Name: 24334-19-8|Ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate|95%
Brand: Ambeed
SKU: A201769
Price: 12.0 USD
Availability: InStock
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Yield	Reaction Conditions	Operation in experiment
	Pyridinderivat (III), H2, Pd;
	Ester (VI), K2CO3;

2
2-[(E)-4-Chloro-pyridin-3-ylimino]-propionic acid ethyl ester [ No CAS ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
272 mg	With pyridine; N-cyclohexyl-cyclohexanamine at 160℃; for 0.666667h; microwave irradiation;

Reference： [1]Lachance, Nicolas; April, Myriam; Joly, Marc-Andre [Synthesis, 2005, # 15, p. 2571 - 2577]

3
[ 617-35-6 ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine; PPTS; Si(OEt)4 / 48 h / 20 °C 2: 272 mg / Cy₂NH; pyridine / Pd(PPh₃)4 / 0.67 h / 160 °C / microwave irradiation

Reference： [1]Lachance, Nicolas; April, Myriam; Joly, Marc-Andre [Synthesis, 2005, # 15, p. 2571 - 2577]

4
[ 20511-15-3 ]
[ 24334-19-8 ]

Reference： [1]Synthesis,2005,p. 2571 - 2577

5
[ 24334-19-8 ]
[ 24334-20-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide; In ethanol; for 1h;Reflux;	General procedure: To a stirred solution of 9a-d (1.3 mmol) in EtOH (12 mL) 2M NaOH was added (1.7 mmol, 1.1 mL).The reaction mixture was heated under reflux for 1h (10a) or 2h (10b) and the solvent was evaporated.Water (10 mL) was added and acetic acid was added until pH 4.0. The desired product was filtered off,dried into the desiccators to afford the desired product. 1H-Pyrrolo[2,3-c]pyridine-2-carboxylic acid (10a). This compound was obtained in 95% yield. Analytical and spectroscopic data are in accordance to those reported in literature.
94%	With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 0 - 20℃; for 2h;	To a stirred solution of ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate 1 (500 mg, 2.63 mmol) in a mixture of THF/water (4: 1, 20 mL) at 0 C, was added LiOH.H20 (166 mg, 3.95 mmol). The reaction mixture was warmed to RT and stirred for 2 h. The reaction mixture was acidified to pH ~4 using sat. aq. citric acid. The precipitated solid was collected via filtration and dried under vacuum to afford compound 2 (400 mg, 94%) as an off-white solid. LCMS Mass: 163.0 (M++l).
		General procedure: 3-Amino-2-chloro-pyridine 4f (150 mg, 1.17 mmol), ethyl pyruvate 8 (0.25 ml, 2.00 mmol), pyridinium p-toluenesulfonate, (73 mg, 0.29 mmol) and tetraethoxy-silane (0.26 ml, 1.18 mmol) were suspended in 0.4 ml pyridine and stirred for 24 h at 20 C. Afterwards Pd[P(C6H6)3]4 (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 ml, 2.06 mmol) were added and the reaction mixture was heated in a microwave oven to 160 C for 20 min. The reaction mixture is diluted with 100 ml dichloromethan and extracted two times with 50 ml of a half saturated aqueous sodium hydrogencarbonat solution. The organic layer was dried with sodium sulfate, the solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P3, yielding 190 mg (1.00 mmol) of 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester. The ester was dissolved in 17 ml ethanol and 5 ml water. To this solution lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 h the pH value of the reaction mixture was adjusted to pH 4 and the solvent is evaporated in vacuum. The crude product was purified using an acid ion exchanger (Strata-X-C, Phenomenex), yielding of 155 mg (82%) of the title compound.

With sodium hydroxide; water; In ethanol; for 1.5h;Heating / reflux;

To a solution of 1H PYRROLO [2,3-c] pyridine-2-carboxylic acid ethyl ester (Preparation 14, 310MG, 1. 6MMOL) in ethanol (20ML) was added 2N sodium hydroxide solution (LML, 2. 0MMOL) and the reaction mixture heated under reflux for 1. 5h then concentrated in vacuo. The residue was dissolved in water (lOmL) and acidified with acetic acid giving an immediate brown precipitate. The solid was filtered and dried to give the title compound as a beige solid. 8N (D2O): 7.11 (1H, s), 7.99 (1H, d), 8.05 (1H, d), 8.85 (1H, s); m/z (ES+) = 163 [M+ H] +.

Reference： [1]Molecules,2014,vol. 19,p. 13342 - 13357
[2]Patent: WO2018/48930,2018,A1 .Location in patent: Paragraph 00283
[3]European Journal of Medicinal Chemistry,2012,vol. 54,p. 660 - 668
[4]Patent: WO2004/104001,2004,A2 .Location in patent: Page 34

6
[ 24334-18-7 ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With iron; ammonium chloride In tetrahydrofuran; ethanol; water for 2h; Reflux;
	With water; iron; ammonium chloride In tetrahydrofuran; ethanol for 2h; Heating / reflux;	1.2.A 1.2 ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate; Method A: To a solution of 3.9 g (16.37 mmol) of product obtained in step 1.1 in 140 ml of ethanol and 60 ml of tetrahydrofuran are added in a single portion 60 ml of saturated aqueous ammonium chloride solution and 5.48 g (98.2 mmol) of iron powder. The reaction mixture is then stirred at reflux for 2 hours. The cooled solution is filtered through Celite, which is rinsed several times with ethyl acetate. After concentrating the filtrate under reduced pressure, the residue is taken up in water and ethyl acetate and the organic phase is washed with saturated aqueous sodium chloride solution and then dried over sodium sulfate. A first crop of 0.7 g (3.68 mmol) of product is isolated. The aqueous phase is concentrated under reduced pressure, the residue is taken up in hot ethyl acetate, the precipitate is removed by filtration and the filtrate is concentrated again. The residue obtained is purified by chromatography on a column of silica gel eluting with a mixture of heptane and ethyl acetate. A further 0.7 g (3.68 mmol) of product is obtained.
	With hydrogen In ethanol at 20℃; for 2.5h;	1.2.B Method B: To a solution of 0.25 g (1.05 mmol) of product obtained in step 1.1 in 10 ml of ethanol is added 0.11 g (0.1 mmol) of 10% palladium-on-charcoal. The reaction mixture is hydrogenated under a pressure of 30 psi for 2 hours 30 minutes at room temperature. After filtering through glass fiber, the filtrate is evaporated under reduced pressure and the crude reaction product obtained is recrystallized from ethanol to give 0.08 g (0.42 mmol) of product.1H NMR (DMSO D6), δ (ppm): 8.9 (s, 1H); 8.3 (d, 1H); 7.7 (dd, 1H); 7.2 (d, 1H); 4.4 (q, 2H); 1.4 (t, 3H).

	With hydrogen In ethanol at 20℃; for 3h;	1 Ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate 1.8 g of 10% palladium-on-charcoal are charged into an autoclave, the atmosphere of which is then made inert with a stream of argon. A solution of 6 g of ethyl 3-(3-nitro-4-pyridyl)-2-oxopropionate in 72 mL of absolute ethanol is added. The reaction medium is then stirred for 3 hours at 20° C. under a pressure of 2 bar of hydrogen. The mixture is then filtered through Celite. The filtrate is concentrated under reduced pressure and oven-dried at 40° C. to give 4 g of ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate, the characteristics of which are as follows: Mass spectrum (EI) m/z=190 [M+], m/z=144 [M-OEt]+
	With iron; ammonium chloride In tetrahydrofuran; ethanol; water for 1h; Heating / reflux;	14 To a solution of 3- (3-nitropyridin-4-yl)-2-oxopropionic acid ethyl ester (Preparation 13, 500MG, 2. 1MMOL) in ethanol (20mL) and THF (LOML) was added saturated ammonium chloride solution (lOmL) and iron powder (700mg, 12. 6MMOL). The reaction was heated under reflux for lh, then filtered through celite and washed through with hot ethyl acetate (3 x 30mL). The combined organic fractions were washed with brine (20mL), dried (MgS04) and concentrated in vacuo to give the title compound as a brown solid. aH (CD30D): 1.44 (3H, t), 4.43 (2H, q), 7.21 (1H, s), 7.69 (1H, d), 8. 12 (1H, d), 8. 80 (1H, s).
	With palladium on activated charcoal; hydrogen In dichloromethane at 20℃;	1.2 1.2 Preparation of compound 1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester (L001-2) Under hydrogen protection, ethyl 3-(3-nitropyridin-4-yl)-2-carbonylpropionate (17.0 g, 70.0 mmol) was dissolved in anhydrous dichloromethane (200 mL), and palladium was added to the reaction solution Carbon (3.4 g) at room temperature overnight.Filtration, concentration of the filtrate under reduced pressure, and separation by silica gel column chromatography after concentration (PE/EA=1/1) to obtain 6.0 g of a yellow oily liquid with a two-step yield of 43.8%.

Reference： [1]Parrino, Barbara; Span, Virginia; Carbone, Anna; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Montalbano, Alessandra [Molecules, 2014, vol. 19, # 9, p. 13342 - 13357]
[2]Current Patent Assignee: SANOFI - US2008/125459, 2008, A1 Location in patent: Page/Page column 8
[3]Current Patent Assignee: SANOFI - US2008/125459, 2008, A1 Location in patent: Page/Page column 8
[4]Current Patent Assignee: SANOFI - US2008/139606, 2008, A1 Location in patent: Page/Page column 5; 7-8
[5]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2 Location in patent: Page 33-34
[6]Current Patent Assignee: WUHAN LL SCIENCE AND TECH DEVELOPMENT; WUHAN LANGLAI TECH DEVELOPMENT - WO2022/12409, 2022, A1 Location in patent: Page/Page column 32

7
[ 24334-19-8 ]
[ 104408-63-1 ]
ethyl 6-acetyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51.6%	In methanol; water; acetic acid	2 2-Ethoxycarbonyl-4,5,6,7-tetrahydro-6-azaindole and 2-ethoxycarbonyl-6-acetyl-4,5,6,7-tetrahydro-6-azaindole EXAMPLE 2 2-Ethoxycarbonyl-4,5,6,7-tetrahydro-6-azaindole and 2-ethoxycarbonyl-6-acetyl-4,5,6,7-tetrahydro-6-azaindole A solution of 2-ethoxycarbonyl-6-azaindole (24.5 g, 0.129 mole) in glacial acetic acid (1 liter) was hydrogenated at 100° C. and 100 psi (6.9 bar) over platinum oxide (3 g) for 24 hours. Further platinum oxide (4 g) was added at this time and hydrogenation continued for a total of 96 hours. The catalyst was removed by filtration and the solvent evaporated under vacuum. The residue was dissolved in water (200 ml) neutralised with 2M sodium hydroxide to pH 11 and the precipitated solid (16.5 g) collected by filtration. The filtrate was extracted with ethyl acetate to provide further product (4 g). The combined solids were dissolved in methanol (50 ml), silica gel (40 g) added and the mixture evaporated to dryness. Chromatography of the adsorbed material on silica gel (300 g) with a chloroform:methanol (20:1) solution removed traces of starting material; further elution with chloroform:methanol (10:1) gave a minor impurity which crystallized upon trituration with diethyl ether as a colourless crystalline solid (3.32 g, 10.9%) m.p. 106°-108° C., which proved to be 2-ethoxycarbonyl-6-acetyl-4,5,6,7-tetrahydro-6-azaindole. Found: C, 61.00; H, 6.98; N, 11.98. C12 H16 N2 O3 requires C, 60.99; H, 6.83; N, 11.86%. Finally elution with chloroform:methanol (5:1) followed by evaporation of the eluents gave 2-ethoxycarbonyl-4,5,6,7-tetrahydro-6-azaindole as a colourless crystalline solid (12.9 g, 51.6%), m.p. 169°-169.5° C. Found: C, 61.71; H, 7.34; N, 14.41. C10 H14 N2 O2 requires C, 61.84; H, 7.26; N, 14.42%.

Reference： [1]Current Patent Assignee: PFIZER INC - US4711882, 1987, A

8
[ 24424-99-5 ]
[ 24334-19-8 ]
[ 104408-90-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	In hexane; ethyl acetate; N,N-dimethyl-formamide	31 1-tert-Butoxycarbonyl-2-ethoxycarbonyl-6-azaindole EXAMPLE 31 1-tert-Butoxycarbonyl-2-ethoxycarbonyl-6-azaindole A stirred suspension of sodium hydride (80%, 0.16 g, 0.0055 mole) in dry N,N-dimethylformamide (5 ml) was treated at 0° C. with a slurry of 2-ethoxycarbonyl-6-azaindole (1.0 g, 0.0053 mole) and stirred at room temperature for 1 hour by which time evolution of hydrogen had ceased and a clear solution was obtained. The mixture was cooled to 0° C., treated with a solution of di-tert-butyl-dicarbonate (1.15 g, 0.0053 mole) and the resulting gel stirred at room temperature for 18 hours. The reaction mixture was poured into ice-water (150 ml) and the solution extracted with ethyl acetate (450 ml); the combined organic extracts were washed with brine (350 ml) and dried over sodium sulphate. Evaporation of the solvents under vacuum gave an orange oil which was chromatographed on silica gel (12 g) eluding first with hexane and then with a mixture of hexane and ethyl acetate 70:30 to give the pure title product as a pale yellow oil (1.37 g, 90%). Found: C, 62.40; H, 6.35; N, 9.84. C15 H18 N2 O4 requires C, 62.05; H, 6.25; N, 9.65%.
90%	Stage #1: 1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: di-<i>tert</i>-butyl dicarbonate In N,N-dimethyl-formamide at 20℃; for 24h;	1.a To a solution ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate (Fisher et al, 1969, above) (480 mg, 2.52 mmol) in DMF (12 mL) at 0°C was added 60% sodium hydride (121 mg, 3.02 mmol, 1.2 eq.). The reaction mixture was stirred at 0°C for 30 min and di-tertbutyl dicarbonate solution (1 M in DMF, 659 mg, 3.02 mmol, 1.2 eq.) was added. The reaction mixture was stirred at it for 24 hours and was partitioned between water and DCM. The combined organic layers were dried over Na2S04 and concentrated. Remaining DMF was evaporated and resulting residue was purified by column chromatography (c-Hex/EtOAc gradient: 80/20 to 30/70 in 25 minutes) to give the title compound (656 mg, 90%). HPLC purity: 99%. *H NMR (300 MHz, CDC13) 8 1.41 (t, 3H, J = 7.1 Hz), 1.67 (s, 9H), 4.42 (q, 2H, J = 7.1 Hz), 7.01 (s, 1H), 7.55 (d, 1H, J = 4.9 Hz), 8.47 (br s, 1H), 9.41 (br s, 1H). Rf (c-Hex/EtOAc 70/30) = 0.2
80%	With dmap In tetrahydrofuran at 20℃; for 4h;	36 Preparation of 1-tert-butyl 2-ethyl 1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate To a solution of 2.0 g ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate (10.5 mmol, 1.0 equiv) and 129 mg 4-dimethylaminopyridine (1.05 mol, 0.1 equiv) in THF (20 mL) was added 2.4 g di-tert-butyl dicarbonate (10.5 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature 4 h. he resulting solution was evaporated under reduced pressure and the residue was purified by column chromatography (silica gel, petroleum ether:ethyl acetate (15:1, v:v)) to afford 2.4 g 1-tert-butyl 2-ethyl 1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate (80 % yield). MS (ESI+) m/z 291 [M+H]+.

74%	With dmap In tetrahydrofuran at 20℃; for 1h;	1-tert-Butyl 2-ethyl 1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate A solution of di-tert-butyl dicarbonate (4.13 g, 18.93 mmol), ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate ( 3.0 g, 15.77 mmol), and DMAP (4.82 g, 39.43 mmol) in THF (80 mL) was stirred at room temperature for 1 h. The volatiles were removed under reduced pressure and the resulting product was purified by an Isco System using EtOAc/hexane gradient (20-70%) to give the desired compound (3.4 g, 74%). 1H NMR (DMSO-d6) δ 9.26 (s, 1 H), 8.45 (d, 1 H), 7.73 (d, 1 H), 7.29 (s, 1 H), 4.36 (m, 2 H), 1.61 (s, 9 H), 1.33 (t, 3 H); m/z 292.
68%	With dmap In tetrahydrofuran at 20℃; for 12h;
	With dmap In dichloromethane at 20℃; Inert atmosphere;	1.3 1.3 Preparation of compound 1-tert-butoxycarbonyl--pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester (L001-3) Under nitrogen protection, ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate (6.0 g, 31.5 mmol) was dissolved in anhydrous dichloromethane (50 mL), and Boc anhydride ( 7.6 g, 34.7 mmol) and DMAP (384 mg, 3.2 mmol), stirred at room temperature overnight.It was concentrated under reduced pressure, and the crude product was separated by silica gel column chromatography (PE/EA=3/1) to obtain 7.5 g of a yellow oily liquid.Yield 82.4%

Reference： [1]Current Patent Assignee: PFIZER INC - US4711882, 1987, A
[2]Current Patent Assignee: MERCK KGAA - WO2006/8303, 2006, A1 Location in patent: Page/Page column 36
[3]Current Patent Assignee: VINCERE BIOSCIENCES - WO2021/50992, 2021, A1 Location in patent: Paragraph 00701-00702
[4]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]
[5]Makida, Yusuke; Saita, Masahiro; Kuramoto, Takahiro; Ishizuka, Kentaro; Kuwano, Ryoichi [Angewandte Chemie - International Edition, 2016, vol. 55, # 39, p. 11859 - 11862][Angew. Chem., 2016, vol. 128, p. 12038 - 12041]
[6]Current Patent Assignee: WUHAN LL SCIENCE AND TECH DEVELOPMENT; WUHAN LANGLAI TECH DEVELOPMENT - WO2022/12409, 2022, A1 Location in patent: Page/Page column 32

9
[ 24334-19-8 ]
[ 104408-63-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogen In acetic acid at 20 - 50℃; for 264h;	2.a Ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate (4.225 g, 22.21 mmol) was dissolved in acetic acid (150 mL) and 5% RI1/AI2O3 (9.144 g, 0.2 eq.) was added. The suspension was hydrogenated (45 Bars) at it for 4 days then at 50°C for 7 days. The catalyst was removedby filtration through a Celite pad, was washed with acetic acid and the filtrate was evaporated. The residue was dissolved in DCM, washed with saturated aqueous solution of NaHCC>3 and aqueous phases were extracted with DCM. The combined organic layers were washed with brine, dried over Na2SC>4 and concentrated to give the title compound (4.183 g, 97%). HPLCpurity: 92%. M+(LC-MS(ESI)): 195, M(LC-MS(ESI)): 193 XH NMR (300 MHz, CDC13) 8 1.31 (t, 3H, J = 7.1 Hz), 2.69 (t, 2H, J = 5.6 Hz), 3.17 (t, 2H, J = 6.0 Hz), 4.00 (s, 2H), 4.25 (q, 2H, J = 7.1 Hz), 6.59 (s, 1H), 8.38 (br s, 1H)

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2006/8303, 2006, A1 Location in patent: Page/Page column 41; 42

10
[ 456-47-3 ]
[ 24334-19-8 ]
[ 920978-82-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 20h;	1.3 1.3 ethyl 1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-c]pyridine-2-carboxylate; To a solution of 2 g (10.52 mmol) of product obtained in step 1.2 in 105 ml of dry tetrahydrofuran, maintained under an inert atmosphere, are successively added with stirring 2.03 g (15.77 mmol) of 3-fluorobenzyl alcohol and then 4.17 g (15.77 mmol) of triphenylphosphine. 2.83 g (15.77 mmol) of diethyl azodicarboxylate are then added dropwise at 0° C. The reaction mixture is then stirred for 20 hours at room temperature, and then concentrated under reduced pressure. The resulting oil is purified by successive chromatographies on a column of silica gel eluting with a mixture of heptane and ethyl acetate. 1.9 g (6.37 mmol) of product are isolated.1H NMR (CDCl3), δ (ppm): 8.8 (s, 1H); 8.3 (d, 1H); 7.6 (d, 1H); 7.2 (s, 1H); 7.1 (m, 1H); 6.85 (m, 2H); 6.65 (m, 1H); 5.8 (s, 2H); 4.3 (q, 2H); 1.3 (t, 3H).

Reference： [1]Current Patent Assignee: SANOFI - US2008/125459, 2008, A1 Location in patent: Page/Page column 8

11
[ 24334-19-8 ]
[ 913181-68-7 ]

Yield	Reaction Conditions	Operation in experiment
51%	With pyridinium hydrobromide perbromide at 0 - 20℃;	10.1 Ethyl 3-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate To a solution of ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate (1.36 g, 7.15 mmol) in pyridine (90 ml) was added dropwise a solution of pyridinium tribromide (2.15 g, 6.72 mmol) in pyridine (20 ml), at 0 °C. The reaction mixture is then stirred overnight at room temperature. 300 ml ice water was added and the resulting suspension stirred for 30 minutes, filtered and the precipitated material washed with water and dried to afford 0.92 g (51 %) of the title compound as a colorless solid. 1H NMR (400 MHz, DMSO) δ 12.76 (s, 1 H), 8.88 (s, 1 H), 8.28 (d, J = 4.8, 1 H), 7.52 (d, J = 4.8, 1 H), 4.41 (d, J = 6.9, 2H), 1.38 (t, J = 6.7, 3H)
	With pyridine; pyridinium hydrobromide perbromide at 5 - 20℃; for 16h;	1 Ethyl 3-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate To a solution of 2.24 g of ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate in 150 mL of pyridine is added dropwise a solution of 3.53 g of pyridinium tribromide in 30 mL of pyridine, at 5° C. The reaction mixture is then stirred for 16 hours at a temperature in the region of 20° C., and then washed with 500 mL of ice-cold water. The suspension is filtered. The resulting solid is washed with water and then dried in a vacuum oven at 40° C. 1.97 g of ethyl 3-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate are obtained, the characteristics of which are as follows: Mass spectrum (EI) m/z=269 [M]+, m/z=189 [M-Br]+, m/z=144 [M-OEt]+
1 g	With N-Bromosuccinimide In acetonitrile at 20℃; for 0.5h;	22.C Step C. Synthesis of ethyl 3-bromo-lH-pyrrolo[2,3-c]pyridine-2-carboxylate A solution of ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate (2.4 g, 12.6 mmol) in MeCN (25 mL) was added NBS(2.7 g, 15.1 mmol). The reaction mixture was stirred at r.t. for 0.5 hr. The mixture was diluted with EtOAc, washed with water and brine. The organic layer was dried over anhy. Na2SO4 and concentrated. The residue was purified by silica gel chromatography (eluted with PE:EtOAc = 10:1 to 2:1) to afford 1 g of ethyl 3-bromo-lH-pyrrolo[2,3-c]pyridine-2- carboxylate. LC-MS (ESI): m/z 269 (M+H)+.

Reference： [1]Current Patent Assignee: LYTIX BIOPHARMA AS - WO2014/198848, 2014, A2 Location in patent: Page/Page column 29; 30
[2]Current Patent Assignee: SANOFI - US2008/139606, 2008, A1 Location in patent: Page/Page column 5; 7
[3]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1 Location in patent: Page/Page column 120

12
[ 85510-81-2 ]
[ 24334-19-8 ]
[ 1093340-36-3 ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide for 0.666667h; Stage #2: 2-fluoro-4-iodo-benzyl bromide In N,N-dimethyl-formamide at 20 - 60℃; for 18.75h;	5 Ethyl 1-(2-fluoro-4-iodo-benzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate To a suspension of methyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate (0.81 g, 4.26 mmol) in DMF (15 ml) was added potassium tert-butoxide (0.72 g, 6.39 mmol). After the resultant red-brown suspension had been stirred for 40 minutes, a solution of 2-fluoro-4-iodobenzyl bromide (2.01 g, 6.39 mmol) in DMF (5 ml) was added dropwise over 10 minutes. The suspension was then heated to 60° C. for 35 minutes before stirring at room temperature for 18 hours. The reaction mixture was concentrated in vacuo, the resultant residue partitioned between dichloromethane (40 ml) and water (30 ml) and the organic layer separated. The aqueous layer was extracted with dichloromethane (2*25 ml) and the combined organic extracts were washed with brine (30 ml) dried over magnesium sulphate, then concentrated in vacuo to provide a residue. The residue was purified by flash chromatography (Si-SPE, dichloromethane:ethyl acetate 100:0 to 50:50 to 0:100 then dichloromethane:methanol 90:10 to 80:20) gave the title compound as a pale cream solid (0.83 g, 46%). LCMS (method B): RT=2.58 min, M+H+=425.

Reference： [1]Current Patent Assignee: CHARLES RIVER LABORATORIES INTERNATIONAL INC; ROCHE HOLDING AG - US2010/216768, 2010, A1 Location in patent: Page/Page column 17

13
[ 95-92-1 ]
[ 180253-66-1 ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
18%	Stage #1: 3-(tert-butyloxycarbonylamino)-4-methyl-pyridine With tert.-butyl lithium In tetrahydrofuran; pentane at -40℃; for 1h; Inert atmosphere; Stage #2: oxalic acid diethyl ester In tetrahydrofuran; pentane at -40 - 20℃; for 21.25h; Inert atmosphere; Stage #3: With hydrogenchloride In tetrahydrofuran; water; pentane for 2h; Heating; Reflux;	5 1H-Pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester To a solution of (4-methyl-pyridin-3-yl)-carbamic acid tert-butyl ester (3.5 g, 16.8 mmol) in anhydrous THF (30 ml) under an atmosphere of argon at -40° C. was added tert-butyl lithium (20.7 ml, 1.7 M in pentanes, 35.2 mmol). The reaction mixture was maintained at -40° C. for 1 hour before a solution of diethyl oxalate (2.5 ml, 18.5 mmol) in THF (30 ml) was added over a 15 minute period. After stirring for 2 hours at 0° C. the reaction was allowed to warm to room temperature and then stirred for a further 19 hours. 2N HCl (110 ml) was cautiously added to the reaction mixture which was then heated at reflux for 2 hours. After cooling, dichloromethane (100 ml) was added to the reaction mixture and the aqueous phase was adjusted to pH 8 and the organic phase was isolated. The aqueous phase was washed with dichloromethane (2*50 ml) and the combined organic layers were dried over magnesium sulfate, then concentrated to afford a light-brown solid. The material was triturated with ethyl acetate and the resultant solid was then collected by filtration to afford the desired product as a beige solid (586 mg, 18%). LCMS (Method B): RT=1.89 min, M+H+=190.

Reference： [1]Current Patent Assignee: CHARLES RIVER LABORATORIES INTERNATIONAL INC; ROCHE HOLDING AG - US2010/216768, 2010, A1 Location in patent: Page/Page column 16-17

14
[ 617-35-6 ]
[ 42166-50-7 ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-oxo-propionic acid ethyl ester; 3-hydrazinopyridine With pyridine; tetraethoxy orthosilicate; pyridinium p-toluenesulfonate at 20℃; for 24h; Stage #2: With tetrakis(triphenylphosphine) palladium⁽⁰⁾; N-Methyldicyclohexylamine at 160℃; for 0.333333h; Microwave irradiation;	4.2.2.1. 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid (5f) General procedure: 3-Amino-2-chloro-pyridine 4f (150 mg, 1.17 mmol), ethyl pyruvate 8 (0.25 ml, 2.00 mmol), pyridinium p-toluenesulfonate, (73 mg, 0.29 mmol) and tetraethoxy-silane (0.26 ml, 1.18 mmol) were suspended in 0.4 ml pyridine and stirred for 24 h at 20 °C. Afterwards Pd[P(C6H6)3]4 (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 ml, 2.06 mmol) were added and the reaction mixture was heated in a microwave oven to 160 °C for 20 min. The reaction mixture is diluted with 100 ml dichloromethan and extracted two times with 50 ml of a half saturated aqueous sodium hydrogencarbonat solution. The organic layer was dried with sodium sulfate, the solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P3, yielding 190 mg (1.00 mmol) of 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester. The ester was dissolved in 17 ml ethanol and 5 ml water. To this solution lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 h the pH value of the reaction mixture was adjusted to pH 4 and the solvent is evaporated in vacuum. The crude product was purified using an acid ion exchanger (Strata-X-C, Phenomenex), yielding of 155 mg (82%) of the title compound.

Reference： [1]Location in patent: experimental part Engelhardt, Harald; De Esch, Iwan J.P.; Kuhn, Daniel; Smits, Rogier A.; Zuiderveld, Obbe P.; Dobler, Julia; Mayer, Moriz; Lips, Sebastian; Arnhof, Heribert; Scharn, Dirk; Haaksma, Eric E.J.; Leurs, Rob [European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668]

15
[ 24334-19-8 ]
[ 1394078-30-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium hydroxide / ethanol; water / 16 h 1.2: pH 4 / Acidic conditions 2.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 20 °C 2.2: 16 h / 20 °C

Reference： [1]Engelhardt, Harald; De Esch, Iwan J.P.; Kuhn, Daniel; Smits, Rogier A.; Zuiderveld, Obbe P.; Dobler, Julia; Mayer, Moriz; Lips, Sebastian; Arnhof, Heribert; Scharn, Dirk; Haaksma, Eric E.J.; Leurs, Rob [European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668]

16
[ 104-83-6 ]
[ 24334-19-8 ]
ethyl 1-(4-chlorobenzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-Chloro-4-(chloromethyl)benzene In N,N-dimethyl-formamide for 14h; Inert atmosphere;

Reference： [1]Sindac, Janice A.; Barraza, Scott J.; Dobry, Craig J.; Xiang, Jianming; Blakely, Pennelope K.; Irani, David N.; Keep, Richard F.; Miller, David J.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2013, vol. 56, # 22, p. 9222 - 9241]

17
[ 24334-19-8 ]
1-(4-chlorobenzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 1.2: 14 h / Inert atmosphere 2.1: sodium hydroxide / ethanol; water / 12 h / 20 °C 2.2: pH Ca_. 4

Reference： [1]Sindac, Janice A.; Barraza, Scott J.; Dobry, Craig J.; Xiang, Jianming; Blakely, Pennelope K.; Irani, David N.; Keep, Richard F.; Miller, David J.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2013, vol. 56, # 22, p. 9222 - 9241]

18
[ 24334-19-8 ]
1-(1-(4-chlorobenzyl)-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)-N-(2-(pyridin-4-yl)ethyl)piperidine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 1.2: 14 h / Inert atmosphere 2.1: sodium hydroxide / ethanol; water / 12 h / 20 °C 2.2: pH Ca_. 4 3.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 18 h / 20 °C / Inert atmosphere

Reference： [1]Sindac, Janice A.; Barraza, Scott J.; Dobry, Craig J.; Xiang, Jianming; Blakely, Pennelope K.; Irani, David N.; Keep, Richard F.; Miller, David J.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2013, vol. 56, # 22, p. 9222 - 9241]

19
[ 24334-19-8 ]
N²-methyl-N-[(4aR,5aS,9S,11aS)-10-oxo-2-(2-phenylethyl)dodecahydro-2H-pyrido[4',3':4,5]pyrrolo[1,2-a]azepin-9-yl]-L-alaninamide dihydrogen chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 14 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere 10.1: hydrogenchloride; water / 1,4-dioxane / 1 h / 20 °C 11.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 11.2: 2 h / 0 - 20 °C 12.1: palladium 10% on activated carbon; hydrogen / methanol / 1 h / 20 °C 13.1: dichloromethane / 1 h / 20 °C 13.2: 20 °C 14.1: hydrogenchloride; water / 1,4-dioxane / 1 h

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

20
[ 24334-19-8 ]
[ 1595087-14-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 13 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere 10.1: hydrogenchloride; water / 1,4-dioxane / 1 h / 20 °C 11.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 11.2: 2 h / 0 - 20 °C 12.1: palladium 10% on activated carbon; hydrogen / methanol / 1 h / 20 °C 13.1: dichloromethane / 1 h / 20 °C 13.2: 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

21
[ 24334-19-8 ]
1-tert-butyl 2-ethyl octahydro-1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap / tetrahydrofuran / 1 h / 20 °C 2: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

22
[ 24334-19-8 ]
6-benzyl 1-tert-butyl 2-ethyl hexahydro-1H-pyrrolo[2,3-c]pyridine-1,2,6(2H)-tricarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: dmap / tetrahydrofuran / 1 h / 20 °C 2: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3: triethylamine / dichloromethane / 0.5 h / 0 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

23
[ 24334-19-8 ]
6-benzyl 1-tert-butyl 2-(hydroxymethyl)hexahydro-1H-pyrrolo[2,3-c]pyridine-1,6(2H)-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: dmap / tetrahydrofuran / 1 h / 20 °C 2: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3: triethylamine / dichloromethane / 0.5 h / 0 °C 4: lithium borohydride / tetrahydrofuran / 2 h / 55 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

24
[ 24334-19-8 ]
6-benzyl 1-tert-butyl 2-formylhexahydro-1H-pyrrolo[2,3-c]pyridine-1,6(2H)-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: dmap / tetrahydrofuran / 1 h / 20 °C 2: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3: triethylamine / dichloromethane / 0.5 h / 0 °C 4: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5: Dess-Martin periodane / dichloromethane / 3 h / 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

25
[ 24334-19-8 ]
6-benzyl 1-tert-butyl 2-ethenylhexahydro-1H-pyrrolo[2,3-c]pyridine-1,6(2H)-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

26
[ 24334-19-8 ]
benzyl 2-ethenyloctahydro-6H-pyrrolo[2,3-c]pyridine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

27
[ 24334-19-8 ]
benzyl 1-((S)-2-(tert-butoxycarbonylamino)pent-4-enoyl)-2-vinylhexahydro-1H-pyrrolo[2,3-c]pyridine-6(2H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

28
[ 24334-19-8 ]
[ 1595087-03-8 ]
[ 1595087-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

29
[ 24334-19-8 ]
[ 1595087-13-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere 10.1: hydrogenchloride; water / 1,4-dioxane / 1 h / 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

30
[ 24334-19-8 ]
[ 1595086-06-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere 10.1: hydrogenchloride; water / 1,4-dioxane / 1 h / 20 °C 11.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 11.2: 2 h / 0 - 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

31
[ 24334-19-8 ]
[ 1595086-08-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1.1: dmap / tetrahydrofuran / 1 h / 20 °C 2.1: 5% rhodium on activated aluminium oxide; hydrogen / tetrahydrofuran / 48 h / 50 °C / 10343.2 Torr 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 4.1: lithium borohydride / tetrahydrofuran / 2 h / 55 °C 5.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / 20 °C 6.2: 3 h / 20 °C 7.1: hydrogenchloride; water / 1,4-dioxane / 2 h / 20 °C 8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 8.2: 20 °C 9.1: Grubbs catalyst first generation / dichloromethane / 40 °C / Inert atmosphere 10.1: hydrogenchloride; water / 1,4-dioxane / 1 h / 20 °C 11.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dichloromethane / 0.25 h / 0 °C 11.2: 2 h / 0 - 20 °C 12.1: palladium 10% on activated carbon; hydrogen / methanol / 1 h / 20 °C

Reference： [1]Hird, Alexander W.; Aquila, Brian M.; Block, Michael H.; Hennessy, Edward J.; Kamhi, Victor M.; Omer, Charles A.; Laing, Naomi M.; Saeh, Jamal C.; Sha, Li; Yang, Bin [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1820 - 1824]

32
[ 24334-19-8 ]
[ 74-88-4 ]
[ 895126-54-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃;	2 General procedure A - N-alkylation General procedure: A mixture of lF/-pyrrolo[2,3-c]pyridine (1 equiv., 0.25-0.5 M) and anhydrous CS2CO3 (1.1-2.0 equiv.) in anhydrous DMF under argon was stirred at 80 °C for 1 h. The reaction mixture was allowed to cool down to ambient temperature. Liquid alkyl halide (1.05-2 equiv.) was added dropwise to the reaction at rt over 0.5-1 h (preferably with a syringe pump). The reaction mixture was stirred for another 10 min, mixed with water and extracted with EtOAc (3x). The combined organic phase was washed with water (lx) and brine (2x), dried over Na2S04, filtered and concentrated in vacuo. The crude product was purified by flash chromatography Example 2: Ethyl l-methyl-lH-pyrrolo[2,3-c]pyridine-2-carboxylate (2) The title compound was prepared from ethyl lH-pyrrolo[2,3-c]pyridine-2- carboxylate (1) (0.85 g, 4.47 mmol) and methyl iodide (0.29 ml_, 4.69 mmol) according to general procedure A. Purification by flash chromatography (MeOH in DCM, 0-10%) afforded an off-white solid (0.69 g, 76% yield). Rf = 0.50 (DCM : MeOH 9: 1); ^ NMR (400 MHz, CDCIs) d 8.89 (s, 1H), 8.30 (d, J = 5.5 Hz, 1H), 7.54 (dd, J = 5.5, 1.1 Hz, 1H), 7.24 (d, J = 0.6 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 4.17 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCIs) d 161.7, 139.2, 136.0, 134.6, 131.0, 130.2, 116.1, 108.5, 61.1, 32.0, 14.3; ESI-HRMS calcd for C11H13N2O2 (M + H+) 205.0972, found 205.0968.
20%	With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere;

Reference： [1]Current Patent Assignee: UNIVERSITY OF SOUTHERN DENMARK - WO2019/106087, 2019, A1 Location in patent: Page/Page column 28; 31
[2]Georgsson, Jennie; Bergström, Fredrik; Nordqvist, Anneli; Watson, Martin J.; Blundell, Charles D.; Johansson, Magnus J.; Petersson, Annika U.; Yuan, Zhong-Qing; Zhou, Yiqun; Kristensson, Lisbeth; Kakol-Palm, Dorota; Tyrchan, Christian; Wellner, Eric; Bauer, Udo; Brodin, Peter; Svensson Henriksson, Anette [Journal of Medicinal Chemistry, 2014, vol. 57, # 14, p. 5935 - 5948]

33
[ 24334-19-8 ]
ethyl 3-(4-hydroxyphenyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridinium hydrobromide perbromide / 0 - 20 °C 2: triethylamine; potassium fluoride; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: LYTIX BIOPHARMA AS - WO2014/198848, 2014, A2

34
[ 24334-19-8 ]
ethyl 3-(3-hydroxyphenyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridinium hydrobromide perbromide / 0 - 20 °C 2: triethylamine; potassium fluoride; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: LYTIX BIOPHARMA AS - WO2014/198848, 2014, A2

35
[ 24334-19-8 ]
N-(2-hydroxyethyl)-3-(4-hydroxyphenyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridinium hydrobromide perbromide / 0 - 20 °C 2: triethylamine; potassium fluoride; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / Inert atmosphere; Reflux 3: ethanol / 100 °C

Reference： [1]Current Patent Assignee: LYTIX BIOPHARMA AS - WO2014/198848, 2014, A2

36
[ 24334-19-8 ]
C₁₆H₁₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridinium hydrobromide perbromide / 0 - 20 °C 2: triethylamine; potassium fluoride; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / Inert atmosphere; Reflux 3: ethanol / 100 °C

Reference： [1]Current Patent Assignee: LYTIX BIOPHARMA AS - WO2014/198848, 2014, A2

37
[ 5832-44-0 ]
[ 24334-19-8 ]

Reference： [1]Molecules,2014,vol. 19,p. 13342 - 13357
[2]Patent: WO2004/104001,2004,A2

38
[ 24334-19-8 ]
6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 1 h / Reflux 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 48 h / 20 °C

Reference： [1]Parrino, Barbara; Span, Virginia; Carbone, Anna; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Montalbano, Alessandra [Molecules, 2014, vol. 19, # 9, p. 13342 - 13357]

39
[ 24334-19-8 ]
6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]
6H,13H-pyrido[4'',3'':4',5']pyrrolo[1',2':4,5]pyrazino[1,2-a]indole-6,13-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / ethanol / 1 h / Reflux 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 1 h / 20 °C 2.2: 48 h / 20 °C

Reference： [1]Parrino, Barbara; Span, Virginia; Carbone, Anna; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Montalbano, Alessandra [Molecules, 2014, vol. 19, # 9, p. 13342 - 13357]

40
[ 24334-19-8 ]
3,10-dimethoxy-6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]
3-methoxy-6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / ethanol / 1 h / Reflux 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 1 h / 20 °C 2.2: 48 h / 20 °C

Reference： [1]Parrino, Barbara; Span, Virginia; Carbone, Anna; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Montalbano, Alessandra [Molecules, 2014, vol. 19, # 9, p. 13342 - 13357]

41
[ 24334-19-8 ]
1,8-dimethoxy-6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]
8-methoxy-6H,13H-bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d]pyrazine-6,13-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / ethanol / 1 h / Reflux 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 1 h / 20 °C 2.2: 48 h / 20 °C

Reference： [1]Parrino, Barbara; Span, Virginia; Carbone, Anna; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Montalbano, Alessandra [Molecules, 2014, vol. 19, # 9, p. 13342 - 13357]

42
[ 617-35-6 ]
[ 20511-15-3 ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
59%		The title compound was prepared according to the published procedure.?3 Notes:Purification of the starting material <strong>[20511-15-3]3-amino-4-chloropyridine</strong> was necessary priorto the reaction by trituration from DCM/MeOH. Freshly purified 3-amino-4- chloropyiridine (colorless crystals) can be stored at 4 C, sealed from light and under argon for more than a year and used for reactions without further purification. The highest yield was achieved by starting from 0.29 g (2.24 mmol) <strong>[20511-15-3]3-amino-4-chloropyridine</strong>. The yield was decreased for larger scale reactions Inorder to produce more of the title compound, the reaction was carried out in 10 equally sized, small batches in parallel. The reaction mixtures were combined for work-up and purification. To a mixture of <strong>[20511-15-3]3-amino-4-chloropyridine</strong> (0.29 g, 2.24 mmol) and PPTS (0.14 g, 0.56 mmol) in a capped microwave vial under argon equipped with a stirring bar were added anhydrous pyridine (0.75 mL), tetraethylorthosilicate (0.50 mL, 2.24 mmol) and ethyl pyruvate (0.51 mL, 4.48 mmol). The reaction mixture was stirred protected from light, at rt for 48 h. Formation of the enamine intermediate was followed by TLC (staining with ninhydrin). The reaction mixture was treated with Pd(PPh3)4 (0.13 g, 0.11 mmol), re-capped and flushed with argon. TEA (0.51 mL, 2.91 mmol) was added and the reaction was heated bymicrowave irradiation at 160 C for 40 mm. After cooling to rt, precipitated product was filtered off and washed with DCM. The filtrate was mixed with water and extracted with DCM (3x). The combined organic phase was washed with brine (2x), dried over Na2504, filtered and concentrated in vacuo. The crude product was separated from major impurities by flash chromatography (0-5% MeOH inDCM), combined with the filtered crude product, dissolved in DCM, treated with activated charcoal, filtered through celite and concentrated in vacuo. The pure product was obtained after recrystallization from toluene as colorless crystals (2.52 g, 59% yield). mp 210-212 C (toluene) {Lit. mp 212-214 C}; Rf = 0.35 (DCM:MeOH 9:1); ?H NMR (400 MHz, CDCI3) O 9.56 (brs, 1H), 8.95 (5, 1H), 8.33(d, J = 5.6 Hz, 1H), 7.60 (dd, J = 5.6, 1.2 Hz, 1H), 7.21 (d, J = 0.9 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 1.44 (t, J = 7.1 Hz, 3H); ?3C NMR (101 MHz, CDCI3) O 161.6, 139.5, 136.0, 133.6, 132.1, 131.0, 116.6, 107.3, 61.8, 14.5; ESI-HRMS calcd for C10H11N2O2 (M + H) 191.0815, found 191.0816.

Reference： [1]Patent: WO2019/106087,2019,A1 .Location in patent: Page/Page column 30
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 11859 - 11862
Angew. Chem.,2016,vol. 128,p. 12038 - 12041,4

43
[ 24334-19-8 ]
C₁₅H₁₈⁽²⁾H₂N₂O₄ [ No CAS ]
C₁₅H₁₈⁽²⁾H₂N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap / tetrahydrofuran / 12 h / 20 °C 2: [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); (S,S)-(R,R)-2,2''-bis[1-(diphenylphosphino)ethyl]-1,1''-biferrocene; deuterium; triethylamine / ethyl acetate / 96 h / 60 °C / 37503.8 Torr

Reference： [1]Makida, Yusuke; Saita, Masahiro; Kuramoto, Takahiro; Ishizuka, Kentaro; Kuwano, Ryoichi [Angewandte Chemie - International Edition, 2016, vol. 55, # 39, p. 11859 - 11862][Angew. Chem., 2016, vol. 128, p. 12038 - 12041]

44
[ 24334-19-8 ]
(-)-1-tert-butyl 2-ethyl 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate [ No CAS ]
(+)-1-tert-butyl 2-ethyl 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap / tetrahydrofuran / 12 h / 20 °C 2: hydrogen; [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); (S,S)-(R,R)-2,2''-bis[1-(diphenylphosphino)ethyl]-1,1''-biferrocene; triethylamine / ethyl acetate / 4 h / 60 °C / 37503.8 Torr

Reference： [1]Makida, Yusuke; Saita, Masahiro; Kuramoto, Takahiro; Ishizuka, Kentaro; Kuwano, Ryoichi [Angewandte Chemie - International Edition, 2016, vol. 55, # 39, p. 11859 - 11862][Angew. Chem., 2016, vol. 128, p. 12038 - 12041]

45
[ 24334-19-8 ]
[ 40068-76-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 0 - 20 °C 2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine; ammonium chloride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: PHARMAKEA INC - WO2018/48930, 2018, A1

46
[ 24334-19-8 ]
(1H-pyrrolo[2,3-c]pyridin-2-yl)methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 0 - 20 °C 2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine; ammonium chloride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: PHARMAKEA INC - WO2018/48930, 2018, A1

47
[ 24334-19-8 ]
tert-butyl ((1H-pyrrolo[2,3-c]pyridin-2-yl)methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 0 - 20 °C 2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine; ammonium chloride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 80 °C / Inert atmosphere 4: sodium hydroxide / 1,4-dioxane; water / 3 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: PHARMAKEA INC - WO2018/48930, 2018, A1

48
[ 24334-19-8 ]
(1H-pyrrolo[2,3-c]pyridin-2-yl)methanamine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 0 - 20 °C 2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine; ammonium chloride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / 0 - 80 °C / Inert atmosphere 4: sodium hydroxide / 1,4-dioxane; water / 3 h / 0 - 20 °C 5: hydrogenchloride / 1,4-dioxane / 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: PHARMAKEA INC - WO2018/48930, 2018, A1

49
[ 24334-19-8 ]
1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-dimethylcarbamoyl-2-(S)-phenylethyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / ethanol / 1.5 h / Heating / reflux 2.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / DMF (N,N-dimethyl-formamide) / 0.5 h / 20 °C 2.2: 72 h / 20 °C

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2

50
[ 24334-19-8 ]
[ 895126-53-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 1.2: 20 °C 2.1: water; sodium hydroxide / ethanol / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF SOUTHERN DENMARK - WO2019/106087, 2019, A1

51
[ 24334-19-8 ]
N-(3-chlorobenzyl)-1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 1.2: 20 °C 2.1: water; sodium hydroxide / ethanol / 20 °C 3.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 3.2: 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: UNIVERSITY OF SOUTHERN DENMARK - WO2019/106087, 2019, A1

52
[ 24334-19-8 ]
(R)-N-(1-(3-chlorophenyl)ethyl)-1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 1.2: 20 °C 2.1: water; sodium hydroxide / ethanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 80 °C / Inert atmosphere 3.2: 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: UNIVERSITY OF SOUTHERN DENMARK - WO2019/106087, 2019, A1

53
[ 64-17-5 ]
methyl 2-hydroxy-3-(3-nitropyridin-4-yl)acrylate [ No CAS ]
[ 24334-19-8 ]

Yield	Reaction Conditions	Operation in experiment
2.4 g	With iron; acetic acid at 70℃; for 2h;	22.B Step B. Synthesis of ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate. To a mixture of methyl 2-hydroxy-3-(3-nitropyridin-4-yl)acrylate (6 g, 26.7 mmol) in EtOH (50 mL) and HOAc (10 mL) was added Fe powder (7.56 g, 135 mmol). The reaction mixture was stirred at 70 °C for 2 hr, filtered through a pad of celite. The filtrate was poured into satd. NaHCO3, extracted with DCM. The combined organic layer was dried over anhy. Na2SO4 and concentrated. The residue was purified by silica gel chromatography (eluted with PE:EtOAc = 10:1 to 2:1) to afford ethyl lH-pyrrolo[2,3-c]pyridine-2-carboxylate 2.4 g. LC-MS (ESI): m/z 191 (M+H)+.

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1 Location in patent: Page/Page column 120

54
[ 24334-19-8 ]
ethyl 3-vinyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C 2: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1

55
[ 24334-19-8 ]
ethyl 1-methyl-3-vinyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C 2.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 0.5 h

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1

56
[ 24334-19-8 ]
ethyl 3-formyl-1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C 2.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 0.5 h 4.1: oxygen; ozone / dichloromethane / -78 °C

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1

57
[ 24334-19-8 ]
5-methyl-3H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyridazin-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C 2.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 0.5 h 4.1: oxygen; ozone / dichloromethane / -78 °C 5.1: hydrazine hydrate / 2-methoxy-ethanol / 2 h / 100 °C

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1

58
[ 24334-19-8 ]
3-(3-methoxybenzyl)-5-methyl-3H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyridazin-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C 2.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere 3.1: sodium hydride / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 0.5 h 4.1: oxygen; ozone / dichloromethane / -78 °C 5.1: hydrazine hydrate / 2-methoxy-ethanol / 2 h / 100 °C 6.1: potassium <i>tert</i>-butylate / N,N-dimethyl-formamide / 0.17 h / 20 °C

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC - WO2020/167976, 2020, A1

59
[ 24334-19-8 ]
N-(4-(N-tert-butylsulfamoyl)phenyl)-1-(4-fluorobenzoyl)-2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: dmap / tetrahydrofuran / 4 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 20 °C 3: trimethylaluminum / toluene / Reflux 4: potassium carbonate / acetone / 1 h / 50 °C

Reference： [1]Current Patent Assignee: VINCERE BIOSCIENCES - WO2021/50992, 2021, A1

60
[ 24334-19-8 ]
1-tert-butyl 2-ethyl 2,3-dihydro-1H-pyrroro[2,3-c]pyridine-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap / tetrahydrofuran / 4 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 20 °C

Reference： [1]Current Patent Assignee: VINCERE BIOSCIENCES - WO2021/50992, 2021, A1

61
[ 24334-19-8 ]
N-(4-(N-tert-butylsulfamoyl)phenyl)-2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: dmap / tetrahydrofuran / 4 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 20 °C 3: trimethylaluminum / toluene / Reflux

Reference： [1]Current Patent Assignee: VINCERE BIOSCIENCES - WO2021/50992, 2021, A1

62
[ 24334-19-8 ]
ethyl 6-(4-((4-(1H-pyrazol-4-yl)phenyl)amino)pyrimidin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: dmap / dichloromethane / 20 °C / Inert atmosphere 2.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 3.1: palladium on activated charcoal; hydrogen / methanol / 20 °C 4.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 4.2: 2 h / 20 °C / Inert atmosphere 5.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 120 °C