Name: 23794-16-3|2-Bromo-1-(2-chloro-4-pyridyl)ethanone|95%
Brand: Ambeed
SKU: A552379
Price: 31.0 USD
Availability: InStock
Rating: 96 (32 reviews)

1
[ 14294-11-2 ]
[ 23794-16-3 ]
[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-pyridin-2-yl-amine [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2007,vol. 182,p. 7 - 14

2
[ 23794-15-2 ]
[ 23794-16-3 ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2007,vol. 182,p. 7 - 14
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 5028 - 5037

3
[ 948914-01-0 ]
[ 23794-16-3 ]
4-nitro-1H-indole-2-carboxylic acid N'-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In methanol Heating;

Reference： [1]Ashalatha; Narayana; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 12, p. 2785 - 2795]

4
[ 948914-03-2 ]
[ 23794-16-3 ]
6-nitro-1H-indole-2-carboxylic acid N'-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In methanol Heating;

Reference： [1]Ashalatha; Narayana; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 12, p. 2785 - 2795]

5
[ 948914-04-3 ]
[ 23794-16-3 ]
7-nitro-N'-[4-(2-chloropyridin-4-yl)-1,3-thiazol-2-yl]-1H-indole-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	In methanol Heating;

Reference： [1]Ashalatha; Narayana; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 12, p. 2785 - 2795]

6
[ 23794-16-3 ]
[ 622-52-6 ]
[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-p-tolyl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In ethanol for 6h; Heating;

Reference： [1]Narayana; Vijaya Raj; Ashalatha; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2007, vol. 182, # 1, p. 7 - 14]

7
[ 23794-16-3 ]
[ 614-78-8 ]
[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-o-tolyl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In ethanol for 6h; Heating;

Reference： [1]Narayana; Vijaya Raj; Ashalatha; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2007, vol. 182, # 1, p. 7 - 14]

8
[ 23794-16-3 ]
[ 4947-89-1 ]
(3-chloro-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2007,vol. 182,p. 7 - 14

9
[ 23794-16-3 ]
[ 117174-84-2 ]
(3-chloro-4-methyl-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2007,vol. 182,p. 7 - 14

10
[ 23794-16-3 ]
[ 41440-07-7 ]
[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-(3-methyl-pyridin-2-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	In ethanol for 6h; Heating;

Reference： [1]Narayana; Vijaya Raj; Ashalatha; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2007, vol. 182, # 1, p. 7 - 14]

11
[ 23794-16-3 ]
[ 17356-08-0 ]
4-(2-chloro-pyridin-4-yl)-thiazol-2-ylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In ethanol for 6h; Heating;
	In ethanol at 70℃;

Reference： [1]Narayana; Vijaya Raj; Ashalatha; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2007, vol. 182, # 1, p. 7 - 14]
[2]Green, Jeremy; Cao, Jingrong; Bandarage, Upul K.; Gao, Huai; Court, John; Marhefka, Craig; Jacobs, Marc; Taslimi, Paul; Newsome, David; Nakayama, Tomoko; Shah, Sundeep; Rodems, Steve [Journal of Medicinal Chemistry, 2015, vol. 58, # 12, p. 5028 - 5037]

12
[ 23794-16-3 ]
[ 3696-23-9 ]
(4-chloro-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In ethanol for 6h; Heating;

Reference： [1]Narayana; Vijaya Raj; Ashalatha; Kumari, N. Suchetha [Phosphorus, Sulfur and Silicon and the Related Elements, 2007, vol. 182, # 1, p. 7 - 14]

13
[ 23794-16-3 ]
[ 1015242-47-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Ethyl isobutyrate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 2h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In tetrahydrofuran at -78 - 20℃;	141.a a) 2-[2-(2-Chloro-pyridin-4-yl)-2-oxo-ethyl]-4-methyl-3-oxo-pentanoic acid ethyl ester. 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (500 mg) is stirred in a mixture of 20 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Ethyl isobutyrate (337 mg) in 5 ml THF is added drop wise to a solution of LiHMDS (2.1 ml 1.0 M solution) in 5 ml THF at - 78 0C. After stirring for 2 hours at -78 0C 2-bromo-1-(2- chloro-pyridin-4-yl)-ethanone (see above) dissolved in 3 ml THF is added drop wise. The reaction mixture is allowed to warm to room temperature overnight. Aqueous NH4Cl solution is added and the mixture is extracted with ethyl acetate. After removal of the solvent the title compound is obtained as a pale yellow oil. 1H-NMR (400 MHz, DMSO-d6): 1.07 (d, 3H), 1.10 (d, 3H), 1.19 (t, 3H), 2.98 (sept, 1 H), 3.50- 3.68 (m, 2H), 4.13 (q, 2H), 4.33 (t, 1H), 7.84 (d, 1H), 7.96 (s, 1H), 8.63 (d, 1H). MS (ESI+) m/z: 312 [MH]+.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2008/34600, 2008, A1 Location in patent: Page/Page column 126-127

14
[ 23794-16-3 ]
4-(5-(2-chloropyridin-4-yl)-3-ethoxycarbonyl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(2-ethoxycarbonylacetyl)piperidine-1-carboxylic acid tert-butyl ester With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In tetrahydrofuran at 0 - 20℃; Stage #3: With ammonium acetate In ethanol at 20℃;	144.b b) 4-[5-(2-Chloro-pyridin-4-yl)-3-ethoxycarbonyl-1 H-pyrrol-2-yl]-piperidine-1 -carboxylic acid tert-butyl ester. NaH (660 mg, 14.5 mmol) is added to a solution of 4-(2-ethoxycarbonyl-acetyl)-piperidine-1- carboxylic acid tert-butyl ester in 150 ml of THF at 0 0C the mixture is allowed to react for 15 min at room temperature to give a clear solution. A solution of 3.5 g (14.9 mmol) 1-(2-chloro- pyridin-4-yl)-ethanone (free base, example 1c) in THF is added. The reaction is stirred for 1 h at 0 0C and at room temperature over night. Ice is added, followed by extraction with ethyl acetate. The combined organic layers are washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. The residue is dissolved in 50 ml of ethanol. After adding 4.20 g(54.5 mmol) NH4OAc the reaction is stirred at room temperature over night. Ice is added, followed by extraction with ethyl acetate. The combined organic layers are washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. The crude product is purified by silica gel chromatography (hexanes-ethyl acetate gradient).1H-NMR (400 MHz, DMSO-d6): 1.27 (t, 3H), 1.47 (s, 9H), 1.75-1.81 (m, 2H), 1.90-1.97 (m,2H), 2.85-2.95 (m, 2H), 3.86 (t, 1H), 4.09-4.14 (m, 2H), 4.31 (q, 2H), 7.09 (s, 1H), 7.39 (d,1H), 7.52 (s, 1H), 8.28 (d, 1 H), 9.91 (s, 1H, NH).MS (ESI+) m/z: 434 [MH]+.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2008/34600, 2008, A1 Location in patent: Page/Page column 131-132

15
[ 286440-10-6 ]
[ 23794-16-3 ]
BrCH₃OC₆H₃CON₂H₂C₃HNSC₅H₃NCl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	In ethanol for 10h; Heating;

Reference： [1]Vijaya Raj; Narayana; Ashalatha; Suchetha Kumari; Sarojini [European Journal of Medicinal Chemistry, 2007, vol. 42, # 3, p. 425 - 429]

16
[ 23794-16-3 ]
[ 151094-90-5 ]
C₁₀H₁₀N₃OS₂CH₂COC₅H₃NCl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium acetate In methanol Heating;

Reference： [1]Ashalatha; Narayana; Vijaya Raj; Suchetha Kumari [European Journal of Medicinal Chemistry, 2007, vol. 42, # 5, p. 719 - 728]

17
[ 23794-16-3 ]
4-[4-(2-chloro(4-pyridyl))(1,3-thiazol-2-yl)]-5-methylthiothiophene-2-carboxamidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetone / 5 h / Heating 2: AlMe₃; NH₄Cl / toluene / Heating

Reference： [1]Subasinghe, Nalin L.; Illig, Carl; Hoffman, James; Rudolph; Wilson, Kenneth J.; Soll, Richard; Randle, Troy; Green, David; Lewandowski, Frank; Zhang, Marie; Bone, Roger; Spurlino, John; DesJarlais, Renee; Deckman, Ingrid; Molloy, Christopher J.; Manthey, Carl; Zhou, Zhau; Sharp, Celia; Maguire, Diane; Crysler, Carl; Grasberger, Bruce [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 11, p. 1379 - 1382]

18
[ 23794-16-3 ]
[ 933986-15-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: carbethoxyacetamidine hydrochloride With sodium ethanolate In ethanol at 0℃; for 0.333333h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In ethanol at 0 - 20℃; for 16h;	1.b b) 2-Amino-5-(2-chloro-pyridin-4-yl)-1 H-pyrrole-3-carboxylic acid ethyl ester2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (3.0 g, 12.8 mmol) is stirred in a mixture of 35 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Carbamimidoyl-acetic acid ethyl ester hydrochloride (4.26 g, 25.6 mmol) (Liebigs Ann. Chem. 1977, 1895) is suspended in 10 ml ethanol and cooled to 0 oC. To this mixture sodium ethoxide (1.74 g, 25.6 mmol) is added. The mixture is stirred for 20 minutes, then 2- bromo-1-(2-chloro-pyridin-4-yl)-ethanone in 10 ml ethanol is added dropwise. After stirring at r.t. for 16 hours the reaction is stopped by adding 100 ml water and the mixture is extracted with ethylacetate. The material obtained after removal of the solvent is used for further steps without purification.1H-NMR (400 MHZ1 DMSO-d6): 1.27 (t, 3H), 4.16 (q, 2H), 5.97 (s, 2H), 6.98 (d, 1 H), 7.44 (dd, 1H), 7.55 (d, 1 H), 8.14 (d, 1H), 11.1 (s, 1 H). MS (ESI+) m/z: 266 [MH]+

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2007/39285, 2007, A1 Location in patent: Page/Page column 18

19
[ 23794-16-3 ]
[ 56-06-4 ]
[ 933986-22-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate; In ethanol; for 16h;Heating / reflux;	To a solution of <strong>[56-06-4]2,6-diamino-4-hydroxypyrimidine</strong> (269 mg, 2.1 mmol) and sodium ethoxide (159 mg, 2.3 mmol) in 8 ml ethanol is added 2-bromo-1-(2-chloro-pyridin-4-yl)-ethanone (500 mg, 2.1 mmol) (free base prepared as described in example 1 b). The mixture is heated under reflux for 16 hours and then quenched by addition of water. The white precipitate which forms is filtered and titurated with ether to give the target molecule.1H-NMR (400 MHZ, DMSO-d6): 6.34 (s, 2H), 7.17 (s, 1H), 7.65 (d, 1 H), 7.77 (s, 1 H), 8.22 (d, 1 H), 10.41 (brs, 1 H), 11.7 (brs, 1 H). MS (ESI+) m/z: 262 [MH]+

Reference： [1]Patent: WO2007/39285,2007,A1 .Location in patent: Page/Page column 21-22

20
2-bromo-1-(2-chloro-4-pyridinyl)-ethanone hydrobromide [ No CAS ]
[ 23794-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In diethyl ether; water	1.b 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (3.0 g, 12.8 mmol) is stirred in a mixture of 35 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Carbamimidoyl-acetic acid ethyl ester hydrochloride (4.26 g, 25.6 mmol) (Liebigs Ann. Chem. 1977, 1895) is suspended in 10 ml ethanol and cooled to 0 oC. To this mixture sodium ethoxide (1.74 g, 25.6 mmol) is added. The mixture is stirred for 20 minutes, then 2- bromo-1-(2-chloro-pyridin-4-yl)-ethanone in 10 ml ethanol is added dropwise. After stirring at r.t. for 16 hours the reaction is stopped by adding 100 ml water and the mixture is extracted with ethylacetate. The material obtained after removal of the solvent is used for further steps without purification.1H-NMR (400 MHZ1 DMSO-d6): 1.27 (t, 3H), 4.16 (q, 2H), 5.97 (s, 2H), 6.98 (d, 1 H), 7.44 (dd, 1H), 7.55 (d, 1 H), 8.14 (d, 1H), 11.1 (s, 1 H). MS (ESI+) m/z: 266 [MH]+
	With sodium hydrogencarbonate In water	141.a a) 2-[2-(2-Chloro-pyridin-4-yl)-2-oxo-ethyl]-4-methyl-3-oxo-pentanoic acid ethyl ester. 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (500 mg) is stirred in a mixture of 20 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Ethyl isobutyrate (337 mg) in 5 ml THF is added drop wise to a solution of LiHMDS (2.1 ml 1.0 M solution) in 5 ml THF at - 78 0C. After stirring for 2 hours at -78 0C 2-bromo-1-(2- chloro-pyridin-4-yl)-ethanone (see above) dissolved in 3 ml THF is added drop wise. The reaction mixture is allowed to warm to room temperature overnight. Aqueous NH4Cl solution is added and the mixture is extracted with ethyl acetate. After removal of the solvent the title compound is obtained as a pale yellow oil. 1H-NMR (400 MHz, DMSO-d6): 1.07 (d, 3H), 1.10 (d, 3H), 1.19 (t, 3H), 2.98 (sept, 1 H), 3.50- 3.68 (m, 2H), 4.13 (q, 2H), 4.33 (t, 1H), 7.84 (d, 1H), 7.96 (s, 1H), 8.63 (d, 1H). MS (ESI+) m/z: 312 [MH]+.

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2007/39285, 2007, A1 Location in patent: Page/Page column 18
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2008/34600, 2008, A1 Location in patent: Page/Page column 126-127

21
[ 23794-16-3 ]
[ 5699-40-1 ]
C₁₀H₁₁ClN₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6142 - 6146

22
[ 23794-16-3 ]
[ 68572-18-9 ]
[ 933986-15-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In methanol at 20℃; for 16h;

Reference： [1]Location in patent: scheme or table Schlapbach, Achim; Feifel, Roland; Hawtin, Stuart; Heng, Richard; Koch, Guido; Moebitz, Henrik; Revesz, Laszlo; Scheufler, Clemens; Velcicky, Juraj; Waelchli, Rudolf; Huppertz, Christine [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6142 - 6146]

23
[ 23794-16-3 ]
[ 621-40-9 ]
[ 1187669-37-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	In ethanol for 1h; Reflux;
94%	Stage #1: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one; (3-methylphenyl)thiourea In ethanol for 1h; Heating; Reflux; Stage #2: With ammonia In ethanol; water at 0 - 20℃; for 1h;	1-87 Example 1-87 4-(2-Chloro-4-pyridinyl)-7V-(3-methylphenyl)-l,3-thiazol-2-amine (150). [0359] 4-(2-Chloro-4-pyridinyl)-7V-(3-methylphenyl)-l,3-thiazol-2-amine (150). A mixture of 2-bromo-l-(2-chloro-4-pyridinyl)ethanone (0.51 g, 2.2 mmol) and 3-methylphenylthiourea (4) (0.36 g, 2.2 mmol) in EtOH (35 mL) was stirred at reflux temperature for 1 h. The mixture was cooled to 20 0C, diluted with water (80 niL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 0 °C for 1 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with EtOAc, to give amine 150 (0.62 g, 94%) as a white powder: mp (EtO Ac/pet, ether) 195-197 0C; 1H NMR δ 10.30 (s, 1 H, NH), 8.45 (br d, J= 5.1 Hz, 1 H, H-6'), 7.93 (br d, J= 1.2 Hz, 1 H, H-3'), 7.87 (dd, J= 5.2, 1.4 Hz, 1 H, H-5'), 7.84 (s, 1 H, H-5), 7.55 (br d, J= 8.0 Hz, 1 H, H-6"), 7.47 (br s, 1 H, H-2"), 7.25 (br t, J= 7.8 Hz, 1 H, H-5"), 6.82 (br d, J= 7.4 Hz, 1 H, H-4"), 2.33 (s, 3 H, CH3); 13C NMR δ 163.6, 151.0 (2), 150.3, 146.2, 144.4, 140.6, 138.1, 128.8, 122.3, 119.7, 117.6, 114.2, 109.1, 21.9; MS m/z 302.5 (MH+, 100%). Anal, calcd for Ci5Hi2ClN3S: C, 59.70; H, 4.01; N, 13.92. Found: C, 59.75; H, 4.07; N, 13.82%.

Reference： [1]Hay, Michael P.; Turcotte, Sandra; Flanagan, Jack U.; Bonnet, Muriel; Chan, Denise A.; Sutphin, Patrick D.; Nguyen, Phuong; Giaccia, Amato J.; Denny, William A. [Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 787 - 797]
[2]Current Patent Assignee: STANFORD UNIVERSITY - WO2009/114552, 2009, A1 Location in patent: Page/Page column 157-158

24
[ 23794-16-3 ]
[ 15827-84-6 ]
[ 1289555-46-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one; 4-aminopyridine-3-carbonitrile In ethanol for 2h; Reflux; Stage #2: With sodium hydrogencarbonate In ethanol for 4h; Reflux;	1.3 6-Aminonicotinonitnle (2 g, 16.8 mmoi) and 2-bromo-1-(2-ch]oro-4-yl)-ethanone (3.9 g, 16.8 mmol) were refluxed in ethanol (100 ml) for 2h. Pale-yellow precipitate formed. NaHC03 (2 g) was added to the cooled reaction mixture and the mixture was refluxed for another 4h. After cooling, the precipitate was filtrated, washed with water and recrystalized from ethyl acetate to give the 2-(2-chloropyridin-4-yl)-6-cyano-imidazo[1 ,2-a]pyridine (1.7 g). 1 H NMR (300 MHz, D SO~cf6) δ: 8.70 (d, 1H) 8.30 (d, 1 H) 7.63 (s, 1 H) 7.35 (d, 1H) 7.29 (d, 1 H) 7.21 (dd, 1 H) 7.14 (dd, H) ; MS (ES) miz (M+H) 255.7

Reference： [1]Current Patent Assignee: GUERBET - WO2011/45415, 2011, A2 Location in patent: Page/Page column 41

25
[ 23794-16-3 ]
[ 1312814-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

26
[ 23794-16-3 ]
[ 1312814-77-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

27
[ 23794-16-3 ]
[ 1312814-47-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

28
[ 23794-16-3 ]
[ 1312814-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

29
[ 23794-16-3 ]
[ 1354531-07-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

30
[ 23794-16-3 ]
[ 1312814-64-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

31
[ 23794-16-3 ]
[ 1312814-22-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

32
[ 23794-16-3 ]
[ 1312814-48-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

33
[ 23794-16-3 ]
[ 1312814-57-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

34
[ 23794-16-3 ]
[ 1312814-60-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

35
[ 23794-16-3 ]
[ 1312814-78-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

36
[ 23794-16-3 ]
[ 1312814-83-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

37
[ 23794-16-3 ]
[ 1312814-73-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

38
[ 23794-16-3 ]
[ 1312814-68-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C

Reference： [1]Oubrie, Arthur; Kaptein, Allard; De Zwart, Edwin; Hoogenboom, Niels; Goorden, Rianne; Van De Kar, Bas; Van Hoek, Maaike; De Kimpe, Vera; Van Der Heijden, Ruud; Borsboom, Judith; Kazemier, Bert; De Roos, Jeroen; Scheffers, Michiel; Lommerse, Jos; Schultz-Fademrecht, Carsten; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 613 - 618]

39
[ 23794-16-3 ]
[ 1260585-11-2 ]
[ 1523413-73-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate In acetonitrile at 20℃;

Reference： [1]Current Patent Assignee: SANOFI - WO2013/190510, 2013, A2 Location in patent: Page/Page column 348

40
[ 14222-60-7 ]
[ 23794-16-3 ]
4-(2-chloropyridin-4-yl)-2-(2-propylpyridin-4-yl)thiazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6572 - 6582

41
[ 23794-16-3 ]
tert-butyl 9,11-dioxo-8-(2,4,6-trimethoxybenzyl)-2,8-diazaspiro[5.5]undecane-2-carboxylate [ No CAS ]
tert-butyl 2'-(2-chloropyridin-4-yl)-4'-oxo-5'-(2,4,6-trimethoxybenzyl)-1',4',5',6'-tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With ammonium acetate; acetic acid In ethanol at 0 - 80℃; for 5h;	2.9 tert-butyl-2^,-(2-chloropyridin-4-yl)-4^,-oxo-5^,-(2,4,6-trimethoxybenzyl)-l^,,4^,,5^,,6'- tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-l-carboxylate (9). tert-butyl-2,-(2-chloropyridin-4-yl)-4,-oxo-5,-(2,4,6-trimethoxybenzyl)-l,,4,,5,,6'- tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-l-carboxylate (9). To a solution of tert-butyl 9,1 l-dioxo-8-(2,4,6-trimethoxybenzyl)-2,8-diazaspiro[5.5]undecane-2-carboxylate 8 (1.0 g, 2.0 mmol) in ethanol (30 mL), 2-bromo-l-(2-chloropyridin-4-yl)ethanone INT-40 (1.0 g, 4.0 mmol) was added at 0 °C. To this ammonium acetate (499 mg, 6 mmol) and acetic acid (250 mg, 4.0 mmol) were added. The resulting mixture was heated at 80 °C and for 5 h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford 9 (350 mg, 27%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 1.36 (s, 9H), 1.56 (s, 2H), 3.0 (d, J = 12.8 Hz, 1H), 3.3 (brs, 1H), 3.72 (s, 7H), 3.76 (s, 4H), 3.82 (brs, 2H), 4.0 (d, J = 13.2 Hz, 1H), 5.0 (brs, 1H), 6.62 (s, 2H), 7.16 (d, J = 2.2 Hz, 1H), 7.68- 7.69 (dd, J = 1.4, 5.3 Hz, 1H), 7.82 ( d, J = 1.4 Hz, 1H), 8.3 (d, J = 4.5 Hz, 1H), 11.5 (s, 1H). MS m/z (M+H): 453.3.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2014/149164, 2014, A1 Location in patent: Paragraph 00612

42
[ 23794-16-3 ]
[ 6228-73-5 ]
4-(2-chloropyridin-4-yl)-2-cyclopropyloxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13.2 g	With silver trifluoromethanesulfonate In ethyl acetate at 70℃; Darkness; Inert atmosphere;	2 Step 2: 4-(2-Chloropyridin-4-yl)-2-cyclopropyloxazole A mixture of 2-bromo-l-(2-chloropyridin-4-yl)ethanone (20 g, 85 mmol), cyclopropanecarboxamide (9.07 g, 106 mmol), AgOTf (43.83 g, 170.6 mmol), and EtOAc (300 mL) was stirred at 70 °C overnight in darkness under N2 and then allowed to cool to rt. Brine (300 mL) was added to the mixture, and the mixture was stirred for 3 h and filtered. The aqueous layer was separated and extracted with EtOAc (3x300 mL). The combined organic layers were washed (2x300 mL saturated NaHC03 and then 200 mL brine), dried (Na2S04), filtered, and concentrated. The residue was purified by silica gel chromatography (petroleum ether/EtOAc = 9/1) to give 4-(2-chloropyridin-4-yl)-2-cyclopropyloxazole (13.2 g, 70%) as a yellow solid. 1H NMR (400 MHz, CDCl3): d 8.38 (d, 1H), 7.92 (s, 1H), 7.66 (d, 1H), 7.49 (d, 1H), 2.17-2.09 (m, 1H), 1.18-1.07 (m, 4H); LCMS 220.9 [M+H]+.

Reference： [1]Current Patent Assignee: METACRINE INC - WO2020/61118, 2020, A1 Location in patent: Paragraph 00459

43
[ 23794-16-3 ]
[ 50607-30-2 ]
[ 724726-05-0 ]

Yield	Reaction Conditions	Operation in experiment
63%	With ammonium acetate In ethanol at 20℃; for 18h;

Reference： [1]Sharninghausen, Liam S.; Brooks, Allen F.; Winton, Wade P.; Makaravage, Katarina J.; Scott, Peter J. H.; Sanford, Melanie S. [Journal of the American Chemical Society, 2020, vol. 142, # 16, p. 7362 - 7367]

44
[ 23794-16-3 ]
C₂₄H₃₄N₂O₇ [ No CAS ]
C₃₁H₃₉ClN₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate In ethanol at 80℃; for 16h;

Reference： [1]Hoogenboom, Niels; Demont, Dennis; de Zwart, Edwin; Verkaik, Saskia; Emmelot, Maaike; van de Kar, Bas; Kaptein, Allard; Barf, Tjeerd [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 52]

45
[ 23794-16-3 ]
5-(2,2-difluoroethyl)-1-methylpiperidine-2,4-dione [ No CAS ]
(rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere;	Intermediate 131 (1167) (rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one (Racemate) (rac)-5-(2,2-Difluoroethyl)-1-methylpiperidine-2,4-dione (see Intermediate 130, 1.00 g), 2- bro o-1-(2-chloropyridin-4-yl)ethan-1-one (1.23 g, 5.23 mmol) and ammonium acetate (1.21 g, 15.7 mmol) were dissolved in 39 ml_ 1-propanol and stirred at 120°C for 4 hours under nitrogen atmosphere. Most of the 1 -propanol was removed under reduced pressure. The residue was diluted with ethyl acetate and 2 M aqueous sodiumhydroxide solution. The layers were separated and the aquoeus layer was extracted with ethyl acetate once. The combined organic layers were dried using a waterresistant filter and the clear filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane. A yellow solid precipitated and was filtered off under vacuo to provide batch 1 of the desired product in 95% purity: 593 mg. The clear filtrate was concentrated under reduced pressure and purified by flash chromatography (25g ultra column, gradient dichloromethane/ethanol 0-10) to provide batch 2 of the target compound in 88% purity: 340 mg. Batch 1 and 2 were combined and used for the following reaction: 932 mg in 90% purity. LC-MS (Method 2): Rt = 0.88 min; MS (ESIpos): m/z = 326 [M+H]+ (1169) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.10 - 2.28 (m, 1 H) 2.32 - 2.46 (m, 1 H) 2.93 (s, 3 H) 3.32 (br dd, 1 H) 3.43 - 3.52 (m, 1 H) 3.72 (dd, 1 H) 6.11 - 6.56 (m, 1 H) 7.17 (d, 1 H) 7.69 (dd, 1 H) 7.80 (d, 1 H) 8.30 (d, 1 H) 11.87 (br s, 1 H).
	With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere;	Intermediate 131 (1167) (rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one (Racemate) (rac)-5-(2,2-Difluoroethyl)-1-methylpiperidine-2,4-dione (see Intermediate 130, 1.00 g), 2- bro o-1-(2-chloropyridin-4-yl)ethan-1-one (1.23 g, 5.23 mmol) and ammonium acetate (1.21 g, 15.7 mmol) were dissolved in 39 ml_ 1-propanol and stirred at 120°C for 4 hours under nitrogen atmosphere. Most of the 1 -propanol was removed under reduced pressure. The residue was diluted with ethyl acetate and 2 M aqueous sodiumhydroxide solution. The layers were separated and the aquoeus layer was extracted with ethyl acetate once. The combined organic layers were dried using a waterresistant filter and the clear filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane. A yellow solid precipitated and was filtered off under vacuo to provide batch 1 of the desired product in 95% purity: 593 mg. The clear filtrate was concentrated under reduced pressure and purified by flash chromatography (25g ultra column, gradient dichloromethane/ethanol 0-10) to provide batch 2 of the target compound in 88% purity: 340 mg. Batch 1 and 2 were combined and used for the following reaction: 932 mg in 90% purity. LC-MS (Method 2): Rt = 0.88 min; MS (ESIpos): m/z = 326 [M+H]+ (1169) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.10 - 2.28 (m, 1 H) 2.32 - 2.46 (m, 1 H) 2.93 (s, 3 H) 3.32 (br dd, 1 H) 3.43 - 3.52 (m, 1 H) 3.72 (dd, 1 H) 6.11 - 6.56 (m, 1 H) 7.17 (d, 1 H) 7.69 (dd, 1 H) 7.80 (d, 1 H) 8.30 (d, 1 H) 11.87 (br s, 1 H).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 162
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 162

46
[ 23794-16-3 ]
1,5,5-trimethylpiperidine-2,4-dione [ No CAS ]
2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere;	Intermediate 141 (1218) 2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one 1,5,5-Trimethylpiperidine-2,4-dione (see Intermediate 140, 1.03 g), 2-bromo-1-(2-chloropyridin- 4-yl)ethan-1-one (1.56 g, 6.64 mmol) and ammonium acetate (1.53 g, 19.9 mmol) were dissolved in 49 mL propanol stirred at 120 °C for 4 hours under argon atmosphere. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane and water. Between both layers a yellow precipitate was formed. It was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 1 of the target compound in 98% purity: 697 mg. The filtrate was extracted with dichloromethane three times, the combined organic layers were washed with water and brine, filtered through a silicone coated filter and concentrated under reduced pressure. The crude product was treated with dichloromethane and sonicated. The undissolved precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 2 of the target compound in 98% purity: 184 mg. Filtrate II was suspended in ~1 mL dichloromethane and diluted with MTBE. The formed precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 3 of the target compound in 76% purity: 73 g. The batches were combined and used for the following reaction. batch 1: (1220) LC-MS (Method 2): Rt = 0.90 min; MS (ESIpos): m/z = 290 [M+H]+ (1221) -NMR (400 MHz, DMSO-d6) d [ppm] = 1.32 (s, 6 H), 2.93 (s, 3 H), 3.31 (s, 2 H), 7.13 (d, 1 H), 7.71 (dd, 1 H), 7.84 (d, 1 H), 8.29 (d, 1 H), 11.58 (br s, 1 H).
	With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere;	Intermediate 141 (1218) 2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one 1,5,5-Trimethylpiperidine-2,4-dione (see Intermediate 140, 1.03 g), 2-bromo-1-(2-chloropyridin- 4-yl)ethan-1-one (1.56 g, 6.64 mmol) and ammonium acetate (1.53 g, 19.9 mmol) were dissolved in 49 mL propanol stirred at 120 °C for 4 hours under argon atmosphere. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane and water. Between both layers a yellow precipitate was formed. It was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 1 of the target compound in 98% purity: 697 mg. The filtrate was extracted with dichloromethane three times, the combined organic layers were washed with water and brine, filtered through a silicone coated filter and concentrated under reduced pressure. The crude product was treated with dichloromethane and sonicated. The undissolved precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 2 of the target compound in 98% purity: 184 mg. Filtrate II was suspended in ~1 mL dichloromethane and diluted with MTBE. The formed precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 3 of the target compound in 76% purity: 73 g. The batches were combined and used for the following reaction. batch 1: (1220) LC-MS (Method 2): Rt = 0.90 min; MS (ESIpos): m/z = 290 [M+H]+ (1221) -NMR (400 MHz, DMSO-d6) d [ppm] = 1.32 (s, 6 H), 2.93 (s, 3 H), 3.31 (s, 2 H), 7.13 (d, 1 H), 7.71 (dd, 1 H), 7.84 (d, 1 H), 8.29 (d, 1 H), 11.58 (br s, 1 H).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 169-170
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 169-170

47
[ 23794-16-3 ]
1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione [ No CAS ]
2-(2-chloropyridin-4-yl)-5-methyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide In propan-1-ol at 120℃; for 8h;	Intermediate 161 (1286) 2-(2-chloropyridin-4-yl)-5- ethyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one To a stirred solution of 1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione (960 mg, 4.59 mmol, see Intermediate 13) in 1-propanol (17 ml) in a microwave tube was added 2-bromo-1-(2- chloropyridin-4-yl)ethan-1-one (1.08 g, 4.59 mmol, see Intermediate 118) and ammonium acetate (1.06 g, 13.8 mmol; CAS-RN:[631-61-8]) and the mixture was stirred at 120° C for 4 h. The mixture was concentrated in vacuum and the residue was heated to 120° C for 4 h. Dichloromethane and an aqueous sodium hydroxide solution (10%, w/v) were added and the mixture was stirred resulting in the precipitation of a solid. The solid was collected by filtration and dried in vacuum to give 1.46 g (92 % yield) of the title compound as a crude product that was used without further purification. (1288) LC-MS (Method 1): Rt = 0.92 min; MS (ESIpos): m/z = 344 [M+H]+ (1289) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.518 (2.24), 2.523 (1.55), 2.669 (0.50), 2.673 (0.53), 2.841 (0.42), 2.871 (0.56), 2.934 (16.00), 3.424 (0.52), 3.440 (1.15), 3.454 (0.71), 3.462 (1.47), 3.468 (1.47), 3.477 (0.83), 3.720 (0.73), 3.740 (0.70), 7.189 (4.92), 7.681 (1.56), 7.685 (1.70), 7.695 (1.58), 7.698 (1.80), 7.800 (2.55), 7.803 (2.47), 8.309 (2.29), 8.323 (2.23).
	With ammonium hydroxide In propan-1-ol at 120℃; for 8h;	Intermediate 161 (1286) 2-(2-chloropyridin-4-yl)-5- ethyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one To a stirred solution of 1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione (960 mg, 4.59 mmol, see Intermediate 13) in 1-propanol (17 ml) in a microwave tube was added 2-bromo-1-(2- chloropyridin-4-yl)ethan-1-one (1.08 g, 4.59 mmol, see Intermediate 118) and ammonium acetate (1.06 g, 13.8 mmol; CAS-RN:[631-61-8]) and the mixture was stirred at 120° C for 4 h. The mixture was concentrated in vacuum and the residue was heated to 120° C for 4 h. Dichloromethane and an aqueous sodium hydroxide solution (10%, w/v) were added and the mixture was stirred resulting in the precipitation of a solid. The solid was collected by filtration and dried in vacuum to give 1.46 g (92 % yield) of the title compound as a crude product that was used without further purification. (1288) LC-MS (Method 1): Rt = 0.92 min; MS (ESIpos): m/z = 344 [M+H]+ (1289) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.518 (2.24), 2.523 (1.55), 2.669 (0.50), 2.673 (0.53), 2.841 (0.42), 2.871 (0.56), 2.934 (16.00), 3.424 (0.52), 3.440 (1.15), 3.454 (0.71), 3.462 (1.47), 3.468 (1.47), 3.477 (0.83), 3.720 (0.73), 3.740 (0.70), 7.189 (4.92), 7.681 (1.56), 7.685 (1.70), 7.695 (1.58), 7.698 (1.80), 7.800 (2.55), 7.803 (2.47), 8.309 (2.29), 8.323 (2.23).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 182-183
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 182-183

48
1-methylpiperidine-2,4-dione [ No CAS ]
[ 23794-16-3 ]
2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.01 g	With ammonium acetate In ethanol at 20℃; for 2h;	Intermediate 99 (1033) 2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-methylpiperidine-2,4-dione (CAS-RN:[118263-97-1], 3.80 g, 29.9 mmol), ammonium acetate (9.19 g, 119 mmol) was added 90.5 ml_ of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 7.00 g, 29.9 mmol). The reaction was stirred at rt for 2 h. To the reaction was added 90 ml_ of water and the mixture was cooled down to 0 °C, stirred for 1 h, filtered and rinsed with water, yielding the desired product as a grey solid. The mother liquor was concentrated under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 4.01 g of the title compound. (1035) LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m/z = 262 [M+H]+ (1036) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (d, 1H), 7.63 (dd, 1H), 7.14 (d, 1 H), 3.56 (t, 2H), 2.99 - 2.87 (m, 5H).
21 g	With ammonium acetate In ethanol at 25℃; for 16h;	Intermediate 119 (1129) 2-(2-chloropyridin-4-yl)-5- ethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a solution of 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one (see Intermediate 118, 32.0 g) in ethanol (320 ml_) were added ammonium acetate (42.1 g, 546 mmol) and 1-methylpiperidine- 2,4-dione (CAS-RN:[118263-97-1], 19.1 g, 150 mmol) in one portion. The mixture was stirred at 25 °C for 16 hours. The reaction mixture was diluted with water (1280 ml_) and filtered. The filter cake was dried to give 21.0 g of the title compound as a yellow solid. (1131) LC-MS (Method 6): Rt = 0.747 min; MS (ESIpos): m/z = 262.2 [M+H]+. (1132) 1H NMR (400 MHz, DMSO-de): d [ppm] = 12.00 (s, 1H) 8.29 (d, 1H), 7.74 (d, 1H), 7.64 (dd, 1.6 Hz, 1 H), 7.15 (d, 1H), 3.56 (t, 2H), 3.95 (t, 2H), 2.92 (s, 3H).
4.01 g	With ammonium acetate In ethanol at 20℃; for 2h;	Intermediate 99 (1033) 2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-methylpiperidine-2,4-dione (CAS-RN:[118263-97-1], 3.80 g, 29.9 mmol), ammonium acetate (9.19 g, 119 mmol) was added 90.5 ml_ of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 7.00 g, 29.9 mmol). The reaction was stirred at rt for 2 h. To the reaction was added 90 ml_ of water and the mixture was cooled down to 0 °C, stirred for 1 h, filtered and rinsed with water, yielding the desired product as a grey solid. The mother liquor was concentrated under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 4.01 g of the title compound. (1035) LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m/z = 262 [M+H]+ (1036) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (d, 1H), 7.63 (dd, 1H), 7.14 (d, 1 H), 3.56 (t, 2H), 2.99 - 2.87 (m, 5H).

21 g

With ammonium acetate In ethanol at 25℃; for 16h;

Intermediate 119 (1129) 2-(2-chloropyridin-4-yl)-5- ethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a solution of 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one (see Intermediate 118, 32.0 g) in ethanol (320 ml_) were added ammonium acetate (42.1 g, 546 mmol) and 1-methylpiperidine- 2,4-dione (CAS-RN:[118263-97-1], 19.1 g, 150 mmol) in one portion. The mixture was stirred at 25 °C for 16 hours. The reaction mixture was diluted with water (1280 ml_) and filtered. The filter cake was dried to give 21.0 g of the title compound as a yellow solid. (1131) LC-MS (Method 6): Rt = 0.747 min; MS (ESIpos): m/z = 262.2 [M+H]+. (1132) 1H NMR (400 MHz, DMSO-de): d [ppm] = 12.00 (s, 1H) 8.29 (d, 1H), 7.74 (d, 1H), 7.64 (dd, 1.6 Hz, 1 H), 7.15 (d, 1H), 3.56 (t, 2H), 3.95 (t, 2H), 2.92 (s, 3H).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 140-141
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 155; 140-141
[3]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 140-141
[4]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 155; 140-141

49
[ 5239-39-4 ]
[ 23794-16-3 ]
2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.91 g	With ammonium acetate In ethanol at 20℃; for 1.5h;	Intermediate 94 (1005) 2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 6,6-dimethylpiperidine-2,4-dione (CAS-RN:[5239-39-4], 2.65 g, 18.8 mmol), ammonium acetate (5.25 g, 68.2 mmol) was added 52 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 4.00 g, 17.1 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 120 mL of water. The mixture was stirred for 2 h at rt, cooled down to 0 °C for 30 min, filtered and rinsed with water, yielding 3.91 g. of the title compound as a green solid. (1007) LC-MS (Method 4): Rt = 1.74 min; MS (ESIpos): m/z = 276 [M+H]+ (1008) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (s, 1 H), 7.68 - 7.58 (m, 1H), 7.13 (t, 1H), 7.07 (s, 1H), 2.80 (s, 2H), 1.26 (s, 6H).
3.91 g	With ammonium acetate In ethanol at 20℃; for 1.5h;	Intermediate 94 (1005) 2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 6,6-dimethylpiperidine-2,4-dione (CAS-RN:[5239-39-4], 2.65 g, 18.8 mmol), ammonium acetate (5.25 g, 68.2 mmol) was added 52 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 4.00 g, 17.1 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 120 mL of water. The mixture was stirred for 2 h at rt, cooled down to 0 °C for 30 min, filtered and rinsed with water, yielding 3.91 g. of the title compound as a green solid. (1007) LC-MS (Method 4): Rt = 1.74 min; MS (ESIpos): m/z = 276 [M+H]+ (1008) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (s, 1 H), 7.68 - 7.58 (m, 1H), 7.13 (t, 1H), 7.07 (s, 1H), 2.80 (s, 2H), 1.26 (s, 6H).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 137-138
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 137-138

50
[ 23794-16-3 ]
[ 1501330-86-4 ]
2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.06 g	With ammonium acetate In ethanol at 20℃; for 1.5h;	Intermediate 108 (1071) 2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-cyclopropylpiperidine-2,4-dione (CAS-RN:[ 1501330-86- 4], 1.27 g, 8.28 mmol) and ammonium acetate (1.91 g, 24.8 mmol) was added 41.4 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS- RN:[23794-16-3], 1.94 g, 8.28 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 60 mL of water and the mixture was cooled down to 0 °C. The reaction was concentrated under vacuum to remove the organic solvent. The aqueous layer was extracted 3 times with ethyl acetate. The organic layers were combined, dried over MgSCL and dried under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 1.06 g of the title compound. (1073) LC-MS (Method 4): Rt = 1.83 min; MS (ESIpos): m/z = 288 [M+H]+ -NMR (400 MHz, DMSO-de) d [ppm] = 12.07 - 11.82 (m, 1H), 8.28 (d, 1H), 7.73 (s, 1H), 7.63 (dd, 1H), 7.14 (d, 1H), 3.53 (t, 2H), 2.87 (t, 2H), 2.61 (dt, 1H), 0.73 (dt, 2H), 0.58 (q, 2H).
1.06 g	With ammonium acetate In ethanol at 20℃; for 1.5h;	Intermediate 108 (1071) 2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-cyclopropylpiperidine-2,4-dione (CAS-RN:[ 1501330-86- 4], 1.27 g, 8.28 mmol) and ammonium acetate (1.91 g, 24.8 mmol) was added 41.4 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS- RN:[23794-16-3], 1.94 g, 8.28 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 60 mL of water and the mixture was cooled down to 0 °C. The reaction was concentrated under vacuum to remove the organic solvent. The aqueous layer was extracted 3 times with ethyl acetate. The organic layers were combined, dried over MgSCL and dried under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 1.06 g of the title compound. (1073) LC-MS (Method 4): Rt = 1.83 min; MS (ESIpos): m/z = 288 [M+H]+ -NMR (400 MHz, DMSO-de) d [ppm] = 12.07 - 11.82 (m, 1H), 8.28 (d, 1H), 7.73 (s, 1H), 7.63 (dd, 1H), 7.14 (d, 1H), 3.53 (t, 2H), 2.87 (t, 2H), 2.61 (dt, 1H), 0.73 (dt, 2H), 0.58 (q, 2H).

Reference： [1]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 147
[2]Current Patent Assignee: BAYER AG; BROAD INSTITUTE; DANA-FARBER CANCER INSTITUTE - WO2022/23339, 2022, A1 Location in patent: Page/Page column 147

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	23794-16-3	MDL No. :	MFCD09702373
Formula :	C₇H₅BrClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BZWBRLWSWBQIBX-UHFFFAOYSA-N
M.W :	234.48	Pubchem ID :	16720431
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.31
TPSA :	29.96 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.1 cm/s

[ CAS No. 23794-16-3 ]

Quality Control of [ 23794-16-3 ]

Related Doc. of [ 23794-16-3 ]

Product Details of [ 23794-16-3 ]

Calculated chemistry of [ 23794-16-3 ]

Physicochemical Properties

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Lipophilicity

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Water Solubility

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[ 23794-16-3 ] Synthesis Path-Downstream 1~50

Related Functional Groups of
[ 23794-16-3 ]

Bromides

Chlorides

Ketones

Related Parent Nucleus of
[ 23794-16-3 ]

Pyridines

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Log Po/w (iLOGP) :	1.61
Log Po/w (XLOGP3) :	2.29
Log Po/w (WLOGP) :	2.31
Log Po/w (MLOGP) :	1.2
Log Po/w (SILICOS-IT) :	2.84
Consensus Log Po/w :	2.05

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

Log S (ESOL) :	-3.01
Solubility :	0.23 mg/ml ; 0.000982 mol/l
Class :	Soluble
Log S (Ali) :	-2.56
Solubility :	0.651 mg/ml ; 0.00278 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.85
Solubility :	0.0328 mg/ml ; 0.00014 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.86

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405	UN#:	3261
Hazard Statements:	H302-H314	Packing Group:	Ⅱ
GHS Pictogram:

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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:
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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
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P411
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P413
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P422
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P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
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P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 23794-16-3 ]

Quality Control of [ 23794-16-3 ]

Related Doc. of [ 23794-16-3 ]

Product Details of [ 23794-16-3 ]

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Physicochemical Properties

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Druglikeness

Water Solubility

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Application In Synthesis of [ 23794-16-3 ]

[ 23794-16-3 ] Synthesis Path-Downstream 1~50

Related Functional Groups of [ 23794-16-3 ]

Bromides

Chlorides

Ketones

Related Parent Nucleus of [ 23794-16-3 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 23794-16-3 ]

Related Parent Nucleus of
[ 23794-16-3 ]