Name: 942070-38-4|1-tert-Butyl 2-methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2-dicarboxylate|98%
Brand: Ambeed
SKU: A761444
Price: 37.0 USD
Availability: InStock
Rating: 98 (22 reviews)

1
[ 942070-38-4 ]
[ 1198605-53-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	at 180℃; for 0.3h;	38 Compound 38F: Methyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrrole-2- carboxylate1-Soc-2-(methoxycarbonyl)pyrrole-4-boronic acid, pinacol ester (900 mg, 2.56 mmol) was heated at 180 °C for 18 min to afford 0.643 mg of the title compound which was used without further purification (99%). 1H NMR (400 MHz, CD3OD) δ 7.27 (d, J = 1.5 Hz, 1 H), 7.10 (d, J = 1.3 Hz, 1 H), 3.82 (s, 3H), 1.31 (s, 12H). MS (ESI): m/z 252.13 [M+H]+. HPLC: tR = 1 .32-TOF: polar_3 min).
76%	at 180℃; for 0.3h;
2.5 g	With zinc dibromide In acetonitrile at 50℃; for 4h;	4.1 Example 4: Preparation of 4-(3-methyl-pyridin-4-yl)-lH-pyrrole-2-carboxylic acid amide Step 1: Preparation of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrole-2- carboxylic acid methyl ester To a mixture of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-pyrrole-l,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (10 g, 28.5 mmol) in MeCN (50 mL) was added ZnBr2 (12.8 g, 57 mmol) at room temperature. The mixture was heated at 50 °C for 4 hours, and then quenched with water (30 mL) and then basified to pH 9 with aqueous ammonia. The aqueous layer was extracted with EtOAc (30 mLx 3). The combined organic layers were dried over anhydrous Na2S04 and then concentrated. The residue was purified by column chromatography to give 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrole-2-carboxylic acid methyl ester as a white solid (2.5 g).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2012/74951, 2012, A1 Location in patent: Page/Page column 101
[2]Kallepalli, Venkata A.; Shi, Feng; Paul, Sulagna; Onyeozili, Edith N.; Maleczka Jr., Robert E.; Smith III, Milton R. [Journal of Organic Chemistry, 2009, vol. 74, # 23, p. 9199 - 9201]
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1 Location in patent: Page/Page column 35

2
[ 25015-63-8 ]
[ 294659-30-6 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 20℃; for 5h; Inert atmosphere; regioselective reaction;
72%	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 80℃; Sealed tube; Inert atmosphere; regioselective reaction;

Reference： [1]Kallepalli, Venkata A.; Shi, Feng; Paul, Sulagna; Onyeozili, Edith N.; Maleczka Jr., Robert E.; Smith III, Milton R. [Journal of Organic Chemistry, 2009, vol. 74, # 23, p. 9199 - 9201]
[2]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

3
4-((2-chloropyridin-4-yl)oxy)aniline [ No CAS ]
[ 942070-38-4 ]
[ 1268621-47-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium carbonate In 1,4-dioxane at 70℃; for 0.5h;	142 Preparation of 1-tert-butyl 2-methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2-dicarboxylate Preparation of 1-tert-butyl 2-methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2-dicarboxylate A 100 ml flask was charged with 4-((2-chloropyridin-4-yl)oxy)aniline (150 mg, 0.68 mmol), 1-tert-butyl 2-methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2-dicarboxylate (260 mg, 0.81 mmol), 2M Na2CO3 solution (0.5 ml, 1.0 mmol), PdCl2(PPh3)2 (5 mg, 0.007 mmol), 10 ml of 1,4-dioxane and 3 ml of water. The mixture was flushed with nitrogen and heated at 70° C. for 30 minutes. The mixture was cooled to room temperature and poured into 100 ml of water. The precipitates were filtered and dried to give the crude, which was further purified by silica gel chromatography eluding with 2-3% MeOH/CHCl3 to give 1-tert-butyl 2-methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2-dicarboxylate as light brown oil. Yield: 240 mg, 86%.
86%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 70℃; for 0.5h; Inert atmosphere;	Preparation of 1-tert-butyl 2-methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2- dicarboxylate Preparation of 1-tert-butyl 2-methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2- dicarboxylateA 100ml flask was charged with 4-((2-chloropyridin-4-yl)oxy)aniline (150mg, 0.68mmol), 1- tert-butyl 2-methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2- dicarboxylate (260mg, 0.81mmol), 2M Na2CO3 solution (0.5ml, 1.0mmol), PdCl2(PPh3)2 (5mg, 0.007mmol), 10ml of 1,4-dioxane and 3ml of water. The mixture was flushed with nitrogen and heated at 70C for 30 minutes. The mixture was cooled to room temperature and poured into 100ml of water. The precipitates were filtered and dried to give the crude, which was further purified by silica gel chromatography eluting with 2-3% MeOH/CHCl3 to give 1-tert-butyl 2- methyl 4-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1,2-dicarboxylate as light brown oil. Yield: 240mg, 86%.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2011/53905, 2011, A1 Location in patent: Page/Page column 102
[2]Current Patent Assignee: ABBVIE INC - WO2015/69287, 2015, A1 Location in patent: Page/Page column 170

4
[ 942070-38-4 ]
[ 1380306-54-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 0.3 h / 180 °C 2: caesium carbonate / N,N-dimethyl-formamide / 16 h / 70 °C 3: potassium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation 4: 5% Pd-CaCO3 / palladium 10% on activated carbon / ethanol / 16 h / 20 °C

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2012/74951, 2012, A1

5
[ 942070-38-4 ]
[ 1380306-56-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 0.3 h / 180 °C 2: caesium carbonate / N,N-dimethyl-formamide / 16 h / 70 °C 3: potassium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2012/74951, 2012, A1

6
[ 942070-38-4 ]
[ 1380306-60-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 0.3 h / 180 °C 2: caesium carbonate / N,N-dimethyl-formamide / 16 h / 70 °C

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2012/74951, 2012, A1

7
[ 942070-38-4 ]
[ 1287793-22-9 ]
[ 1287793-23-0 ]

Yield	Reaction Conditions	Operation in experiment
48%	With caesium carbonate In 1,2-dimethoxyethane; water for 16h; Reflux;	76 Example 76 7-(5-carboxy-1H-pyrrol-3-yl)-2-(3-fluorophenyl)-2H-[1,2,3]-triazolo[4,5-f]quinoline-9-carboxylic acid (Compound 76) Compound 75 (60 mg, 0.18 mmol) obtained in Example 75, 1-(tert-butoxycarbonyl)-2-(methoxycarbonyl)pyrrole-4-boronic acid pinacol ester (92 mg, 0.26 mmol), and cesium carbonate (171 mg, 0.53 mmol) were dissolved in a mixed solvent of DME and water (4:1, 1.75 mL). To this, a 1,1'-[bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (13 mg, 0.018 mmol) was added, and the mixture was refluxed for 16 hours. After the mixture was cooled to room temperature, insoluble compounds were filtered and removed, and 4 mol/L hydrochloric acid was added to the filtrate. The precipitate was filtered and collected, and thus the title Compound 76 (35 mg, 48%) was obtained. 1H-NMR (DMSO-d6) δ: 12.27 (1H, s), 8.28-8.21 (2H, m), 8.16 (1H, dd, J=8.2, 1.6 Hz), 8.08 (1H, ddd, J=9.9, 2.2, 2.2 Hz), 8.06-7.98 (2H, m), 7.77 (1H, ddd, J=8.2, 8.2, 3.2 Hz), 7.58 (1H, dd, J=2.2, 1.6 Hz), 7.45 (1H, ddd, J=8.2, 8.2, 2.7 Hz). ESI-MS (m/z) 418 [M+H]+.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - US2012/196854, 2012, A1 Location in patent: Page/Page column 47

8
[ 942070-38-4 ]
[ 1287793-22-9 ]
[ 1287793-66-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-ethyl-N,N-diisopropylamine In water; N,N-dimethyl-formamide; acetonitrile for 23h; Reflux;	118 Example 118 7-{5-(methoxycarbonyl)-1H-pyrrol-3-yl}-2-(3-fluorophenyl)-2H-[1,2,3]triazolo[4,5-f]quinoline-9-carboxylic acid (Compound 118) Compound 75 (120 mg, 0.35 mmol) obtained in Example 75, 1-(tert-butoxycarbonyl)-2-(methoxycarbonyl)pyrrole-4-boronic acid pinacol ester (148 mg, 0.42 mmol), diisopropylethylamine (0.27 mL, 2.1 mmol), and a 1,1'-[bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (29 mg, 0.035 mmol) were suspended in a mixed solvent of acetonitrile and water (6:1, 3.5 mL), and the mixture was refluxed for 23 hours. After the mixture was cooled to room temperature, DMF was added thereto. Insoluble compounds were filtered and removed, and hydrochloric acid was added to the filtrate. The precipitate was filtered and collected, and thus the title Compound 118 (138 mg, 91%) was obtained. 1H-NMR (DMSO-d6) δ: 12.45 (1H, s), 8.28-8.22 (2H, m), 8.18-7.94 (4H, m), 7.76 (1H, ddd, J=8.3, 8.3, 6.3 Hz), 7.65 (1H, dd, J=2.1, 2.1 Hz), 7.45 (1H, ddd, J=8.8, 8.8, 2.5 Hz), 3.83 (3H, s). ESI-MS (m/z) 430 [M+H]+.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - US2012/196854, 2012, A1 Location in patent: Page/Page column 52

9
[ 73183-34-3 ]
[ 294659-30-6 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 0.333333h; Inert atmosphere; Microwave irradiation; Sealed tube;
76%	Stage #1: bis(pinacol)diborane With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether Inert atmosphere; Sonication; Stage #2: methyl 1-(tert-butyloxycarbonyl)pyrrole-2-carboxylate at 80℃; for 0.333333h; Inert atmosphere; Microwave irradiation;	1 1 -tert-Butyl 2-methyl 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrrole- 1,2- dicarboxylate 4,4,4’,4’,5 ,5 ,5 ‘,5’-Octamethyl-2,2’-bi(1 ,3 ,2-dioxaborolane) (59.2 g, 233.08 mmol), (1,5- cyclooctadiene)(methoxy) iridium (I) dimer (1 .177 g, 1.78 mmol) and 4,4’-di-tert-butyl- 2,2’-bipyridine (0.953 g, 3.55 mmol) were placed in a 500 mL three-necked flask, which was purged with nitrogen. Degassed MTBE (500 mL) was added and the mixture was stirred and sonicated until a clear brown solution was obtained. 1-tert-butyl 2-methyl 1H-pyrrole-1,2-dicarboxylate (Sigma Aldrich) (50 g, 221.98 mmol) was added and flushed with nitrogen. The solution was heated in a microwave reactor at 80 °C for 20 minutes. The mixtures were combined and evaporated. The crude product was purified by flash silica chromatography, elution gradient 50 to 100% DCM in heptane to afford 1 -tert-butyl 2-methyl 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrrole- 1 ,2-dicarboxylate(59.3g, 76%) as a white crystalline solid.
68%	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 65℃; for 2h;	1-tert-Butyl 2-Methyl 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2-dicarboxylate (1e)²³ Bis(pinacolato)diboron (10.65 g, 41.96 mmol), (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (0.424 g, 0.64 mmol) and 4,4′-di-tertbutyl-2,2′-bipyridine (BBBPY, 0.354 g, 1.32 mmol) were placed in a250 mL three-necked flask, which was purged with N2. Degassed tertbutylmethyl ether (MTBE) (100 mL) was added and the mixture wasstirred until a clear brown solution was obtained. 1-tert-Butyl 2-methyl 1H-pyrrole-1,2-dicarboxylate24 (9.00 g, 39.96 mmol) was addedand the mixture stirred at 65 °C for 2 h. The reaction was cooled toRT and concentrated in vacuo. The crude product was purified byflash silica gel chromatography with DCM as eluent. Fractions wereevaporated to afford a liquid. Heptane (60 mL) was added and thesolution was left stirring overnight. The resultant precipitate was filteredand washed with 5% DCM in heptane; yield: 9.60 g (68%); offwhitesolid (Lit.23 mp 133-135 °C).1H NMR (500 MHz, CDCl3): = 1.31 (s, 12 H), 1.58 (s, 9 H), 3.82 (s, 3H), 7.12 (d, J = 1.7 Hz, 1 H), 7.68 (d, J = 1.7 Hz, 1 H).MS (ES+): m/z = 297 ([M + H]+ - OtBu).

With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 100℃; for 1h; Microwave irradiation;

Reference： [1]Ward, Richard A.; Anderton, Mark J.; Bethel, Paul; Breed, Jason; Cook, Calum; Davies, Emma J.; Dobson, Andrew; Dong, Zhiqiang; Fairley, Gary; Farrington, Paul; Feron, Lyman; Flemington, Vikki; Gibbons, Francis D.; Graham, Mark A.; Greenwood, Ryan; Hanson, Lyndsey; Hopcroft, Philip; Howells, Rachel; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Li, Yongchao; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; McCabe, James; McGuire, Thomas; Rawlins, Philip; Roberts, Karen; Sandin, Linda; Simpson, Iain; Swallow, Steve; Tang, Jia; Tomkinson, Gary; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2019, vol. 62, # 24, p. 11004 - 11018]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1 Location in patent: Page/Page column 102
[3]Howells, Rachel L.; Lamont, Scott G.; McGuire, Thomas M.; Hughes, Samantha; Borrows, Rachel; Fairley, Gary; Feron, Lyman J. L.; Greenwood, Ryan D. R.; Lenz, Eva; Grant, Emma; Simpson, Iain [Synthesis, 2022, vol. 54, # 9, p. 2267 - 2281]
[4]McMurray, Lindsay; Beck, Elizabeth M.; Gaunt, Matthew J. [Angewandte Chemie - International Edition, 2012, vol. 51, # 37, p. 9288 - 9291][Angew. Chem. Int. Ed., 2012, vol. 124, # 37, p. 9422 - 9425,4]

10
[ 942070-38-4 ]
[ 609-73-4 ]
[ 52635-93-5 ]

Yield	Reaction Conditions	Operation in experiment
692 mg	Stage #1: 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester; o-nitroiodobenzene With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In water; butan-1-ol at 100℃; for 1h; Stage #2: With N,N-dimethyl-formamide In water for 1h; Heating;

Reference： [1]McMurray, Lindsay; Beck, Elizabeth M.; Gaunt, Matthew J. [Angewandte Chemie - International Edition, 2012, vol. 51, # 37, p. 9288 - 9291][Angew. Chem. Int. Ed., 2012, vol. 124, # 37, p. 9422 - 9425,4]

11
[ 942070-38-4 ]
[ 1413063-63-4 ]
[ 1413064-08-0 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate In 1,4-dioxane; water at 100℃; for 4h; Inert atmosphere;	9.1 Step 1: Under N2, a mixture of acetic acid 2-bromo-6-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-benzyl ester (preparation described in intermediate-4, 300 mg, 0.699 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (270 mg, 0.769 mmol), Pd(dppf)Cl2 (171 mg, 0.21 mmol) and K2CO3 (289 mg, 2.19 mmol) in dioxane (15 mL) and water (3 mL) was heated at 100° C. for 4 h. The mixture was concentrated to dryness. The residue was purified by silica gel column chromatography (eluted with petroleum ether/ethyl acetate with a ratio of 2/1) to give 4-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (160 mg, yield 40%). LC-MS calcd for C32H35N3O7 (m/e) 573.25, obsd 473 [M-Boc+1]+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2012/295885, 2012, A1 Location in patent: Page/Page column 39

12
[ 156237-78-4 ]
[ 73183-34-3 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
4.1 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; for 3h; Inert atmosphere;	1.3 Step 3: Preparation of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-pyrrole-l,2- dicarboxylic acid 1-tert-butyl ester 2-methyl ester A mixture of 4-bromo-pyrrole-l,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (10 g, 33 mmol), bis(pinacolato)diboron (18 g, 66 mmol), KOAc (6.2 g, 66 mmol), Pd(dppf)Cl2 (1 g, 1.5 mmol) in 1,4-dioxane (150 mL) under nitrogen protection was stirred at 100 °C for 3 hours. The mixture was filtered through a Celite pad, and the filtrate was concentrated. The residue was purified by column chromatography to give 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)- pyrrole-l,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (4.1 g) as a white solid.
180 g	With bis-triphenylphosphine-palladium(II) chloride; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; for 3h; Inert atmosphere;	Step 2: Preparation of compound M6 The compound M6-2 (100.000g) and pinacol diborate (167.000g) were dissolved in dioxane (500mL), potassium acetate (81.000g), (PPh3)2PdCl2 (5.000g) and Pd(dppf)2Cl2 (5.000g) were added, vacuum N2 replacement three times, the mixture was incubated at 100°C and reacted for 3hrs. After the reaction was completed, cooled down to below 50°C, desolvated, added petroleum ether (500mL), filtered, after desolventization, added petroleum ether (1000mL) again, stired for 45min, filtered. The filtrated was cooled to 0-5°C, there was solid precipitation , which was filtered and dried to obtain 180.000 g of compound. LC-MS [M+H]+=352.2.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1 Location in patent: Page/Page column 29-30
[2]Current Patent Assignee: BETTA PHARMACEUTICALS CO LTD - EP3805217, 2021, A1 Location in patent: Paragraph 0098; 0100

13
[ 942070-38-4 ]
4-(3-phenylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: zinc dibromide / acetonitrile / 4 h / 50 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol / 3 h / Reflux; Inert atmosphere 4.1: sodium hydroxide; water / ethanol / 4 h / Reflux 5.1: sodium hydrogencarbonate; HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 2 h / 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

14
[ 942070-38-4 ]
4-(2-hydroxypyridin-4-yl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

15
[ 942070-38-4 ]
4-(2-hydroxypyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 3: sodium hydroxide; water / ethanol / 1 h / 80 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

16
[ 942070-38-4 ]
4-(2-hydroxypyridin-4-yl)-1H-pyrrole-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: zinc dibromide / acetonitrile / 4 h / 50 °C 2.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,4-dioxane; water / 2 h / Inert atmosphere; Reflux 3.1: sodium hydroxide; water / ethanol / 1 h / 80 °C 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 3 h / 20 °C 4.2: 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

17
[ 942070-38-4 ]
4-(2-tert-butoxycarbonylaminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux 2: sodium hydroxide; water / methanol / 2 h / Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

18
[ 942070-38-4 ]
4-(2-aminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux 2: sodium hydroxide; water / methanol / 2 h / Reflux 3: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

19
[ 942070-38-4 ]
4-(2-aminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux 2.1: sodium hydroxide; water / methanol / 2 h / Reflux 3.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0.5 h / 20 °C 4.2: 2 h / 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

20
[ 942070-38-4 ]
4-(3-methylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

21
[ 942070-38-4 ]
4-(3-methylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux 3: sodium hydroxide; water / ethanol / 2 h / Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

22
[ 942070-38-4 ]
4-(3-methylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: zinc dibromide / acetonitrile / 4 h / 50 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Inert atmosphere; Reflux 3.1: sodium hydroxide; water / ethanol / 2 h / Reflux 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0.5 h / 20 °C 4.2: 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

23
[ 942070-38-4 ]
4-(3-bromopyridin-4-yl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

24
[ 942070-38-4 ]
4-(3-bromopyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere 3: sodium hydroxide; water / ethanol / 4 h / Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

25
[ 942070-38-4 ]
4-(3-bromopyridin-4-yl)-1H-pyrrole-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: zinc dibromide / acetonitrile / 4 h / 50 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere 3.1: sodium hydroxide; water / ethanol / 4 h / Reflux 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 0.5 h / 20 °C 4.2: 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

26
[ 942070-38-4 ]
4-(3-phenylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol / 3 h / Reflux; Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

27
[ 942070-38-4 ]
4-(3-phenylpyridin-4-yl)-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: zinc dibromide / acetonitrile / 4 h / 50 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol; water / 3 h / Reflux; Inert atmosphere 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / ethanol / 3 h / Reflux; Inert atmosphere 4: sodium hydroxide; water / ethanol / 4 h / Reflux

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1

28
[ 942070-38-4 ]
[ 207799-10-8 ]
4-(2-tert-butoxycarbonylaminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In ethanol; water; for 3h;Inert atmosphere; Reflux;	A mixture of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-pyrrole-l,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (180 mg, 0.72 mmol), (4-bromo-pyridin-2-yl)-carbamic acid tert-butyl ester (235 mg, 0.86 mmol), Cs2C03 (468 mg, 1.44 mmol) and Pd(dppf)Cl2 (73 mg, 0.1 mmol) in EtOH (4 mL) and water (1 mL) was refluxed under N2 protection for 3 hours. The reaction mixture was poured into water (30 mL). The aqueous layer was extracted with EtOAc (30 mLx3). The combined organic layers were dried over anhydrous Na2S04 and then concentrated to give crude 4-(2-tert-butoxycarbonylamino-pyridin-4-yl)-lH-pyrrole-2-carboxylic acid methyl ester (300 mg) as a brown solid which was used in the next step without purification.

Reference： [1]Patent: WO2014/154723,2014,A1 .Location in patent: Page/Page column 30

29
[ 24424-99-5 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 3 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: dmap / acetonitrile / 1 h / 20 °C / Inert atmosphere 2: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine / hexane / 80 °C / Sealed tube; Inert atmosphere
	Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 1 h / 0 °C / Inert atmosphere 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1
[2]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]
[3]Current Patent Assignee: BETTA PHARMACEUTICALS CO LTD - EP3805217, 2021, A1

30
[ 934-05-4 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 3 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 1 h / 0 °C / Inert atmosphere 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/154723, 2014, A1
[2]Current Patent Assignee: BETTA PHARMACEUTICALS CO LTD - EP3805217, 2021, A1

31
[ 1193-62-0 ]
[ 942070-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap / acetonitrile / 1 h / 20 °C / Inert atmosphere 2: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine / hexane / 80 °C / Sealed tube; Inert atmosphere

Reference： [1]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

32
[ 942070-38-4 ]
[ 52635-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate / water; butan-1-ol / 16 h / 35 °C / Sealed tube; Inert atmosphere 2: N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere

Reference： [1]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

33
[ 942070-38-4 ]
methyl 1-(6-ethoxy-4-ethyl-6-oxohex-4-enyl)-4-(2-nitrophenyl)-1H-pyrrole-2-carboxylate [ No CAS ]
methyl 1-(6-ethoxy-4-ethyl-6-oxohex-4-enyl)-4-(2-nitrophenyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate / water; butan-1-ol / 16 h / 35 °C / Sealed tube; Inert atmosphere 2.1: N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 1.17 h / 0 - 20 °C / Inert atmosphere 3.2: 6 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

34
[ 942070-38-4 ]
methyl 1-(6-ethoxy-4-ethyl-6-oxohex-4-enyl)-4-(2-nitrophenyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate / water; butan-1-ol / 16 h / 35 °C / Sealed tube; Inert atmosphere 2.1: N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 1.17 h / 0 - 20 °C / Inert atmosphere 3.2: 20 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

35
[ 942070-38-4 ]
[ 577-19-5 ]
1-tert-butyl 2-methyl 4-(2-nitrophenyl)-1H-pyrrole-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In water; butan-1-ol at 35℃; for 16h; Sealed tube; Inert atmosphere;

Reference： [1]Kholod, Inga; Vallat, Olivier; Buciumas, Ana-Maria; Neels, Antonia; Neier, Reinhard [European Journal of Organic Chemistry, 2014, vol. 2014, # 35, p. 7865 - 7877]

36
[ 1780-31-0 ]
[ 942070-38-4 ]
1-tert-butyl 2-methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane; water at 22 - 80℃; for 4h; Inert atmosphere;
64.2%	With dichlorobis(di-tert-butyl(3-sulfopropyl)phosphonio)palladate(II); potassium carbonate In 1,4-dioxane; water at 20 - 40℃; for 1h; Inert atmosphere;
63.8%	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane; water at 22 - 80℃; for 4h; Inert atmosphere;	1 1 -tert-Butyl 2-methyl 4-(2-chloro-5 -methylpyrimidin-4-yl)- 1 H-pyrrole- 1 ,2-dicarboxylate Pd(PPh3)4 (0.982 g, 0.85 mmol) was added to a de-gassed solution of 2,4-dichloro-5-methylpyrimidine (Sigma-Aldrich) (4.62 g, 28.33 mmol), 1-tert-butyl 2-methyl 4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrrole- 1 ,2-dicarboxylate (9.95 g, 28.33 mmol)and potassium phosphate (18.04 g, 84.99 mmol) in dioxane (120 ml) and water (30 ml) at 22 °C under nitrogen. The resulting solution was stirred at 80 °C for 4 hours. The reaction mixture was concentrated and diluted with EtOAc (150 mL), and brine (100 mL). The layers were partitioned, then the aqueous extracted with further EtOAC (2 x 150 mL).Combined organics were evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution solvent 5-50% EtOAc in heptane. Pure fractions were evaporated to dryness to afford 1 -tert-butyl 2-methyl 4-(2-chloro-5- methylpyrimidin-4-yl)-1H-pyrrole-1,2-dicarboxylate (6.36 g, 63.8 %) as a white solid.‘H NMR (400 MHz, DMSO, 30°C) 1.56 (9H, s), 2.41 -2.47 (3H, m), 3.83 (3H, s), 7.39(1H, d), 8.01 (1H, d), 8.61 (1H, d). m/z: ES+ [M-Boc] 252

36.102 g

With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane; water at 80℃; for 3h; Inert atmosphere;

22.1 Step 1: Preparation of compound 22b 1-Boc-2-(methoxycarbonyl)pyrrole-4-boronic acid pinacol ester (M6, 21.500g) and 2,4-dichloro-5-methylpyrimidine (22a, 10.000g) were dissolved in dioxane (200mL). Potassium phosphate (39.000g), Pd(PPh3)4 (2.100g) and water (50mL) were added, vacuumed and replaced with N2 three times. The mixture was incubated at 80°C for 3hrs. After the reaction was completed, concentrated under reduced pressure to remove dioxane, added 100 mL of water, extracted with EtOAc (150 mL 2). The organic phases was combined, washed the organic phase with 100 mL of saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. 36.102g of the residue was separated by column chromatography. LC-MS [M+H]+=352.1.

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Ward, Richard A.; Anderton, Mark J.; Bethel, Paul; Breed, Jason; Cook, Calum; Davies, Emma J.; Dobson, Andrew; Dong, Zhiqiang; Fairley, Gary; Farrington, Paul; Feron, Lyman; Flemington, Vikki; Gibbons, Francis D.; Graham, Mark A.; Greenwood, Ryan; Hanson, Lyndsey; Hopcroft, Philip; Howells, Rachel; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Li, Yongchao; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; McCabe, James; McGuire, Thomas; Rawlins, Philip; Roberts, Karen; Sandin, Linda; Simpson, Iain; Swallow, Steve; Tang, Jia; Tomkinson, Gary; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2019, vol. 62, # 24, p. 11004 - 11018]
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1 Location in patent: Page/Page column 103
[4]Current Patent Assignee: BETTA PHARMACEUTICALS CO LTD - EP3805217, 2021, A1 Location in patent: Paragraph 0131-0132

37
[ 942070-38-4 ]
(3R)-7-(2-chloro-5-methylpyrimidin-4-yl)-3-methyl-3,4-dihydropyrrolo[1 ,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 16 h / 22 - 100 °C / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 22 °C 5: ammonia / methanol; dichloromethane / 18 h / 20 °C
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 22 °C 5: ammonia / dichloromethane; methanol / 20 h / 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

38
[ 942070-38-4 ]
(3R)-7-(2-chloro-5-methylpyrimidin-4-yl)-3-methyl-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo [1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 16 h / 22 - 100 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 18 h / 20 °C 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 22 °C / Inert atmosphere 6.2: 18 h / 22 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 20 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 18.17 h / 20 - 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

39
[ 942070-38-4 ]
(3S)-3-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo [1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 22 °C / Inert atmosphere 6.2: 3 h / 22 °C / Inert atmosphere 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 3 h / 22 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

40
[ 942070-38-4 ]
(S)-methyl 1-(2-((tert-butoxycarbonyl)amino)propyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

41
[ 942070-38-4 ]
(S)-methyl 1-(2-aminopropyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

42
[ 942070-38-4 ]
(3S)-7-(2-chloro-5-methylpyrimidin-4-yl)-3-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C 5: ammonia / methanol; dichloromethane / 5 h / 22 °C
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5: ammonia / dichloromethane; methanol / 5 h / 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

43
[ 942070-38-4 ]
(+/-)-methyl 1-(3-methoxy-2-methyl-2-(((6-methylpyridin-2-yl)methyl)amino)propyl)-4-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 16 h / 25 - 100 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 3 h / 25 - 80 °C / Inert atmosphere 5: hydrogenchloride / methanol / 12 h / 20 °C / Inert atmosphere 6: sodium tetrahydroborate; methanol / 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

44
[ 942070-38-4 ]
(+/-)-methyl 1-(2-amino-3-methoxy-2-methylpropyl)-4-(5-methyl-2-((1-methyl-1Hpyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 16 h / 25 - 100 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 3 h / 25 - 80 °C / Inert atmosphere 5: hydrogenchloride / methanol / 12 h / 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

45
[ 942070-38-4 ]
(+/-)-methyl 1-(2-((tert-butoxycarbonyl)amino)-3-methoxy-2-methylpropyl)-4-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 16 h / 25 - 100 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 3 h / 25 - 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

46
[ 942070-38-4 ]
(+/-)-methyl 1-(2-((tert-butoxycarbonyl)amino)-3-methoxy-2-methylpropyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 16 h / 25 - 100 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

47
[ 942070-38-4 ]
(3S)-7-(2-chloro-5-methylpyrimidin-4-yl)-3-methyl-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1 (2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 22 °C / Inert atmosphere 6.2: 3 h / 22 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 3 h / 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

48
[ 942070-38-4 ]
7’-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2’-((6-methylpyridin-2-yl)methyl)-2’,4’-dihydro-1‘H-spiro[oxetane-3,3‘-pyrrolo[1 ,2-a]pyrazin]-1‘-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: caesium carbonate / acetonitrile / 0.5 h / 25 - 60 °C 4.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere 5.1: palladium on activated charcoal; hydrogen / methanol / 12 h / 25 °C 6.1: tetrahydrofuran / 1 h / 25 - 70 °C / Inert atmosphere 6.2: 12 h / 25 °C 7.1: ammonia / ethanol / 72 h / 25 - 45 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

49
[ 942070-38-4 ]
methyl 4-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-1-((3-(((6-methylpyridin-2-yl)methyl)amino)oxetan-3-yl)methyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: caesium carbonate / acetonitrile / 0.5 h / 25 - 60 °C 4.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere 5.1: palladium on activated charcoal; hydrogen / methanol / 12 h / 25 °C 6.1: tetrahydrofuran / 1 h / 25 - 70 °C / Inert atmosphere 6.2: 12 h / 25 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

50
[ 942070-38-4 ]
methyl 1-((3-aminooxetan-3-yl)methyl)-4-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: caesium carbonate / acetonitrile / 0.5 h / 25 - 60 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere 5: palladium on activated charcoal; hydrogen / methanol / 12 h / 25 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

51
[ 942070-38-4 ]
methyl 1-((3-(((benzyloxy)carbonyl)amino)oxetan-3-yl)methyl)-4-(5-methyl-2-((1-methyl1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: caesium carbonate / acetonitrile / 0.5 h / 25 - 60 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

52
[ 942070-38-4 ]
methyl 1-((3-(((benzyloxy)carbonyl)amino)oxetan-3-yl)methyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: caesium carbonate / acetonitrile / 0.5 h / 25 - 60 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

53
[ 942070-38-4 ]
(3R)-3-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 16 h / 22 - 100 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 18 h / 20 °C 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 22 °C / Inert atmosphere 6.2: 18 h / 22 °C / Inert atmosphere 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 83 °C / Inert atmosphere
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 20 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 18.17 h / 20 - 22 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 83 °C / Inert atmosphere

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

54
[ 942070-38-4 ]
(S)-3-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((2-methyl-2H-1,2,3-triazol-4-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 18 h / 80 °C / Inert atmosphere
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 18 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

55
[ 942070-38-4 ]
(S)-7-(2-chloro-5-methylpyrimidin-4-yl)-3-methyl-2-((2-methyl-2H-1,2,3-triazol-4-yl)methyl)-3,4-dihydropyrrolo [1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

56
[ 942070-38-4 ]
methyl 1-(2-((tert-butoxycarbonyl)amino)-3-methoxypropyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: dichlorobis(di-tert-butyl(3-sulfopropyl)phosphonio)palladate(II); potassium carbonate / water; 1,4-dioxane / 1 h / 20 - 40 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 18 h / 50 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1
[2]Ward, Richard A.; Anderton, Mark J.; Bethel, Paul; Breed, Jason; Cook, Calum; Davies, Emma J.; Dobson, Andrew; Dong, Zhiqiang; Fairley, Gary; Farrington, Paul; Feron, Lyman; Flemington, Vikki; Gibbons, Francis D.; Graham, Mark A.; Greenwood, Ryan; Hanson, Lyndsey; Hopcroft, Philip; Howells, Rachel; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Li, Yongchao; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; McCabe, James; McGuire, Thomas; Rawlins, Philip; Roberts, Karen; Sandin, Linda; Simpson, Iain; Swallow, Steve; Tang, Jia; Tomkinson, Gary; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2019, vol. 62, # 24, p. 11004 - 11018]

57
[ 942070-38-4 ]
(S)-2-(2-methoxyethyl)-3-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 22 °C / Inert atmosphere 6.2: 3 h / 22 °C / Inert atmosphere 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 3 h / 22 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

58
[ 942070-38-4 ]
(3S)-7-(2-chloro-5-methylpyrimidin-4-yl)-2-(2-methoxyethyl)-3-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: 18-crown-6 ether; potassium carbonate / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / methanol; dichloromethane / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 22 °C / Inert atmosphere 6.2: 3 h / 22 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 5 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 3 h / 22 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

59
[ 942070-38-4 ]
C₂₀H₂₇ClN₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

60
[ 942070-38-4 ]
(x)CH₄O₃S*C₂₄H₂₆N₈O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 20 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 22 °C 5.1: ammonia / dichloromethane; methanol / 20 h / 22 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 - 22 °C / Inert atmosphere 6.2: 18.17 h / 20 - 22 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 83 °C / Inert atmosphere 8.1: acetone / Reflux

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

61
[ 942070-38-4 ]
methyl 1-(1-((tert-butoxycarbonyl)amino)propan-2-yl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.22 h / 0 °C / Inert atmosphere 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

62
[ 942070-38-4 ]
methyl 1-(1-aminopropan-2-yl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.22 h / 0 °C / Inert atmosphere 3.2: 1 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

63
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-4-methyl-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.22 h / 0 °C / Inert atmosphere 3.2: 1 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 5.1: sodium tris(acetoxy)borohydride; sodium acetate / methanol / 1.02 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

64
[ 942070-38-4 ]
4-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo [1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.22 h / 0 °C / Inert atmosphere 3.2: 1 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 5.1: sodium tris(acetoxy)borohydride; sodium acetate / methanol / 1.02 h / 0 - 20 °C / Inert atmosphere 6.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 1 h / 120 °C / Inert atmosphere; Sealed tube; Microwave irradiation

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

65
[ 942070-38-4 ]
7’-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2’-((6-methylpyridin-2-yl)methyl)-2’,4’-dihydro-1‘H-spiro[cyclopropane-1,3’-pyrrolo[1,2-a]pyrazin]-1‘-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.83 h / 80 °C / Inert atmosphere; Microwave irradiation 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

66
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-2-[(6-methyl-2-pyridyl)methyl]spiro[4H-pyrrolo[1,2-a]pyrazine-3,1‘-cyclopropane]-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.83 h / 80 °C / Inert atmosphere; Microwave irradiation 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

67
[ 942070-38-4 ]
2’-(2-methoxyethyl)-7’-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2’,4’-dihydro-1‘H-spiro [cyclopropane-1,3‘-pyrrolo[1,2-a]pyrazin]-1‘-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.83 h / 80 °C / Inert atmosphere; Microwave irradiation 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

68
[ 942070-38-4 ]
(tert-butoxycarbonyl)(1-((4-(2-chloro-5-methylpyrimidin-4-yl)-2-(methoxycarbonyl)-1Hpyrrol-1-yl)methyl)cyclopropyl)sulfamic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

69
[ 942070-38-4 ]
methyl 1-((1-aminocyclopropyl)methyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

70
[ 942070-38-4 ]
3-(methoxymethyl)-3-methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 16 h / 25 - 100 °C 4: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / 1,4-dioxane / 3 h / 25 - 80 °C / Inert atmosphere 5: hydrogenchloride / methanol / 12 h / 20 °C / Inert atmosphere 6: sodium tetrahydroborate; methanol / 20 °C / Inert atmosphere 7: trimethylaluminum / toluene / 1 h / 25 - 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

71
[ 942070-38-4 ]
7-(2-chloro-5-methyl-pyrimidin-4-yl)spiro[2,4-dihydropyrrolo[1,2-a]pyrazine-3,1’-cyclopropane]-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C 5: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.83 h / 80 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

72
[ 942070-38-4 ]
7’-(2-chloro-5-methylpyrimidin-4-yl)-2’-(2-methoxyethyl)-2’,4’-dihydro-1‘H-spiro[cyclopropane-1,3‘-pyrrolo[1,2-a]pyrazin]-1‘-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 18 h / 22 - 50 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.83 h / 80 °C / Inert atmosphere; Microwave irradiation 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

73
[ 942070-38-4 ]
7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; magnesium sulfate / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h / 22 °C 7.1: trimethylaluminum / tetrahydrofuran; toluene / 0.5 h / 22 - 150 °C / Inert atmosphere; Microwave irradiation 8.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 8 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: magnesium sulfate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h 7.1: trimethylaluminum / tetrahydrofuran; toluene / 0.5 h / 22 - 150 °C / Microwave irradiation; Inert atmosphere 8.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 1 h / 100 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

74
[ 942070-38-4 ]
methyl 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

75
[ 942070-38-4 ]
methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-1-(2-hydroxyethyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

76
[ 942070-38-4 ]
methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-1-(2-oxoethyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

77
[ 942070-38-4 ]
methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-1-(2-(((6-methylpyridin-2-yl)methyl)amino)ethyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; magnesium sulfate / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h / 22 °C
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: magnesium sulfate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

78
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; 1,4-dioxane / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C / Inert atmosphere 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; magnesium sulfate / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h / 22 °C 7.1: trimethylaluminum / tetrahydrofuran; toluene / 0.5 h / 22 - 150 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 22 °C / Inert atmosphere 3.2: 4 h / 60 °C 4.1: triethylamine tris(hydrogen fluoride) / tetrahydrofuran / 3.5 h / 22 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: magnesium sulfate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; N,N-dimethyl acetamide / 0.17 h / 22 °C 6.2: 20 h 7.1: trimethylaluminum / tetrahydrofuran; toluene / 0.5 h / 22 - 150 °C / Microwave irradiation; Inert atmosphere

Reference： [1]Ward, Richard A.; Bethel, Paul; Cook, Calum; Davies, Emma; Debreczeni, Judit E.; Fairley, Gary; Feron, Lyman; Flemington, Vikki; Graham, Mark A.; Greenwood, Ryan; Griffin, Nicola; Hanson, Lyndsey; Hopcroft, Philip; Howard, Tina D.; Hudson, Julian; James, Michael; Jones, Clifford D.; Jones, Christopher R.; Lamont, Scott; Lewis, Richard; Lindsay, Nicola; Roberts, Karen; Simpson, Iain; St-Gallay, Steve; Swallow, Steve; Tang, Jia; Tonge, Michael; Wang, Zhenhua; Zhai, Baochang [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3438 - 3450]
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

79
[ 942070-38-4 ]
3,3-dimethyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-(trifluoromethyl)pyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

80
[ 942070-38-4 ]
methyl 1-(2-amino-2-methylpropyl)-4-(2-chloro-5-methylpyrimidin-4-yl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

81
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-3,3-dimethyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

82
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-3,3-dimethyl-2-((6-(trifluoromethyl)pyridin-2-yl)methyl)-3,4-dihydropyrrolo [1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

83
[ 942070-38-4 ]
2-(2-methoxyethyl)-3,3-dimethyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

84
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-2-(2-methoxyethyl)-3,3-dimethyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

85
[ 942070-38-4 ]
3,3-dimethyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 18 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

86
[ 942070-38-4 ]
7-(2-chloro-5-methylpyrimidin-4-yl)-3,3-dimethyl-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

87
[ 942070-38-4 ]
3,3-dimethyl-2-((1-methyl-1H-pyrazol-5-yl)methyl)-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / water; 1,4-dioxane / 4 h / 22 - 80 °C / Inert atmosphere 2.1: hydrogenchloride / 1,4-dioxane; methanol / 18 h / 22 °C 3.1: potassium carbonate; 18-crown-6 ether / 1,4-dioxane / 24 h / 22 - 100 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; methanol / 72 h / 20 °C 5.1: trimethylaluminum / toluene; 2-methyltetrahydrofuran / 0.67 h / 80 °C / Microwave irradiation; Inert atmosphere 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 6.2: 18.17 h / 20 °C 7.1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / <i>tert</i>-butyl alcohol / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/162325, 2016, A1

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CAS No. :	942070-38-4	MDL No. :	MFCD11855974
Formula :	C₁₇H₂₆BNO₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IKRSLFIYLPMLIF-UHFFFAOYSA-N
M.W :	351.20	Pubchem ID :	44557750
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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

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. 942070-38-4 ] {[proInfo.proName]}

Quality Control of [ 942070-38-4 ]

Related Doc. of [ 942070-38-4 ]

Product Details of [ 942070-38-4 ]

Safety of [ 942070-38-4 ]

Application In Synthesis of [ 942070-38-4 ]

[ 942070-38-4 ] Synthesis Path-Downstream 1~87

Related Functional Groups of
[ 942070-38-4 ]

Organoboron

Amides

Esters

Related Parent Nucleus of
[ 942070-38-4 ]

Pyrroles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 942070-38-4 ] {[proInfo.proName]}

Quality Control of [ 942070-38-4 ]

Related Doc. of [ 942070-38-4 ]

Product Details of [ 942070-38-4 ]

Safety of [ 942070-38-4 ]

Application In Synthesis of [ 942070-38-4 ]

[ 942070-38-4 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 942070-38-4 ]

Organoboron

Amides

Esters

Related Parent Nucleus of [ 942070-38-4 ]

Pyrroles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 942070-38-4 ]

Related Parent Nucleus of
[ 942070-38-4 ]