Name: 479553-01-0|1H-Pyrrolo[2,3-b]pyridine-4-carboxylic acid|97%
Brand: Ambeed
SKU: A239719
Rating: 91 (35 reviews)

1
[ 479553-01-0 ]
[ 915141-82-1 ]
[ 915141-78-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 2h;	Stir, at room temperature, a mixture of 238 mg of 4-(6-chloro-1H-benzimidazol-2-yl)-9H-fluorene-9(R,S)-amine, 152 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 106 mg of 1-hydroxybenzotriazole (HOBT) and 128 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> in 5 ml of dry dimethylformamide. After 2 hours, evaporate the reaction medium to dryness under vacuum, take the residue up with 50 ml of a saturated solution of sodium bicarbonate, triturate the suspension, and filter the precipitate over sintered glass. The solid is washed with 80 ml of saturated solution of sodium bicarbonate and then 80 ml of water. The solid is taken up in 75 ml of toluene and the whole is evaporated to dryness under vacuum. The solid is chromatographed on silica gel, eluting with a mixture of methanol and dichloromethane (7.5/92.5 by volume). In this way, we obtain 180 mg of (6-chloro-1H-benzimidazol-2-yl)-9H-fluoren-9(R,S)-yl]amide of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, in the form of a beige foam with the following characteristics:Melting point (Kofler)=212 C. (decomp).TLC (SiO2) Rf=0.3 (methanol-dichloromethane 10/90 by volume).NMR spectrum (400 MHz-delta in ppm-DMSO-d6) 6.41 (d, J=8.5 Hz, 1H); 6.91 (dd, J=2.0 and 3.5 Hz, 1H); 7.26 (t, J=7.5 Hz, 1H); 7.31 (dd, J=2.0 and 8.5 Hz, 1H); 7.35 (t, J=7.5 Hz, 1H); 7.47 (d, J=5.0 Hz, 1H); 7.52 (t, J=7.5 Hz, 1H); 7.55 (d, J=8.0 Hz, 1H); 7.62 (m, 2H); from 7.64 to 7.78 (m spread-out, 2H); 7.66 (d, J=7.5 Hz, 1H); 7.77 (d, J=7.5 Hz, 1H); 8.29 (d, J=5.0 Hz, 1H); 9.28 (d, J=8.5 Hz, 1H); 11.85 (m broad, 1H); 13.15 (m spread-out, 1H).

Reference： [1]Patent: US2008/153837,2008,A1 .Location in patent: Page/Page column 66

2
[ 479553-01-0 ]
[ 915141-88-7 ]
[ 915141-83-2 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 1.5h;	Stir, at room temperature, a mixture of 220 mg of 4-(6-bromo-1H-benzimidazol-2-yl)-9H-fluoren-9(R,S)-amine, 123 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 87 mg of 1-hydroxybenzotriazole (HOBT) and 105 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> in 5 ml of dry dimethylformamide. After 1.5 hours, evaporate the reaction medium to dryness under vacuum, take the residue up with 50 ml of a saturated solution of sodium bicarbonate, triturate the suspension and filter the precipitate over sintered glass. The solid is washed with 75 ml of saturated solution of sodium bicarbonate and then 100 ml of water. The solid is taken up in toluene and the whole is evaporated to dryness under vacuum. The solid is chromatographed on silica gel, eluting with a mixture of methanol and dichloromethane (5/95 by volume). In this way, we obtain 214 mg of (6-bromo-1H-benzimidazol-2-yl)-9H-fluoren-9(R,S)-yl]amide of 1H-pyrrolo-[2,3-b]pyridine-4-carboxylic acid, in the form of an off-white solid with the following characteristics:Melting point (Kofler)=206 C. (decomp).TLC (SiO2) Rf=0.4 (methanol-dichloromethane 10/90 by volume).NMR spectrum (400 MHz-delta in ppm-DMSO-d6): 6.41 (d, J=8.5 Hz, 1H); 6.91 (dd, J=2.0 and 3.5 Hz, 1H); 7.26 (t broad, J=7.5 Hz, 1H); 7.35 (d broad, J=7.5 Hz, 1H); 7.42 (dd, J=2.0 and 8.5 Hz, 1H); 7.47 (d, J=5.0 Hz, 1H); 7.51 (t, J=7.5 Hz, 1H); 7.56 (d broad, J=7.5 Hz, 1H); from 7.60 to 7.69 (m, 4H); 7.76 (d broad, J=7.5 Hz, 1H); 7.87 (m spread-out, 1H); 8.30 (d, J=5.0 Hz, 1H); 9.28 (d, J=8.5 Hz, 1H); 10.85 (m broad, 1H); 13.15 (m spread-out, 1H).

Reference： [1]Patent: US2008/153837,2008,A1 .Location in patent: Page/Page column 66-67

3
[ 124-38-9 ]
[ 348640-06-2 ]
[ 479553-01-0 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-bromo-lH-pyrrolo[2,3-£]pyridine (490 mg, 2.49 mmol) in dry TetaF (15 mL) at -78 0C is added n-BuLi (1.6 M in hexanes) in 10 min. After stirring 45 min at that temperature, crushed dry ice is added. The cold bath is removed and the reaction is allowed to warm up to rt. The solvent is evaporated, and the light yellow solid is dissolved in water (20 mL) and extracted with EtOAc (2x25 mL). The aqueous is acidified with IN HCl to peta = 4; and the white precipitate is collected by filtration, washed with water, and dried in vacuo. MS m/z 163.3 (M + 1).

Reference： [1]Patent: WO2008/144253,2008,A1 .Location in patent: Page/Page column 28

4
[ 926663-69-6 ]
[ 479553-01-0 ]
[ 1086422-72-1 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of lH-pyrrolo[2,3-&]pyridine-4-carboxylic acid (59mg, 0.364 mmol) and etaATU (274 mg, 0.721 mmol) in dry DMF (3 mL) is added DIEA (189 muL, 1.09 mmol). After stirring at rt for 10 min, 1/6 portion of the reaction is added to a vial containing N-(3-amino- phenyl)-3-trifluoromethyl-benzamide (25 mg, 0.089 mmol). After stirring for 2.5 h, sodium hydroxide solution (IN, 0.1 mL) is added and reaction is stirred at 60 0C for 4 hr. An additional 0.25 mL INNaOH is added, and the reaction mixture is stirred for 30 min. The reaction is neutralized with IN HCl (0.35 mL), and purified by etaPLC to give an off-white powder as trifluoroacetic acid salt. 1H nuMR 400 MHz (DMSO-J6) delta 11.89 (s, IH), 10.50 (s, IH), 10.45 (s, 1H), 8.32 (m, 2H), 8.26 (s, IH), 8.23(d, J = 8.0 Hz, IH), 7.91(d, J = 7.6Hz, IH), 7.73 (t, J = 8.0 Hz, IH), 7.57 (t, J = 6.8 Hz, IH), 7.51(m, IH), 7.47-7.43 (m, 2H), 7.30(t, J = 8.0, IH), 6.71 (dd, J = 2.0, 3.2 Hz, IH); MS m/z 425.2 (M + 1).

Reference： [1]Patent: WO2008/144253,2008,A1 .Location in patent: Page/Page column 28-29

5
[ 618446-36-9 ]
[ 479553-01-0 ]

Yield	Reaction Conditions	Operation in experiment
84%		A mixture of 1-acetyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile (1.80 g, 11.10 mmol), 2 M aqueous sodium hydroxide solution (25 mL) and ethanol (25 mL) was stirred at 90 C. for 16 hr. The reaction mixture was neutralized with hydrochloric acid and diluted with water. The precipitate was collected by filtration, and washed with water and diethyl ether to give the title compound (1.51 g, yield 84%) as pale-yellow crystals.melting point >300 C.1H NMR (DMSO-d6) delta 6.87 (1H, dd, J=1.8, 3.3 Hz), 7.56 (1H, d, J=4.8 Hz), 7.65 (1H, t, J=3.3 Hz), 8.34 (1H, d, J=4.8 Hz), 11.95 (1H, brs), 13.31 (1H, brs).

Reference： [1]Patent: US2010/69381,2010,A1 .Location in patent: Page/Page column 67

6
[ 479553-01-0 ]
[ 1021018-44-9 ]
[ 1021018-37-0 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 20h;	Stage 5: In a 25 mL three-necked flask, dissolve 400 mg of 4-(benzofuran-2-yl)-9H-fluoren-9(R,S)-yl)-amine, obtained in Stage 4, in 9 mL of dimethylformamide, then add successively 283 mg of hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 90 mg of 1-hydroxybenzotriazole (HOBT) and 218 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, then stir for 20 hours at room temperature. Then add 50 mL of water, drain the precipitate that formed and wash it with water and then with a saturated solution of sodium bicarbonate. Purify the raw solid obtained by flash chromatography on silica gel (20-40 mum), eluting with a mixture of dichloromethane and methanol (90-10 by volume). We thus obtain 59 mg of [4-(benzofuran-2-yl)-9H-fluoren-9(R,S)-yl)]-amide of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> in the form of a beige solid with the following characteristics:Melting point (Kofler)>260 C.Mass spectrum (E/I): m/z=441 (M+)1H NMR spectrum (400 MHz, delta in ppm, DMSO-d6): 6.41 (d, J=8.5 Hz, 1H); 6.90 (s broad, 1H); 7.19 (d, J=8.0 Hz, 1H); 7.25 (s, 1H); 7.28 (t partially masked, J=8.0 Hz, 1H); from 7.32 to 7.53 (m, 5H); 7.62 (m, 3H); 7.69 (d, J=8.0 Hz, 1H); 7.73 (d, J=8.0 Hz, 1H); 7.79 (d, J=8.0 Hz, 1H); 8.29 (d, J=5.0 Hz, 1H); 9.25 (d, J=8.5 Hz, 1H); 11.85 (m broad, 1H).

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 17

7
[ 479553-01-0 ]
[ 1021018-52-9 ]
[ 1021018-46-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 20h;	Stage 4: In a 25 mL three-necked flask, dissolve 180 mg of [4-(quinolin-3-yl)-9H-fluoren-9(R,S)-yl]-amine, obtained in Stage 3, in 4 mL of dimethylformamide, then add successively 123 mg of hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 40 mg of 1-hydroxybenzotriazole (HOBT) and 104 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, then stir for 20 hours at room temperature. Then add 30 mL of water, drain the precipitate that formed and wash it with water and then with a saturated solution of sodium bicarbonate. Purify the raw solid obtained by flash chromatography on silica gel (20-40 mum), eluting with a mixture of dichloromethane and methanol (90-10 by volume). We thus obtain 130 mg of [(4-quinolin-3-yl)-9H-fluoren-9(R,S)-yl]-amide of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> in the form of a white solid with the following characteristics:Melting point (Kofler)>260 C.Mass spectrum (E/I): m/z=452 (M+)1H NMR spectrum (400 MHz, delta in ppm, DMSO-d6): 6.43 (d, J=8.5 Hz, 1H); 6.74 (dt, J=8.0 Hz, 1H); 6.92 (dd, J=2.0 and 3.5 Hz, 1H); 7.12 (t, J=7.5 Hz, 1H); 7.29 (t, J=7.5 Hz, 1H); 7.43 (d, J=7.5 Hz, 1H); 7.47 (d, J=5.0 Hz, 1H); 7.49 (t, J=7.5 Hz, 1H); from 7.60 to 7.67 (m, 2H); from 7.70 to 7.75 (m, 2H); 7.88 (t broad, J=7.5 Hz, 1H); 8.12 (d, J=8.5 Hz, 1H); 8.17 (d, J=8.5 Hz, 1H); 8.30 (d, J=5.0 Hz, 1H); 8.53 (m spread out, 1H); 9.01 (m spread out, 1H); 9.26 (d, J=8.5 Hz, 1H); 11.85 (m broad, 1H).

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 18

8
[ 479553-01-0 ]
[ 1021018-60-9 ]
[ 1021018-54-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 20h;	Stage 4: In a 25 mL three-necked flask, dissolve 230 mg of 4-(6-fluoro-pyridin-3-yl-9H-)-fluoren-9(R,S)-yl]-amine, obtained in Stage 3, in 7 mL of dimethylformamide, then add successively 175 mg of hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 57 mg of 1-hydroxybenzotriazole (HOBT) and 149 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, then stir for 20 hours at room temperature. Then add 30 mL of water, drain the precipitate formed and wash it with water and then with a saturated solution of sodium bicarbonate. Purify the raw solid obtained by flash chromatography on silica gel (20-40 mum), eluting with a mixture of dichloromethane and ethanol (95-05 by volume). We thus obtain 184 mg of [4-(6-fluoro-pyridin-3-yl)-9H-fluoren-9-(R,S)-yl]-amide of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, in the form of a pink solid with the following characteristics:Melting point (Kofler)>260 C.Mass spectrum (E/I): m/z=420 (M+)1H NMR spectrum (400 MHz, delta in ppm, DMSO-d6): 6.40 (d, J=8.5 Hz, 1H); 6.80 (d, J=7.5 Hz, 1H); 6.91 (dd, J=2.0 and 3.5 Hz, 1H); 7.21 (t, J=7.5 Hz, 1H); from 7.29 to 7.34 (m, 2H); 7.41 (dd, J=2.5 and 8.5 Hz, 1H); 7.55 (d, J=5.0 Hz, 1H); 7.56 (t, J=7.5 Hz, 1H); 7.61 (m, 2H); 7.65 (d, J=7.5 Hz, 1H); 8.11 (m spread out, 1H); 8.28 (d, J=5.0 Hz, 1H); 8.35 (m spread out, 1H); 9.23 (d, J=8.5 Hz, 1H); 11.85 (m broad, 1H).

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 19

9
[ 479553-01-0 ]
[ 1021018-68-7 ]
[ 1021018-70-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 20h;	Stage 4: In a 25 mL three-necked flask, dissolve 375 mg of the tert-butyl ester of 2-[9(R,S)-amino-9H-fluoren-4-yl-]-indole-1-carboxylic acid obtained in Stage 3, in 8 mL of dimethylformamide, then add successively 200 mg of hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 65 mg of 1-hydroxybenzotriazole (HOBT) and 169 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, then stir for 20 hours at room temperature. Then add 200 mL of water, drain the precipitate formed and wash it with water, with a saturated solution of sodium bicarbonate and then with petroleum ether. We thus obtain 400 mg of tert-butyl ester of 2-{(R,S)-9-[(1H-pyrrolo[2,3-b]pyridine-4-carbonyl)-amino]-9H-fluoren-4-yl}-indole-1-carboxylic acid in the form of a pale yellow solid, to be used as it is and having the following characteristics:Mass spectrum (E/I): m/z=540 (M+)

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 19

10
[ 479553-01-0 ]
[ 1021019-80-6 ]
[ 1021019-71-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	Stage 6: In a 50 mL flask, stir under argon overnight at room temperature, 94 mg of 4-{imidazo[1,2-a]pyridin-2-yl}-9H-fluoren-9(R,S)-yl-amine obtained in the preceding stage, 51 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong>, 61 mg of EDCI and 21 mg of HOBt in 10 mL of DMF. After evaporating the reaction mixture to dryness under vacuum, take up the residue in 15 mL of distilled water and extract with 3×15 mL of ethyl acetate. Wash the combined organic phases with 10 mL of a saturated solution of sodium bicarbonate, 2×10 mL of distilled water, 10 mL of saturated solution of sodium chloride, and dry over magnesium sulphate. After evaporating to dryness under vacuum, chromatograph the residue on silica gel (40-63 mum), eluting with a mixture of dichloromethane-ethanol (92.5:7.5). We thus obtain 38 mg of 4-{imidazo[1,2-a]pyridin-2-yl}-9H-fluoren-9(R,S)-yl-amide of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> in the form of white crystals with the following characteristics:Melting point (Kofler): 270 C.Mass spectrum (LC/SM): m/z 441 (M+)1H NMR spectrum (400 MHz-DMSO-d6) delta in ppm: 6.39 (d, J=8.5 Hz, 1H); 6.91 (dd, J=2.0 and 3.5 Hz, 1H); 7.00 (dt, J=1.5 and 7.5 Hz, 1H); 7.21 (dt, J=1.5 and 7.5 Hz, 1H); from 7.28 to 7.39 (m, 2H); 7.42 (t, J=7.5 Hz, 1H); 7.47 (d, J=5.5 Hz, 1H); 7.50 (d, J=7.5 Hz, 1H); 7.59 (d, J=7.5 Hz, 1H); 7.62 (m, 3H); 7.69 (d, J=7.5 Hz, 1H); 8.20 (s, 1H); 8.29 (d, J=5.5 Hz, 1H); 8.63 (d, J=7.5 Hz, 1H); 9.26 (d, J=8.5 Hz, 1H); 11.9 (s broad, 1H).

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 27

11
[ 64-17-5 ]
[ 479553-01-0 ]
[ 1261588-72-0 ]

Yield	Reaction Conditions	Operation in experiment
90%		A mixture of <strong>[479553-01-0]7-azaindole-4-carboxylic acid</strong> (10.4g, 64 mmol), thionyl chloride(17.8 g, 150 mmol), and ethyl alcohol (150 mL) was heated to reflux. After the reaction was complete (by TLC), the mixture was concentrated, basified to pH 9 with aqueous potassium carbonate, and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash column chromatography to give lnt-8 (11.0 g, 90%). 1H NMR (400 MHz, CDCl3) delta 10.51 (brs, IH), 8.45 (d, J= 4.4 Hz, IH), 7.75 (d, J = 4.4 Hz, IH), 7.54 (s, IH), 7.08 (d, J= 2.0 Hz, IH), 4.50 (q, J= 7.2 Hz, 2H), 1.49 (t, J= 7.2 Hz, 3H).

Reference： [1]Patent: WO2011/23081,2011,A1 .Location in patent: Page/Page column 52-53

12
[ 271-63-6 ]
[ 479553-01-0 ]

Reference： [1]Patent: WO2011/23081,2011,A1

13
[ 55052-28-3 ]
[ 479553-01-0 ]

Reference： [1]Patent: WO2011/23081,2011,A1
[2]Patent: WO2012/127506,2012,A1

14
[ 344327-11-3 ]
[ 479553-01-0 ]

Yield	Reaction Conditions	Operation in experiment
98.5%		Step 2: li^-pyrrolo^^-^pyridine^-carboxylic acid (22)A mixture of compound 21 (17 g, 118.7 mmol), NaOH (47 g, 1 187.6 mmol), ethanol (170 mL) and water (170 mL) was heated at 80 C for 16 h. After cooling to room temperature, ethanol was removed under reduced pressure. The residue was diluted with water (200 mL) and washed : with ethyl acetate (100 mL). Aqueous layer was acidified with cone, hydrochloric acid, solid precipitated was filtered to afford lH-pyrrolo [2,3-&]pyridine-4- carboxylic acid 19.0 g (98.5%). 1HNMR (400MHZ, OMSO-d6): delta 13.43 (br s, 1H), 1 1.97 (br s, 1H), 8.34 (d, J= 4.8 Hz, 1H), 7.56 (d, J= 4.8 Hz, 1H), 6.87-6.86 (m, 1H).
80%		A mixture of Int-7 (11.5 g, 80 mmol), sodium hydroxide (32g, 800 mmol), water (100 mL), and ethyl alcohol (100 mL) was heated to reflux. After 6 h, the reaction mixture was cooled to room temperature and neutralized and acidified with concentrated hydrochloric acid. The solids were collected by filtration to afford 7-azaindole-4- carboxylic acid (10.4 g, 80%), which was used directly in the next step without purification.

Reference： [1]Patent: WO2012/127506,2012,A1 .Location in patent: Page/Page column 65
[2]Patent: WO2011/23081,2011,A1 .Location in patent: Page/Page column 52

15
1H-pyrrolo[2,3-b]pyridine 1-oxide meta-chlorobenzoic acid salt [ No CAS ]
[ 479553-01-0 ]

Reference： [1]Patent: WO2011/23081,2011,A1

16
[ 479553-01-0 ]
[ 936549-95-0 ]

Reference： [1]Patent: WO2011/23081,2011,A1

17
[ 479553-01-0 ]
[ 1268390-67-5 ]

Reference： [1]Patent: WO2011/23081,2011,A1

18
[ 479553-01-0 ]
[ 1268390-66-4 ]

Reference： [1]Patent: WO2011/23081,2011,A1

19
[ 479553-01-0 ]
1-(2-methoxy-5-chlorophenyl)-3-[1-(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-2,3-dihydro-1H-indol-4-yl]urea hydrochloride [ No CAS ]

Reference： [1]Patent: WO2011/23081,2011,A1

20
[ 479553-01-0 ]
[ 1268390-71-1 ]

Reference： [1]Patent: WO2011/23081,2011,A1

21
[ 479553-01-0 ]
1-(2-methoxy-5-chlorophenyl)-3-[1-(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-1H-indol-4-yl]urea hydrochloride [ No CAS ]

Reference： [1]Patent: WO2011/23081,2011,A1
[2]Patent: WO2011/23081,2011,A1

22
[ 479553-01-0 ]
[ 1268390-73-3 ]

Reference： [1]Patent: WO2011/23081,2011,A1
[2]Patent: WO2011/23081,2011,A1

23
[ 479553-01-0 ]
[ 1268390-74-4 ]

Reference： [1]Patent: WO2011/23081,2011,A1

24
[ 479553-01-0 ]
[ 1268390-75-5 ]

Reference： [1]Patent: WO2011/23081,2011,A1

25
[ 479553-01-0 ]
[ 1268390-76-6 ]

Reference： [1]Patent: WO2011/23081,2011,A1

26
[ 479553-01-0 ]
[ 1201748-37-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

27
[ 479553-01-0 ]
[ 1190312-37-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

28
[ 479553-01-0 ]
[ 1261744-93-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

29
[ 479553-01-0 ]
[ 1261476-04-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

30
[ 479553-01-0 ]
[ 1312812-82-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

31
[ 479553-01-0 ]
[ 18107-18-1 ]
[ 351439-07-1 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; hexane; dichloromethane; at 20℃; for 0.5h;Inert atmosphere;	1H-Pyrrolo[2,3-b]pyridine-4-carboxylic acid (1.00 g, 6.17 mmol) was dissolved in DCM/MeOH 3:1 at rt. TMS-diazomethane (4.0 mL, 8.02 mmol, 2M in hexane) was added dropwise and the reaction stirred for 30 min. Excess TMS-diazomethane was quenched by dropwise addition of AcOH and the reaction stirred for a further 10 min. A 10 % aqueous solution of NaHCO3 was added and the mixture was extracted with DCM. The combined organic phases were dried with a phase separator and concentrated in vacuo to give the crude methyl 1H-pyrrolo[2,3-b]pyridine-4-carboxylate which was used with no further purification. Methyl 1H-pyrrolo[2,3-b]pyridine-4-carboxylate (50 mg, 0.28 mmol) was dissolved in DME (1 mL) and 3-chloroperbenzoic acid (74 mg, 0.30 mmol) was added at rt. The reaction was stirred for 16 h and then more 3-chloroperbenzoic acid (25 mg, 0.10 mmol) was then added. After 3.5 h a further portion of 3-chloroperbenzoic acid (25 mg, 0.10 mmol) was added. After 2 h an additional portion of 3-chloroperbenzoic acid (17 mg, 0.07 mmol) was added. The reaction mixture was stirred for a further 1 h and then added onto an SCX-2 cation exchange column. The column was washed with DCM, then MeOH and then eluted with a mixture of NH3/MeOH. The NH3/MeOH fraction was concentrated in vacuo leaving the final product 4-(methoxycarbonyl)-1H-pyrrolo[2,3-b]pyridine 7-oxide (46 mg, 84 %).

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3039 - 3053

32
[ 479553-01-0 ]
[ 1201748-22-2 ]
[ 1201747-93-4 ]

Yield	Reaction Conditions	Operation in experiment
		Stage 5: In a 100 ml round-bottomed flask, a mixture of 51 mg of 5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine obtained according to the preceding stage, 28 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> (which can be obtained according to WO 2003/000688), 37 mg of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI) and 26 mg of 1-hydroxybenzotriazole (HOBt) in 5 ml of dimethylformamide is stirred for 4 hours under argon at ambient temperature. The reaction medium is evaporated to dryness under vacuum. The residue is triturated from 20 ml of water and then filtered. The solid is washed with a saturated solution of sodium bicarbonate and taken up in a mixture of dichloromethane and methanol, and the solution is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 mum), elution being carried out with a mixture of dichloromethane and methanol (98/2 v/v). 47 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> [5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amide are obtained in the form of a solid, the characteristics of which are the following:1H NMR spectrum: (400 MHz, delta in ppm, DMSO-d6): 6.22 to 6.28 (m, 2H); 6.40 (d, J=8.2 Hz, 1H); 6.89 (dd, J=3.4 and 2.0 Hz, 1H); 7.33 (t, J=7.7 Hz, 1H); 7.44 (d, J=5.1 Hz, 1H); 7.61 (dd, J=3.4 and 2.5 Hz, 1H); 7.64 (d, J=6.2 Hz, 1H); 7.67 (broad d, J=7.7 Hz, 1H); 7.84 (d, J=7.7 Hz, 1H); 7.85 (broad m, 1H); 8.28 (d, J=5.1 Hz, 1H); 8.33 (d, J=6.2 Hz, 1H); 9.01 (s, 1H); 9.29 (d, J=8.2 Hz, 1H); 11.84 (broad m, 1H); 13.47 (broad m, 1H).Mass spectrum (LC/MS Method A): Retention time Tr (min)=2.39; [M+H]+: m/z 432; [M-H]-: m/z 430.

Reference： [1]Patent: US2011/184015,2011,A1 .Location in patent: Page/Page column 23

33
[ 479553-01-0 ]
5-(6-fluoro-1H-benzimidazol-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine acetate [ No CAS ]
[ 1201746-40-8 ]

Yield	Reaction Conditions	Operation in experiment
		Stage 7: A mixture of 42 mg of 5-(6-fluoro-1H-benzimidazol-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine acetate obtained according to the preceding stage, 19 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> (which can be obtained according to WO 2003/000688), 39 mg of o-((ethoxycarbonyl)cyanomethylene-amino)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU) and 16 mul of diisopropylethylamine in 3 ml of N-methylpyrrolidone is stirred in a 100 ml round-bottomed flask. After 1 hour, the reaction medium is evaporated to dryness, the residue is taken up with 30 ml of a saturated solution of sodium bicarbonate and the aqueous phase is extracted with 4 times 30 ml of ethyl acetate. The combined organic phases are washed with 3 times 30 ml of a saturated solution of sodium chloride, dried over magnesium sulphate, and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 mum), elution being carried out with a gradient of methanol (2% to 5% v/v) in dichloromethane, and then on a second column of silica gel (15-40 mum), elution being carried out with pure ethyl acetate. 12 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> [5-(6-fluoro-1H-benzimidazol-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amide are obtained in the form of a brown solid, the characteristics of which are the following:1H NMR spectrum: (400 MHz, delta in ppm, DMSO-d6): 6.22 to 6.28 (m, 2H); 6.40 (d, J=7.8 Hz, 1H); 6.89 (dd, J=3.4 and 2.0 Hz, 1H); 7.13 (broad m, 1H); 7.33 (t, J=7.6 Hz, 1H); 7.38 (broad m, 1H); 7.44 (d, J=4.9 Hz, 1H); 7.52 to 7.83 (m, 5H); 8.28 (d, J=4.9 Hz, 1H); 9.30 (d, J=7.8 Hz, 1H); 11.85 (broad m, 1H); 13.14 (s, 1H).Mass spectrum (LC/MS Method A): Retention time Tr (min)=3.53; [M+H]+: m/z 449; [2M+H]+: m/z 897; [M+2H+ CH3CN]2+: m/z 245.5 (base peak).

Reference： [1]Patent: US2011/184015,2011,A1 .Location in patent: Page/Page column 21

34
[ 479553-01-0 ]
5-quinolin-3-yl-9H-pyrrolo[1,2-a]indol-9-ylamine acetate [ No CAS ]
[ 1201747-36-5 ]

Yield	Reaction Conditions	Operation in experiment
		Stage 4: In a 100 ml round-bottomed flask under argon, a mixture of 116 mg of 5-quinolin-3-yl-9H-pyrrolo[1,2-a]indol-9-ylamine acetate obtained according to the preceding stage, 63 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> (which can be obtained according to WO 2003/000688), 82 mg of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI) and 58 mg of 1-hydroxybenzotriazole (HOBt) in 7.5 ml of dimethylformamide is stirred at ambient temperature for 18 hours. The reaction medium is evaporated to dryness under vacuum, 50 ml of water are added to the residue, and the suspension is stirred for 1 hour. The solid is filtered and washed with water, then with a saturated solution of sodium bicarbonate and again with water. The resulting product is spin-filter-dried overnight and then the solid is taken up in a mixture of methanol and dichloromethane (10/90 v/v), and the solvent is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 mum), elution being carried out with a mixture of methanol and dichloromethane (3/97 v/v). 53 mg of <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> (5-quinolin-3-yl-9H-pyrrolo[1,2-a]indol-9-yl)amide are obtained in the form of a beige solid, the characteristics of which are the following:1H NMR spectrum: (300 MHz, delta in ppm, DMSO-d6): 6.09 (broad d, J=3.2 Hz, 1H); 6.13 (t, J=3.2 Hz, 1H); 6.24 (dm, J=3.2 Hz, 1H); 6.44 (broad d, J=8.3 Hz, 1H); 6.90 (broad d, J=3.3 Hz, 1H); 7.32 (t, J=7.7 Hz, 1H); 7.41 to 7.47 (m, 2H); 7.60 to 7.67 (m, 2H); 7.73 (m, 1H); 7.88 (m, 1H); 8.10 to 8.18 (m, 2H); 8.29 (d, J=5.0 Hz, 1H); 8.57 (broad m, 1H); 9.04 (broad m, 1H); 9.33 (d, J=8.3 Hz, 1H); 11.89 (broad m, 1H).Mass spectrum (LC/MS Method C): Retention time Tr (min)=2.36; [M+H]+: m/z 442; [M-H]-: m/z 440.

Reference： [1]Patent: US2011/184015,2011,A1 .Location in patent: Page/Page column 22

35
[ 479553-01-0 ]
[ 915138-80-6 ]
[ 915140-03-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7206 - 7219

36
[ 479553-01-0 ]
[ 915138-80-6 ]
C₂₇H₁₈N₆O [ No CAS ]
C₂₇H₁₈N₆O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7206 - 7219

37
[ 479553-01-0 ]
[ 62-53-3 ]
1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid phenyl amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.2%		Step 3: lH-pyrrolo[2,3-b]pyridine-4-carboxylic acid phenyl amide (23)To a cooled solution of compound 22 (19 g, 1 17.7 mmol) in DMF (200 mL), aniline (21.4 mL, 234.35 mmol), HATU (89.1 g, 234.35 mmol) and N,N-diisopropylethylamine (60.7 mL, 351.35 mmol) were added under argon atmosphere and stirred at room temperature for 16 h. To the reaction mixture IN NaOH (40 mL) was added and heated at 80 C for 4 h, additional IN NaOH (190 mL) was added and heating continued for 1 h. The reaction mixture was cooled and poured on ice, resulting solid was filtered, crystallized from methanol to afford lH-pyrrolo[2,3-b]pyridine-4-carboxylic acid phenyl amide 18.7 g (67.2%). VHNMR (400MHz, OMSO-d6): delta 1 1.95 (br s, 1H), 10.49 (br s, 1H), 8.38 (d, J= 7.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.50 (d, J= 7.2 Hz, 1H), 7.38 (t, J= 7.6 Hz, 2H), 7.13 (t, J = 7.2 Hz, 1H), 6.77 (d, J= 1.6 Hz, 1H). LCMS:- M+1 = 238

Reference： [1]Patent: WO2012/127506,2012,A1 .Location in patent: Page/Page column 65

38
[ 479553-01-0 ]
[ 1401447-86-6 ]

Reference： [1]Patent: WO2012/127506,2012,A1

39
[ 479553-01-0 ]
[ 1401447-87-7 ]

Reference： [1]Patent: WO2012/127506,2012,A1

40
[ 479553-01-0 ]
[ 1401447-88-8 ]

Reference： [1]Patent: WO2012/127506,2012,A1

41
[ 479553-01-0 ]
[ 1401447-89-9 ]

Reference： [1]Patent: WO2012/127506,2012,A1

42
[ 479553-01-0 ]
[ 1428264-81-6 ]
[ 1448440-72-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 3053 - 3074

43
[ 479553-01-0 ]
[ 78473-00-4 ]
C₁₅H₈Cl₂N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.87%		Under ice-cooling, oxalyl chloride (391.0mg, 3.08mmol) was added 1H- pyrrolo [2,3-b] pyridine-4-carboxylic acid (100.0mg, 0.62mmol) in dichloromethane (5mL) solution, 2 drops DMF as a catalyst, 40 reaction was heated 2h.The reaction mixture was concentrated, the resulting residue was dissolved in DMF (5mL) in a solution of <strong>[78473-00-4]4-amino-3,5-dichloro-benzonitrile</strong> at -5 (173.0mg, 0.93mmol) and sodium hydride (60%, 74.0 mg, 1.85mmol) in DMF (5mL) solution of reaction at room temperature 12h.Completion of the reaction, the reaction solution was added water (20 mL) to quench the reaction, and extracted with dichloromethane (30mL × 3), the combined organic phases were dried over anhydrous Na2SO4Dried, filtered, and concentrated under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluent: CH2Cl2/ MeOH (v / v) = 15/1), then after recrystallization from isopropanol to give a white solid 12.0mg, yield: 5.87%.

Reference： [1]Patent: CN105566321,2016,A .Location in patent: Paragraph 0257; 0258; 0259; 0260; 0261

44
[ 345954-83-8 ]
[ 640-68-6 ]
[ 479553-01-0 ]
(R)-N-(1-(3-cyanoazetidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1H-pyrrolo[2,3-b]pyridine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2%		The 1H- pyrrolo [2,3-b] pyridine-4-carboxylic acid (250mg, 1.54mmol) was dissolved in N, N- dimethylformamide (5mL) added successively HATU (879.6mg, 2.31mmol), diisopropylethyl amine (403muL, 2.3mmol) and D- valine (270.9mg, 2.31mmol), stirred at rt for 12h, and then continue to add HATU (879.6mg, 2.31mmol), DIPEA (403muL, 2.31mmol) and 3-cyano-ring butylamine hydrochloride (273mg, 2.31mmol), stirred at room temperature 12h, was added a saturated brine (10 mL) quenched and extracted with dichloromethane (15mL × 3), dried, concentrated and subjected to column chromatography separation (eluent: CH2Cl2/ MeOH (v / v) = 30/1), and then by preparative thin layer chromatography to give 10mg of white solid, yield: 2.0%.

Reference： [1]Patent: CN105566321,2016,A .Location in patent: Paragraph 0304; 0305; 0306; 0307; 0308

45
[ 5348-42-5 ]
[ 479553-01-0 ]
5,6-dichloro-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-benzo[d]imidazole [ No CAS ]

Reference： [1]Patent: WO2018/191146,2018,A1

46
[ 5348-42-5 ]
[ 479553-01-0 ]
N-(2-amino-4,5-dichlorophenyl)-1H-pyrrolo[2,3-b]pyridine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 15h;	[00788] To a solution of 4,5-dichlorobenzene-1,2-diamine (200 mg, 1.13 mmol) and <strong>[479553-01-0]1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid</strong> (201 mg, 1.24 mmol ) in DMF (10 mL) was added DIPEA (730 mg, 5.65 mmol) followed by HATU (645 mg, 1.69 mmol) and stirred at rt for 15 h. The solution was diluted with water (200 mL) and extracted with ethyl acetate (100 mL). The organic phase was washed with water (100 mL x 2), and brine (100 mL), dried (Na2S04), filtered and concentrated in vacuo, the crude product was used directly for the next step.

Reference： [1]Patent: WO2018/191146,2018,A1 .Location in patent: Paragraph 00788

47
[ 479553-01-0 ]
(E)-2-hydroxy-1-(methyl(oxo)(phenyl)-λ⁶-sulfaneylidene)guanidine [ No CAS ]
((5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-3-yl)imino)(methyl)(phenyl)-λ⁶-sulfanone [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9187 - 9199

48
[ 479553-01-0 ]
(S)-3-(3,5-difluorophenyl)-2,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine hydrochloride [ No CAS ]
(S)-(3-(3,5-difluorophenyl)-2,7-dimethyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)(1H-pyrrolo[2,3-b]pyridin-4-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 1h; Inert atmosphere;	A Step A: (S)-(3-(3,5-Difluorophenyl)-2,7-dimethyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)(1H-pyrrolo[2,3-b]pyridin-4-yl)methanone To a solution of (S)-3-(3,5-difluorophenyl)-2,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine, Intermediate 39, (50 mg, 0.19 mmol) in dichloromethane (DCM) (1.5 mL) was added HATU (144 mg, 0.38 mmol), followed by DIPEA (0.1 mL, 0.66 mmol) and 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid (62 mg, 0.38 mmol), and the mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with water and the aqueous layer extracted with DCM (*2). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by flash column chromatography (SiO2; 0-15% MeOH in DCM) to afford the title compound (76 mg, 99% yield). MS (ESI): mass calcd. for C22H19F2N5O, 407.2; m/z found, 408.2 [M+H]+.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2020/102303, 2020, A1 Location in patent: Paragraph 0371; 0711

49
[ 479553-01-0 ]
4-(ethoxycarbonyl)-1H-pyrrolo[2,3-b]pyridine 7-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: thionyl chloride / 0.5 h / 0 - 20 °C 1.2: 8 h / Reflux 2.1: 3-chloro-benzenecarboperoxoic acid / ethyl acetate / 3 h / 0 - 20 °C