866545-96-2|1-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone| Ambeed

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Quality Control of [ 866545-96-2 ] Purity: 98% SDS Specification

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Product Details of [ 866545-96-2 ]

CAS No. :	866545-96-2
Formula :	C₉H₇BrN₂O
M.W :	239.07
SMILES Code :	CC(C1=CNC2=NC=C(Br)C=C21)=O
MDL No. :	MFCD12403936
InChI Key :	AYSQNMFURHMHBB-UHFFFAOYSA-N
Pubchem ID :	59699914

Safety of [ 866545-96-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 866545-96-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 866545-96-2 ]
Downstream synthetic route of [ 866545-96-2 ]

[ 866545-96-2 ] Synthesis Path-Upstream 1~2

1
[ 75-36-5 ]
[ 183208-35-7 ]
[ 866545-96-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	at 20℃; for 6 h;	Step 1: Synthesis of 1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone. To a stirring solution of aluminum chloride (6.77 g, 50.75 mmol) suspended in anhydrous CH₂Cl₂ (100 mL) under N₂ was added 5-bromo-1H-pyrrolo[2,3-b]pyridine (2.00 g, 10.15 mmol). The reaction solution was stirred for 1 hour at ambient temperature whereupon acetyl chloride (3.61 mL, 50.75 mmol) was added dropwise and the resulting solution was stirred for 5 more hours. The reaction was cooled to 0° C. in an ice bath and quenched carefully by addition of MeOH until the solution became clear. The reaction was concentrated under vacuum. H₂O was added and 1 N NaOH was added dropwise until the pH=4. The product was extracted into ethyl acetate and the organic layer was washed with a saturated solution of sodium potassium tartrate to remove any remaining aluminum salts. The organic layer was dried over Na₂SO₄ and concentrated under vacuum. The material was redissolved in ethyl acetate and filtered through a bed of silica gel. The filtrate was concentrated to afford the title compound as an orange solid (2.25 g, 93percent yield). ¹H NMR (500 MHz, d₆-DMSO) δ 12.70 (br s, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.55 (s, 1H), 8.40 (d, J=2.5 Hz, 1H), 2.46 (s, 3H). MS: m/z 238.9/240.9 (M+H⁺).
93%	Stage #1: With aluminum (III) chloride In dichloromethane at 20℃; for 1 h; Stage #2: for 5 h;	To a stirring solution of aluminum chloride (6.77 g, 50.75 mmol) suspended in anhydrous CH₂Cl₂ (100 mL) under N₂ was added 5-bromo-1H -pyrrolo[2,3-δ]pyridine (2.00 g, 10.15 mmol). The reaction solution was stirred for 1 hour at ambient temperature whereupon acetyl chloride (3.61 mL, 50.75 mmol) was added dropwise and the resulting solution was stirred for 5 more hours. The reaction was cooled to 0 °C in an ice bath and quenched carefully by addition of MeOH until the solution became clear. The reaction was concentrated under vacuum. H₂O was added and 1 N NaOH was added dropwise until the pH = 4. The product was extracted into ethyl acetate and the organic layer was washed with a saturated solution of sodium potassium tartrate to remove any remaining aluminum salts. The organic layer was dried over Na₂SO* and concentrated under vacuum. The material was redissolved in ethyl acetate and filtered through a bed of silica gel. The filtrate was concentrated to afford the title compound as an orange <n="79"/>solid (2.25 g, 93percent yield). ¹H NMR (500 MHz, ^-DMSO) δ 12.70 (br s, 1H), 8.56 (d, J = 2.5 Hz, 1H),8.55 (s, 1H), 8.40 (d, J = 2.5 Hz, 1H), 2.46 (s, 3H). MS: m/z 238.9/240.9 (M + H⁺).
87%	Stage #1: With aluminum (III) chloride In dichloromethane at 20℃; for 1 h; Stage #2: at 20℃;	5-Bromo-1H-pyrrolo[2,3-b]pyridine (5 g, 25.2 mmol) was added to aluminum chloride (16.8 g, 126.2 mmol) in dichloromethane (200 ml) under nitrogen. The mixture was allowed to stir at room temperature for 1 hour. Acetyl chloride (9 ml, 126.2 mmol) in dichloromethane was added drop wise and the reaction was allowed to proceed at room temperature overnight. Next day the reaction was cooled to 0° C. and quenched with methanol (500 ml) until the reaction turned clear. The reaction was concentrated under vacuum and resuspended in water (300 ml). The pH was adjusted to 4 with 7N sodium hydroxide solution and then extracted with ethyl acetate (300 ml.x.3). The combined organic layers were extracted with saturated sodium potassium tartrate and brine and dried with Na₂SO₄. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 1-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)-ethanone (5.2 g, 87percent yield). ¹H NMR (500 MHz, DMSO-d6) δ 2.48 (s, 3H), 8.41 (s, 1H), 8.57 (s, 1H), 8.58 (s, 1H). MS: m/z 241.0 (M+H⁺).

References: [1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7212 - 7215.
[2] Patent: US2006/30583, 2006, A1, . Location in patent: Page/Page column 61-62.
[3] Patent: WO2008/124849, 2008, A2, . Location in patent: Page/Page column 77-78.
[4] Patent: US2008/261921, 2008, A1, . Location in patent: Page/Page column 141-142.
[5] Patent: US2011/82138, 2011, A1, . Location in patent: Page/Page column 65.
[6] Patent: WO2014/111496, 2014, A1, . Location in patent: Page/Page column 100; 101.
[7] Patent: WO2016/142310, 2016, A1, . Location in patent: Page/Page column 65-66.

2
[ 75-36-5 ]
[ 866545-96-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: With aluminum (III) chloride In dichloromethane at 20℃; for 1 h; Stage #2: at 20℃; for 18 h;	7-Azaindole 13 (2.16g, 0.011 mol) was dissolved in 75 mL of dry DCM. Aluminium trichloride (4.36 g, 0.0327 mol) was added to the solution and the reaction mixture was stirred for 1 h at rt. Acetyl chloride (1.16 mL, 0.0164 mol) was adde dropwise to the mixture and stirred at rt for 18 h. 20 rnL of methanol was added and the reaction for 1 h. Concentrated in vacuo and suspended in water-EtOAc mixture. Extraction with EtOAc and drying of the organic gave, after concentration in vacuo, 2.37 g (91percent) of compound 14. 1H NMR CDCl3 9.5 (bs, 1H), 8.8 (s, 1H), 8.5 (s, 1H), 7.9 (s, 1H), 2.4 (s, 3H).

References: [1] Patent: WO2005/95400, 2005, A1, . Location in patent: Page/Page column 330; 331.

[ 866545-96-2 ] Synthesis Path-Downstream 1~17

1
[ 75-36-5 ]
[ 866545-96-2 ]

Yield	Reaction Conditions	Operation in experiment
91%		7-Azaindole 13 (2.16g, 0.011 mol) was dissolved in 75 mL of dry DCM. Aluminium trichloride (4.36 g, 0.0327 mol) was added to the solution and the reaction mixture was stirred for 1 h at rt. Acetyl chloride (1.16 mL, 0.0164 mol) was adde dropwise to the mixture and stirred at rt for 18 h. 20 rnL of methanol was added and the reaction for 1 h. Concentrated in vacuo and suspended in water-EtOAc mixture. Extraction with EtOAc and drying of the organic gave, after concentration in vacuo, 2.37 g (91%) of compound 14. 1H NMR CDCl3 9.5 (bs, 1H), 8.8 (s, 1H), 8.5 (s, 1H), 7.9 (s, 1H), 2.4 (s, 3H).

References: [1]Patent: WO2005/95400,2005,A1 .Location in patent: Page/Page column 330; 331.

2
[ 75-36-5 ]
[ 183208-35-7 ]
[ 866545-96-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	aluminum (III) chloride; In dichloromethane; at 20℃; for 6h;	Step 1: Synthesis of 1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone. To a stirring solution of aluminum chloride (6.77 g, 50.75 mmol) suspended in anhydrous CH2Cl2 (100 mL) under N2 was added 5-bromo-1H-pyrrolo[2,3-b]pyridine (2.00 g, 10.15 mmol). The reaction solution was stirred for 1 hour at ambient temperature whereupon acetyl chloride (3.61 mL, 50.75 mmol) was added dropwise and the resulting solution was stirred for 5 more hours. The reaction was cooled to 0 C. in an ice bath and quenched carefully by addition of MeOH until the solution became clear. The reaction was concentrated under vacuum. H2O was added and 1 N NaOH was added dropwise until the pH=4. The product was extracted into ethyl acetate and the organic layer was washed with a saturated solution of sodium potassium tartrate to remove any remaining aluminum salts. The organic layer was dried over Na2SO4 and concentrated under vacuum. The material was redissolved in ethyl acetate and filtered through a bed of silica gel. The filtrate was concentrated to afford the title compound as an orange solid (2.25 g, 93% yield). 1H NMR (500 MHz, d6-DMSO) delta 12.70 (br s, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.55 (s, 1H), 8.40 (d, J=2.5 Hz, 1H), 2.46 (s, 3H). MS: m/z 238.9/240.9 (M+H+).
93%		To a stirring solution of aluminum chloride (6.77 g, 50.75 mmol) suspended in anhydrous CH2Cl2 (100 mL) under N2 was added 5-bromo-1H -pyrrolo[2,3-delta]pyridine (2.00 g, 10.15 mmol). The reaction solution was stirred for 1 hour at ambient temperature whereupon acetyl chloride (3.61 mL, 50.75 mmol) was added dropwise and the resulting solution was stirred for 5 more hours. The reaction was cooled to 0 C in an ice bath and quenched carefully by addition of MeOH until the solution became clear. The reaction was concentrated under vacuum. H2O was added and 1 N NaOH was added dropwise until the pH = 4. The product was extracted into ethyl acetate and the organic layer was washed with a saturated solution of sodium potassium tartrate to remove any remaining aluminum salts. The organic layer was dried over Na2SO* and concentrated under vacuum. The material was redissolved in ethyl acetate and filtered through a bed of silica gel. The filtrate was concentrated to afford the title compound as an orange <n="79"/>solid (2.25 g, 93% yield). 1H NMR (500 MHz, ^-DMSO) delta 12.70 (br s, 1H), 8.56 (d, J = 2.5 Hz, 1H),8.55 (s, 1H), 8.40 (d, J = 2.5 Hz, 1H), 2.46 (s, 3H). MS: m/z 238.9/240.9 (M + H+).
87%		5-Bromo-1H-pyrrolo[2,3-b]pyridine (5 g, 25.2 mmol) was added to aluminum chloride (16.8 g, 126.2 mmol) in dichloromethane (200 ml) under nitrogen. The mixture was allowed to stir at room temperature for 1 hour. Acetyl chloride (9 ml, 126.2 mmol) in dichloromethane was added drop wise and the reaction was allowed to proceed at room temperature overnight. Next day the reaction was cooled to 0 C. and quenched with methanol (500 ml) until the reaction turned clear. The reaction was concentrated under vacuum and resuspended in water (300 ml). The pH was adjusted to 4 with 7N sodium hydroxide solution and then extracted with ethyl acetate (300 ml×3). The combined organic layers were extracted with saturated sodium potassium tartrate and brine and dried with Na2SO4. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 1-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)-ethanone (5.2 g, 87% yield). 1H NMR (500 MHz, DMSO-d6) delta 2.48 (s, 3H), 8.41 (s, 1H), 8.57 (s, 1H), 8.58 (s, 1H). MS: m/z 241.0 (M+H+).

		Aluminum trichloride (846 mg) was added to a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (250 mg) in dichloromethane (5 ml) at room temperature over 10 minutes. Subsequently, acetyl chloride (135 mul) was added and the mixture was stirred at room temperature for 5 hours. The reaction solution was poured into ice-cold water and separated by adding dichloromethane. The resulting organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developed with methanol-chloroform) to give the title compound (186 mg).MS (ESI) m/z: 239 (M+H)+.1H-NMR (CDCl3) delta: 2.55 (3H, s), 7.98 (1H, d, J=2.8 Hz), 8.45 (1H, d, J=2.3 Hz), 8.85 (1H, d, J=1.8 Hz), 10.28 (1H, br s).
	With aluminum (III) chloride; In dichloromethane; at 0 - 20℃;Inert atmosphere;	To a soluition of 5-bromo-lH-pyrrolo[2,3-b]pyridine(30 g, 0.15 mol) and aluminium chloride (100 g, 0.75 mol) in dichloromethane (2000 mL) was added dropwise acetyl chloride (102 mL, 1.44 mol) over 1 h under nitrogen atmosphere at 0 C. The reaction mixture was warmed to RT and stirred overnight. Methanol (150 mL) was added dropwise at 0 C, and the resulting mixture was concentrated to dryness in vacuo. The resulting crude was dissolved in ice -water, basified with saturated sodium bicarbonate to pH 4 - 5 and extracted with ethyl acetated (3 x 3000 mL). The combined organic layer were washed with brine, dried over sodium sulfate and concentrated to dryness in vacuo affording crude l-(5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone as a yellow solid (330 g, 93 % after 10 batch repeat) used for the next step without any further purification: NMR (DMSO, 400 MHz): delta 12.675 (s, 1H), 8.537-8.543 (d, J = 2.4 Hz, 1H), 8.506 (s, 1H), 8.371-8.377 (d, J = 2.4 Hz, 1H), 2.445 (s, 3H).
	With aluminum (III) chloride; In dichloromethane; at 0 - 20℃;Inert atmosphere;	Preparative Example 6 Step 1: l-(5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone To a soluition of 5-bromo-lH-pyrrolo[2,3-b]pyridine(30 g, 0.15 mol) and aluminium chloride (100 g, 0.75 mol) in dichloromethane (2000 mL) was added dropwise acetyl chloride (102 mL, 1.44 mol) over 1 h under nitrogen atmosphere at 0 C. The reaction mixture was warmed to RT and stirred overnight. Methanol (150 mL) was added dropwise at 0 C, and the resulting mixture was concentrated to dryness in vacuo. The resulting crude was dissolved in ice -water, basified with saturated sodium bicarbonate to pH 4 - 5 and extracted with ethyl acetated (3 x 3000 mL). The combined organic layer were washed with brine, dried over sodium sulfate and concentrated to dryness in vacuo affording crude l-(5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone as a yellow solid (330 g, 93 % after 10 batch repeat) used for the next step without any further purification: lH NMR (DMSO, 400 MHz): delta 12.675 (s, 1H), 8.537-8.543 (d, = 2.4 Hz, 1H), 8.506 (s, 1H), 8.371- 8.377 (d, J = 2.4 Hz, 1H), 2.445 (s, 3H).

References: [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7212 - 7215.
[2]Patent: US2006/30583,2006,A1 .Location in patent: Page/Page column 61-62.
[3]Patent: WO2008/124849,2008,A2 .Location in patent: Page/Page column 77-78.
[4]Patent: US2008/261921,2008,A1 .Location in patent: Page/Page column 141-142.
[5]Patent: US2011/82138,2011,A1 .Location in patent: Page/Page column 65.
[6]Patent: WO2014/111496,2014,A1 .Location in patent: Page/Page column 100; 101.
[7]Patent: WO2016/142310,2016,A1 .Location in patent: Page/Page column 65-66.

3
[ 866545-96-2 ]
[ 5815-08-7 ]
1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-dimethylamino-propenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	at 100℃; for 6.5h;	Step 2: Synthesis of 1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-dimethylamino-propenone. To <strong>[866545-96-2]1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone</strong> (2.25 g, 9.41 mmol) was added tert-butoxybis(dimethylamino)methane (5.83 mL, 28.23 mmol) (neat) and refluxed in an oil bath at 100 C. for 6.5 hours. The reaction was cooled and titrated with diethyl ether. The solid was filtered and dried under vacuum to afford the title compound as an orange powder (1.93 g, 70% yield). 1H NMR (500 MHz, d6-DMSO) delta 8.67 (d, J=2.5 Hz, 1H), 8.37 (s, 1H), 8.31 (d, J=2.0 Hz, 1H), 7.57 (d, J=12.5 Hz, 1H), 5.78 (d, J=12.0 Hz, 1H), 2.49 (s, 6H).
70%	at 100℃; for 6.5h;Heating / reflux;	To l-(5-bromo-1H -pyrrolo[2,3-b]pyridin-3-yl)-ethanone (2.25 g, 9.41 mmol) was added tert- butoxybis(dimethylamino)methane (5.83 mL, 28.23 mmol) (neat) and refluxed in an oil bath at 100 C for6.5 hours. The reaction was cooled and titrated with diethyl ether. The solid was filtered and dried under vacuum to afford the title compound as an orange powder (1.93 g, 70% yield). 1H NMR (500 MHz, dg-DMSO) delta 8.67 (d, J= 2.5 Hz, 1H), 8.37 (s, 1H), 8.31 (d, J = 2.0 Hz, 1H), 7.57 (d, J = 12.5 Hz, 1H), 5.78(d, J = 12.0 Hz, 1H), 2.49 (s, 6H).

References: [1]Patent: US2006/30583,2006,A1 .Location in patent: Page/Page column 61-62.
[2]Patent: WO2008/124849,2008,A2 .Location in patent: Page/Page column 77; 78.

4
[ 866545-96-2 ]
[ 76513-69-4 ]
[ 73183-34-3 ]
[ 1071454-96-0 ]

Yield	Reaction Conditions	Operation in experiment
92%		To a 250 ml 3-neck flask, <strong>[866545-96-2]1-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)-ethanone</strong> (2.2 g, 9.3 mmol) and DMF (50 ml) were added. The solution was cool to -40 C. under nitrogen, and sodium hydride (0.3 g, 11.2 mmol) was added in 2 batches. The mixture was stirred at -40 C. for 1 hour. A solution of SEM-Cl (2 ml, 11.2 mmol) in DMF (10 ml) was added dropwise and the resulting mixture was allowed to stir at -40 C. for another 2 hours. The reaction was quenched with saturated NH4Cl (40 ml) and worked up with ethyl acetate, brine, dried with Na2SO4 and concentrated to dryness. The crude intermediate, bis(pinacolato)diboron (4.8 g, 18.6 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (341 mg, 0.5 mmol), and sodium acetate (2.3 g, 28 mmol) in DMF (20 ml) were stirred at 100 C. overnight. The mixture was allowed to cool to room temperature and was then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica gel chromatography of the crude using a gradient of ethyl acetate and hexane afforded 1-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl-1-2(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)-ethanone (3.6 g, 92% yield). 1H NMR (500 MHz, DMSO-d6) delta 0.03 (s, 9H), 0.92 (m, 2H), 1.28 (s, 3H), 1.43 (s, 12H), 3.67 (m, 2H), 5.78 (s, 2H), 8.68, (m, 1H), 8.82 (s, 1H), 8.89 (m, 1H). MS: m/z 417.2 (M+H+).

References: [1]Patent: US2008/261921,2008,A1 .Location in patent: Page/Page column 141-142.

5
[ 866545-96-2 ]
[ 1073354-99-0 ]
C₁₄H₁₂N₄O [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7212 - 7215.

6
[ 866545-96-2 ]
[ 1261082-91-0 ]
[ 1261082-81-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7212 - 7215.

7
[ 866545-96-2 ]
[ 1620574-96-0 ]

References: [1]Patent: WO2014/111496,2014,A1 .

8
[ 866545-96-2 ]
[ 1620574-97-1 ]

References: [1]Patent: WO2014/111496,2014,A1 .
[2]Patent: WO2016/142310,2016,A1 .

9
[ 866545-96-2 ]
[ 1256819-54-1 ]

References: [1]Patent: WO2014/111496,2014,A1 .
[2]Patent: WO2016/142310,2016,A1 .

10
[ 866545-96-2 ]
[ 1620574-98-2 ]

References: [1]Patent: WO2014/111496,2014,A1 .
[2]Patent: WO2016/142310,2016,A1 .

11
[ 866545-96-2 ]
[ 98-59-9 ]
[ 1052633-38-1 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of l-(5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone (50 g, 0.21 mol) in tetrahydrofuran (1400 mL) was added sodium hydride (8.8 g, 0.22 mol, 60 %) at 0 C. After the mixture was stirred for 1 h at 0 C a solution of 4-methylbenzene-l-sulfonyl chloride (48.3 g, 0.25 mol) in tetrahydrofuran (300 mL) was added dropwise at 0 C. The resulting mixture was warmed up to RT and stirred overnight. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 xlOOO mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to dryness in vacuo affording crude l-(5-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone as yellow solid (75 g, yield: 90 %), which was used for the next step without further purification: NMR (400 MHz, DMSO-d6): delta 8.884 (s, 1H), 8.532-8.573 (m, 2H), 8.054-8.075 (d, J = 12 Hz, 2H), 7.442-7.463 (d, J = 8.4 Hz, 2H), 2.578 (s, 3H), 2.347 (s, 3H
		Step 2: l-(5-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone To a solution of l-(5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone (50 g, 0.21 mol) in tetrahydroiuran (1400 niL) was added sodium hydride (8.8 g, 0.22 mol, 60 %) at 0 C. After the mixture was stirred for 1 h at 0 C a solution of 4-methylbenzene-l-sulfonyl chloride (48.3 g, 0.25 mol) in tetrahydroiuran (300 mL) was added dropwise at 0 C. The resulting mixture was warmed up to RT and stirred overnight. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 xlOOO mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to dryness in vacuo affording crude l-(5-bromo-l-tosyl-lH-pyrrolo[2,3- b]pyridin-3-yl)ethanone as yellow solid (75 g, yield: 90 %), which was used for the next step without further purification: H NMR (400 MHz, DMSO-d6): delta 8.884 (s, 1H), 8.532-8.573 (m, 2H), 8.054- 8.075 (d, = 12 Hz, 2H), 7.442-7.463 (d, = 8.4 Hz, 2H), 2.578 (s, 3H), 2.347 (s, 3H).

References: [1]Patent: WO2014/111496,2014,A1 .Location in patent: Page/Page column 101.
[2]Patent: WO2016/142310,2016,A1 .Location in patent: Page/Page column 66.

12
[ 866545-96-2 ]
2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-(2-(trifluoromethyl)pyridin-4-yl)acetamide [ No CAS ]
2-(4-(3-acetyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-fluorophenyl)-N-(2-(trifluoromethyl)pyridin-4-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; N,N-dimethyl-formamide; acetonitrile; at 105℃; for 12h;Inert atmosphere;	A mixture of <strong>[866545-96-2]1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone</strong> ( 39, 0.10 g, 0.42 mmol), 2-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-[2-(trifluoromethyl)-4-pyridyl]acetamide (38, 0.19 g, 0.45 mmol), 2.5 M aqueous potassium carbonate (0.5 ml) and [1,1?-bis(diphenylphosphino)ferrocene] dichloropalladium(II) dichloromethane complex (0.04 g, 0.05 mmol) in acetonitrile/ DMF was flushed with argon and allowed to stir at 105 C. for 12 hours. The reaction mixture was filtered through celite and then concentrated under reduced pressure. The crude material was dissolved in ethyl acetate and washed with aqueous ammonium chloride followed by brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was suspended in diethyl ether, sonicated, and heated. The liquid was removed and a brown solid remained. This material was purified by silica gel flash column chromatography eluting with 0-10% methanol in dichloromethane to provide compound P-0031. MS ESI [M+H+]+=457.25.

References: [1]Patent: US2017/267660,2017,A1 .Location in patent: Paragraph 0632; 0634.

13
[ 866545-96-2 ]
[ 875639-38-6 ]