Name: 800402-07-7|6-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid|98%
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1
[ 800402-07-7 ]
[ 123665-42-9 ]
6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (1-dimethylcarbamoyl-2-(S)-phenethyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) for 22h;	266 DIPEA (155PLL, 0. 89MMOL), HOBt (43mg, 0.28mmol) and 6-CHLORO-LH- pyrrolo [2,3b] pyridine-2-carboxylic acid (Preparation 110, 50MG, 0. 25MMOL) was added to a stirred solution of 2-(USD)-AMINO-N, N-dimethyl-3-phenyl propionamide hydrochloride (Preparation 8, 61mg, 0. 27MMOL) in DMF (4mL). After 5min EDCI (63mg, 0. 33MMOL) was added and the reaction stirred for 22h. Purification by column chromatography (SI02, 95: 5 CH2CL2/MEOH) afforded the title compound. m/z (ES+) = 370. 93 [M+ H] + ; RT = 3.62min.

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2 Location in patent: Page 149

2
6-chloro-3-iodo-pyridin-2-ylamine [ No CAS ]
[ 127-17-3 ]
[ 800402-07-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 105℃; for 3h;	12 Preparation 12 : 6-Chloro-lH-pyrrolo[2,3b]pyridine-2-carboxylic acid; To a dry solution of 6-chloro-3-iodo-pyridin-2-ylamine (Preparation 11, 2.8Og, l l.Ommol) in DMF (8OmL) under argon was added pyruvic acid (2.29mL, 33.0mmol), DABCO (3.7Og, 33.0mmol) then palladium(II)acetate (124mg, 0.55mmol) and the mixture purged with argon for 20min. The reaction was heated to 1050C (bath temp.) for 3h before being allowed to cool to rt. Solvent was removed in vacuo then crude material partitioned between EtOAc (10OmL) and water (75mL). The organic layer was separated and washed with water (2x75mL) before being extracted into 2M NaOH (2x75mL). The aqueous layer was acidified to pH 3 with 2M HCl and extracted into EtOAc(2xl00mL). Organic layers were combined, dried (MgSO4) and concentrated in vacuo. The residue was suspended in water and the filtrate removed to give the title compound, m/z (ES+) = 196.91 [M+ H]+; RT = 3.07min.
	With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 110℃; for 3h; Inert atmosphere;	D.4 Step 4: Synthesis of 6-Chloro-lH-pyrrolo[2,3-b]pyridine-2-carboxylic acidTo a solution of 6-chloro-3-iodopyridin-2-amine (24 g, 94 mmol) in DMF is added DABCO (32 g, 283 mmol) and pyruvic acid (20 mL, 283 mmol). The mixture is degassed by bubbling argon gas through the mixture for 20 min. Pd(OAc)2 (1 g, 4.7 mmol) is added and the mixture is again degassed. The reaction mixture is heated at 110 °C for 3 h, and the solvent is evaporated to afford the title compound as a viscous liquid (36 g, >99%) which is used in the next step without purification.
	With 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate In N,N-dimethyl-formamide at 110℃;

	With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 105℃; for 3.5h; Inert atmosphere;	A solution of 6-chloro-3-iodo-pyridin-2-ylamine (0.73 mmol), pyruvic acid (3.2 equiv., 2.32 mmol, 161.5 ^L) and DABCO (3.0 equiv., 0.27 g, 2.18 mmol) in anhydrous DMF was taken in a sealed tube and the solution was purged with Argon for 3 minutes. Pd(OAc)2 (10 mol%, 18.5 mg) was next added and the system was again purged with Argon for 3 minutes. The reaction mixture was heated at 105 °C for 3.5 h in an oil bath. The solution was allowed to cool down to room temperature, diluted with EtOAc and filtered through Celite. The filtrate was concentrated under reduced pressure and the residue was taken up in EtOAc. The organic layer was washed with water and was dried and concentrated. The crude acid 13-4 was forwarded to the next step without further purification.
	With 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate In N,N-dimethyl-formamide at 20 - 105℃; for 3.33h; Inert atmosphere;	1.d Synthesis of 6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (5) Compound (4) (2.80g, 11.0mmol) was dissolved in DMF (30mL), was added pyruvic acid (2.29ml, 33.0mmol), DABCO (3.70g, 33.0mmol), Pd (OAc) 2 (54mg, 0.25mmol), argon and stirred for 20min, then rise Temperature to 105 ° C (external temperature), stirred for 3h, cooled to room temperature, evaporated to dryness under reduced pressure, added ethyl acetate (100 mL), water (75mL), Liquid separation, the organic phase was washed with aqueous 2MNaOH (2 x 75 mL) wash, water (2 x 75 mL), the organic phase was dried over anhydrous sodium sulfate, Concentrated to give compound (5)
	With 1,4-diaza-bicyclo[2.2.2]octane In DMF (N,N-dimethyl-formamide) at 105℃; for 3h;	110 To a dry solution of 6-chloro-3-iodo-pyridin-2-ylamine (Preparation 109, 2.80g, 11.0mmol) in DMF (80mL) under argon was added PYRUVIC acid (2. 29ML, 33. 0MUNOL), DABCO (3.70g, 33. 0MMOL) then palladium (II) acetate (124mg, 0. 55MMOL) and the mixture purged with argon for 20min. The reaction was heated to 105°C (bath temp. ) for 3h before being allowed to cool to rt. Solvent was removed in vacuo then crude material partitioned between ethyl acetate (lOOmL) and water (75mL). The organic layer was separated and washed with water (2x75mL) before being extracted into 2M NAOH (2x75mL). The aqueous layer was acidified to pH 3 with 2M HCl and extracted into ethyl acetate (2XLOOML). Organic layers were combined, dried (MGS04) and concentrated I71 vacuo. The residue was suspended in water and the filtrate removed to give the title compound. m/z (ES+) = 196.91 [M+ H] +, RT = 3. 07MIN.

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2006/59164, 2006, A2 Location in patent: Page/Page column 23
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71725, 2011, A1 Location in patent: Page/Page column 50
[3]Location in patent: scheme or table Chowdhury, Sarwat; Sessions, E. Hampton; Pocas, Jennifer R.; Grant, Wayne; Schröter, Thomas; Lin, Li; Ruiz, Claudia; Cameron, Michael D.; Schürer, Stephan; Lograsso, Philip; Bannister, Thomas D.; Feng, Yangbo [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 23, p. 7107 - 7112]
[4]Current Patent Assignee: FENG, Yangbo; CHEN, Yen Ting; SESSIONS, Hampton; MISHRA, Jitendra K.; CHOWDHURY, Sarwat; YIN, Yan; LOGRASSO, Philip; LUO, Jun-Li; BANNISTER, Thomas; SCHROETER, Thomas - WO2011/50245, 2011, A1 Location in patent: Page/Page column 119
[5]Current Patent Assignee: BEIJING UNIVERSITY OF TECHNOLOGY - CN105294688, 2016, A Location in patent: Paragraph 0040-0042
[6]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2 Location in patent: Page 72-73

3
[ 800402-07-7 ]
[ 1534-90-3 ]
2-(S)-[(6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid ethyl eter [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; for 16.0h;	To a solution OF 6-CHLORO-LH-PYRROLO [2,3b] pyridine-2-carboxylic acid (Preparation 110,450mg, 2. 29MMOL) in DMF (20mL) was added 4-fluoro phenylalanine ethyl ester hydrochloride (624mg, 2. 52MMOL), DIPEA (1.40mL, 8. 01MMOL) and HOBt. (386mg, 2.52mmol) and the reaction stirred. After 5min EDCI (570mg, 2. 98mmol) was added and stirring continued for 16HR. Solvent was removed in vacuo then crude material partitioned between ethyl acetate (75mL) and water (50mL). Organics were washed with NAHCO3 solution (3X50ML) then brine (2X50ML), dried (MgS04) and THE solvent removed in vacuo to give the title compound. m/z (ES+) = 389.90 [M+ H] + ; RT = 3. 79MIN.

Reference： [1]Patent: WO2004/104001,2004,A2 .Location in patent: Page 151

4
[ 800402-07-7 ]
[ 5468-37-1 ]
6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (2-oxo-2-phenethyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In ethanol at 20℃; for 16h;	270 To a solution OF 6-CHLORO-LH-PYRROLO [2,3b] pyridine-2-carboxylic acid (Preparation 110,60mg, 0.31mmol) in ethanol (5ML) was added 2- aminoacetophenone hydrochloride (58MG, 0. 34MMOL), N-METHYHNORPHOLINE 74µL, 0. 67MMOL) and DMTMM (198mg, 0. 67MMOL) and the reaction stirred at rt for 16h. Solvent was removed in vacuo and the resulting residue partitioned between ethyl acetate (20mL) and water (20mL). Organics were washed with 1M HCl (20mL), water (20mL), NAHCO3 solution (2X20ML) then brine (20mL) before being dried (MGS04) and solvent concentrated in vacuo. Purification by column chromatography (SI02, 2: 1 Pet. Ether/EtOAc then 97: 3 CH2CL2/MEOH) gave the title compound.

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2 Location in patent: Page 151

5
[ 800402-07-7 ]
[ 85115-10-2 ]
6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid; 3-amino-1,2,3,4-tetrahydroquinolin-2-one With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.0833333h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h;	1 Example 1: 6-Chloro-lH-pyrrolo[2,3-b]pyridine-2-carboxylic acid (2-oxo-l,2,3,4- tetrahydroquinolin-3-yl)amide; To a solution of 3-amino-3,4-dihydro-lH-quinolin-2-one (Preparation 15, 27mg, 0.17mmol) in DMF (4mL) was added 6-chloro-lH-pyrrolo[2,3b]pyridine-2-carboxylic acid (Preparation 12, 30mg, 0.15mmol), HOBt (26mg, 0.17mmol) and DIPEA (66μL, 0.38mmol) and the reaction stirred for 5min. EDCI (35mg, 0.18mmol) was added and the reaction stirred at rt for 16h. Solvent was removed in vacuo and the residue partitioned between EtOAc (3OmL) and water (3OmL). Organics were washed with water (3OmL), NaHCO3 solution (2x25mL) then brine (2x25mL) before being dried (MgSO4) and concentrated in vacuo. Purification by Prep HPLC afforded the title compound. δH(d6 DMSO): 8.20 (IH, d), 1.29-1 Al (4H, m), 7.00-6.89 (2H, m), 4.80-4.70 (IH, m), 3.21-3.06 (2H, m); m/z (ES+) = 341.09 [M+ H]+; RT = 3.33min.

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2006/59164, 2006, A2 Location in patent: Page/Page column 40

6
[ 800402-07-7 ]
[ 127-09-3 ]
[ 1311569-08-0 ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol at 110℃; for 15h; Autoclave; Inert atmosphere;	D.6 Step 6: Synthesis of diethyl lH-pyrrolo[2,3-b]pyridine-2,6-dicarboxylateReagents are charged into a 600 mL autoclave in the following order: ethanol (350 mL), sodium acetate (17.0 g, 200 mmol), 6-chloro-lH-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester (24 g, 107 mmol), l,l'-bis-(diphenylphosphino)ferrocene (2.5 g, 2.25 mmol [2.25 mol%]), and palladium acetate (180 mg, 0.75 mmol [0.75 mol %]). The air in the autoclave is replaced with carbon monoxide and the pressure is adjusted to 250 psi. The reaction is then heated to 110 °C for 15 h. The reaction mixture is cooled to room temperature and is filtered through Celite. The solvent is replaced with 500 mL EtOAc followed by 100 mL aqueous wash. The organic layer is concentrated to 50 mL EtOAc and is then heated to 60 °C. After cooling to room temperature, the solids are filtered to afford 20 g of the title compound. The mother liquor is concentrated and is purified by flash column chromatography using gradient elution of 20-60% ethyl acetate in hexanes to afford an additional 3.5 g of title compound which affords total of 23.5 g in 84% isolated yield.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71725, 2011, A1 Location in patent: Page/Page column 51

7
[ 800402-07-7 ]
[ 64-17-5 ]
[ 287384-84-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride at 0℃; for 16.5h; Reflux;	D.5 Step 5: Synthesis of ethyl 6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate HC1 gas is bubbled through a solution of 6-chloro-lH-pyrrolo[2,3-b]pyridine-2- carboxylic acid (36 g, 183 mmol) in ethanol (500 mL) at 0 °C for 30 min. The reaction mixture is then heated at reflux for 16 h. The solvent is evaporated and the residue is diluted with CH2CI2 and filtered. The filtrate is evaporated and the residue is washed with diethyl ether (2 x 250 mL). The organic layers are dried (Na2S04) and concentrated. The crude residue is purified by passing through the column of neutral alumina, eluting with 10% EtOAc/hexane to afford the title compound as a white solid (10 g, 25%).

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71725, 2011, A1 Location in patent: Page/Page column 50-51

8
[ 86847-84-9 ]
[ 800402-07-7 ]

Reference： [1]Patent: WO2011/71725,2011,A1
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7107 - 7112
[3]Patent: WO2011/50245,2011,A1
[4]Patent: CN105294688,2016,A
[5]Patent: WO2004/104001,2004,A2

9
[ 800402-05-5 ]
[ 800402-07-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogenchloride / methanol / water / 5 h / 110 °C 2: 1,4-diaza-bicyclo[2.2.2]octane / palladium diacetate / N,N-dimethyl-formamide / 3 h / 110 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 14 h / Reflux 2: 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate / N,N-dimethyl-formamide / 110 °C
	Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 6 h / 72 °C 2: 1,4-diaza-bicyclo[2.2.2]octane / palladium diacetate / N,N-dimethyl-formamide / 3.5 h / 105 °C / Inert atmosphere

	Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane; water / 2 h / 80 °C 2: 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate / N,N-dimethyl-formamide / 3.33 h / 20 - 105 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: hydrogenchloride / water / 4.5 h / Heating / reflux 2: 1,4-diaza-bicyclo[2.2.2]octane / palladium diacetate / DMF (N,N-dimethyl-formamide) / 3 h / 105 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71725, 2011, A1
[2]Chowdhury, Sarwat; Sessions, E. Hampton; Pocas, Jennifer R.; Grant, Wayne; Schröter, Thomas; Lin, Li; Ruiz, Claudia; Cameron, Michael D.; Schürer, Stephan; Lograsso, Philip; Bannister, Thomas D.; Feng, Yangbo [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 23, p. 7107 - 7112]
[3]Current Patent Assignee: FENG, Yangbo; CHEN, Yen Ting; SESSIONS, Hampton; MISHRA, Jitendra K.; CHOWDHURY, Sarwat; YIN, Yan; LOGRASSO, Philip; LUO, Jun-Li; BANNISTER, Thomas; SCHROETER, Thomas - WO2011/50245, 2011, A1
[4]Current Patent Assignee: BEIJING UNIVERSITY OF TECHNOLOGY - CN105294688, 2016, A
[5]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2004/104001, 2004, A2

10
[ 800402-07-7 ]
[ 1311568-14-5 ]