Name: 26166-92-7|5-Bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione|98%
Brand: Ambeed
SKU: A992553
Price: 6.0 USD
Availability: InStock
Rating: 92 (28 reviews)

1
[ 86-90-8 ]
[ 24666-56-6 ]
[ 26166-92-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium acetate; acetic acid;Heating / reflux;	5.52 l-f2-CHLQRO-PHENYLV3-r2-(2.6-DIOXO-PIPERIDIN-3-YLV1.3- DIOXO-2.3-DIHYDRO- 1H-ISOINDOL-5-YLMETHYL1-UREAStep .: A mixture of <strong>[86-90-8]4-bromophthalic anhydride</strong> (10.0 g, 44.1 mmol), rac-a- aminoglutarimide hydrochloride (7.25 g, 44.0 mmol) and sodium acetate (3.61 g, 44.0 mmol) in acetic acid (150 mL) was heated to reflux overnight. The reaction mixture was cooled to room temperature, and the solvent was evaporated under vacuum. The residue was stirred in water (170 mL) for 3 hours, and the resulting solid was filtered, washed with additional water (80 mL), and dried under vacuum, to afford 13.8 g of 5-bromo-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l ,3-dione, in 93% yield; 1H NMR (DMSO-(Z6) delta 2.03-2.10 (m, IH), 2.43-2.63 (m, 2H), 2.82-2.97 (m, IH), 5.17 (dd, J = 12.8 Hz, J = 5.3 Hz, IH), 7.85-7.88 (d, J = 7.9 Hz, IH), 8.10 (dd, J = 7.9 Hz, J = 1.7 Hz, IH), 8.16 (d, J = 1.7 Hz, IH), 1 1.15 (s, IH); 13C NMR (DMSCW6) delta 21.9, 30.9, 49.2, 125.3, 126.4, 128.5, 130.1, 133.2, 137.6, 165.9, 166.4, 169.7, 172.7; Anal. Calcd for C13H9N2O4Br: C, 46.32; H, 2.69; N, 8.31. Found: C, 46.23; H, 2.47; N, 8.41.
92%	With sodium acetate; In acetic acid; at 20 - 80℃; for 16h;	To a solution of <strong>[86-90-8]4-bromophthalic anhydride</strong> (15.0 g, 66.1 mmol, CAS86-90-8) in acetic acid (225 mL) was added 2,6-dioxopiperidin-3-amine hydrochloride (10.87 g, 66.1 mmol, CAS24666-56-6) and sodium acetate (5.42 g, 66.07 mmol) at rt. The reaction mixture was heated to 80 C. and stirred for 16 h. The resulting reaction mixture was cooled to rt and concentrated on a rotary evaporator. The obtained residue was suspended in water (255 mL) and the resulting mixture was cooled to 0 C. The resulting slurry was stirred at 0 C. for 1 h. The resulting precipitate was filtered, washed with water (60 mL) and dried under vacuum to give the title compound (20.44 g, 92%) as a purple solid. LC-MS (ESI+) m/z 336.9 (M+H)+.
60%	With potassium acetate; acetic acid; at 90℃; for 12h;	To a solution of 3-aminopiperidine-2,6-dione (7.98 g, 48.4 mmol, HCl salt, CAS24666-56-6), KOAc (13.4 g, 136 mmol) in HOAc (200 mL) was added 5-bromoisobenzofuran-1,3-dione (10.0 g, 44.0 mmol, CAS282-73-5). The mixture was then heated to 90 C. and stirred for 12 hours. On completion, the mixture was cooled down to 25 C. and diluted with water (800 mL), and then filtered to give a filter cake. The filter cake was stirred in DCM (20 mL) for 1 hour and filtered to give a filter cake. The filter cake was dried in vacuo to give the title compound (9.00 g, 60% yield) as a blue solid. 1H NMR (400 MHz, DMSO-d6) delta 11.15 (s, 1H), 8.15 (d, J=1.2 Hz, 1H), 8.10 (dd, J=1.6, 8.0 Hz, 1H), 7.87 (d, J=8.0 Hz, 1H), 5.17 (dd, J=5.6, 12.8 Hz, 1H), 2.95-2.83 (m, 1H), 2.65-2.52 (m, 2H), 2.11-2.00 (m, 1H).

Reference： [1]Patent: WO2008/27542,2008,A2 .Location in patent: Page/Page column 75
[2]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 2384; 2385
[3]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 2736; 2737
[4]Patent: WO2018/140809,2018,A1 .Location in patent: Paragraph 00423

2
[ 26166-92-7 ]
[ 557-21-1 ]
[ 1010100-21-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	In N,N-dimethyl-formamide at 120℃; for 3h;	5.5.52.2 Step 2: DMF (300 mL) was degassed via nitrogen sparge for 1 hour and 5-bromo- 2-(2,6-dioxo-piperidin-3-yl)-isoindole-l ,3-dione (13.7 g, 40.6 mmol), zinc cyanide (2.86 g, 24.4 mmol), tris(dibenzylideneacetone)dipaliadium (0.74 g, 0.80 mmol) and 1,1 '- bis(diphenylphosphino)ferrocene (0.90 g, 1.6 mmol) were added. The reaction mixture was heated to 120 0C for 3 hours, cooled to 600C, and filtered through Celite. The filter was washed with additional DMF (160 mL), and the filtrate was evaporated under vacuum. The residue was stirred in water (300 mL) for 2 days and filtered, washed with additional water, and dried under vacuum. The resulting solid was triturated with acetone (300 mL) for 1 hour and filtered, and the solid was washed with additional acetone (300 mL) and dried under vacuum. The resulting solid was refluxed in methanol for 1 hour, cooled to room temperature, filtered, washed with additional methanol, and dried to give 1 1.1 g of 2-(2,6-dioxo-piperidin-3-yl)-l,3-dioxo-2,3-dihydro-lH-isoindoIe-5- carbonitrile, in 96% yield; mp > 260 0C; 1H NMR (DMSO-J6) δ 2.03-2.12 (m, IH), 2.43-2.64 (m, 2H), 2.83-2.97 (m, IH), 5.22 (dd, J = 12.8 Hz, J = 5.2 Hz, IH), 8.12 (d, J = 7.8 Hz, IH), 8.38 (dd, J = 7.8 Hz, J = 1.4 Hz, I H), 8.49 (s, IH), 1 1.17 Cs, I H); 13C NMR (DMSO-^6) δ 21.8, 30.9, 49.3, 1 17.0, 1 17.4, 124.2, 127.3, 131.8, 134.5, 139.1, 165.6, 165.9, 169.5, 172.7; Anal. Calcd for C14H9N3O4 + 0.3 H2O: C, 58.26; H, 3.35; N, 14.56. Found: C, 58.01 ; H, 3.01 ; N, 14.37.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2008/27542, 2008, A2 Location in patent: Page/Page column 75

3
[ 86-90-8 ]
(RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate [ No CAS ]
[ 26166-92-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 650 - 662
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5819 - 5824

4
[ 26166-92-7 ]
[ 141-32-2 ]
C₂₀H₂₀N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 50℃; for 3h;

Reference： [1]Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin, Melvin; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824]

5
[ 111-34-2 ]
[ 26166-92-7 ]
C₁₉H₂₀N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 50℃; for 3h;

Reference： [1]Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin, Melvin; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824]

6
[ 88-12-0 ]
[ 26166-92-7 ]
C₁₉H₁₇N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 50℃; for 3h;

Reference： [1]Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin, Melvin; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824]

7
[ 26166-92-7 ]
[ 292638-85-8 ]
C₁₇H₁₄N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 50℃; for 3h;

Reference： [1]Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin, Melvin; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824]

8
[ 930-68-7 ]
[ 26166-92-7 ]
C₁₉H₁₆N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Methyldicyclohexylamine; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 50℃; for 3h;

Reference： [1]Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin, Melvin; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824]

9
[ 35161-71-8 ]
[ 26166-92-7 ]
[ 1216805-74-1 ]

Yield	Reaction Conditions	Operation in experiment
21%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

10
[ 26166-92-7 ]
[ 917-92-0 ]
[ 1216805-29-6 ]

Yield	Reaction Conditions	Operation in experiment
76%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 18h; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

11
[ 26166-92-7 ]
[ 14918-21-9 ]
[ 1216805-75-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

12
[ 26166-92-7 ]
[ 71597-85-8 ]
[ 1216805-53-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: 5-bromo-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione; (p-hydroxyphenyl)boronic acid With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; Stage #2: With hydrogenchloride In tetrahydrofuran; water Inert atmosphere; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

13
[ 26166-92-7 ]
[ 153624-46-5 ]
[ 1216805-57-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

14
[ 26166-92-7 ]
[ 107-19-7 ]
[ 1216805-32-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Inert atmosphere; Microwave irradiation;	1 Step 1-2-(2,6-Dioxo-3-piperidyl)-5-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione A mixture of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (1.00 g, 2.97 mmol, Intermediate GA), prop-2-yn-1-ol (333 mg, 5.93 mmol, CAS107-19-7), Pd(PPh3)2Cl2 (208 mg, 297 umol), CuI (56.5 mg, 297 umol) and TEA (5.40 g, 53.4 mmol, 7.43 mL) in DMF (4 mL) was degassed and purged with N2 gas 3 times, and then the mixture was stirred at 80° C. for 0.5 hr under microwave. On completion, the mixture was extracted with EA (2×100 mL), the organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to give the title compound (800 mg, 86% yield) as light white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 7.96-7.90 (m, 3H), 5.48 (t, J=6.0 Hz, 1H), 5.17 (dd, J=5.2, 12.8 Hz, 1H), 4.38 (d, J=6.0 Hz, 2H), 2.96-2.84 (m, 1H), 2.70-2.54 (m, 2H), 2.13-2.03 (m, 1H).
72%	With copper (I) iodide; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 8h; Reflux;
72%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Reflux;

48%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 4h; Inert atmosphere; Reflux; chemoselective reaction;
36%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 75℃; Inert atmosphere;	72.1 Step 1: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-(3-hydroxyprop-1-yn-1-yl)isoindoline-1,3-dione ( 72-1) 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (3.0 g, 8.90 mmol),prop-2-yn-1-ol (0.78 mL, 12.82 mmol) and N,N-diisopropyldiamine (3.1 mL, 17.80 mmol) was added to a mixture of CuI (576 mg, 3.03 mmol) in N,N-dimethylformamide (45 mL), and the mixture was substituted with argon gas. Pd(PPh3)2Cl2 (1.0 g, 1.42 mmol) was added, and the mixture was stirred at 75°C overnight. The mixture was extracted with dichloromethane and water, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated.The residue was recrystallized from toluene to obtain the title compound (1.0 g, yield 36%).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3400; 3401
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1 Location in patent: Page/Page column 168-169
[3]Current Patent Assignee: CULLGEN SHANGHAI - WO2021/170109, 2021, A1 Location in patent: Page/Page column 257-258
[4]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]
[5]Current Patent Assignee: J2H BIOTECH INC - KR2022/35014, 2022, A Location in patent: Paragraph 0873-0874; 0876-0877

15
[ 26166-92-7 ]
[ 536-74-3 ]
[ 1216805-69-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

16
[ 26166-92-7 ]
[ 115-19-5 ]
[ 1216805-71-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

17
[ 26166-92-7 ]
[ 153624-38-5 ]
[ 1216805-28-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

18
[ 26166-92-7 ]
[ 195062-57-8 ]
[ 1216805-51-4 ]

Yield	Reaction Conditions	Operation in experiment
38%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

19
[ 26166-92-7 ]
[ 149104-90-5 ]
[ 1216805-25-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; N-Methyldicyclohexylamine; sodium hydroxide; tri tert-butylphosphoniumtetrafluoroborate In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

20
[ 26166-92-7 ]
[ 123088-59-5 ]
[ 1216805-54-7 ]

Yield	Reaction Conditions	Operation in experiment
37%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

21
[ 26166-92-7 ]
[ 98-80-6 ]
[ 1216805-49-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-Methyldicyclohexylamine; sodium hydroxide In tetrahydrofuran at 20℃; Inert atmosphere; Reflux; chemoselective reaction;

Reference： [1]Location in patent: experimental part Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662]

22
[ 26166-92-7 ]
[ 1066-54-2 ]
2-(2,6-dioxopiperidin-3-yl)-5-((trimethylsilyl)ethynyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.7%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine Inert atmosphere; Reflux;	Suspended 5-bromo-2-(2,6-dioxopiperidin-3 -yl)isoindoline- 1,3 -dione (3-1) (1.01 g, 2.99 mmol) in 8 mL DIPA and purged with nitrogen for 15 mm. Added copper iodide (0.05, 28.4 mg,0.1495 mmol) and dichlorobis(tripheny (0.05, 104 mg, 0.1495 mmol), followed by nitrogen purge for another 15 mm. Then added ethynyltrimethylsilane (537 tL, 3.88 mmol) reflux for overnight. Diisopropylamine was removed under reduced vacuum, subject to isco 0-15% MeOHIDCM to give 2-(2,6-dioxopiperidin-3 -yl)-5-((trimethylsilyl)ethynyl)isoindoline- 1,3 -dione (680 mg, 1.91 mmol, 64.7 %) as an oil. LCMS (ES+): m/z 355 [M + H]
57%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 80℃; for 2h; Inert atmosphere;	27.2 The second step: 2-(2,6-dioxo-3-piperidinyl)-5-(2-trimethylsilylacetylene)isoindoline-1,3-dione (27c) Put 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (see WO2009145899 for synthesis method)(0.500g, 1.48mmol) was dissolved in 10mL of tetrahydrofuran, and diisopropylethylamine (0.268g, 2.08mmol) was added,Add bis(triphenylphosphorus) palladium dichloride (0.0521g, 0.0742mmol) and cuprous iodide (0.0282g, 0.148mmol) under nitrogen protection,Then slowly add ethynyltrimethylsilane (0.168g, 1.71mmol) dropwise, and react at 80°C for 2 hours after the addition.Cool to room temperature, add 20 mL water and 50 mL dichloromethane, separate the layers, wash the organic layer with 10 mL saturated sodium chloride,Dry with anhydrous sodium sulfate, concentrate under reduced pressure, and separate and purify the crude product by silica gel column chromatography (petroleum ether/ethyl acetate (v/v)=100:0-7:3),Obtained 2-(2,6-dioxo-3-piperidinyl)-5-(2-trimethylsilylacetylene)isoindoline-1,3-dione (27c) (0.300g, yield : 57%).

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197056, 2017, A1 Location in patent: Page/Page column 356
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A Location in patent: Paragraph 1160-1163; 1169-1174

23
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-ethynylisoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine / Inert atmosphere; Reflux 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197056, 2017, A1

24
[ 26166-92-7 ]
5-(1-(7-(4-((S)-6-(4-chlorophenyl)-1,4-dimethyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-8-yl)-1H-pyrazol-1-yl)heptyl)-1H-1,2,3-triazol-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine / Inert atmosphere; Reflux 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 3: N-ethyl-N,N-diisopropylamine; copper(l) iodide / 1,4-dioxane / 20 °C

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197056, 2017, A1

25
[ 86-90-8 ]
[ 31140-42-8 ]
[ 26166-92-7 ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1508 - 1512

26
[ 85535-45-1 ]
[ 26166-92-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1,1'-carbonyldiimidazole; dmap / tetrahydrofuran / 16 h / Reflux 2: 2,2,2-trifluoroethanol / 2 h / 150 °C / Microwave irradiation; Sealed tube

Reference： [1]Burslem, George M.; Ottis, Philipp; Jaime-Figueroa, Saul; Morgan, Alicia; Cromm, Philipp M.; Toure, Momar; Crews, Craig M. [ChemMedChem, 2018, vol. 13, # 15, p. 1508 - 1512]

27
[ 26166-92-7 ]
tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate / N,N-dimethyl-formamide; lithium hydroxide monohydrate / 90 °C 2: palladium on activated charcoal; hydrogen / tetrahydrofuran; methanol / 40 °C
	Multi-step reaction with 2 steps 1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: potassium carbonate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / ethyl acetate / 20 °C

	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; tripotassium phosphate tribasic / 1,4-dioxane / 100 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / tetrahydrofuran / 20 °C
	Multi-step reaction with 2 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: tripotassium phosphate tribasic; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / N,N-dimethyl-formamide / 2 h / 90 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 25 °C

Reference： [1]Current Patent Assignee: ARVINAS - WO2018/140809, 2018, A1
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[3]Current Patent Assignee: ARVINAS - WO2021/77010, 2021, A1
[4]Current Patent Assignee: NURIX THERAPEUTICS INC; GILEAD SCIENCES INC - WO2021/226262, 2021, A1
[5]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[6]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1
[7]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1
[8]Current Patent Assignee: PRELUDE THERAPEUTICS INCORPORATED - WO2022/99117, 2022, A1

28
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(piperidin-4-yl)isoindole-1,3-dione hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate / N,N-dimethyl-formamide; lithium hydroxide monohydrate / 90 °C 2: palladium on activated charcoal; hydrogen / tetrahydrofuran; methanol / 40 °C 3: hydrogenchloride / ethyl acetate
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / N,N-dimethyl-formamide / 2 h / 90 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 25 °C 3: hydrogenchloride / dichloromethane; 1,4-dioxane / 1 h / 25 °C

Reference： [1]Current Patent Assignee: ARVINAS - WO2018/140809, 2018, A1
[2]Current Patent Assignee: PRELUDE THERAPEUTICS INCORPORATED - WO2022/99117, 2022, A1

29
[ 26166-92-7 ]
[ 1219827-56-1 ]
C₂₆H₂₉N₃O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 140℃; for 0.666667h; Microwave irradiation;

Reference： [1]Current Patent Assignee: ARVINAS - WO2018/140809, 2018, A1 Location in patent: Paragraph 00423

30
[ 26166-92-7 ]
4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester [ No CAS ]
tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; potassium carbonate In 1,4-dioxane at 100℃; for 3h; Inert atmosphere;	Step 1: Synthesis of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]- 3,6-dihydro-2H-pyridine-1-carboxylate Into a 250-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (1.0 g, 2.96 mmol , 1.0 equiv), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1- carboxylate (1.8g, 5.9 mmol, 2.0 equiv), dioxane , K2CO3 (1.23g, 8.9 mmol, 3 equiv), Pd(dppf)Cl2 (217.0 mg, 0.29 mmol, 0.1 equiv). The resulting solution was stirred for 3 h at 100 . The reaction mixture was cooled to room temperature with a water bath. The reaction was then quenched by the addition of water. The resulting solution was extracted with ethyl acetate (100 mL). The resulting mixture was washed with brine. The mixture was dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 1.2 g (92%) of tert-butyl 4-[2-(2,6-dioxopiperidin- 3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate as a solid. MS (ES+): m/z 340.15[MH+].
82%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; tripotassium phosphate tribasic In N,N-dimethyl-formamide at 90℃; for 2h; Inert atmosphere;	Stepl: tert-butyl 4-[2-(2, 6-dioxopiperidin-3-yl)-l,3-dioxoisoindol-5-yl]-3, 6-dihydro-2H-pyridine- 1- carboxylate A solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-l, 3-dione (500 mg, 1.48 mmol), N-Boc-l,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (459 mg, 1.48 mmol), K3PO4 (787 mg, 3.71 mmol) and Pd(dppf)2Cl2 (218 mg, 0.30 mmol) in DMF (10 mL) was stirred at 90 °C for 2 h under nitrogen. The resulted mixture was diluted with water, and extracted with EA. The organic layers were combined, washed with brine, dried over Na2SO4 , filtered, and concentrated. The residue was purified by silica gel chromatography (PE / EA = 1 / 1) to afford the desired product (532 mg, 82% yield) as a yellow oil. LCMS calculated for C23H26N3O6 (M+H)+m/z =440.2 ; found: 384.0 (M+H-56).
82%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; tripotassium phosphate tribasic In N,N-dimethyl-formamide at 90℃; for 2h; Inert atmosphere;	Stepl: tert-butyl 4-[2-(2, 6-dioxopiperidin-3-yl)-l,3-dioxoisoindol-5-yl]-3, 6-dihydro-2H-pyridine- 1- carboxylate A solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-l, 3-dione (500 mg, 1.48 mmol), N-Boc-l,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (459 mg, 1.48 mmol), K3PO4 (787 mg, 3.71 mmol) and Pd(dppf)2Cl2 (218 mg, 0.30 mmol) in DMF (10 mL) was stirred at 90 °C for 2 h under nitrogen. The resulted mixture was diluted with water, and extracted with EA. The organic layers were combined, washed with brine, dried over Na2SO4 , filtered, and concentrated. The residue was purified by silica gel chromatography (PE / EA = 1 / 1) to afford the desired product (532 mg, 82% yield) as a yellow oil. LCMS calculated for C23H26N3O6 (M+H)+m/z =440.2 ; found: 384.0 (M+H-56).

29%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; tripotassium phosphate tribasic In 1,4-dioxane at 100℃; Inert atmosphere;	76.2 Step 2: Synthesis of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol- 5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate. To a mixture of 5-bromo-2-(2,6- dioxopiperidin-3-yl)isoindole-1,3-dione (2.0 g, 5.93 mmol, 1 equiv) and tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (2.2 g, 7.1 mmol, 1.2 eq.) in dioxane (50 mL) were added K3PO4(2.52 g, 11.9 mmol, 2 equiv) and Pd(PPh3)2Cl2(0.83 g, 1.2 mmol, 0.2 equiv). The resulting mixture was stirred at 100 °C overnightunder nitrogenatmosphere. The resulting mixture was concentrated under vacuum and the residue was purified by Chromatography A to yield the title compound (840 mg, 29% yield).
29%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; tripotassium phosphate tribasic In 1,4-dioxane at 100℃; Inert atmosphere;	76.2 Step 2: Synthesis of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol- 5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate. To a mixture of 5-bromo-2-(2,6- dioxopiperidin-3-yl)isoindole-1,3-dione (2.0 g, 5.93 mmol, 1 equiv) and tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (2.2 g, 7.1 mmol, 1.2 eq.) in dioxane (50 mL) were added K3PO4(2.52 g, 11.9 mmol, 2 equiv) and Pd(PPh3)2Cl2(0.83 g, 1.2 mmol, 0.2 equiv). The resulting mixture was stirred at 100 °C overnightunder nitrogenatmosphere. The resulting mixture was concentrated under vacuum and the residue was purified by Chromatography A to yield the title compound (840 mg, 29% yield).
20.5%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 16h;	46.2 Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H- pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine- 1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent) in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 h at 80 oC under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6- dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil. LCMS (ESI) m/z: [M+H]+ =440.
20.5%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 16h; Inert atmosphere;	10.2 Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent ), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent)in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere.The resulting mixture was stirred for 16 h at 80 °C under a nitrogen atmosphere.The resulting mixture was concentrated under reduced pressure.The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil.LCMS (ESI) m/z: [M+H]+ =440.
20.5%		2 Step 2: Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent) in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 h at 80° C. under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil. LCMS (ESI) m/z: [M+H]+=440.
20.5%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 16h; Inert atmosphere;	10.2 Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent) in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 h at 80° C. under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil. LCMS (ESI) m/z: [M+H]+=440.
20.5%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 16h; Inert atmosphere;	10.2 Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent) in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 h at 80° C. under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil. LCMS (ESI) m/z: [M+H]+=440.
20.5%	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 16h; Inert atmosphere;	10.2 Step 2: Preparation of tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate To a stirred solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (3.00 g, 8.899 mmol, 1.00 equivalent), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (3.30 g, 10.672 mmol, 1.20 equivalent ), K3PO4 (5.67 g, 26.712 mmol, 3.00 equivalent)in dioxane (20.00 mL) and H2O (4.00 mL) was added Pd(PPh3)2Cl2 (0.62 g, 0.883 mmol, 0.10 equivalent) at room temperature under nitrogen atmosphere.The resulting mixture was stirred for 16 h at 80 °C under a nitrogen atmosphere.The resulting mixture was concentrated under reduced pressure.The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (8/1) to afford tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (0.8 g, 20.5%) as a colorless oil.LCMS (ESI) m/z: [M+H]+ =440.
	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 90℃;

Reference： [1]Current Patent Assignee: ARVINAS - WO2021/77010, 2021, A1 Location in patent: Paragraph 00782; 00783
[2]Current Patent Assignee: PRELUDE THERAPEUTICS INCORPORATED - WO2022/99117, 2022, A1 Location in patent: Paragraph 431
[3]Current Patent Assignee: PRELUDE THERAPEUTICS INCORPORATED - WO2022/99117, 2022, A1 Location in patent: Paragraph 431
[4]Current Patent Assignee: NURIX THERAPEUTICS INC; GILEAD SCIENCES INC - WO2021/226262, 2021, A1 Location in patent: Page/Page column 198
[5]Current Patent Assignee: NURIX THERAPEUTICS INC; GILEAD SCIENCES INC - WO2021/226262, 2021, A1 Location in patent: Page/Page column 198
[6]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1 Location in patent: Page/Page column 324-325
[7]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1 Location in patent: Page/Page column 125-126
[8]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1
[9]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1 Location in patent: Paragraph 0442; 0445-0446
[10]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1 Location in patent: Paragraph 0442; 0445-0446
[11]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1 Location in patent: Page/Page column 125-126
[12]Current Patent Assignee: ARVINAS - WO2018/140809, 2018, A1 Location in patent: Paragraph 00458

31
[ 26166-92-7 ]
[ 927-74-2 ]
C₁₇H₁₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In tetrahydrofuran at 70℃; for 12h;

Reference： [1]Current Patent Assignee: ARVINAS - WO2018/140809, 2018, A1 Location in patent: Paragraph 00461

32
[ 86-90-8 ]
[ 2353-44-8 ]
[ 26166-92-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium acetate; acetic acid; at 120℃; for 5h;	[0176] A solution of 5-bromoisobenzofuran-l,3-dione (2.0 g, 8.8 mmol), 3- aminopiperidine-2,6-dione (1.4 g, 8.8 mmol) and AcONa (1.4 g, 17.6 mmol) in AcOH (25 mL) was heated at l20C for 5 h. The mixture was concentrated, and the residue was washed with water followed by MeOH and DCM to give 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-l,3- dione (2.7 g, 90% yield) as a solid. MS (ESI) m/z 359.0 [M+Na]+.
81%	With triethylamine; In acetonitrile; at 80℃; for 12h;	5-Bromo-benzofuran-1,3-dione (P1) (2.93 g, 8.7 mmol) and 3-aminopiperidine-2,6-dione (2.57 g, 11.3 mmol) were dissolved in CH3CN (30 mL) ), TEA (2.8 mL, 7.57 mmol), refluxed at 80 C for 12 h. TLC detected the end of the reaction. The reaction solution was extracted with ethyl acetate and water, the organic layer was rotary evaporation to give a white solid P2, 81% yield.

Reference： [1]Patent: WO2019/241274,2019,A1 .Location in patent: Paragraph 0176
[2]Patent: CN110078725,2019,A .Location in patent: Paragraph 0048; 0079; 0081-0083

33
[ 634926-63-9 ]
[ 26166-92-7 ]
tert-butyl (2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h;	1 Step 1-Tert-butyl N-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]prop-2-ynoxy]ethyl]carbamate To a solution of tert-butyl N-(2-prop-2-ynoxyethyl)carbamate (2.36 g, 11.8 mmol synthesized via Step 1 on Intermediate CP), 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (2.00 g, 5.93 mmol, Intermediate GA) in DMF (4.00 mL) was added CuI (112 mg, 593 umol), Pd(PPh3)2Cl2 (416 mg, 593 umol), and TEA (10.8 g, 106 mmol). The mixture was stirred at 80° C. for 0.5 hr. On completion, the mixture was concentrated in vacuo. The mixture was purified by silica gel column (PE:EA=1:1) to give the title compound (2.60 g, 96% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.2 (s, 1H), 8.01 (s, 1H), 8.00 (s, 2H), 6.97-6.87 (m, 1H), 5.28-5.17 (m, 1H), 4.52 (s, 2H), 3.66-3.55 (m, 2H), 3.25-3.17 (m, 2H), 2.95-2.89 (m, 1H), 2.71-2.63 (m, 1H), 2.62-2.58 (m, 1H), 2.17-2.09 (m, 1H), 1.43 (s, 9H).
94%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.583333h; Inert atmosphere;	2 Step 2-Tert-butyl (2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl)carbamate 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.4 g, 1.19 mmol, Intermediate CO), CuI (22.6 mg, 119 umol) and Pd(PPh3)2Cl2 (83.3 mg, 119 umol) were put into a microwave tube. Then tert-butyl N-(2-prop-2-ynoxyethyl)carbamate (473 mg, 2.37 mmol), TEA (2.16 g, 2.98 mL, 21.4 mmol) and DMF (3 mL) were added into the tube. The mixture was degassed with nitrogen for 5 minutes. The sealed tube was then heated at 80° C. for 30 minutes under microwave. On completion, the reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (SiO2) to give the title compound (510 mg, 94% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.92 (s, 1H), 7.87-7.78 (m, 2H), 5.03-4.96 (m, 1H), 4.94 (s, 1H), 4.43 (s, 2H), 3.67 (t, J=5.2 Hz, 2H), 3.39 (d, J=5.2 Hz, 2H), 2.96-2.90 (m, 1H), 2.88-2.80 (m, 1H), 2.79-2.71 (m, 1H), 2.21-2.13 (m, 1H), 1.45 (s, 9H).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3064; 3065
[2]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2386; 2388

34
[ 26166-92-7 ]
[ 869310-84-9 ]
tert-butyl (2-(2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethoxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h;	2 Step 2-Tert-butyl (2-(2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethoxy)ethyl)carbamate To a solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (300 mg, 890 umol, Intermediate CO) and tert-butyl N-[2-(2-prop-2-ynoxyethoxy)ethyl]carbamate (433 mg, 1.78 mmol) in DMF (8 mL) was added Pd(PPh3)2Cl2 (62.5 mg, 88.9 umol), TEA (1.62 g, 16.0 mmol, 2.23 mL) and CuI (16.9 mg, 88.9 umol). The reaction mixture was heated at 80° C. for 30 minutes under microwave. On completion, the mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether: Ethyl acetate=5:1 to 1:0) to give the title compound (440 mg, 89% yield) as a yellow solid. LC-MS (ESI+) m/z 400.1 (M+H-100)+.
89%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Microwave irradiation;	2 Step 2 - Tert-butyl (2-(2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl]oxy)ethoxy)ethyl)carbamate To a solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (300 mg, 890 umol, Intermediate CO) and tert-butyl N-[2-(2-prop-2-ynoxyethoxy)ethyl]carbamate (433 mg, 1.78 mmol) in DMF (8 mL) was added Pd(PPh3)2Cl2 (62.5 mg, 88.9 umol), TEA (1.62 g, 16.0 mmol, 2.23 mL) and Cul (16.9 mg, 88.9 umol). The reaction mixture was heated at 80 °C for 30 minutes under microwave. On completion, the mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether: Ethyl acetate = 5: 1 to 1:0) to give the title compound (440 mg, 89% yield) as ayellow solid. LC-MS (ESI+) m/z 400.1 (M+H-100)+.
89%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Microwave irradiation;	2 Step 2 - Tert-butyl (2-(2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl]oxy)ethoxy)ethyl)carbamate To a solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (300 mg, 890 umol, Intermediate CO) and tert-butyl N-[2-(2-prop-2-ynoxyethoxy)ethyl]carbamate (433 mg, 1.78 mmol) in DMF (8 mL) was added Pd(PPh3)2Cl2 (62.5 mg, 88.9 umol), TEA (1.62 g, 16.0 mmol, 2.23 mL) and Cul (16.9 mg, 88.9 umol). The reaction mixture was heated at 80 °C for 30 minutes under microwave. On completion, the mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether: Ethyl acetate = 5: 1 to 1:0) to give the title compound (440 mg, 89% yield) as ayellow solid. LC-MS (ESI+) m/z 400.1 (M+H-100)+.

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2391; 2393
[2]Current Patent Assignee: KYMERA THERAPEUTICS INC - WO2021/188948, 2021, A1 Location in patent: Paragraph 001218; 001221-001222
[3]Current Patent Assignee: KYMERA THERAPEUTICS INC - WO2021/188948, 2021, A1 Location in patent: Paragraph 001218; 001221-001222

35
[ 26166-92-7 ]
[ 57260-71-6 ]
tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With RuPhos Pd G₂; caesium carbonate In 1,4-dioxane at 80℃; for 15h; Inert atmosphere;	1 Step 1-Tert-butyl 4-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]piperazine-1-carboxylate 5-Bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (0.5 g, 1.48 mmol, Intermediate GA), tert-butyl piperazine-1-carboxylate (552 mg, 2.97 mmol), Cs2CO3 (966 mg, 2.97 mmol) and [2-(2-aminophenyl)phenyl]-chloro-palladium; dicyclohexyl-[2-(2,6-diisopropoxyphenyl)phenyl]-phosphane (115 mg, 148 umol, CAS1375325-68-0) in dioxane (10 mL) was degassed and then heated to 80° C. for 15 hours under N2. On completion, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography to give the title compound (100 mg, 14% yield) as a yellow solid. LC-MS (ESI+) m/z 465.1 (M+Na)+.

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2924; 2925

36
[ 26166-92-7 ]
tert-butyl methyl(2-(2-(prop-2-yn-1-yloxy)ethoxy)ethyl)carbamate [ No CAS ]
tert-butyl N-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-5-yl]prop-2-ynoxy]ethoxy]ethyl]-N-methylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Microwave irradiation;	1 Step 1-Tert-butyl N-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]prop-2-ynoxy]ethoxy]ethyl]-N-methyl-carbamate To a solution of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (3.73 g, 11.0 mmol, Intermediate GA) and tert-butyl N-methyl-N-[2-(2-prop-2-ynoxyethoxy)ethyl]carbamate (3.70 g, 14.3 mmol, Intermediate FY) in DMF (30 mL) was added Pd(PPh3)2Cl2 (776 mg, 1.11 mmol), TEA (20.1 g, 199 mmol) and CuI (210 mg, 1.11 mmol). The mixture was heated at 80° C. for 30 minutes under microwave. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by silica gel chromatography (PE:EA=1:1) to give the title compound (5.50 g, 96% yield) as brown oil. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.91 (s, 1H), 7.87-7.78 (m, 2H), 4.99 (dd, J=5.6, 12.4 Hz, 1H), 4.48 (s, 2H), 3.80-3.73 (m, 2H), 3.71-3.66 (m, 2H), 3.65-3.58 (m, 2H), 3.45-3.35 (m, 2H), 2.98-2.94 (m, 1H), 2.93 (s, 3H), 2.88-2.70 (m, 2H), 2.21-2.13 (m, 1H), 1.46 (s, 9H).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2745; 2746

37
[ 26166-92-7 ]
tert-butyl N-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-5-yl]methyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 3 h / 100 °C / Inert atmosphere 2: hydrogen / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / 30 °C / 2585.81 Torr
	Multi-step reaction with 2 steps 1: 1-methyl-pyrrolidin-2-one / 2 h / 180 °C / Microwave irradiation 2: hydrogen / methanol / 48 h
	Multi-step reaction with 2 steps 1: 1-methyl-pyrrolidin-2-one / 2 h / 180 °C / Microwave irradiation 2: hydrogen / methanol / 48 h / 20 °C

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1
[2]Current Patent Assignee: BIOTHERYX INC - WO2019/241274, 2019, A1
[3]Current Patent Assignee: BIOTHERYX INC; YU - US2020/369679, 2020, A1

38
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(3-hydroxypropyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride / N,N-dimethyl-formamide / 0.5 h / 80 °C / Inert atmosphere; Microwave irradiation 2: hydrogen; 10% palladium hydroxide on charcoal; palladium 10% on activated carbon / tetrahydrofuran / 3 h / 20 °C / 775.74 Torr
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper(l) iodide / tetrahydrofuran / 8 h / Reflux 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 760.05 Torr

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1

39
[ 26166-92-7 ]
5-[3-[4-[4-amino-3-(difluoromethyl)pyrazol-1-yl]-1-piperidyl]propyl]-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine; copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride / N,N-dimethyl-formamide / 0.5 h / 80 °C / Inert atmosphere; Microwave irradiation 2: hydrogen; 10% palladium hydroxide on charcoal; palladium 10% on activated carbon / tetrahydrofuran / 3 h / 20 °C / 775.74 Torr 3: triethylamine / dichloromethane / 3 h / 20 °C 4: sodium hydrogencarbonate; potassium iodide / acetonitrile / 16 h / 80 °C
	Multi-step reaction with 5 steps 1: triethylamine; copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride / N,N-dimethyl-formamide / 0.5 h / 80 °C / Inert atmosphere 2: hydrogen; 10% palladium hydroxide on charcoal; palladium 10% on activated carbon / tetrahydrofuran / 2 h / 20 °C 3: triethylamine / dichloromethane / 3 h / 20 °C 4: sodium hydrogencarbonate; potassium iodide / acetonitrile / 16 h / 80 °C 5: hydrogen; platinum(IV) oxide / tetrahydrofuran / 16 h / 20 °C / 775.74 Torr

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1
[2]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1

40
[ 26166-92-7 ]
tert-butyl N-methyl-N-[2-(prop-2-yn-1-yloxy)ethyl]carbamate [ No CAS ]
tert-butyl N-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-5-yl]prop-2-ynoxy]ethyl]-N-methylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h;	1 Step 1-Tert-butyl N-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]prop-2-ynoxy]ethyl]-N-methyl-carbamate To a solution of tert-butyl N-methyl-N-(2-prop-2-ynoxyethyl)carbamate (2.53 g, 11.8 mmol, Intermediate GK) and 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (2.00 g, 5.93 mmol, Intermediate GA) in DMF (4.00 mL) was added TEA (10.8 g, 106 mmol), CuI (112 mg, 593 umol) and Pd(PPh3)2Cl2 (416 mg, 593 umol), and the reaction mixture was heated at 80° C. for 30 min under microwave. On completion, the mixture was concentrated in vacuo. The mixture was purified by silica gel column (PE:EA=1:1) to give the title compound (2.7 g, 96% yield) as yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.93 (s, 1H), 7.89-7.79 (m, 2H), 5.02-4.96 (m, 1H), 4.44 (s, 2H), 3.73 (s, 2H), 3.48 (s, 2H), 2.97 (s, 3H), 2.96-2.91 (m, 1H), 2.89-2.82 (m, 1H), 2.82-2.73 (m, 1H), 2.22-2.15 (m, 1H), 1.48 (s, 9H).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3043; 3044

41
[ 26166-92-7 ]
[ 1219810-90-8 ]
tert-butyl (15-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6,9,12-tetraoxapentadec-14-yn-1-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 5-bromo-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione; tert-butyl N-[2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethyl]carbamate With copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Stage #2: With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 70℃; Inert atmosphere;	1 Step 1-tert-butyl (15-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6,9,12-tetraoxapentadec-14-yn-1-yl)carbamate In a flame dried reaction assembly equipped with nitrogen bubbler was prepared a solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (1.0 g, 3.0 mmol, Intermediate CO) and tert-butyl (3,6,9,12-tetraoxapentadec-14-yn-1-yl)carbamate (1.18 g, 3.56 mmol, Intermediate EW) in DMF (20 mL) at rt. Cuprous iodide (0.11 g, 0.59 mmol) and TEA (5.0 mL, 36.0 mmol) were sequentially added to the reaction mixture at rt. The resulting reaction mixture was degassed with argon for 10-15 min. Then Pd(PPh3)2Cl2 (0.02 g, 0.029 mmol) was added to the reaction mixture and argon purging was continued for 5-10 min. The reaction mixture was then heated at 70° C. and stirred for 0.5 h under argon atmosphere. The resulting reaction mixture was then cooled to rt and concentrated on a rotary evaporator. The obtained crude product was purified by gradient column chromatography using neutral alumina as stationary phase and DCM/IPA as a mobile phase. The title compound (1.1 g, 63%) was isolated as a light yellow viscous oil which solidified upon standing overnight at 0-5° C. temperature. LC-MS (ESI+) m/z 488.0 (M-100+H)+.
32.1%	With copper(l) iodide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20 - 65℃; for 2h; Inert atmosphere;	1 General procedure for preparation of compound 9d To a solution of Compound 9f (187 mg, 554 umol) in THF (5 mL ) was added Cul (15 mg, 78.7 umol) and DIPEA (585 mg, 4.53 mmol) at 20-25 °C under N2, then Pd(dppf)Cl2•CH2Cl2 (38 mg, 46.5 umol) and Compound 9c (150 mg, 452 umol) was added to the solution at 20-25 °C und er N2, then it was stirred at 60-65 °C for 2 hrs. LCMS showed the MS of Comp ound 9d was detected (RT = 0.903 min M/Z+1 = 588), TLC (Petroleum ether: Ethyl acetate = 0:1 ) showed the Compound 9c (Rf = 0.67) was consumed up, a new spot was detected (Rf = 0.30). The reaction solution was cooled to 20-30 °C, then it was quenched with acetic acid to pH = 3-4 and poured into water (10 mL ), then extracted with ethyl acetate (10 mL *2), the combined organic layer was washed with brine (5 mL) dried over Na2SO4, filtrated and concentrated under reduce pressure to afford the crude product. Then it was purified by silica gel column chromatography (SiO2, Petroleum ether: ethyl acetate = 10:1 -5:1 - 0:1 , the spot (Rf = 0.30) was collected). Compound 9d (90 mg, 145 umol, 32.1 % yield) was obtained as a colorless oil, which was confirmed by LCMS, RT = 0.897 min, M/Z+1 - 100 = 488), 1H-NMR. 1H NMR: 400 MHz, CDCl3 d 7.94 (s, 1 H), 7.81 -7.88 (m, 1 H), 7.70-7.79 (m, 1 H), 7.26-7.48 (m, 1 H), 4.91 (dd, J = 12.4, 5.2 Hz, 1 H), 4.94-5.00 (m, 1 H), 4.40 (s, 1 H), 4.21 (s, 1 H), 4.13 (s, 1 H), 3.61 -3.75 (m, 12H), 3.55 (t, J = 5.2 Hz, 2H), 3.26-3.36 (m, 2H), 2.71 - 2.95 (m, 2H), 2.13-2.23 (m, 1 H), 1.37 (s, 9H). LCMS: (Method 1 ), RT = 0.903 min, M/Z+1 = 588

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2399; 2400
[2]Current Patent Assignee: MERCK KGAA - WO2020/152067, 2020, A1 Location in patent: Page/Page column 52; 76-77

42
[ 26166-92-7 ]
[ 92136-39-5 ]
tert-butyl N-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-5-yl]prop-2-ynyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Microwave irradiation;	1 Step 1-Tert-butyl N-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]prop-2-ynyl]carbamate To a solution of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (1 g, 2.97 mmol Intermediate GA) and tert-butyl N-prop-2-ynylcarbamate (920 mg, 5.93 mmol) in DMF (4 mL) was added Pd(PPh3)2Cl2 (208 mg, 296 umol) TEA (5.40 g, 53 mmol, 7.43 mL) and CuI (57 mg, 296 umol). The mixture was stirred at 80° C. for 0.5 hr under microwave. On completion, the mixture was concentrated in vacuo, the residue was purified by silica gel chromatography to give the title compound (1.3 g, 95% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.01-7.81 (m, 3H), 5.17 (dd, J=5.2, 12.8 Hz, 1H), 4.10-4.03 (m, 2H), 3.33 (s, 1H), 2.94-2.84 (m, 1H), 2.73-2.53 (m, 2H), 2.13-2.02 (m, 1H), 1.47-1.36 (m, 9H); LC-MS (ESI+) m/z 434.0 (M+Na)+.

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3035; 3036

43
[ 26166-92-7 ]
[ 124045-51-8 ]
tert-butyl N-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-5-yl]prop-2-ynyl]-N-methylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine at 80℃; for 0.5h;	1 Step 1-Tert-butyl N-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]prop-2-ynyl]-N-methyl-carbamate To a mixture of tert-butyl N-methyl-N-prop-2-ynyl-carbamate (1.00 g, 5.93 mmol, Intermediate IY) and 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (1.00 g, 2.97 mmol, Intermediate GA) in DMF (4 mL) was added CuI (56.4 mg, 296 umol), TEA (5.40 g, 53.3 mmol, 7.43 mL) and Pd(PPh3)2Cl2 (208 mg, 296 umol). The reaction mixture was heated at 80° C. for 0.5 hour under microwave. On completion, the reaction mixture was diluted with water (30 mL) and extracted with EA (3×50 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give a residue. The residue was purified by column chromatography to give the title compound (1.20 g, 95% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 7.96-7.88 (m, 3H), 5.16 (dd, J=5.6, 12.8 Hz, 1H), 4.33 (s, 2H), 3.33 (s, 3H), 2.89-2.83 (m, 1H), 2.64-2.51 (m, 2H), 2.10-2.02 (m, 1H), 1.42 (s, 9H).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3031; 3032

44
[ 193269-78-2 ]
[ 26166-92-7 ]
tert-butyl 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2′,4′,6′- triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′ -biphenyl)]palladium(II) methanesulfonate methanesulfonate; caesium carbonate In 1,4-dioxane at 90℃; for 2h; Inert atmosphere;	1 Step 1-Tert-butyl 3-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]amino]azetidine-1-carboxylate A mixture of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (500 mg, 1.48 mmol, Intermediate GA), tert-butyl 3-aminoazetidine-1-carboxylate (383 mg, 2.22 mmol, CAS193269-78-2), Brettphos-G3 (134 mg, 148 umol), and Cs2CO3 (1.45 g, 4.45 mmol) in dioxane (50 mL) was degassed and purged with N2 3 times. Then the mixture was stirred at 90° C. for 2 hours under N2 atmosphere. On completion, the mixture was concentrated in vacuo. The residue was purified by pre-HPLC to give the title compound (90.0 mg, 13% yield) as yellow solid. LC-MS (ESI+) m/z 451.1 (M+Na)+.

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 2929; 2930

45
[ 557-21-1 ]
[ 26166-92-7 ]
[ 1010100-21-6 ]

Yield	Reaction Conditions	Operation in experiment
52%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere;	1 Step 1-2-(2,6-Dioxo-3-piperidyl)-1,3-dioxo-isoindoline-5-carbonitrile To a solution of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (450 mg, 1.33 mmol, Intermediate GA), Zn(CN)2 (94.0 mg, 800 umol) in DMF (15.0 mL) was added Pd(PPh3)4 (154 mg, 133 umol). The mixture was stirred at 100° C. for 3 hours under N2. On completion, the mixture was diluted with H2O (50 mL), filtered and the solid was dried in vacuo. The solid was triturated with PE:EA=5:1 (30 mL), filtered and the solid was dried in vacuo to give the title compound (200 mg, 52% yield) as purple solid. 1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.49 (s, 1H), 8.38 (dd, J=1.2, 7.6 Hz, 1H), 8.12 (d, J=7.6 Hz, 1H), 5.26-5.17 (m, 1H), 2.97-2.89 (m, 1H), 2.65-2.58 (m, 1H), 2.57-2.52 (m, 1H), 2.12-2.05 (m, 1H).

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3039; 3040

46
[ 26166-92-7 ]
[ 764-48-7 ]
2-(2,6-dioxo-3-piperidyl)-5-[2-(2-hydroxyethoxy)ethyl]isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With tris-(dibenzylideneacetone)dipalladium(0); N-Methyldicyclohexylamine; In 1,4-dioxane; at 25℃; for 16h;	To a solution of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (2.00 g, 5.93 mmol Intermediate GA), 2-vinyloxyethanol (1.05 g, 11.8 mmol) in dioxane (15.0 mL) was added P(t-Bu)3 (2.40 g, 1.19 mmol, 10 wt %), Pd2(dba)3 (543 mg, 593 umol) and N-cyclohexyl-N-methyl-cyclohexanamine (1.51 g, 7.71 mmol), and the mixture was stirred at 25 C. for 16 hrs. On completion, the mixture was concentrated in vacuo. The mixture was purified by silica gel column (EA) to give the title compound (2.00 g, 97% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 11.13 (s, 1H), 7.91 (s, 1H), 7.79-7.76 (m, 1H), 7.72 (s, 1H), 7.71-7.67 (m, 1H), 6.08 (d, J 12.8 Hz, 1H), 5.17-5.10 (m, 1H), 4.91-4.86 (m, 1H), 3.96 (t, J=4.8 Hz, 2H), 3.70-3.63 (m, 2H), 2.95-2.84 (m, 1H), 2.65-2.57 (m, 1H), 2.57-2.53 (m, 1H), 2.11-2.01 (m, 1H).

Reference： [1]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 3053; 3054

47
[ 26166-92-7 ]
[ 5390-04-5 ]
2-(2,6-dioxopiperidin-3-yl)-5-(5-hydroxypent-1-yn-1-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 0.5h; Inert atmosphere;	1 Step 1-2-(2,6-Dioxo-3-piperidyl)-5-(5-hydroxypent-1-ynyl)isoindoline-1,3-dione A mixture of 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (1.00 g, 2.97 mmol, Intermediate GA), pent-4-yn-1-ol (499 mg, 5.93 mmol), Pd(PPh3)2Cl2 (208 mg, 296 umol), CuI (56.0 mg, 296 umol) and TEA (5.40 g, 53.3 mmol, 7.43 mL) in DMF (4 mL) was degassed and purged with N2 gas 3 times. The mixture was stirred at 80° C. for 0.5 hr under microwave. On completion, the mixture was extracted with EA (2×100 mL). The organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to give the title compound (900 mg, 89% yield) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 7.94-7.78 (m, 3H), 5.17 (dd, J=5.6, 12.8 Hz, 1H), 4.57 (t, J=5.2 Hz, 1H), 3.55 (q, J=6.0 Hz, 2H), 2.97-2.84 (m, 1H), 2.67-2.55 (m, 4H), 2.15-2.02 (m, 1H), 1.77-1.70 (m, 2H).
37.6%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 50℃; for 4h;	1.3 Step 3: preparation of 2-(2, 6-dioxopiperidin-3-yl)-5-(5-hydroxypent-1-yn-1-yl)isoindoline- 1, 3-dione (Intermediate 4) To a stirred solution of Intermediate 3 (5.0 g, 14.8 mmol, 1.0 equiv), Pd(PPh3)2Cl2 (2.1 g, 3.0 mmol, 0.2 equiv), and copper(l) iodide (0.56 g, 3.0 mmol, 0.2 equiv) in tetrahydrofuran (40 ml_) were added DIEA (19.2 g, 148.3 mmol, 10.0 equiv) and pent-4-yn-1-ol (3.7 g, 44.5 mmol, 3.0 equiv) dropwise at room temperature. The resulting mixture was stirred for 4 h at 50 °C. The resulting mixture was filtered, the filter cake was washed with THF (3 x 50 ml_). The filtrate was concentrated under reduced pressure and concentrated. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (1 :1) to afford Intermediate 4 (1.9 g, 37.6%) as a yellow solid. LCMS (ESI) m/z: [M+H]+ = 341.

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - US2019/192668, 2019, A1 Location in patent: Paragraph 3393; 3394
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2021/155321, 2021, A2 Location in patent: Page/Page column 316; 317

48
[ 26166-92-7 ]
5-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione TFA salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-methyl-pyrrolidin-2-one / 2 h / 180 °C / Microwave irradiation 2: hydrogen / methanol / 48 h 3: dichloromethane / 1 h
	Multi-step reaction with 3 steps 1: 1-methyl-pyrrolidin-2-one / 2 h / 180 °C / Microwave irradiation 2: hydrogen / methanol / 48 h / 20 °C 3: dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: BIOTHERYX INC - WO2019/241274, 2019, A1
[2]Current Patent Assignee: BIOTHERYX INC; YU - US2020/369679, 2020, A1

49
[ 26166-92-7 ]
copper(l) cyanide [ No CAS ]
[ 1010100-21-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	In 1-methyl-pyrrolidin-2-one at 180℃; for 2h; Microwave irradiation;	19 [0177] A solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-l,3-dione (1.0 g, 3.0 mmol) and CuCN (0.8 g, 9.0 mmol) in NMP (8 mL) was heated at l80°C under microwave for 2 h. The mixture was filtered, diluted with water, and extracted with EA. The combined organic layers were washed with brine, dried over Na2S04, filtered, and concentrated. The residue was washed with MeOH and DCM to give 2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindoline-5- carbonitrile (600 mg, 71% yield) as a solid. MS (ESI) m/z 306.0 [M+Na]+.
71%	In 1-methyl-pyrrolidin-2-one at 180℃; for 2h; Microwave irradiation;	7 To a solution of 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione 31 (1.0 g, 3.0 mmol) in 1-methyl-2-pyrrolidinone (8 mL) was added CuCN (0.8 g, 9.0 mmol). The mixture was stirred at 180° C. for 2 h under microwave and then filtered. The filtrate was diluted with H2O and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was triturated with MeOH/DCM (1:10) to give 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carbonitrile 32 (600 mg) in 71% yield. MS (ESI) m/z: 306.0 [M+Na]+.

Reference： [1]Current Patent Assignee: BIOTHERYX INC - WO2019/241274, 2019, A1 Location in patent: Paragraph 0177
[2]Current Patent Assignee: BIOTHERYX INC; YU - US2020/369679, 2020, A1 Location in patent: Paragraph 1290-1291; 1293

50
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(3-(4-(6-(6-((R)-2-(3-fluorophenyl) pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper(l) iodide / tetrahydrofuran / 8 h / Reflux 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 760.05 Torr 3: triethylamine / dichloromethane / 20 °C 4: potassium carbonate; sodium iodide / acetonitrile / 5 h / 80 °C
	Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / Reflux 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C 3: triethylamine / dichloromethane / 20 °C 4: sodium iodide; potassium carbonate / acetonitrile / 5 h / 80 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2021/170109, 2021, A1

51
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-((E)-3-(4-(6-(6-((R)-2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)-3-oxoprop-1-en-1-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / dimethyl sulfoxide / 16 h / 90 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 1-hydroxy-7-aza-benzotriazole / dimethyl sulfoxide; 1-methyl-pyrrolidin-2-one / 16 h / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / dimethyl sulfoxide / 16 h / 90 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 1-hydroxy-7-aza-benzotriazole; 4-methyl-morpholine / dimethyl sulfoxide / 16 h / 20 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2021/170109, 2021, A1

52
[ 26166-92-7 ]
3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)propyl 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper(l) iodide / tetrahydrofuran / 8 h / Reflux 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 760.05 Torr 3: triethylamine / dichloromethane / 20 °C
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / Reflux 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C 3: triethylamine / dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2021/170109, 2021, A1

53
[ 26166-92-7 ]
[ 79-10-7 ]
(E)-3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In dimethyl sulfoxide at 90℃; for 16h;
42%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In dimethyl sulfoxide at 90℃; for 16h;

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/38415, 2020, A1 Location in patent: Page/Page column 189
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2021/170109, 2021, A1 Location in patent: Page/Page column 278

54
[ 26166-92-7 ]
tert-butyl 3-(3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)propoxy)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / N,N-dimethyl-formamide / 16 h / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / ethanol / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / N,N-dimethyl-formamide / 90 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2020/81450, 2020, A1
[2]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2021/91575, 2021, A1

55
[ 26166-92-7 ]
3-{3-[2-(2,6- dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]propoxy}propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / N,N-dimethyl-formamide / 16 h / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / ethanol / 2 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / N,N-dimethyl-formamide / 90 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2020/81450, 2020, A1
[2]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2021/91575, 2021, A1

56
[ 26166-92-7 ]
[ 488150-84-1 ]
tert-butyl 3-({3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]prop-2-yn-1-yl}oxy)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.2%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide for 16h; Inert atmosphere;	23.1 Step 1 : 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-l,3-dione (347 mg, 1.03 mmol), (PPhs^PdCh (43.4 mg, 0.06 mmol), Cul (19.6 mg, 0.10 mmol) were added to a vial. The vial was evacuated and backfilled with N2 5 times. DMF (0.00 g, 1.03 mmol), /f/V-butyl 3-(prop-2-yn-l-yloxy)propanoate (190 mg, 1.03 mmol) and triethylamine (1.72 mL, 12.4 mmol) were added and the mixture was allowed to stir at 90 °C overnight. The mixture was filtered through Si02 washing with EtOAc/MeOH, concentrated and purified by HPLC (5-95% MeCN in H20 with 0.1% TFA) to afford tert- butyl 3-({3-[2-(2,6- dioxopiperidin-3-yl)-l,3-dioxoisoindol-5-yl]prop-2-yn-l-yl}oxy)propanoate (173 mg, 38.2%).
38.2%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 90℃; Inert atmosphere;	2.I.2 Step 2: 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione (347.00 mg, 1.03 mmol), (PPh3)2PdCl2 (43.4 mg, 0.06 mmol), and CuI (19.6 mg, 0.10 mmol) were added to a vial. The vial was evacuated and backfilled with N25 times. DMF (5 mL), tert-butyl 3-(prop-2-yn-1-yloxy)propanoate (189.6 mg, 1.03 mmol) and triethylamine (1.72 mL, 12.4 mmol) were added and the mixture was allowed to stir at 90 °C overnight. The mixture was purified by HPLC (5-95% MeCN in H2O with 0.1% TFA) to afford tert-butyl 3-({3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]prop-2-yn-1-yl}oxy)propanoate (173 mg, 38.2%). LCMS: C23H24N2O7 requires: 440, found: m/z = 441 [M+H]+.

Reference： [1]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2020/81450, 2020, A1 Location in patent: Paragraph 0657; 0658
[2]Current Patent Assignee: NURIX THERAPEUTICS INC - WO2021/91575, 2021, A1 Location in patent: Paragraph 0587; 0589

57
[ 26166-92-7 ]
14-(t-butoxycarbonylamino)tetradecanoic acid [ No CAS ]
C₃₂H₄₆N₄O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40 mg	With 1-methyl-1H-imidazole; N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate In N,N-dimethyl-formamide; acetonitrile at 20 - 25℃; for 12h; Inert atmosphere;	1 General procedure for preparation of compound 1m To a solution of compound 1 h (80 mg, 232 umol) and Compound 1 h_1 (60 mg, 219 umol) in ACN (4 mL ) and DMF (2 mL ) was added TCFH (151 mg, 538 umol) and NMI (125 mg, 1.52 mmol) under N2 at 20-25 °C, after addition, the mixture was stirred at 20-25 °C for 1 2 hrs. The reaction solution was quenched with AcOFI (2 mL ), then it was poured into water (10 mL ) and extracted with ethyl acetate (10 mL 2), the organic layer was washed with brine (10 mL ), dried over Na2SO4, filtrated and concentrated under reduce pressure. The crude was purified by Pre-HPLC (column: Phenomenex luna C18 15025mm* 10um; mobile phase: [water (0.1 %TFA)-ACN]; B%: 59%-89%, 10 min), then it was concentrated under reduce pressure to afford Compound 1 m (40 mg) as a colorless oil. LCMS: (method 1 ), RT = 1.125 min, m/z = 543

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2020/152067, 2020, A1 Location in patent: Page/Page column 52; 116-117

58
[ 26166-92-7 ]
tert-butyl 4-(2-(2,6-dioxopiperidin-3-yl)-1-hydroxy-3-oxoisoindolin-5-yl)piperidine-1-carboxylate [ No CAS ]
tert-butyl 4-(2-(2,6-dioxopiperidin-3-yl)-3-hydroxy-1-oxoisoindolin-5-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C 3: glacial acetic acid; zinc / 2 h / 60 °C
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C 3: glacial acetic acid; zinc / 2 h / 60 °C
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C 3: glacial acetic acid; zinc / 2 h / 60 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[3]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1

59
[ 26166-92-7 ]
3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione [ No CAS ]
3-(1-oxo-6-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2.1: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C 3.1: glacial acetic acid; zinc / 2 h / 60 °C 3.2: 2 h / 20 °C
	Multi-step reaction with 3 steps 1.1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C 3.1: glacial acetic acid; zinc / 2 h / 20 - 60 °C 3.2: TES / 2 h / 20 °C
	Multi-step reaction with 3 steps 1.1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2.1: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C 3.1: glacial acetic acid; zinc / 2 h / 60 °C 3.2: 2 h / 20 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[3]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1

60
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(piperidin-4-yl)isoindole-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 3 steps 1: potassium carbonate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / ethyl acetate / 20 °C 3: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

	Multi-step reaction with 3 steps 3: trifluoroacetic acid
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[2]Current Patent Assignee: ARVINAS - WO2021/77010, 2021, A1
[3]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[4]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1
[5]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1

61
[ 26166-92-7 ]
3-[3-hydroxy-1-oxo-5-(piperidin-4-yl)-3H-isoindol-2-yl]piperidine-2,6-dione [ No CAS ]
3-[1-hydroxy-3-oxo-5-(piperidin-4-yl)-1H-isoindol-2-yl]piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4: glacial acetic acid; zinc / 2 h / 25 °C
	Multi-step reaction with 4 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4: glacial acetic acid; zinc / 2 h / 25 °C
	Multi-step reaction with 4 steps 1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4: glacial acetic acid; zinc / acetonitrile / 2 h / 25 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[3]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1

62
[ 26166-92-7 ]
3-[5-[1-([4-[6-(azetidin-1-yl)-2-methyl-1-oxo-2,7-naphthyridin-4-yl]-2,6-dimethoxyphenyl]methyl)piperidin-4-yl]-3-hydroxy-1-oxo-3H-isoindol-2-yl]piperidine-2,6-dione [ No CAS ]
3-[5-[1-([4-[6-(azetidin-1-yl)-2-methyl-1-oxo-2,7-naphthyridin-4-yl]-2,6-dimethoxyphenyl]methyl)piperidin-4-yl]-1-hydroxy-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C 2.1: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 12 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4.1: glacial acetic acid; zinc / 2 h / 25 °C 4.2: 4 h / 25 °C
	Multi-step reaction with 4 steps 1.1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 12 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4.1: glacial acetic acid; zinc / 2 h / 25 °C 4.2: 4 h / 25 °C
	Multi-step reaction with 4 steps 1.1: tripotassium phosphate tribasic; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 16 h / 80 °C / Inert atmosphere 2.1: hydrogen; palladium on activated charcoal / tetrahydrofuran / 12 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 4.1: glacial acetic acid; zinc / 2 h / 25 °C 4.2: 4 h / 25 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160192, 2020, A1
[2]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2022/25880, 2022, A1
[3]Current Patent Assignee: FOGHORN THERAPEUTICS INC - US2022/48906, 2022, A1

63
[ 26166-92-7 ]
C₂₅H₂₈N₆O₂ [ No CAS ]
C₃₈H₃₆N₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 12h; Inert atmosphere;	7-Cyclopentyl-2-((4-(5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-ynamido)phenyl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide 3o. To a solution of 10o (0.11 g, 0.25 mmol) in DMF (3 mL) was added 9b (0.10 g, 0.31mmol), Pd(PPh3)Cl2 (18 mg, 0.030 mmol), CuI (5.1 mg, 0.030 mmol), DIPEA (0.40 mL ,2.5 mmol) under 70c °C for 12 h. The mixture was concentrated in vacuum. Theresidue was washed with H2O (5 mL), filtered and dried over anhydrous Na2SO4. Theresidue was purified by column chromatography on silica gel (dichloromethane :methanol= 50:1) to afford compound 3o as a yellow solid (75 mg, 43 %).

Reference： [1]Wei, Mingming; Zhao, Rui; Cao, Yuting; Wei, Yujiao; Li, Ming; Dong, Zhiqiang; Liu, Yulin; Ruan, Hao; Li, Ying; Cao, Sheng; Tang, Zhiwen; Zhou, Yuanyuan; Song, Wei; Wang, Yubo; Wang, Jiefu; Yang, Guang; Yang, Cheng [European Journal of Medicinal Chemistry, 2021, vol. 209]

64
[ 26166-92-7 ]
C₂₆H₃₀N₆O₂ [ No CAS ]
C₃₉H₃₈N₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 12h; Inert atmosphere;	7-Cyclopentyl-2-((4-(5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-ynamido)phenyl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide 3o. General procedure: To a solution of 10o (0.11 g, 0.25 mmol) in DMF (3 mL) was added 9b (0.10 g, 0.31mmol), Pd(PPh3)Cl2 (18 mg, 0.030 mmol), CuI (5.1 mg, 0.030 mmol), DIPEA (0.40 mL ,2.5 mmol) under 70c °C for 12 h. The mixture was concentrated in vacuum. Theresidue was washed with H2O (5 mL), filtered and dried over anhydrous Na2SO4. Theresidue was purified by column chromatography on silica gel (dichloromethane :methanol= 50:1) to afford compound 3o as a yellow solid (75 mg, 43 %).

Reference： [1]Wei, Mingming; Zhao, Rui; Cao, Yuting; Wei, Yujiao; Li, Ming; Dong, Zhiqiang; Liu, Yulin; Ruan, Hao; Li, Ying; Cao, Sheng; Tang, Zhiwen; Zhou, Yuanyuan; Song, Wei; Wang, Yubo; Wang, Jiefu; Yang, Guang; Yang, Cheng [European Journal of Medicinal Chemistry, 2021, vol. 209]

65
[ 26166-92-7 ]
C₂₇H₃₂N₆O₂ [ No CAS ]
C₄₀H₄₀N₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 12h; Inert atmosphere;	7-Cyclopentyl-2-((4-(5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-ynamido)phenyl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide 3o. General procedure: To a solution of 10o (0.11 g, 0.25 mmol) in DMF (3 mL) was added 9b (0.10 g, 0.31mmol), Pd(PPh3)Cl2 (18 mg, 0.030 mmol), CuI (5.1 mg, 0.030 mmol), DIPEA (0.40 mL ,2.5 mmol) under 70c °C for 12 h. The mixture was concentrated in vacuum. Theresidue was washed with H2O (5 mL), filtered and dried over anhydrous Na2SO4. Theresidue was purified by column chromatography on silica gel (dichloromethane :methanol= 50:1) to afford compound 3o as a yellow solid (75 mg, 43 %).

Reference： [1]Wei, Mingming; Zhao, Rui; Cao, Yuting; Wei, Yujiao; Li, Ming; Dong, Zhiqiang; Liu, Yulin; Ruan, Hao; Li, Ying; Cao, Sheng; Tang, Zhiwen; Zhou, Yuanyuan; Song, Wei; Wang, Yubo; Wang, Jiefu; Yang, Guang; Yang, Cheng [European Journal of Medicinal Chemistry, 2021, vol. 209]

66
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(7-(4-(4-((5-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino)phenyl)piperazin-1-yl)hept-1-yn-1-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C 3: potassium carbonate; sodium iodide / acetonitrile / 16 h / 80 °C
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C 3: potassium carbonate; sodium iodide / acetonitrile / 16 h / 80 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

67
[ 26166-92-7 ]
5-(7-(4-(4-(8-(3,5-difluoro-4-(morpholinomethyl)phenyl)quinoxalin-2-yl)-1H-pyrazol-1-yl)piperidin-1-yl)hept-1-yn-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C 3: potassium carbonate; sodium iodide / 16 h / 80 °C
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C 3: potassium carbonate; sodium iodide / 16 h / 80 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

68
[ 26166-92-7 ]
7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hept-6-yn-1-yl 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: triethylamine / dichloromethane / 16 h / 20 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

69
[ 26166-92-7 ]
2-(2,6-dioxopiperidin-3-yl)-5-(7-hydroxyheptyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

70
[ 26166-92-7 ]
7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)heptyl 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C 3: triethylamine / dichloromethane / 16 h / 20 °C
	Multi-step reaction with 3 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C 3: triethylamine / dichloromethane / 16 h / 20 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

71
[ 26166-92-7 ]
[ 30964-00-2 ]
7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hept-6-ynoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 80℃; for 16h;	336.1 Step 1: Synthesis of 7- (2- (2, 6-dioxopiperidin-3-yl) -1, 3-dioxoisoindolin-5-yl) hept-6-ynoic acid A mixture of 5-bromo-2- (2, 6-dioxopiperidin-3-yl) isoindoline-1, 3-dione (100 mg, 298 umol) , Pd (dppf) Cl2(22 mg, 29.8 umol) , hept-6-ynoic acid (56 mg, 447 umol) , CuI (6 mg, 29.8 umol) and DIPEA (116 mg, 894 umol) in DMSO (6 mL) was stirred at 80 for 16 h. The reaction mixture was purified by reverse-phase chromatography to give the desired product (45 mg, 39%yield) as a light yellow solid. MS (ESI) m/z: 381.1 [M-H]-.
39%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 80℃; for 16h;	336.1 Step 1: Synthesis of 7- (2- (2, 6-dioxopiperidin-3-yl) -1, 3-dioxoisoindolin-5-yl) hept-6-ynoic acid A mixture of 5-bromo-2- (2, 6-dioxopiperidin-3-yl) isoindoline-1, 3-dione (100 mg, 298 umol) , Pd (dppf) Cl2(22 mg, 29.8 umol) , hept-6-ynoic acid (56 mg, 447 umol) , CuI (6 mg, 29.8 umol) and DIPEA (116 mg, 894 umol) in DMSO (6 mL) was stirred at 80 for 16 h. The reaction mixture was purified by reverse-phase chromatography to give the desired product (45 mg, 39%yield) as a light yellow solid. MS (ESI) m/z: 381.1 [M-H]-.

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1 Location in patent: Page/Page column 171
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1 Location in patent: Page/Page column 156

72
[ 26166-92-7 ]
[ 30964-00-2 ]
7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)heptanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C
	Multi-step reaction with 2 steps 1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; N-ethyl-N,N-diisopropylamine; copper (I) iodide / dimethyl sulfoxide / 16 h / 80 °C 2: palladium on activated charcoal; hydrogen / methanol / 16 h / 25 °C

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1

73
[ 26166-92-7 ]
[ 63478-76-2 ]
2-(2,6-dioxopiperidin-3-yl)-5-(7-hydroxyhept-1-yn-1-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 80℃; for 16h;	340.1 Step 1: Synthesis of 2- (2, 6-dioxopiperidin-3-yl) -5- (7-hydroxyhept-1-yn-1-yl) isoindoline-1, 3-dione A mixture of 5-bromo-2- (2, 6-dioxopiperidin-3-yl) isoindoline-1, 3-dione (100 mg, 298 umol) , Pd (dppf) Cl2 (22 mg, 29.8 umol) , hept-6-yn-1-ol (56 mg, 447 umol) , CuI (6 mg, 29.8 umol) and DIPEA (116 mg, 894 umol) in DMSO (6 mL) was stirred at 80 for 16 h. The reaction mixture was purified by reverse-phase chromatography to give the desired product (61 mg, 48%yield) as a light yellow solid. MS (ESI) m/z: 369.1 [M+H]+.
48%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; copper (I) iodide; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 80℃; for 16h;	340.1 Step 1: Synthesis of 2- (2, 6-dioxopiperidin-3-yl) -5- (7-hydroxyhept-1-yn-1-yl) isoindoline-1, 3-dione A mixture of 5-bromo-2- (2, 6-dioxopiperidin-3-yl) isoindoline-1, 3-dione (100 mg, 298 umol) , Pd (dppf) Cl2 (22 mg, 29.8 umol) , hept-6-yn-1-ol (56 mg, 447 umol) , CuI (6 mg, 29.8 umol) and DIPEA (116 mg, 894 umol) in DMSO (6 mL) was stirred at 80 for 16 h. The reaction mixture was purified by reverse-phase chromatography to give the desired product (61 mg, 48%yield) as a light yellow solid. MS (ESI) m/z: 369.1 [M+H]+.

Reference： [1]Current Patent Assignee: CULLGEN SHANGHAI - WO2020/200291, 2020, A1 Location in patent: Page/Page column 173
[2]Current Patent Assignee: CULLGEN SHANGHAI - WO2022/68933, 2022, A1 Location in patent: Page/Page column 158

74
[ 287193-01-5 ]
[ 26166-92-7 ]
tert-butyl 3-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.6%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran; N,N-dimethyl-formamide Inert atmosphere;	1.2 tert-butyl3-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]azetidine-1- carboxylate Weigh 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (for synthesis method see WO2009145899) (1.7 g, 5.04 mmol), use 15 mL Tetrahydrofuran and 3mL DMF were dissolved in a 100mL single-necked round bottom flask, and 3-ethynylazetidine-1-carboxylic acid tert-butyl ester (1a) (1.37g, 7.56mmol),Ditriphenylphosphine palladium dichloride (350mg, 0.504mmol), cuprous iodide (97mg, 0.504mmol) and triethylamine (2.55g, 25.21mmol) were heated to 75°C under a nitrogen atmosphere to react overnight. Concentrate under reduced pressure to remove tetrahydrofuran, add 20 mL of water to the residue, extract with ethyl acetate (25 mL x 2), combine the organic phases, wash with 30 mL of saturated brine, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a crude product, crude silica gel Purified by column chromatography to obtain 3-[2-[2-(2-(2,6-dioxo-3-piperidinyl)-1,3-dioxoisoindolin-5-yl]ethynyl ] Tert-butyl azetidine-1-carboxylate (1b), brown-yellow solid (1.8 g, yield: 81.6%).
62%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 70℃; for 12h;	22.1 The first step: 3-[2-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]aza Tert-Butyl Cyclobutane-1-carboxylate (22b) 3-ethynyl azetidine-1-carboxylic acid tert-butyl ester (22a) (see WO2014165075 for synthesis method)(0.32g, 1.77mmol) and 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (see WO2009145899 for synthesis method)(0.50g, 1.48mmol) was added to 5mL of tetrahydrofuran, and then 2mL of triethylamine was added,Pd(PPh3)2Cl2(0.1g, 0.15mmol) andCuI (0.05g, 0.26mmol), heated to 70 degrees and stirred for 12 hours.Cool to room temperature, filter, remove the solvent from the filtrate under reduced pressure, and separate and purify the residue by silica gel column chromatography (DCM/MeOH(v/v)=100/1-30/1),Get 3-[2-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]azetidin- Tert-Butyl 1-carboxylate (22b) (0.4 g, yield: 62%).
62%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;	1.1 The first step: 3-[2-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]aza Tert-Butyl Cyclobutane-1-carboxylate (1b) The tert-butyl 3-ethynylazetidine-1-carboxylate (1a) (see WO2014165075 for the synthesis method) (0.32g, 1.77mmol)And 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (see WO2009145899 for synthesis method) (0.50g, 1.48mmol)Add to 5mL tetrahydrofuran,Then add 2mL triethylamine,Add Pd(PPh3)2Cl2(0.1g, 0.15mmol) and CuI(0.05g, 0.26mmol) in sequence under nitrogen protection,The temperature was raised to 70°C and stirred for 12 hours.Cool to room temperature, filter, remove the solvent from the filtrate under reduced pressure, and separate and purify the residue by silica gel column chromatography (DCM/MeOH(v/v)=100/1-30/1) to give 3-[2-[2-( 2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl)ethynyl)azetidin-1-carboxylic acid tert-butyl ester (1b)( 0.4g, yield: 62%).

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN113527260, 2021, A Location in patent: Paragraph 0281; 0284; 0290-0294
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A Location in patent: Paragraph 1062-1071
[3]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A Location in patent: Paragraph 0321; 0324-0329

75
[ 26166-92-7 ]
tert-butyl 2-(2-ethynyl-7-azaspiro[3.5]nonan-7-yl)acetate [ No CAS ]
tert-butyl 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)ethynyl)-7-azaspiro[3.5]nonan-7-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 70℃; Inert atmosphere;	28.6 The sixth step:2-(2-((2-(2,6-dioxopyridin-3-yl)-1,3-dioxoisoindolin-5-yl)ethynyl)-7-azaspiro[3.5]non-7-yl)tert-butyl acetate (28g) The 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (see WO2009145899 for synthesis method) (280mg, 0.83mmol)And tert-butyl 2-(2-ethynyl-7-azaspiro[3.5]non-7-yl)acetate (28f) (240mg, 0.91mmol) dissolved in 5mL tetrahydrofuran and 5mL triethylamine,Replace with nitrogen three times, add cuprous iodide (8mg, 0.04mmol) and triphenylphosphine palladium dichloride (58mg, 0.08mmol), Nitrogen replacement three times, the reaction was stirred at 70 degrees overnight. Spin directly to dry the solvent, and the crude product is separated and purified by silica gel column chromatography (dichloromethane/methanol (v/v)=20:1), Get 2-(2-((2-(2,6-dioxopyridin-3-yl)-1,3-dioxoisoindolin-5-yl)ethynyl)Tert-butyl -7-azaspiro[3.5]non-7-yl)acetate (28g) (350mg, yield: 70%).
70%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 70℃; Inert atmosphere;	2.6 The sixth step: 2-(2-((2-(2,6-dioxopyridin-3-yl)-1,3-dioxoisoindolin-5-yl)ethynyl)-7- Azaspiro[3.5]non-7-yl) tert-butyl acetate (2g) The 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (see WO2009145899 for synthesis method) (280mg, 0.83mmol)And tert-butyl 2-(2-ethynyl-7-azaspiro[3.5]non-7-yl)acetate (2f) (240mg, 0.91mmol) dissolved in 5mL tetrahydrofuran and 5mL triethylamine,Replace with nitrogen three times,Add cuprous iodide (8mg, 0.04mmol)And triphenylphosphine palladium dichloride (58mg, 0.08mmol),Replace with nitrogen three times,The reaction was stirred at 70°C overnight.The solvent was spin-dried directly, and the crude product was separated and purified by silica gel column chromatography (dichloromethane/methanol (v/v)=20:1) to obtain 2-(2-((2-(2,6-dioxopyridine-3) -Yl)-1,3-dioxoisoindolin-5-yl)ethynyl)-7-azaspiro[3.5]non-7-yl)tert-butyl acetate (2g) (350mg, yield : 70%).

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A Location in patent: Paragraph 1186-1189; 1215-1219
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A Location in patent: Paragraph 0356; 0359; 0385-0389

76
[ 26166-92-7 ]
5-[2-(azetidin-3-yl)ethynyl]-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione hydrochlorate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 12 h / 70 °C 2: hydrogenchloride / ethyl acetate / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / tetrahydrofuran / 12 h / 70 °C / Inert atmosphere 2: hydrogenchloride / ethyl acetate; water / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / tetrahydrofuran; N,N-dimethyl-formamide / Inert atmosphere 2: hydrogenchloride / ethyl acetate; water / 2 h / 20 °C

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A
[3]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN113527260, 2021, A

77
[ 26166-92-7 ]
tert-butyl 2-[4-[3-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]azetidin-1-yl]-1-piperidyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 12 h / 70 °C 2.1: hydrogenchloride / ethyl acetate / 2 h / 20 °C 3.1: triethylamine / methanol / 0.33 h 3.2: 1 h / 20 °C
	Multi-step reaction with 3 steps 1.1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / tetrahydrofuran / 12 h / 70 °C / Inert atmosphere 2.1: hydrogenchloride / ethyl acetate; water / 2 h / 20 °C 3.1: triethylamine / methanol / 0.33 h 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A

78
[ 26166-92-7 ]
2-[4-[3-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]azetidin-1-yl]-1-piperidyl]acetic acid ditrifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 12 h / 70 °C 2.1: hydrogenchloride / ethyl acetate / 2 h / 20 °C 3.1: triethylamine / methanol / 0.33 h 3.2: 1 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 20 °C
	Multi-step reaction with 4 steps 1.1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / tetrahydrofuran / 12 h / 70 °C / Inert atmosphere 2.1: hydrogenchloride / ethyl acetate; water / 2 h / 20 °C 3.1: triethylamine / methanol / 0.33 h 3.2: 1 h / 20 °C 4.1: dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112010858, 2020, A
[2]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A

79
[ 26166-92-7 ]
4-(but-3-yn-1-yloxy)-2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-N-methylthiazole-5-carboxamide [ No CAS ]
2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)oxy)thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 20℃; for 24h;	5.1.2.4. 2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)-Nmethylthiazole-5-carboxamide (PG4). Intermediate 23a (74 mg,0.2 mmol, 1.0 equiv) was dissolved in DMF (4 mL). P5 (65 mg,0.2 mmol, 1.0 equiv), CuI (11.5 mg, 0.06 mmol, 0.3 equiv) andPd(Ph3P)Cl2 (8.2 mg, 0.04 mmol, 0.2 equiv) were sequentially addedto the reaction solution, and the reaction was stirred at roomtemperature for 24 h. The solvent was evaporated under a vacuumto give the crude product which was purified by column chromatography(DCM/MeOH 30/1, v/v) to obtain compound PG4 as alight white solid (42 mg, 34% yield), 95.8% HPLC purity. 1H NMR(300 MHz, DMSO-d6, d ppm): 11.00 (s, 1H), 7.72 (d, J 3.3 Hz, 1H),7.63e7.60 (m, 1H), 7.51 (t, J 3.2 Hz, 1H), 4.74 (s, 1H), 4.59 (s, 1H),4.38 (d, J 9.2 Hz, 1H), 4.26 (d, J 9.2 Hz, 1H), 3.35 (s, 1H), 3.13 (s,2H), 3.00 (s, 3H), 2.81 (s, 2H), 2.74 (s, 2H), 2.59 (t, J 9.3 Hz, 1H),2.36 (d, J 6.3 Hz, 1H), 1.98 (d, J 6.3 Hz, 1H), 1.14 (s, 3H), 0.85 (s,5H); 13C NMR (75 MHz, DMSO-d6, d ppm): 173.5, 173.2, 171.3, 168.1,162.2, 150.4, 160.4, 153.6, 149.7, 144.2, 141.0, 134.5, 132.4, 129.0,123.1, 119.0, 115.4, 110.7, 109.1, 95.8, 77.2, 70.5, 55.3, 52.0, 47.4, 28.2,26.8, 22.7, 16.1, 14.7, 8.3; HRMS (m/z): calcd C31H29N6O6S [M H],613.1864; found, 613.1848.

Reference： [1]Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng [European Journal of Medicinal Chemistry, 2021, vol. 210]

80
[ 26166-92-7 ]
2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-N-methyl-4-(pent-4-yn-1-yloxy)thiazole-5-carboxamide [ No CAS ]
2-(2-cyclopropaneamidopyridin-4-yl)-4-({5-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]pent-4-yn-1-yl}oxy)-N-methyl-1,3-thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 20℃; for 24h;	5.1.2.4. 2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)-Nmethylthiazole-5-carboxamide (PG4). General procedure: Intermediate 23a (74 mg,0.2 mmol, 1.0 equiv) was dissolved in DMF (4 mL). P5 (65 mg,0.2 mmol, 1.0 equiv), CuI (11.5 mg, 0.06 mmol, 0.3 equiv) andPd(Ph3P)Cl2 (8.2 mg, 0.04 mmol, 0.2 equiv) were sequentially addedto the reaction solution, and the reaction was stirred at roomtemperature for 24 h. The solvent was evaporated under a vacuumto give the crude product which was purified by column chromatography(DCM/MeOH 30/1, v/v) to obtain compound PG4 as alight white solid (42 mg, 34% yield), 95.8% HPLC purity.

Reference： [1]Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng [European Journal of Medicinal Chemistry, 2021, vol. 210]

81
[ 26166-92-7 ]
C₁₉H₂₀N₄O₄S [ No CAS ]
2-(2-cyclopropaneamidopyridin-4-yl)-4-[2-({3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]prop-2-yn-1-yl}oxy)ethoxy]-1,3-thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 20℃; for 24h;	5.1.2.4. 2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)-Nmethylthiazole-5-carboxamide (PG4). General procedure: Intermediate 23a (74 mg,0.2 mmol, 1.0 equiv) was dissolved in DMF (4 mL). P5 (65 mg,0.2 mmol, 1.0 equiv), CuI (11.5 mg, 0.06 mmol, 0.3 equiv) andPd(Ph3P)Cl2 (8.2 mg, 0.04 mmol, 0.2 equiv) were sequentially addedto the reaction solution, and the reaction was stirred at roomtemperature for 24 h. The solvent was evaporated under a vacuumto give the crude product which was purified by column chromatography(DCM/MeOH 30/1, v/v) to obtain compound PG4 as alight white solid (42 mg, 34% yield), 95.8% HPLC purity.

Reference： [1]Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng [European Journal of Medicinal Chemistry, 2021, vol. 210]

82
[ 26166-92-7 ]
C₁₉H₂₀N₄O₄S [ No CAS ]
2-(2-cyclopropaneamidopyridin-4-yl)-4-[2-({3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]prop-2-yn-1-yl}oxy)ethoxy]-N-methyl-1,3-thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 20℃; for 24h;	5.1.2.4. 2-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)-Nmethylthiazole-5-carboxamide (PG4). General procedure: Intermediate 23a (74 mg,0.2 mmol, 1.0 equiv) was dissolved in DMF (4 mL). P5 (65 mg,0.2 mmol, 1.0 equiv), CuI (11.5 mg, 0.06 mmol, 0.3 equiv) andPd(Ph3P)Cl2 (8.2 mg, 0.04 mmol, 0.2 equiv) were sequentially addedto the reaction solution, and the reaction was stirred at roomtemperature for 24 h. The solvent was evaporated under a vacuumto give the crude product which was purified by column chromatography(DCM/MeOH 30/1, v/v) to obtain compound PG4 as alight white solid (42 mg, 34% yield), 95.8% HPLC purity.

Reference： [1]Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng [European Journal of Medicinal Chemistry, 2021, vol. 210]

83
[ 86-90-8 ]
3-aminoperidine-2,6-dione [ No CAS ]
[ 26166-92-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: 4-bromophthalic anhydride; 3-aminoperidine-2,6-dione With triethylamine In tetrahydrofuran for 18h; Reflux; Stage #2: With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran for 48h; Reflux;	5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (P2) In a round-bottom flask, 4-bromo phthalic anhydrus (2.3 g, 10 mmol, 1.0 equiv) and3-aminoperidine-2,6-dione P1 (1.4 g, 11 mmol, 1.1 equiv) were mixed in THF (250mL). TEA (1.7 mL, 12 mmol, 1.2 equiv) was added. The resulting reaction mixture washeated to reflux for 18 h. After cooling to ambient temperature, N,N'-dicyclohexylcarbodiimide (2.2 g, 10.5 mmol, 1.05 equiv) and catalytic 4-dimethylaminopyridine were added. The reaction mixture was heated to reflux for 48h. Evaporation of most of the solvent afforded a crude product, which was purified byflash column chromatography with DCM/MeOH to obtain the product P2 as a slightlyyellow solid (2.7 g, 79% yield).

Reference： [1]Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng [European Journal of Medicinal Chemistry, 2021, vol. 210]

84
[ 26166-92-7 ]
[ 76003-29-7 ]
tert-butyl 4-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]-3-oxo-piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 3h; Inert atmosphere;	18.1 The first step: tert-butyl 4-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl]-3-oxo-piperazine -1-carboxylate (18b) willTert-Butyl 3-oxo-1-piperazinecarboxylate(0.1g, 0.5mmol),3a (0.167g, 0.5mmol),Cesium carbonate (0.325g, 1.0mmol),Xant-Phos (0.058g, 0.10mol),Pd2(dba)3(0.05g, 0.05mmol)Dissolved in 10mL dioxane,Replace with nitrogen three times,Warm up to 110°C, react for 3 hours,After the reaction is completed, filter with suction, concentrate under reduced pressure, and column chromatography to obtain tert-butyl 4-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindoline- 5-yl]-3-oxo-piperazine-1-carboxylate (18b) (0.05 g, 20%).

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A Location in patent: Paragraph 0764; 0767-0772

85
[ 26166-92-7 ]
tert-butyl 2-(4-ethynyl-1-piperidinyl)acetate [ No CAS ]
tert-butyl 2-[4-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]ethynyl]-1-piperidyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.3%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 70℃; for 4h; Inert atmosphere;	3.1 The first step: 2-[4-[2-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl]ethynyl ]-1-piperidinyl]tert-butyl acetate (3c) Compound 2-(4-ethynyl-1-piperidinyl) tert-butyl acetate (3b) (see WO2014165075 for synthesis method) (0.067g, 0.30mmol)And 5-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (3a) (see WO2009145899 for synthesis method) (0.10g, 0.30mmol)Add to 5mL tetrahydrofuran,Then add 2mL triethylamine,Add Pd(PPh3)2Cl2(0.1g, 0.15mmol) and CuI(0.05g, 0.26mmol) in sequence under nitrogen protection,The temperature was raised to 70°C and stirred for 4 hours.Cool to room temperature, filter, remove the solvent from the filtrate under reduced pressure, and separate and purify the residue by silica gel column chromatography (DCM/MeOH(v/v)=100/1-30/1) to give 2-[4-[2-[ 2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-isoindolin-5-yl)ethynyl)-1-piperidinyl)tert-butyl acetate ( 3c) (0.10g, yield: 70.3%).

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112390785, 2021, A Location in patent: Paragraph 0400; 0403-0408

86
[ 28418-88-4 ]
(RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate [ No CAS ]
[ 26166-92-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine In tetrahydrofuran for 72h; Reflux;

Reference： [1]Nutt, Michael J.; Yee, Yeung Sing; Buyan, Amanda; Andrewartha, Neil; Corry, Ben; Yeoh, George C.T.; Stewart, Scott G. [European Journal of Medicinal Chemistry, 2021, vol. 217]

87
[ 26166-92-7 ]
[ 62-53-3 ]
[ 1216805-49-0 ]

Yield	Reaction Conditions	Operation in experiment
99%	With [Pd₂(dba)₃]*CHCl₃; potassium carbonate; XPhos In 1,4-dioxane at 90℃; for 18h; Schlenk technique; Inert atmosphere;	4.8. General procedure for Buchwald-Hartwig amination reactions General procedure: To a flame-dried Schlenk flask was added the following insequence, under an inert atmosphere of argon: 4-iodothalidomide(200 mg, 0.52 mmol), XPhos (40 mg, 0.083 mmol) Pd2(dba)3CHCl3(22 mg, 0.021 mmol) K2CO3 (144 mg, 1.04 mmol) 1,4-dioxane(2 mL) and The desired aniline (0.89 mmol). The reaction mixturewas stirred at 90 C for 18 h and the resulting mixture then cooledto room temperature, diluted with ethyl acetate (10 mL) andfiltered through a pad of Celite. The filter cake was washed withethyl acetate (ca. 40 mL) and the resulting filtrate adsorbed to silica.Purification by flash column chromatography (ethyl acetate/hexanes)gave the desired aminated thalidomide analogue.

Reference： [1]Nutt, Michael J.; Yee, Yeung Sing; Buyan, Amanda; Andrewartha, Neil; Corry, Ben; Yeoh, George C.T.; Stewart, Scott G. [European Journal of Medicinal Chemistry, 2021, vol. 217]

88
[ 26166-92-7 ]
[ 99-88-7 ]
C₂₂H₂₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With [Pd₂(dba)₃]*CHCl₃; potassium carbonate; XPhos In 1,4-dioxane at 90℃; for 18h; Schlenk technique; Inert atmosphere;	4.8. General procedure for Buchwald-Hartwig amination reactions General procedure: To a flame-dried Schlenk flask was added the following insequence, under an inert atmosphere of argon: 4-iodothalidomide(200 mg, 0.52 mmol), XPhos (40 mg, 0.083 mmol) Pd2(dba)3CHCl3(22 mg, 0.021 mmol) K2CO3 (144 mg, 1.04 mmol) 1,4-dioxane(2 mL) and The desired aniline (0.89 mmol). The reaction mixturewas stirred at 90 C for 18 h and the resulting mixture then cooledto room temperature, diluted with ethyl acetate (10 mL) andfiltered through a pad of Celite. The filter cake was washed withethyl acetate (ca. 40 mL) and the resulting filtrate adsorbed to silica.Purification by flash column chromatography (ethyl acetate/hexanes)gave the desired aminated thalidomide analogue.

Reference： [1]Nutt, Michael J.; Yee, Yeung Sing; Buyan, Amanda; Andrewartha, Neil; Corry, Ben; Yeoh, George C.T.; Stewart, Scott G. [European Journal of Medicinal Chemistry, 2021, vol. 217]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	26166-92-7	MDL No. :	MFCD30188073
Formula :	C₁₃H₉BrN₂O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MWMSBQXTHIEBNT-UHFFFAOYSA-N
M.W :	337.13	Pubchem ID :	44435680
Synonyms :

Signal Word:	Warning	Class:
Precautionary Statements:	P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313	UN#:
Hazard Statements:	H315-H319	Packing Group:
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
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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.
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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

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 26166-92-7 ] {[proInfo.proName]}

Quality Control of [ 26166-92-7 ]

Related Doc. of [ 26166-92-7 ]

Product Details of [ 26166-92-7 ]

Safety of [ 26166-92-7 ]

Application In Synthesis of [ 26166-92-7 ]

[ 26166-92-7 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry