of 3 hours to a refluxing solution of 6.10 g of 2-aminomethylphenylamine and 14 ml triethylamine in 100 ml of tetrahydrofuran. Once addition was complete, the reaction mixture was stirred for a further 2.5 hours while being refluxed. The precipitated solid was filtered out, thoroughly washed with tetrahydrofuran and the combined filtrates were evaporated under a vacuum. The resultant crude product was purified by column chromatography on silica gel 60 (0.040-0.063 mm) from E. Merck, Darmstadt, with chloroform/methanol=10/1 as the eluent. 5.60 g (48% of theoretical) of the title compound were obtained in the form of crystals, which melted at 48 to 54 C.

Reference： [1]Patent: WO2005/116008,2005,A1 .Location in patent: Page/Page column 8-9
[2]Patent: US2007/155967,2007,A1

8
[ 62595-74-8 ]
[ 89-97-4 ]
[ 730240-80-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; triethylamine; In methanol; diethyl ether; cyclohexane; ethyl acetate; N,N-dimethyl-formamide;	Step 2 3-(2-chlorobenzylamino) piperidine-2,6-dione; hydrochloride A solution of 0.39 g of the product from step 1 and 0.71 g 2-chlorobenzylamine in 8 ml N,N-dimethylformamide was stirred for 36 hours at 20 C. After evaporation in vacuo the oily residue was dissolved in 25 ml methanol and the solution stirred for two hours with 1 g Amberlyst A-21. It was filtered, 2 g silica gel were added to the filtrate and it was evaporated until dry. The adsorbed substance was placed in a chromatography column and the product was eluted with a mixture of ethyl acetate/cyclohexane (1/2>1/1) containing 1% triethylamine. The residue remaining after evaporation of the product fractions was dissolved in 10 ml methanol and 25 ml each of diethyl ether saturated with hydrogen chloride and diethyl ether were added to the solution. The precipitated hydrochloride was separated off and recrystallized from methanol/diethyl ether. 0.24 g (41% of theoretical) of the title compound were obtained in the form of crystals, which melted at 217 C. with decomposition. 1H-NMR (DMSO-d6): 2.15-2.34 (1H, m); 2.40-2.56 (1H, m); 2.60-2.80 (2H, m); 4.35 (1H, t, J=13.5 Hz); 4.45 (2H, d, J=13.8 Hz); 7.40-7.94 (4H, m).

Reference： [1]Patent: US2003/64987,2003,A1

9
[ 1121-89-7 ]
[ 62595-74-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With bromine; In chloroform; at 110℃; for 1.5h;	13.1 Synthesis of 3-bromopiperidine-2,6-dione a37Bromine (4.5 ml, 87.8 mmol) is added to a suspension of piperidine-2,6-dione a36 (10.2 g, 50.3 mmol) suspended in chloroform (20 ml) and the mixture is stirred in a closed vessel for 90 minutes at a bath temperature of 1 100C. After cooling, the vessel is opened and stirring is continued until no more hydrogen bromide escapes. The reaction mixture is evaporated in vacuo. The residue is dissolved in ethanol and evaporated to afford 17.1 g of 3-bromopiperidine-2,6-dione a37 as white crystals.Yield: 99 %.LC-MS (MH+): 193.
55%	With bromine; In chloroform; at 20 - 110℃; for 1.5h;Inert atmosphere; Sealed tube;	This compound was prepared using a literature procedure1. In a sealed reaction vessel, glutarimide (2g, 17.68 mmol) was dissolved in dry chloroform under argon atmosphere and Br2 (908.54 uL, 1 equiv.) was added via a syringe at room temperature. The reaction mixture heated at 110 C (oil bath) for 1h, cap was removed and further stirred at r.t. for 30 minutes. The crude product was evaporated and brown solid was purified using SiO2 column chromatography (EtOAc-hexane, 0%-100% gradient elution). The product was obtained as a white crystalline solid (0.93 g, 55%). HPLC-MS (ESI): m/z 192.0 [100%, (M+H)+].1H NMR (400 MHz, Chloroform-d) delta 7.92 (s, 1H), 4.63 (app t, J = 3.5 Hz, 1H), 3.00-2.91 (m, 1H), 2.72-2.70 (m, 1H), 2.68- 2.66 (m, 1H), 2.36- 2.28 (m, 1H).
54.5%	With bromine; In chloroform; at 113℃; for 1.5h;Sealed tube;	To a stirred solution of piperidine-2,6-dione (30 g, 0.266 mol) in CHCl3 (60 mL) was added Br2 (13.5 mL, 0.265 mol) in a sealed tube, then the reaction mixture was heated to 113 oC for 1.5 h. The color of the reaction mixture changed from deep yellow to pale yellow. The mixture was cooled to r.t. and transferred to a round bottom flask, concentrated to dry. To the residue was added 100 mL ice water, basified to pH = ~ 8 with saturated NaHCO3, extracted with DCM (100 mL x 5). The organic layers were dried with Na2SO4, filtered, concentrated to dry to give crude product, which was dissolved in a solution of DCM: EtOAc = 1:1 (~90 mL), then heated to 80 oC, after the solid was completely dissolved, stopped the heating treatment, cooled to r.t. for overnight. The solution was filtered; the solid was collected, dried under vacuum to give the desired product 3-bromopiperidine-2,6-dione (15.7 g) as a white solid. The filtrate was concentrated to give the crude product, and the crude product was purified by column chromatography on silica gel eluting with DCM : Petroleum ether : EtOAc = 5:5:1 to DCM : Petroleum ether : EtOAc = 5:5:2 to obtain the second batch of desired product (12 g) as a white solid (total yield: 54.5 %). 1H NMR (400 MHz, DMSO-d6) delta 11.06 (s, 1H), 5.00- 4.78 (m, 1H), 2.69- 2.54 (m, 2H), 2.45 (dd, J = 10.0, 5.1 Hz, 1H), 2.17-2.12 (m, 1H).

54.5%	With bromine; In chloroform; at 113℃; for 1.5h;Sealed tube;	To a stirred solution of piperidine-2,6-dione (30 g, 0.266 mol) in CHCl3 (60 mL) was added Br2 (13.5 mL, 0.265 mol) in a sealed glass tube, then the reaction mixture was heated to 113 C. for 1.5 h. The mixture was cooled to r.t. and transferred to a round bottom flask and concentrated. To the residue was added 100 mL ice water, and the solution was basified to pH=8 with saturated NaHCO3 aqueous, then extracted with DCM (100 mL×5). The organic layer was dried with Na2SO4, filtered, and concentrated to give crude product, which was dissolved in a solution of DCM:EtOAc=1:1 (90 mL), then heated to 80 C. After the solid was completely dissolved, the heating was stopped and the solution was cooled to r.t. for overnight. The solution was filtered, the solid was collected, and dried under vacuum to give desired compound (15.7 g) as a white solid. The filtrate was also concentrated to dry to give crude product, which was purified by column chromatography on silica gel eluting with DCM:Petroleum ether:EtOAc=5:5:1 to DCM:Petroleum ether:EtOAc=5:5:2 to obtain desired the second batch pure product (12 g) as a white solid (total yield: 54.5%). 1H NMR (400 MHz, DMSO-d6) delta 11.06 (s, 1H), 5.00-4.78 (m, 1H), 2.69-2.54 (m, 2H), 2.45 (dd, J=10.0, 5.1 Hz, 1H), 2.17-2.12 (m, 1H).
44%	With bromine; In 1,1,2-trichloroethane; at 20 - 110℃; for 3h;	Bromine (9.1 ml, 177 mmol, 1 eq) is added to a solution of glutarimide x54 (20 g, 177 mmol, 1 eq) in 1 ,1 ,2-trichloroethane (60 ml) at room temperature. The mixture is stirred for 2 h at 110 0C, then 1 h at room temperature. The mixture is evaporated to dryness and the residue is purified by chromatography over silicagel (dichloromethane) to afford 14.6 g of 3-bromopiperidine-2, 6-dione x55 as white crystals. Yield: 44 %. LC-MS (MH+): 193.
44.3%	With bromine; In 1,1,2-trichloroethane; at 20 - 110℃; for 3h;	Bromine (6.4 g, 0.04 mol) was added to a solution of piperidine-2,6-dione (4.5 g,0.04 mol) in 14 mL of 1 , 1 ,2-trichloroethane at room temperature. The mixture was allowed to stir for 2 hours at 1 10 C and then for 1 hour at room temperature. The reaction mixture was concentrated in vacuo and the resulting residue was purified using flash chromatography on silica gel (eluted with PE : EtOAc = 5 : 1 ~ 2 : 1) to provide 3.4 g of 3-bromopiperidine-2,6- dione (yield: 44.3 %) as white solid. 1H-NMR (CDC13, 400 MHz) delta 8.34 (s, 1H), 4.64 (t, / = 3.6 Hz, 1H), 2.91-3.00 (m, 1H), 2.66-2.73 (m, 1H), 2.28-2.47 (m, 2H).
44.3%	With bromine; In 1,1,2-trichloroethane; at 20 - 110℃; for 3h;	Bromine (6.4 g, 0.04 mol) was added to a solution of piperidine-2,6-dione (4.5 g,0.04 mol) in 14 mL of 1 , 1 ,2-trichloroethane at room temperature. The mixture was allowed to stir for 2 hours at 1 10 C and then for 1 hour at room temperature. The reaction mixture was concentrated in vacuo and the resulting residue was purified using flash chromatography on silica gel (eluted with PE : EtOAc = 5 : 1 ~ 2 : 1) to provide 3.4 g of 3-bromopiperidine-2,6- dione (yield: 44.3 %) as white solid. 1H-NMR (CDC13, 400 MHz) delta 8.34 (s, 1H), 4.64 (t, / = 3.6 Hz, 1H), 2.91-3.00 (m, 1H), 2.66-2.73 (m, 1H), 2.28-2.47 (m, 2H).
44.3%	With bromine; In 1,1,2-trichloroethane; at 20 - 110℃; for 3h;	Step 1-Synthesis of 5-bromopyridine-3-carbothioamide Bromine (6.4 g, 0.04 mol) was added to a solution of piperidine-2,6-dione (4.5 g, 0.04 mol) in 14 mL of 1,1,2-trichloroethane at room temperature. The mixture was allowed to stir for 2 hours at 110 C. and then for 1 hour at room temperature. The reaction mixture was concentrated in vacuo and the resulting residue was purified using flash chromatography on silica gel (eluted with PE:EtOAc=5:1?2:1) to provide 3.4 g of 3-bromopiperidine-2,6-dione (yield: 44.3%) as white solid. 1H-NMR (CDCl3, 400 MHz) delta 8.34 (s, 1H), 4.64 (t, J=3.6 Hz, 1H), 2.91?3.00 (m, 1H), 2.66?2.73 (m, 1H), 2.28?2.47 (m, 2H).
38%	With bromine; In chloroform; at 110℃; for 4h;Inert atmosphere; Sealed tube;	To a stirred solution of piperidine-2,6-dione (5 g, 44.20 mmol) in CHCb (10 mL) was added Br2(2.25 mL) in one portion at room temperature under nitrogen atmosphere. The reaction mixture was sealed in a tube and stirred for 4 hours at 110 C. The resulting mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with 50% ethyl acetate in petroleum ether to afford 3-bromopiperidine-2,6-dione as a pink solid (3.2 g, 38%): NMR (300 MHz, DMSO-i) delta 11.05 (br s, 1H), 4.89 (dd, J= 5.2, 3.9 Hz, 1H), 2.60 (dt, J= 9.8, 4.7 Hz, 2H), 2.46 (ddd, J= 9.6, 5.1, 3.9 Hz, 1H), 2.15 (dq, J= 14.9, 4.9 Hz, 1H); LC/MS (ESI, m/z): [(M + 1)]+= 192.1, 194. 1.
38%	With bromine; In chloroform; at 110℃; for 4h;Inert atmosphere; Sealed tube;	To a stirred solution of piperidine-2,6-dione (5 g, 44.20 mmol) in CHCb (10 mL) was added Br2 (2.25 mL) in one portion at room temperature under nitrogen atmosphere. The reaction mixture was sealed in a tube and stirred for 4 hours at 110 C. The resulting mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with 50% ethyl acetate in petroleum ether to afford 3-bromopiperidine-2,6-dione as a pink solid (3.2 g, 38%): NMR (300 MHz, DMSO-i) delta 11.05 (br s, 1H), 4.89 (dd, J= 5.2, 3.9 Hz, 1H), 2.60 (dt, J= 9.8, 4.7 Hz, 2H), 2.46 (ddd, J= 9.6, 5.1, 3.9 Hz, 1H), 2.15 (dq, J= 14.9, 4.9 Hz, 1H); LC/MS (ESI, m/z): [(M + 1)]+ = 192.1, 194. 1.
	With bromine; In ethanol; chloroform;	Step 1 3-bromopiperidine-2,6-dione 4.5 ml bromine were added to 10.2 g glutarimide suspended in 20 ml chloroform and the mixture was stirred in a closed vessel for 90 minutes at a bath temperature of 110 C. After cooling, the vessel was opened and stirring was continued until no more hydrogen bromide escaped. The reaction mixture was evaporated in vacuo, the residue dissolved in ethanol and evaporated again. 17.1 g (99% of theoretical) of the title compound remained in the form of practically white crystals, which melted at 76 to 83 C.
	With bromine; In chloroform; at 110℃; for 0.75h;	To a 48mL glass pressure reaction vessel fitted with a Teflon screw cap was added piperidine-2,6-dione (2.00g, 17.7mmol) and Br2 (2.82g, 0.90mL, 17.7mmol) in chloroform (15mL). The reaction mixture was then heated in a Kugelroehr oven at 110C (45min). The solvent was removed and the crude bromoglutarimide 7 was then dissolved in acetone (5mL) followed by the addition of sodium azide (3.44g, 53.1mmol) whereupon the reaction mixture turned blue-purple. The reaction mixture was stirred at room temperature (24h) and then directly applied to a silica gel column. Elution with hexane/ethyl acetate (1:1) gave a mixture of unreacted 3-bromopiperidine-2,6-dione 7 and 3-azidopiperidine-2,6-dione 8 (1:1). The mixture of azide 8 and unreacted bromide 7 was again dissolved in acetone (5mL) and sodium azide (1.15g, 17.7mmol) was added and stirring of the blue-purple reaction mixture was continued at room temperature (24h). Column chromatography (hexane/ethyl acetate, 1:1) of the reaction mixture gave pure 3-azidopiperidine-2,6-dione 9 as an off-white amorphous solid (1.44g, 53% from glutarimide): mp 144-145C; Rf 0.24 (TLC stains blue with heat); 1H NMR (400MHz, CDCl3) delta 4.21 (dd, J=9.6Hz, 8.4Hz, 1H), 2.78 (dt, J=18.4Hz, 5.6Hz, 1H) 2.63-2.54 (m, 1H), 2.23-2.16 (m, 1H), 2.04-1.95 (m, 1H). 13C NMR (400MHz, CDCl3) delta 170.7, 169.2, 58.2, 29.1, 24.0. FTIR (neat) 3090, 2112, 1710, 1676cm-1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C5H6N4O2: 155.0491, Found: 155.0569.

Reference： [1]Patent: WO2009/92764,2009,A1 .Location in patent: Page/Page column 74-75
[2]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 111-112
[3]Patent: WO2019/140387,2019,A1 .Location in patent: Paragraph 00429; 00430; 00431
[4]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 3208; 3209
[5]Patent: WO2008/12010,2008,A1 .Location in patent: Page/Page column 89
[6]Patent: WO2013/33901,2013,A1 .Location in patent: Page/Page column 56
[7]Patent: WO2013/34047,2013,A1 .Location in patent: Page/Page column 66-67
[8]Patent: US2014/199263,2014,A1 .Location in patent: Paragraph 0199
[9]ChemMedChem,2011,vol. 6,p. 1559 - 1565
[10]Patent: WO2019/60742,2019,A1 .Location in patent: Paragraph 00357; 00358
[11]Patent: WO2019/60693,2019,A1 .Location in patent: Paragraph 00289-00290
[12]Patent: US2003/64987,2003,A1
[13]Tetrahedron,2016,vol. 72,p. 6136 - 6141

10
[ 25984-63-8 ]
[ 62595-74-8 ]
[ 1174737-83-7 ]

Yield	Reaction Conditions	Operation in experiment
48%	In isopropyl alcohol; for 2h;Reflux;	13.2 Synthesis of 2-(4-hydroxyphenyl)-6,7-dihydro[1 ,3]thiazolo[4,5-b]pyridin-5(4H)- one a39.A mixture of <strong>[25984-63-8]4-hydroxythiobenzamide</strong> a38 (50.0 g, 0.33 mmol, 1 eq) and 3- bromopiperidine-2,6-dione a37 (69.0 g, 0.36 mmol, 1.1 eq) in 2-propanol (500 ml) is heated under reflux for 2 h. The solid is dissolved on reaching circa 600C before the product starts to precipitate out. The resulting yellow suspension is cooled to 20C, slowly filtered, and washed with fresh 2-propanol (2 x 100 ml). The crude product(70.5 g) is taken up with 2:1 ethanol/water (3.7 I) at 700C. A remaining undissolved impurity is filtered off. The filtrate is heated at reflux for 30 minutes, then the clear solution is allowed to drift slowly to room temperature overnight while stirring. The sandy crystals are collected, reslurried in ethanol (200 ml) for 1 hour, then re-isolated and dried in vacuo at 50-80C to afford 38.7 g of 2-(4-hydroxyphenyl)-6,7- dihydro[1 ,3]thiazolo[4,5-b]pyridin-5(4H)-one a39 as a pale yellow-green powder.Yield: 48 %.1 H NMR (DMSO) delta 10.62 (s, 1 H), 10.01 (s, 1 H), 7.67 (d, J = 7 Hz, 2 H), 6.83 (d, J = 7 Hz, 2 H), 2.94 (t, J = 7.3 Hz, 2 H), 2.59 (t, J = 7.3 Hz, 2 H).

Reference： [1]Patent: WO2009/92764,2009,A1 .Location in patent: Page/Page column 74-75

11
[ 62595-74-8 ]
[ 1004763-36-3 ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 1559 - 1565

12
[ 62595-74-8 ]
4-acetyl-2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-4,5,6,7-tetrahydro[1,3]thiazolo[4,5-b]pyridine [ No CAS ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 1559 - 1565

13
[ 62595-74-8 ]
[ 1426940-57-9 ]

Reference： [1]Patent: WO2013/33901,2013,A1
[2]Patent: US2014/199263,2014,A1
[3]Patent: WO2013/34047,2013,A1

14
[ 62595-74-8 ]
[ 1426942-65-5 ]

Reference： [1]Patent: WO2013/33901,2013,A1
[2]Patent: WO2013/34047,2013,A1

15
[ 62595-74-8 ]
[ 1426940-60-4 ]

Reference： [1]Patent: WO2013/33901,2013,A1
[2]Patent: US2014/199263,2014,A1
[3]Patent: WO2013/34047,2013,A1

16
[ 62595-74-8 ]
[ 1426942-66-6 ]

Reference： [1]Patent: WO2013/33901,2013,A1
[2]Patent: US2014/199263,2014,A1
[3]Patent: WO2013/34047,2013,A1

17
[ 62595-74-8 ]
[ 1383994-79-3 ]
[ 1426942-64-4 ]

Yield	Reaction Conditions	Operation in experiment
51%	In ethanol; for 48h;Reflux;	A mixture of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (3.84 g, 20 mmol) and 5-bromo-2- methoxypyridine-3-carbothioamide (3.71 g, 15 mmol) in 100 mL of dry ethanol was heated to reflux and allowed to stir at this temperature for 48 hours After being cooled to roomtemperature, the precipitate was collected by filtration, washed with cooled ethanol, and dried to provide 2-(5-bromo-2-methoxypyridin- 3-yl)-6,7-dihydrothiazolo[4,5- b]pyridin-5(4H)-one (2.6 g, yield: 51%). 1H-NMR (DMSO-J6, 300 MHz) delta 10.75 (s, 1H), 8.47 (d, / = 2.4 Hz, 1H), 8.38 (d, / = 2.4 Hz, 1H), 4.09 (s, 3H), 3.02 (t, / = 7.6 Hz, 2H), 2.62 (t, / = 7.6 Hz, 2H). MS (M+H)+: 340 7 342.
51%	In ethanol; for 48h;Reflux;	A mixture of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (3.84 g, 20 mmol) and 5-bromo-2- methoxypyridine-3-carbothioamide (3.71 g, 15 mmol) in 100 mL of dry ethanol was heated to reflux and allowed to stir at this temperature for 48 hours After being cooled to roomtemperature, the precipitate was collected by filtration, washed with cooled ethanol, and dried to provide 2-(5-bromo-2-methoxypyridin- 3-yl)-6,7-dihydrothiazolo[4,5- b]pyridin-5(4H)-one (2.6 g, yield: 51%). 1H-NMR (DMSO-J6, 300 MHz) delta 10.75 (s, 1H), 8.47 (d, / = 2.4 Hz, 1H), 8.38 (d, / = 2.4 Hz, 1H), 4.09 (s, 3H), 3.02 (t, / = 7.6 Hz, 2H), 2.62 (t, / = 7.6 Hz, 2H). MS (M+H)+: 340 7 342.
51%	In ethanol; for 48h;Reflux;	Step B-Synthesis of 2-(5-bromo-2-methoxypyridin-3-yl)-6,7-dihydrothiazolo[4,5-b]pyridin-5(4H)-one A mixture of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (3.84 g, 20 mmol) and 5-bromo-2-methoxypyridine-3-carbothioamide (3.71 g, 15 mmol) in 100 mL of dry ethanol was heated to reflux and allowed to stir at this temperature for 48 hours After being cooled to room temperature, the precipitate was collected by filtration, washed with cooled ethanol, and dried to provide 2-(5-bromo-2-methoxypyridin-3-yl)-6,7-dihydrothiazolo[4,5-b]pyridin-5(4H)-one (2.6 g, yield: 51%). 1H-NMR (DMSO-d6, 300 MHz) delta 10.75 (s, 1H), 8.47 (d, J=2.4 Hz, 1H), 8.38 (d, J=2.4 Hz, 1H), 4.09 (s, 3H), 3.02 (t, J=7.6 Hz, 2H), 2.62 (t, J=7.6 Hz, 2H). MS (M+H)+: 340/342.

Reference： [1]Patent: WO2013/33901,2013,A1 .Location in patent: Page/Page column 56
[2]Patent: WO2013/34047,2013,A1 .Location in patent: Page/Page column 67
[3]Patent: US2014/199263,2014,A1 .Location in patent: Paragraph 0201

18
[ 62595-74-8 ]
3-(4-((1-oxoisoindolin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

19
[ 62595-74-8 ]
3-(4-phenyl-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

20
[ 62595-74-8 ]
3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

21
[ 62595-74-8 ]
3-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

22
[ 62595-74-8 ]
3-(4-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

23
[ 62595-74-8 ]
3-(4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

24
[ 62595-74-8 ]
2-(1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl)isoindoline-1,3-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

25
[ 62595-74-8 ]
3-(4-(1-oxoisoindolin-2-yl)-1H-1,2,3-triazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

26
[ 62595-74-8 ]
2-((1-(2,6-dioxopiperidin-3-yl)-1H-1,2,3-triazol-4-yl)methyl)isoindoline-1,3-dione [ No CAS ]

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

27
[ 62595-74-8 ]
3-azidopiperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.44g	With sodium azide; In acetone; at 20℃; for 48h;	To a 48mL glass pressure reaction vessel fitted with a Teflon screw cap was added piperidine-2,6-dione (2.00g, 17.7mmol) and Br2 (2.82g, 0.90mL, 17.7mmol) in chloroform (15mL). The reaction mixture was then heated in a Kugelroehr oven at 110C (45min). The solvent was removed and the crude <strong>[62595-74-8]bromoglutarimide</strong> 7 was then dissolved in acetone (5mL) followed by the addition of sodium azide (3.44g, 53.1mmol) whereupon the reaction mixture turned blue-purple. The reaction mixture was stirred at room temperature (24h) and then directly applied to a silica gel column. Elution with hexane/ethyl acetate (1:1) gave a mixture of unreacted <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> 7 and 3-azidopiperidine-2,6-dione 8 (1:1). The mixture of azide 8 and unreacted bromide 7 was again dissolved in acetone (5mL) and sodium azide (1.15g, 17.7mmol) was added and stirring of the blue-purple reaction mixture was continued at room temperature (24h). Column chromatography (hexane/ethyl acetate, 1:1) of the reaction mixture gave pure 3-azidopiperidine-2,6-dione 9 as an off-white amorphous solid (1.44g, 53% from glutarimide): mp 144-145C; Rf 0.24 (TLC stains blue with heat); 1H NMR (400MHz, CDCl3) delta 4.21 (dd, J=9.6Hz, 8.4Hz, 1H), 2.78 (dt, J=18.4Hz, 5.6Hz, 1H) 2.63-2.54 (m, 1H), 2.23-2.16 (m, 1H), 2.04-1.95 (m, 1H). 13C NMR (400MHz, CDCl3) delta 170.7, 169.2, 58.2, 29.1, 24.0. FTIR (neat) 3090, 2112, 1710, 1676cm-1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C5H6N4O2: 155.0491, Found: 155.0569.

Reference： [1]Tetrahedron,2016,vol. 72,p. 6136 - 6141

28
[ 62595-74-8 ]
[ 14321-27-8 ]
3-(benzyl(ethyl)amino)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	In tetrahydrofuran; at 85℃; for 16h;	General procedure: This compound was obtained as a dark grey solid (29 mg, 22%) from MA6-019 (100 mg, 1 equiv.) and N-benzylethylamine (70.4 mg) using the general method 1 (Scheme 1) (reaction temperature 85C, solvent THF (1.0 mL), reaction time 16 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, up to 15% MeOH). HPLC: 98% [tR = 9.4 min, 20:80 MeOH-water, 0.1% TFA, 20 min]. HPLC-MS (ESI): m/z 247 (M+H)+; HRMS (ESI+): m/z calcd for C14H18N2O2 (M+H)+ 247.1445, found 247.1372.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 127

29
[ 91-21-4 ]
[ 62595-74-8 ]
3-(3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 72℃; for 1.5h;	General procedure: This compound was obtained as a beige solid (126 mg, 66%) from MA6-019 (150 mg, 1 equiv.) and 1,2,3,4- tetrahydroisoquinoline (99.1 uL, 1 equiv.) using the general procedure method 1 (Scheme 1) (reaction temperature 72 C, solvent THF (0.5 mL), DIPEA (272 muL) reaction time 1.5 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, up to 10% MeOH). Mp: 178 C (dec). HPLC: 98% [tR = 8.3 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6): delta 10.68 (s, 1H, disappeared on D2O shake), 7.11-7.08 (m, 3H), 7.05-7.00 (m, 1H), 3.92 (d, J = 14.9 Hz, 1H), 3.79 (d, J = 14.9 Hz, 1H), 3.63 (dd, J = 11.2, 4.4 Hz, 1H), 2.99 (dt, J = 11.5, 5.8 Hz, 1H), 2.88 (dt, J = 11.4, 5.4 Hz, 1H), 2.77 (q, J = 5.8 Hz, 2H), 2.65-2.53 (m, 2H), 2.21-2.09 (m, 1H), 1.97-1.87 (m, 1H). HPLC- MS (ESI): m/z 245.2 [100%, (M+H)+]. LC-MS (ESI+): 245.1 [100%, (M+Na)+], 267.1 [40%, (M+Na)+]. HRMS (ESI+): m/z calcd for C14H16N2O2 (M+H)+ 245.1284, found 245.1285.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112

30
[ 91-21-4 ]
[ 62595-74-8 ]
3-(isoindolin-2-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	In tetrahydrofuran; at 72℃; for 14h;	This compound was obtained as a dark grey solid (79 mg, 66%) from MA6-019 (100 mg, 1 equiv.) and 1,2,3,4-tetrahydroisoquinoline (62.0 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction temperature 72 C, solvent THF (1.0 mL), reaction time 14 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, up to 12% MeOH). HPLC: 95% [tR = 9.4 min, Gradient 5-95% IPA-water , 20 min].1H NMR (400 MHz, DMSO- d6): delta 10.72 (s, 1H), 7.25-7.18 (m, 4H), 4.10 (d, J = 10.8, 2H), 4.04 (d, J = 10.8, 2H), 3.61 (dd, J = 8.8, 4.8 Hz, 1H), 2.57 (t, J = 6.4 Hz, 2H), 2.107-2.011 (m, 2H); HPLC-MS (ESI): m/z 231 (M+H)+.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 126

31
[ 30798-64-2 ]
[ 62595-74-8 ]
3-(7-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 15h;	General procedure: The MA7-098 was obtained as a white solid (16 mg, 18%) from MA6-019 (64.3 mg, 1 equiv.) and MA7-073 (50 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction was carried out at room temperature, solvent DMF (1.5 mL), DIPEA (116 muL), reaction time 15 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH:DCM, up to 12% MeOH). HPLC: 93% [tR = 7.34 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6): delta 10.6 (brs, 1H), 9.12 (brs, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.52 (dd, J = 8.4, 2.8 Hz, 1H), 6.40 (d, J = 2.8 Hz, 1H), 3.80 (d, J = 14.8 Hz, 1H), 3.68 (d, J = 14.8 Hz, 1H), 3.58 (dd, J = 10.8, 4.4 Hz, 1H), 2.96-2.90 (m, 1H), 2.85-2.79 (m, 1H), 2.65-2.52 (m, 4H), 2.18-2.08 (m, 1H), 1.92- 1.88 (m, 1H); HPLC-MS (ESI): m/z 261 (M+H)+.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112-113

32
[ 3973-62-4 ]
[ 62595-74-8 ]
3-phenyl-[1,3'-bipiperidine]-2',6'-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	General procedure: This compound was obtained from MA6-019 (100 mg, 0.52 mmol.) and <strong>[3973-62-4]3-phenylpiperidine</strong> (83.9 mg, 0.52 mmol.) using the general method 1 (Scheme 1) (reaction was carried out at room temperature, solvent DMF (0.5 mL), DIPEA (181.4 muL) reaction time ~16 h). The pure MA7-081 (59 mg, 39%) was obtained as a beige solid after SiO2 chromatography with DCM: MeOH (gradient elution, up to 15% MeOH). The HPLC-MS showed 2 diastereoisomers (peak retention time, tR = 6.86 and 7.04 min.). Both peaks showed HPLC-MS (ESI): m/z 273 (M+H)+.1H NMR (400 MHz, DMSO-d6): delta 11.44 (brs, 1H), 10.14 (brs, 1H), 7.37-7.28 (m, 5H), 4.57 (4.57, 1H), 3.25-3.16 (br m, 2H), 3.09-3.02 (brm, 2H), 2.71-2.65 (br m, 2H), 2.38-2.14 (m, 3H),.92-1.83 (m, 2H), 1.77-1.65 (m, 1H).

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112-114

33
[ 62595-74-8 ]
[ 100-46-9 ]
[ 351432-17-2 ]

Yield	Reaction Conditions	Operation in experiment
30%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;	General procedure: This compound was obtained from MA6- 019 (100 mg, 0.52 mmol.) and benzylamine (56.89 muL, 0.52 mmol.) using the general method 1 (Scheme 1) (reaction was carried out at room temperature, solvent DMF (0.5 mL), DIPEA (181 muL), reaction time ~18 h). The pure MA7-090 (31 mg, 30%) was obtained as an oil after SiO2 chromatography using MeOH/DCM gradient elution (product was eluted with 7% MeOH). HPLC: 97% [tR = 9.8 min, MeOH:water 10:80 (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6) delta 10.73 (brs, 1H), 7.35-7.21 (m, 5H), 3.80 (s, 2H), 3.30-3.29 (m, overlapped with H2O peak, 2H), 2.74 (brs, 1H), 2.07-2.01 (m, 2H), 1.78-1.68 (m, 1H); HPLC-MS (ESI): m/z 219 (M+H)+.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 114

34
[ 109-01-3 ]
[ 62595-74-8 ]
3-(4-methylpiperazin-1-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	at 20℃; for 2h;	General procedure: This compound was obtained from MA6-019 (50 mg, 0.26 mmol.) and N-methylpiperazine (434.7 muL, 3.91 mmol.) using the general method 1 (Scheme 1) (reaction was carried out at room temperature, reaction time ~2 h). Aqueous NaHCO3 (5 mL) was added to the reaction mixture, and the solid obtained was filtered. The pure MA7-144-2 (45 mg, 82%) was obtained as a grey solid after trituration with EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6) delta 10.62 (brs, 1H), 3.31 (dd, overlapped with the water peak, 1H), 2.66-2.53 (m, 5H), 2.4-2.45 (m, 1H, overlapped with DMSO), 2.27 (br s, 4H), 2.13 (s, 3H), 2.06-1.96 (m, 1H), 1.87-1.79 (m, 1H); HPLC-MS (ESI): m/z 212 (M+H)+.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 115

35
[ 62595-74-8 ]
[ 103-67-3 ]
3-(benzyl-methyl-amino)-piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In N,N-dimethyl-formamide; at 20℃; for 16h;	Pre aration of 3- Benzyl-methyl-amino)-piperidine-2,6-dione (Compound 1) (0790) (0791) A solution of <strong>[62595-74-8]3-bromo-piperidine-2,6-dione</strong> (2-1) (6 g, 31.25 mmol) and benzyl-methyl- amine (2-2) (10g, 78.125 mmol) in DMF (30 mL) was stirred at ambient temperature 16 hours. The reaction mixture was then concentrated under reduced pressure and the crude mixture was purified by column chromatography (silica, gradient: 0-25% EtOAc in hexane) to afford 3-(benzyl- methyl-amino)-piperidine-2,6-dione (Compound 1) (6 g, 83%) as a grey solid. 1H NMR (400 MHz, DMSO-d6) delta 10.63 (s, 1H), 7.32 (s, 4H), 7.23 (brs, 1H), 3.76 (s, 2H), 3.60 (dd, J = 11.74, 4.34 Hz, 1H), 2.63-2.51 (m, 1H), 2.46-2.41 (m, 1H), 2.13-2.03 (m, 1H), 1.95-1.91 (m, 1H); LC MS: ES+ 233.2.
	In tetrahydrofuran; at 72℃; for 16h;	General procedure: This was obtained as a beige solid (126 mg, 66%) from MA6-019 (150 mg, 1 equiv.) and N-methyl-1-phenylmethanamine (94.7 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction temperature 72 C, solvent THF, reaction time ~16 h). The title compound was purified by triturating the crude product using EtOAc/hexane. HPLC: 89% [tR = 8.0 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6) delta 10.64 (s, 1H), 7.38-7.29 (m, 4H), 7.27-7.18 (m, 1H), 3.76 (s, 2H), 3.60 (dd, J = 12.1, 4.7 Hz, 1H), 2.61 (ddd, J = 17.5, 12.4, 5.4 Hz, 1H), 2.57-2.53 (m, 1H), 2.24 (s, 3H), 2.09 (qd, J = 12.5, 4.7 Hz, 1H), 1.97- 1.88 (m, 1H). HPLC-MS (ESI): m/z 233.2 [100%, (M+H)+]. LC-MS (ESI+): 255.1 [100%, (M+Na)+], 267.1 [40%, (M+Na)+]. HRMS (ESI+): m/z calcd for C13H16N2O2 (M+H)+ 233.12845, found 233.12835.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 250
[2]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 115

36
[ 62595-74-8 ]
[ 617-89-0 ]
3-[(furan-2-ylmethyl)amino]piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 62℃; for 18h;	General procedure: Using general method 1 (Scheme 1), MA6-122-1 was obtained as a green oil (71 mg, 44%) by heating MA6-019 (150 mg, 0.78 mmol) and furfurylamine (104.4 uL, 1 equiv.) at 62 C using DMF (1.0 mL) and DIPEA (1 equiv.) (reaction time, 18 h). Purification was carried out using SiO2 chromatography (eluent:MeOH-DCM, 0 to 12% MeOH). HPLC: 99% [tR = 11.0 min, MeOH:water 80:20,with 0.1% TFA, 20 min]. 1H NMR (400 MHz, DMSO-d6) delta 10.72 (s, 1H), 7.55 (dd, J = 1.8, 0.8 Hz, 1H), 6.37 (dd, J = 3.1, 1.8 Hz, 1H), 6.31- 6.17 (m, 1H), 3.78 (d, J = 5.9 Hz, 2H), 3.29 (s, 1H), 2.66 (brs, 1H), 2.53- 2.49 (m, 2H), 2.03 (dq, J = 13.2, 4.9 Hz, 1H), 1.80-1.56 (m, 1H). HPLC- MS (ESI): m/z 209.2 [100%, (M+H)+]. LC-MS (ESI+): 231.0 [100%, (M+Na)+]. HRMS (ESI+): m/z calcd for C10H12N2O3 (M+H)+ 209.09207, found 209.09190.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 115-116

37
[ 62595-74-8 ]
[ 1745-07-9 ]
3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	at 20℃; for 18h;	General procedure: This was obtained from 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (100.6 mg) and MA6-019 (100 mg) using the general method 1 (Scheme 1) (reaction was carried out at room temperature, reaction time ~18 h). Aqueous NaHCO3 (5 mL) was added to the reaction mixture, and extracted with EtOAc (2 x 5 mL), dried (Na2SO4), evaporated to obtain the crude product, which was triturated with EtOAc/hexanes to provide the pure compound MA7-051 as an off white solid (107 mg, 75%). HPLC: >96% [tR = 7.7 min, 5-95% gradient MeOH, water (with 0.1% TFA), 20 min]. 1H NMR (400 MHz, DMSO) delta 10.64 (s, 1H), 6.65 (s, 1H), 6.60 (s, 1H), 3.83-3.72 (m, 2H), 3.69 (s, 3H), 3.68 (s, 3H), 3.58 (d, J = 8.0, 1H), 2.95-2.89 (m, 1H), 2.86-2.80 (m, 1H), 2.65-2.75 (m, 2H), 2.65-2.52 (m, 2H), 2.20-2.08 (m, 1H), 1.95-1.85 (m, 1H). HRMS (ESI+): m/z calcd for C16H21N2O4 (M+H)+ 305.1495, found 305.1489, m/z calcd for C16H20N2O4Na (M+Na)+ 327.1315, found 327.1315. HPLC-MS: HPLC-MS (ESI+): m/z 305.2 [100%, (M+H)+], 631.3 [10%, (2M+Na)+].

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 118

38
[ 62595-74-8 ]
[ 82771-60-6 ]
3-(7-chloro-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 16h;	7- Chloro-1,2,3,4-tetrahydroisoquinoline (75.0 mg) was dissolved in DMF (0.7 mL). MA6-019 (86.0 mg) and DIPEA (a56.8 muL) were added into the mixture and stirred for 16 h. Purification by washing with aq. NaHCO3 (5 mL) and trituration from ethyl acetate/hexanes gave MA7-074 as a biege solid (77 mg, 62%). HPLC: >99% [tR = 11.6 min, 15% MeOH, 85 water (with 0.1% TFA), 20 min]. 1H NMR (400 MHz, DMSO) delta 10.71 (s, 1H), 7.17-7.11 (m , 3H), 3.94 (d, J = 16 Hz, 1H), 3.79 (d, J = 16 Hz, 1H), 3.65 (dd J = 8.0, J = 4.0, 1H), 2.90-2.95 (m, 1H), 2.90-2.81 (m, 1H), 2.70-2.80 (m, 2H), 2.65-2.50 (m, 2H), 2.20-2.08 (m, 1H), 1.95-1.85 (m, 1H). HRMS (ESI+): m/z calcd for C14H16ClN2O2 (M+H)+ 279.0894, found 279.0894, m/z calcd for C14H15ClN2O2Na (M+Na)+ 301.0714, found 301.0711. HPLC-MS: HPLC-MS (ESI+): m/z 279.2 [40%, (M+H)+], 277.1 [100%, (M-H)-].

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 119

39
[ 62595-74-8 ]
1,2,3,4-tetrahydroisoquinolin-6-amine bishydrochloride [ No CAS ]
3-(6-amino-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21 mg		General procedure: Using general method 1 (Scheme 1), MA7-096 was obtained as a yellow solid (21 mg, 22%). First 1,2,3,4-tetrahydroisoquinolin-6-amine bis-hydrochloride (79.9 mg, 0.36 mmol) was heated with DIPEA (123.2 muL, 0.72 mmol) in DMF (0.5 ml) at 70 C for 10 min. The mixture was cooled and MA6-019 (70 mg, 0.36 mmol) added and stirred and at room temperature for18 h. Purification by SiO2 column chromtorgaphy and trituration wit DCM/hexanes gave MA7-096. 1H NMR (400 MHz, DMSO-d6) delta 10.66 (s, 1H), 6.64 (d, J = 8.1 Hz, 1H), 6.31 (dd, J = 8.1, 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H), 4.76 (s, 2H), 3.68 (d, J = 13.8 Hz, 1H), 3.58 (d, J = 13.8 Hz, 1H), 3.51 (dd, J = 10.7, 4.3 Hz, 1H), 2.90-2.71 (m, 2H), 2.73- 2.54 (m, 3H), 2.15-2.04 (m, 1H), 1.89 (dq, J = 13.8, 4.9 Hz, 1H). HPLC-MS (ESI+): m/z 260.2 [100%, (M+H)+]. m/z calcd for C14H17N3O2 (M+H)+ 260.1394, found 260.1397.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 116-117

40
[ 62595-74-8 ]
[ 1009-17-2 ]
[ 76-05-1 ]
N-(2-(2,6-dioxopiperidin-3-ylamino)ethyl)benzamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20 mg		General procedure: Using general method 1 (Scheme 1), this was obtained as an off white solid (20 mg) by heating MA6-019 (58.5 mg, 0.30 mmol) and MA6-095 (50 mg, 0.3 mmol, see Scheme 3) at 60 C using DMF (0.5 mL) and DIPEA (159 muL, 0.9 mmol.) (reaction time, 16 h). The crude mixture was purified by preperative HPLC using gradient elution of MeOH-water, 5-95% with 0.1 TFA to obtain pure MA6-105.TFA salt .1H NMR (400 MHz, DMSO- d6) delta 11.39 (s, 1H), 9.22 (brs, 1H), 9.11 (brs, 1H), 8.70 (t, J = 5.6 Hz, 1H), 7.89-7.85 (m, 2H), 7.58-7.54 (m, 1H), 7.52-7.47 (m, 2H), 4.35 (broad d, 1H), 3.68-3.56 (m, 2H), 3.21 (brs, 2H), 2.69-2.65 (s, 2H), 2.33-2.26 (m, 1H), 2.08-1.97 (m, 1H); HPLC-MS (ESI): ): m/z 276 [100%, (M+H)+].

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 124

41
[ 62595-74-8 ]
[ 6108-74-3 ]
N-{3-[(2,6-dioxopiperidin-3-yl)amino]propyl}benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; for 6h;	General procedure: Using general method 1 (Scheme 1), this was obtained as a purple solid (11 mg, 14%) by heating MA6-019 (53.9 mg, 0.78 mmol) and MA6-094 (50 mg, 1 equiv.) at 60 C using DMF (1.0 mL) and DIPEA (1 equiv.) (reaction time, 6 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, 0 to 20% MeOH). HPLC: 87% [tR = 10.7 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6) delta 10.72 (s, 1H), 8.49 (t, J = 5.5 Hz, 1H), 7.88- 7.79 (m, 2H), 7.55- 7.48 (m, 1H), 7.48-7.39 (m, 2H), 3.41- 3.36 (m, 1H), 3.32- 3.28 (m, 1H), 2.74- 2.58 (m, 2H), 2.56- 2.52 (m, 2H), 2.05 (dt, J = 13.2, 4.9 Hz, 1H), 1.75-1.68 (m, 3H). HPLC-MS (ESI): ): m/z 290.2 [100%, (M+H)+]. LC- MS (ESI+): 312.1 [100%, (M+Na)+]. HRMS (ESI+): m/z calcd for C19H15N3O3 (MH)+ 289.14426, found 289.14431.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 123-124

42
[ 496-15-1 ]
[ 62595-74-8 ]
3-(indolin-1-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	In tetrahydrofuran; at 70℃; for 16h;	General procedure: This was obtained as a beige solid (62 mg, 53%) from MA6-019 (150 mg, 1 equiv.) and indoline (62.0 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction temperature 70 C, solvent THF, reaction time 16 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, up to 15% MeOH). HPLC: 99% [tR = 13.6 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6) delta 10.81 (s, 1H), 7.01 (J = 7.2, 0.8 Hz, 1H), 6.93 (td, J = 7.8, 0.8 Hz, 1H), 6.53 (td, J = 7.4, 0.9 Hz, 1H), 6.48 (d, J = 7.8 Hz, 1H), 4.63 (dd, J = 13.1, 4.9 Hz, 1H), 3.41 (ddd, J = 9.6, 8.4, 5.9 Hz, 1H), 3.27 (q, J = 9.3 Hz, 1H), 2.99- 2.87 (m, 2H), 2.79 (ddd, J = 17.4, 13.5, 5.4 Hz, 1H), 2.62-2.58 (m, 1H), 2.20 (qd, J = 13.1, 4.4 Hz, 1H), 2.01- 1.92 (m, 1H). HPLC-MS (ESI): ): m/z 231.2 [100%, (M+H)+]. LC-MS (ESI+): 231.1 [100%, (M+H]. HRMS (ESI+): m/z calcd for C13H14N2O2 (M)+ 230.1055, found 230.1056.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 124

43
[ 15205-27-3 ]
[ 62595-74-8 ]
3-((benzo[d][1,3]dioxol-5-ylmethyl)(methyl)amino)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	In N,N-dimethyl-formamide; at 20℃; for 15h;	General procedure: The MA7-088 was obtained as an off white solid (31 mg, 26%) from MA6-019 (81.4 mg, 1 equiv.) and MA7-086 (970 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction was stirred at r.t., solvent DMF, reaction time 15 h). Purification was carried out using SiO2 chromatography (eluent: MeOH-DCM, up to 10% MeOH). HPLC: 100% [tR = 4.53 min, 5-20:80 MeOH-water with 0.1% TFA, 20 min].1H NMR (400 MHz, DMSO-d6): delta 10.636 (brs, 1H), 6.89 (d, J = 1.2 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.76 (dd, J = 8.0, 1.6 Hz, 1H), 5.97 (appt, J = 0.8 Hz 2H), 3.65 (d, J = 5.2 Hz, 2H), 3.57 (dd, J = 12, 4.8 Hz, 1H), 2.63-2.55 (m, 1H), 2.52-2.47 (m, 1H), 2.22 (s, 3H), 2.11-2.00 (m, 1H), 1.93-1.88 (m, 1H); HPLC-MS (ESI): m/z 277 (M+H)+.

Reference： [1]Patent: WO2017/161119,2017,A1 .Location in patent: Page/Page column 112; 128

44
[ 13327-27-0 ]
[ 62595-74-8 ]
3-(3-methyl-6-oxopyridazin-1(6H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13.3%		Preparation of 3-(3-Methyl-6-oxopyridazin-1(6H)-yl)piperidine-2,6-dione (Compound 148) (1193) (1194) Compound 148 To a stirred solution of 6-methylpyridazin-3(2H)-one 4-1 (300 mg, 2.72 mmol) ) in THF (10ml) at -30 C was added LiHMDS (4.08 ml, 4.08 mmol), reaction mixture stirred for 1h followed by addition of 3-bromopiperidine-2,6-dione 2-1 (522 mg, 2.72 mmol), gradually warming up to room temperature and finally heating under reflux overnight. After complete consumption of 4-1 as evident from TLC, the reaction mass was quenched with ice water, volatiles stripped off, residue partitioned between ethyl acetate and water, combined organic extracts dried over sodium sulphate, concentrated, the residual crude purified by column chromatography (elution with 2% MeOH/DCM) to afford 3-(3-methyl-6-oxopyridazin- 1(6H)-yl)piperidine-2,6-dione Compound 148 (80.0 mg, 361 mumol, 13.3%) as an off white solid. 1H NMR (400 MHz, DMSO-d6) delta 10.99 (brs, 1H), 7.36 (d, J = 9.44 Hz, 1H), 6.93 (d, J = 9.44 Hz, 1H), 5.60- 5.62 (m, 1H), 2.82- 2.89 (m, 1H), 2.44- 2.66 (m, 2H), 2.25 (s, 3H), 2.05 (m, 1H). LC MS: ES+ 222.3

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 296-297

45
[ 2166-31-6 ]
[ 62595-74-8 ]
3-(6-oxo-3-phenylpyridazin-1(6H)-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.1%		Preparation of 3-(6-Oxo-3-phenylpyridazin-1(6H)-yl)piperidine-2,6-dione (Compound 149): (1199) To a stirred solution of 6-phenylpyridazin-3(2H)-one 3 (200 mg, 1.16 mmol) in THF(5 mL ) at -30C was added LiHMDS (1.74 mL, 1.74 mmol), stirred for 1h followed by addition of 3- bromopiperidine-2,6-dione 4 (266 mg, 1.39 mmol). The reaction mixture was thereafter gradually warmed up to room temperature followed by heating under reflux overnight. After complete consumption of Cpd-3 as evident from TLC, the reaction mixture was quenched with ice water, volatiles stripped off, residue partitioned between ethyl acetate and water, combined organic extracts dried over sodium sulphate, concentrated, the residual crude purified by preparative TLC to afford 3-(6-oxo-3-phenylpyridazin-1(6H)-yl)piperidine-2,6-dione (Compound 149) (69.4 mg, 245 mumol, 21.1 %) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) delta 11.08 (s, 1H), 8.10 (d, J = 9.72 Hz, 1H), 7.87- 7.88 (m, 2H), 7.48- 7.50 (m, 3H), 7.13 (d, J = 9.96 Hz), 5.80- 5.83 (m, 1H), 2.89- 2.92 (m, 1H), 2.61- 2.64 (m, 2H), 2.17 (m, 1H). LC MS: ES+ 284.3

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 298

46
[ 62595-74-8 ]
[ 1103507-90-9 ]
tert-butyl 4-(1-(2,6-dioxopiperidin-3-yl)-6-oxo-1,6-dihydropyridazin-3-yl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.7%		Preparation of tert-Butyl 4-(1-(2,6-dioxopiperidin-3-yl)-6-oxo-1,6-dihydropyridazin-3- yl)piperazine-1-carboxylate (Compound 150): (1207) To a stirred solution of tert-butyl 4-(6-oxo-1,6-dihydropyridazin-3-yl)piperazine-1- carboxylate 6-5 (150 mg, 535 mumol) in THF (5mL ) at -30C was added LiHMDS (802 muL, 802 mumol), stirred for 1h followed by addition of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> 2-1 (123 mg, 642 mumol). The reaction mixture was thereafter gradually warmed up to room temperature followed by heating under reflux overnight. After complete consumption of 6-5 as evident from TLC, the reaction mixture was quenched with ice water, volatiles stripped off, residue partitioned between ethyl acetate and water, combined organic extracts dried over sodium sulphate, concentrated, the residual crude purified by preparative HPLC to afford tert-butyl 4-(1-(2,6-dioxopiperidin-3-yl)-6- oxo-1,6-dihydropyridazin-3-yl)piperazine-1-carboxylate (Compound 150) (89.3 mg, 228 mumol, 42.7 %) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) delta 10.95 (brs, 1H), 7.55 (d, J = 9.92Hz, 1H), 6.91 (d, J = 9.92Hz, 1H), 5.56- 5.57 (m, 1H), 3.38 (s, 4H), 3.19 (s, 4H), 2.82- 2.88 (m, 1H), 2.59- 2.50 (m, 2H), 2.02 (m, 1H), 1.40 (s, 9H). LC MS: ES+ 390.5; LCMS: calculated for [M - H]+ 390.19; found 390.5

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 300-301

47
[ 92-54-6 ]
[ 62595-74-8 ]
C₁₅H₁₉N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80 - 100℃;	General procedure: General procedure- A To a stirred solution of 2-1 (1.0 mmol) in DMF (3 mL) was added Anilines 9-1 (2.5 mmol). The resulting solution was heated at 80C-100C for 5-24 hours to produce 9-2. Reaction mixture was then cooled to room temperature and evaporated under reduced pressure. Crude reaction mass was purified by reverse phase preparative HPLC, following the methods as are given below, to afford pure 9-3. Compound 161 was synthesized following General approach (DMF/heating). Yield:28%; 1H NMR (400 MHz, DMSO-d6) delta 10.65 (s, 1H), 7.19 (t, J = 7.76 Hz, 2H), 6.92 (d, J = 8.04 Hz, 2H), 6.76 (t, J = 7.10 Hz, 1H), 3.44 (dd, J = 10.42, 3.86 Hz, 1H), 3.10 (brs, 4H), 2.84-2.77 (m, 2H), 2.77-2.72 (m, 2H), 2.54-2.49 (m, 2H), 2.08-2.01 (m, 1H), 1.90-1.85 (m, 1H); LC MS: ES+ 274.0.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 308-309

48
[ 936-44-7 ]
[ 62595-74-8 ]
C₁₅H₁₈N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 70 - 100℃;	General procedure: General procedure- B To a stirred solution of 2-1 (1.0 mmol) in Dioxane (3 mL) was added Anilines 9-1 (2.5 mmol). The resulting solution was heated at 70C-100C for 5-24 hours to produce 9-2. Reaction mixture was then cooled to room temperature and evaporated under reduced pressure. Crude reaction mass was purified by reverse phase preparative HPLC, following the methods as are given below, to afford pure 9-3. Compound 164 was synthesized following General approach (DIPEA/Dioxane). Yield:30%; 1H NMR (400 MHz, DMSO-d6) delta 10.66 (d, J = 9.84 Hz, 1H), 7.27 (s, 4H), 7.18 (s, 1H), 3.32-3.25 (m, 2H), 3.12-3.02 (m, 1H), 2.89-2.85 (m, 2H), 2.70-2.65 (m, 1H), 2.56-2.48 (m, 2H), 2.23-2.19 (m, 1H), 2.01-1.97 (m, 2H), 1.81-1.77 (m, 1H); LC MS: ES+ 259.3.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 308; 310

49
[ 62595-74-8 ]
C₁₁H₁₅NO₂*(x)ClH [ No CAS ]
C₉H₁₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 0 - 70℃; for 16h;Sealed tube;	Scheme 13: (1258) To a stirred solution of 2-1 (400 mg, 2.083 mmol) in dioxane (2 mL) was added DIPEA (1.088 mL, 6.25 mmol) at 0C in a sealed tube. 13-1 (525 mg, 2.292 mmol) was added to the reaction mixture. It was heated at 70C for 16 hours. It was concentrated under reduced pressure and purified by column chromatography using (silica, gradient 0%-2% Methanol in DCM) to obtain Compound 174 as a white solid. Yield:2%; 1H NMR (400 MHz, DMSO-d6) delta 10.88 (s, 1H), 4.78 (dd, J = 13.04, 4.80 Hz, 1H), 3.31-3.24 (m, 1H), 3.22-3.16 (m, 1H), 2.85-.2.76 (m, 1H), 2.55-2.49 (m, 1H), 2.29-2.15 (m, 3H), 1.999-1.91 (m, 2H), 1.82-1.76 (m, 1H); LC MS: ES+ 197.26.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 314-315

50
[ 1849-01-0 ]
[ 62595-74-8 ]
3-(3-methyl-2-oxo-2.3-dihydro-1H-1.3-benzodiazol-1-yl)piperidine-2.6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%		To a stirred solution of <strong>[1849-01-0]1-methyl-2,3-dihydro-1H-1,3-benzodiazol-2-one</strong> (217 mg, 1.46 mmol) in DMF (2 mL) was added NaH (64.5 mg, 1.61 mmol, 60% w/w dispersed into mineral oil) at 0 C under nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0 C. To the above mixture was added dropwise a solution of 3-bromopiperidine-2,6-dione(140.6 mg, 0.73 mmol) in DMF (0.5 mL) at 0 C. The resulting mixture was stirred for additional 3 hours at room temperature. The resulting mixture was quenched with AcOH (0.5 mL) and was concentrated under reduced pressure. The crude product was purified by prep-HPLC with the following conditions: Column: XBridge Shield RP18 EVO Column, 5 urn, 19 x 150 mm; Mobile Phase A: water (plus 0.05% FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 10% B to 35% B in 7 min; Detector: UV 220 nm; Rt: 6.30 min. Desired fractions were collected and concentrated under reduced pressure. The residue was lyophilized to afford 3-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-2,6-dione, 2, as a white solid (30.4 mg, 21%): 1H NMR (400 MHz, DMSO-d6) delta 1 1.03 (br s, 1H), 7.13 - 6.97 (m, 4H), 5.30 (dd, J = 12.7, 5.4 Hz, 1H), 3.35 (s, 3H), 2.90 - 2.78 (m, 1H), 2.73 - 2.49 (m, 2H), 2.03 - 1.90 (m, 1H); LC/MS (ESI, m/z): [(M + 1)]+= 260.2.
21%		To a stirred solution of l-methyl-2,3-dihydro-lH-l,3-benzodiazol-2-one (217 mg, 1.46 mmol) in DMF (2 mL) was added NaH (64.5 mg, 1.61 mmol, 60% w/w dispersed into mineral oil) at 0 C under nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0 C. To the above mixture was added dropwise a solution of 3-bromopiperidine-2,6-dione(140.6 mg, 0.73 mmol) in DMF (0.5 mL) at 0 C. The resulting mixture was stirred for additional 3 hours at room temperature. The resulting mixture was quenched with AcOH (0.5 mL) and was concentrated under reduced pressure. The crude product was purified by prep-HPLC with the following conditions: Column: XBridge Shield RP18 EVO Column, 5 um, 19 x 150 mm; Mobile Phase A: water (plus 0.05% FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 10% B to 35% B in 7 min; Detector: UV 220 nm; Rt: 6.30 min. Desired fractions were collected and concentrated under reduced pressure. The residue was lyophilized to afford 3-(3-methyl-2-oxo-2,3-dihydro-lH- l,3-benzodiazol-l-yl)piperidine-2,6-dione, 1-2, as a white solid (30.4 mg, 21%): NMR (400 MHz, OMSO-d6) delta 11.03 (br s, 1H), 7.13 - 6.97 (m, 4H), 5.30 (dd, J= 12.7, 5.4 Hz, 1H), 3.35 (s, 3H), 2.90 - 2.78 (m, 1H), 2.73 - 2.49 (m, 2H), 2.03 - 1.90 (m, 1H); LC/MS (ESI, m/z): [(M + 1)]+ = 260.2.
5%		Scheme 15: (1264) (1265) To a THF solution (2 mL) of 15-1 (100 mg, 674 mumol) was added NaH (13.4 mg, 337 mumol) under Nitrogen atmosphere. The resultant solution was heated at 60oC for 30 minutes. To the hot reaction mixture was added a THF solution (2 mL) of 2-1 (64.7 mg, 337 mumol) drop wise and the heating was continued for another 5 hours to produce Compound 176. It was then cooled to room temperature, diluted with 20% IPA-DCM solution, washed with water and brine. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Crude mass was purified by column chromatography (silica, gradient: 0-3% MeOH in DCM) to afford Compound 176 (3.5 mg, 13 mumol, 5%). 1H NMR (400 MHz, DMSO-d6) delta 11.10 (s, 1H), 7.19 (d, J = 7.6 Hz, 1H), 7.15- 7.01 (m, 3H), 5.38 (s, 1H), 3.25 (s, 3H), 2.90-2.87 (m, 1H), 2.72-2.50 (m, 2H), 2.07-2.05 (m, 1H). LC MS: ES+ 260.3.

Reference： [1]Patent: WO2019/60742,2019,A1 .Location in patent: Paragraph 00362; 00363
[2]Patent: WO2019/60693,2019,A1 .Location in patent: Paragraph 00294-00295
[3]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 316-317

51
[ 62595-74-8 ]
[ 76003-29-7 ]
tert-butyl 4-(2,6-dioxopiperidin-3-yl)-3-oxopiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19.8%		A 50 mL 2 neck RB flask was charged with (Reverse addition protocol) tert-butyl 3- oxopiperazine-1-carboxylate (15-1) (520 mg, 2.60 mmol) in Tetrahydrofuran (10 mL ) was added sodium hydride (103 mg, 2.60 mmol) at 0C. The reaction mixture was heated at 60C for 30 mints. This hot reaction mass was added drop wise to a preheated (at 60oC), THF solution of 3- bromopiperidine-2,6-dione (47-2) (250 mg, 1.30 mmol). The reaction mixture was allowed to stir at the same temperature for another 3 hours. The RM was diluted with cold water and extracted with EtOAc (3 x 10 mL), washed with brine (10 mL), dried (Na2SO4) and evaporated. The crude was purified by silica gel column chromatography by using 0-1% MeOH in EtOAc as eluting to provide tert-butyl 4-(2,6-dioxopiperidin-3-yl)-3-oxopiperazine-1-carboxylate (49-1) (80.0 mg, 256 mumol, 19.8 %) as a Off-white solid. LC/MS (ES+): m/z 312 [M + H]+
15%		To a stirred solution of 16-1 (125 mg, 0.625 mmol) in DMF (2 mL) was added NaH (60%) (31 mg, 0.781 mmol) at 0C. Reaction mixture was stirred for 30 minutes at 60C then added 2-1 (100 mg, 0.521 mmol) at same temperature. It was then heated at 60C for 4 hours. Reaction mixture was diluted with water and extracted with 20% IPA/DCM. Organic part was washed with brine, followed by dried over anhydrous sodium sulfate and concentrated, crude was isolated via column chromatography by using (silica, gradient 0%-1%Methanol in Ethyl acetate to afford Compound 190 as off white solid. Yield:15%;

Reference： [1]Patent: WO2017/197056,2017,A1 .Location in patent: Page/Page column 387
[2]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 321-322

52
[ 62595-74-8 ]
[ 1445779-80-5 ]
C₁₅H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%		Step-2 To a stirred solution of 17-3 (70 mg, 397 mumol) in DMF (5 mL) was added sodium hydride (31.6 mg, 794 mumol). The reaction was heated to 60C under nitrogen for 30 minutes. 2-1 (76.2 mg, 397 mumol) was added to the reaction mixture and the heating was continued for 3 hours. It was cooled to room temperature and quenched with ice water (10 mL ). It was extracted with ethyl acetate. Organic part was dried over sodium sulfate, reduced in vacuo. The crude residue was purified by column chromatography (silica, gradient 0%-2% Methanol in DCM) to provide (Compound 192) as a white solid. Yield:12%; 1H NMR (400 MHz, DMSO-d6) delta 10.90 (s, 1H), 7.24 (t, J = 7.2 Hz, 2H), 6.94 (d, J = 7.25 Hz, 2H), 6.80 (d, J = 7.0 Hz, 1H), 5.05 (brs, 1H), 3.89-.79 (m, 2H), 3.55-3.51 (m, 1H), 3.43-3.32 (m, 3H), 2.84-2.76 (m, 1H), 2.56-2.49 (m, 1H), 2.42-2.33 (m, 1H), 1.90-1.85 (m, 1H); LC MS: ES+ 288.26.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 323

53
[ 62595-74-8 ]
C₉H₁₃N₃O₃*(x)ClH [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

54
[ 62595-74-8 ]
tert-butyl 4-((2,6-dioxopiperidin-3-yl)(methyl)carbamoyl)piperidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

55
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-N-methylpiperidine-4-carboxamide trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

56
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-4-(methoxymethoxy)-N-methylbenzamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

57
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-4-hydroxy-N-methylbenzamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

58
[ 62595-74-8 ]
tert-butyl 4-(N-(2,6-dioxopiperidin-3-yl)-N-methylsulfamoyl)piperidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

59
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-N-methylpiperidine-4-sulfonamide trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

60
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-N-methyl-4-nitrobenzenesulfonamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

61
[ 62595-74-8 ]
4-amino-N-(2,6-dioxopiperidin-3-yl)-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

62
[ 62595-74-8 ]
2-amino-N-(2,6-dioxopiperidin-3-yl)-N-methylisonicotinamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

63
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-4-hydroxy-N-methylcyclohexane-1-carboxamide [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

64
[ 62595-74-8 ]
tert-butyl 3-((2,6-dioxopiperidin-3-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

65
[ 62595-74-8 ]
N-(2,6-dioxopiperidin-3-yl)-N-methylpyrrolidine-3-carboxamide trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

66
[ 62595-74-8 ]
3-methylamino-piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

67
[ 62595-74-8 ]
[ 6872-06-6 ]
3-(2-methyl-2,3-dihydro-indol-1-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃; for 16h;Sealed tube;	Preparation of 3-(2-Methyl-2,3-dihydro-indol-1-yl)-piperidine-2,6-dione (Compound 208) (1334) (1335) To a mixture of 29-1 (300 mg, 2.25 mmol) and 2-1 (432 mg, 2.25 mmol) in DMF (2 mL) was added N,N-Diisopropylethylamine (0.77 muL, 4.50 mmol). The resulting solution was heated in a sealed tube at 80oC for 16 hours to produce Compound 208. Reaction mixture was then cooled to room temperature, diluted with water and extracted with Ethyl acetate. The combined Ethyl acetate extract was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Crude mass was purified by column chromatography (silica, gradient: 0-20% Ethyl acetate in Hexane) to afford Compound 208 (65.0 mg, 266 mumol, 12 %) as brown solid.1H NMR (400 MHz, DMSO-d6) delta 10.80 (d, J = 9.7 Hz, 1H), 6.98-6.97 (m, 1H), 6.88 (d, J = 9.2 Hz, 1H), 6.57- 6.47 (m, 1H), 6.30-6.19 (m, 1H), 4.39 (t, J = 14.1 Hz, 1H), 3.93-3.80 (m, 1H), 3.25- 3.09 (m, 2H), 2.79-2.74 (m, 2H), 2.24-2.20 (m, 1H), 1.89-1.81 (m, 1H), 1.22 (d, J = 6.3 Hz, 3H). LC MS: ES+ 245.32.

Reference： [1]Patent: WO2017/197051,2017,A1 .Location in patent: Page/Page column 338-339

68
[ 62595-74-8 ]
[ 6872-06-6 ]
3-(2-methyl-indol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2017/197051,2017,A1

69
[ 62595-74-8 ]
(S)-3-amino-N-(2-(3-(cyclopropylmethoxy)-4-fluorophenyl)-2-hydroxybutyl)propane-1-sulfonamide [ No CAS ]
N-((S)-2-(3-(cyclopropylmethoxy)-4-fluorophenyl)-2-hydroxybutyl)-3-((2,6-dioxopiperidin-3-yl)amino)propane-1-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.3%		To a stirred solution of 30 (0.23 g, 0.614 mmol) in dry THF (5 mL), Et3N (0.26 g, 1.84 mmol) was added and stirred at room temperature for 20 mm. A solution of 31 (0.117 g, 0614 mmol) in THF (5 mL) was added dropwise and stirred at room temperature for 90 mm. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic layer were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography using 5% MeOH in DCM to afford the product. Yield: 0.007 g, 2.3 %; HPLC purity: 92.18%; LCMS: observed mass; 486.15 (M + 1). ?H NMR (400 MHz, DMSO-d6) 10.68 (s, 1H), 7.16-7.06 (m, 2H), 6.97-6.88 (m, 1 H), 6.64 (t, J= 6.3 Hz, 1H), 4.92 (s, 1H), 3.88 (dd, J 7.1, 1.6 Hz, 2H),3.33 -3.08 (m, 3H), 2.92 (m, J 15.5, 7.6, 7.1 Hz, 2H), 2.71 -2.49 (m, 3H), 2.01-1.99 (m, 1H), 1.80- 1.59 (m, 5H), 1.31 - 1.15 (m, 3H), 0.66-0.53 (m, 5H), 0.37-0.29 (m, 2H).

Reference： [1]Patent: WO2018/98204,2018,A1 .Location in patent: Paragraph 0802

70
[ 62595-74-8 ]
tert-butyl 4-(6-oxo-1H-pyridazin-4-yl)piperazine-1-carboxylate [ No CAS ]
tert-butyl 4-(1-(2,6-dioxopiperidin-3-yl)-6-oxo-1,6-dihydropyridazin-4-yl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
190 mg	With sodium hydride; In dimethyl sulfoxide; at 25℃; for 12h;	To a solution of tert-butyl 4-(6-oxo-1H-pyridazin-4-yl)piperazine-1-carboxylate (950 mg, 3.39 mmol, 1 eq) in dimethylsulfoxide (15 mL) was added sodium hydride (271 mg, 6.78 mmol, 60% purity, 2 eq) at 25 C. followed by the addition of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (650 mg, 3.39 mmol, 1 eq). The mixture was stirred at 25 C. for 12 hours. The resulting mixture was filtered and quenched by addition of water (200 mL), and extracted with ethyl acetate (50 mL3). The combined organic phase was washed with brine (50 mL3), dried over anhydrous sodium sulfate, filtered and concentrated under reduce pressure. The residue was purified by semi-preparative reverse phase HPLC (column: Phenomenex luna C18 250*50 mm, 10 um; mobile phase: [water(0.225% formic acid)-ACN]; B %: 16%-46% in 30 min). Tert-butyl 4-[1-(2,6-dioxo-3-piperidyl)-6-oxo-pyridazin-4-yl]piperazine-1-carboxylate (190 mg, 0.48 mmol, 14% yield) was obtained as a white solid. LC/MS (ESI) m/z: 392.1 [M+1]+; 1H NMR (400 MHz, DMSO) delta 8.02 (s, 1H), 7.72 (d, J=2.8 Hz, 1H), 5.74 (dd, J=5.3, 11.6 Hz, 1H), 3.62-3.53 (m, 4H), 3.34 (s, 4H), 2.95-2.83 (m, 1H), 2.82-2.58 (m, 2H), 2.27-2.17 (m, 1H), 1.49 (s, 9H).

Reference： [1]Patent: US2018/215731,2018,A1 .Location in patent: Paragraph 1209; 1210; 1739

71
[ 62595-74-8 ]
3-(6-oxo-4-(piperazin-1-yl)pyridazin-1(6H)-yl)piperidine-2,6-dione [ No CAS ]