1001070-33-2|5-Bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine| Ambeed

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Quality Control of [ 1001070-33-2 ] Purity: 98% SDS Specification

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Product Details of [ 1001070-33-2 ]

CAS No. :	1001070-33-2
Formula :	C₁₃H₉BrN₂O₂S
M.W :	337.19
SMILES Code :	O=S(N1C=CC2=CC(Br)=CN=C21)(C3=CC=CC=C3)=O
MDL No. :	MFCD08741546
InChI Key :	DWNWTAKXBHBRBH-UHFFFAOYSA-N
Pubchem ID :	24229246

Safety of [ 1001070-33-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H319
Precautionary Statements:	P305+P351+P338

Application In Synthesis of [ 1001070-33-2 ]

* 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.

Downstream synthetic route of [ 1001070-33-2 ]

[ 1001070-33-2 ] Synthesis Path-Downstream 1~35

Yield	Reaction Conditions	Operation in experiment
84%		General procedure: 5-Chloro-1H-pyrrolo[3,2-b]pyridine (Preparation 21 c, 2 g, 13.11 mmol) was added to a suspension of sodium hydride (60%, 0.70 g, 17.5 mmol) in 10 ml N,N-dimethylformamide at 0C and mixture was stirred for 30 min. Then benzenesulfonyl chloride (2 ml, 15.51 mmol) was added and reaction was stirred at room temperature for 1 h. The mixture was partitioned between ethyl acetate and water, organic layer was dried (MgSO4), filtered and concentrated. Purification by normal phase chromatography (0% to 100%, hexane - diethyl ether) afforded the title compound as a white solid (2.85 g, 74% yield).

2
[ 1001070-33-2 ]
[ 74-88-4 ]
[ 1111638-01-7 ]

Yield	Reaction Conditions	Operation in experiment
64.1%		To a solution of diispropylamine (2.52 g, 24.91 mmol) in anhydrous Tetrahydrofuran (THF, 50 mL) n-BuLi (2 M, 9.25 mL, 23.13 mmol) was added dropwise at -78 C and stirring at -78 C under N2 for 30 min. To the mixture a solution of compound 18 (3 g, 8.90 mmol) in anhydrous THF (20 mL) was added and stirred at -78 C for 40 min. To the mixture a solution of compound MeI (3.78 g, 26.69 mmol) in anhydrous THF (20 mL) was added at -78 C and stirred 25 C for 2 h. The mixture was quenched with sat. NH4Cl solution and extracted with Ethyl acetate (EtOAc, 100 mL * 3). The organic phase was washed with brine, dried over Na2SO4, concentrated and purified by column chromatography on silica (PE:EA = 40:1) to give compound 19 as a white solid (2.0 g, 64.1% yield). 1H NMR (400 MHz, DMSO-d6) delta 8.36 (s, 1H, Ar-H), 8.17 (s, 1H, Ar-H), 8.13-8.05 (m, 2H, Ar-H), 7.72-7.70 (t, J = 7.5 Hz, 1H, Ar-H), 7.63-7.59 (t, J = 7.8 Hz, 2H, Ar-H), 6.56 (s, 1H, Ar-H), 2.71 (s, 3H, CH3). ESI-MS m/z: 351.11, 353.11 (M+H)+.
60%		Preparation of Method A Intermediate 3: l-Benzenesulfonyl-5-bromo-2-methyl-lH- pyr rolo [2,3-b] pyridine[0426] To a solution of diisopropylamine (2.8 eq, 1.66 mmol, 240 mu) in THF (2 ml) at - 10C is added n-butyllithium (1.6 M in hexane, 2.6 eq, 1.54 mmol, 965 1) dropwise. The mixture is allowed to stir for 30 min and then cooled to -35C. A solution of compound 2 (1 eq., 200 mg, 0.593 mmol) in THF is added dropwise and the mixture is stirred for 30 min at -35C. lodomethane (3 eq, 1.78 mmol, 111 mu) is added in a dropwise fashion and the mixture is stirred for 2 h while warming up to room temperature. The reaction is quenched by addition of a saturated NH4C1 solution, extracted with EtOAc and purified by silica gel chromatography (stepwise gradient of 0 to 15 > EtOAc in hexane). 126 mg (0.359 mmol, 60%>) of compound 3 are obtained. 1H NMR (CDC13, 300 MHz): delta 8.37 (d, J= 2.4 Hz, 1H), 8.12 (m, 2 H), 7.81 (d, J = 2.4 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 2H), 6.24 (d, J= 1.2 Hz, 1H), 2.73 (d, J= 1.2 Hz, 3H). MS (m/z): 352 (M+H).
60%		To a solution of diisopropylamine (2.8 eq, 1.66 mmol, 240 muKappa) in THF (2 ml) at -10C is added w-butyllithium (1.6 M in hexane, 2.6 eq, 1.54 mmol, 965 1) dropwise. The mixture is allowed to stir for 30 min and then cooled to -35C. A solution of compound 2 (1 eq., 200 mg, 0.593 mmol) in THF is added dropwise and the mixture is stirred for 30 min at -35C. Iodomethane (3 eq, 1.78 mmol, 1 11 muKappa) is added in a dropwise fashion and the mixture is stirred for 2 h while warming up to room temperature. The reaction is quenched by addition of a saturated NH4C1 solution, extracted with EtOAc and purified by silica gel chromatography (stepwise gradient of 0 to 15% EtOAc in hexane). 126 mg (0.359 mmol, 60%) of compound 3 are obtained. XH NMR (CDC13, 300 MHz): delta 8.37 (d, J= 2.4 Hz, 1H), 8.12 (m, 2 H), 7.81 (d, J= 2.4 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 2H), 6.24 (d, J= 1.2 Hz, lH), 2.73 (d, J= 1.2 Hz, 3H). MS (m/z): 352 (M+H).

57.7%

Preparation of 5-bromo-1-(4-bromophenylsulfonyl)-2-methyl-1 H-pyrrolo[2,3-b]pyridine (B-7-5) <n="75"/>B-7-4 B-7-5To a suspension of 5-bromo-1-(phenylsulfonyl)-1 H-pyrrolo[2,3-b]pyridine (B-7-4) (10 g, 0.03 mol) in THF (50 mL) was added dropwise LDA (200 mL, 0.21 M in THF) at -78 0C. The mixture was stirred at -78 C for one hour. Then MeI (5.2 g 0.038 mol) was added dropwise at -78 0C. The reaction was stirred at -7O0C for3 hours, and then stirred at room temperature overnight. LC-MS showed the reaction was complete. Water (200 mL) and EtOAc (100 mLchi3) were added into the mixture. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated to give 5-bromo-1-(4-bromophenylsulfonyl)-2-methyl-1 H- pyrrolo[2,3-b]pyridine (B-7-5) (6 g, 57.7%) as a light yellow solid. 1HNMR (400 MHz, CDCI3): delta 8.390- 8.385 (d, 1 H), 8.176-8.145 (d, 2H), 7.828-7.823 (d, 1 H), 7.613-7.576 (t, 1 H), 7.517-7.479 (t, 2H), 6.254 (s, 1 H), 2.748 (s, 3H).

References: [1]Bioorganic Chemistry,2016,vol. 65,p. 146 - 158.
[2]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 582 - 586.
[3]Patent: WO2011/149950,2011,A2 .Location in patent: Page/Page column 151-152.
[4]Patent: WO2014/85795,2014,A1 .Location in patent: Paragraph 0393.
[5]Patent: WO2009/16460,2009,A2 .Location in patent: Page/Page column 73-74.

3
[ 1001070-33-2 ]
[ 97674-02-7 ]
[ 1111638-61-9 ]

Yield	Reaction Conditions	Operation in experiment
	bis-triphenylphosphine-palladium(II) chloride; In toluene;Heating / reflux;	Preparation of 5-(1-ethoxyvinyl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (H-1 -3)To a solution of compound H-1-2 (110 g, 0.33 mol) and 2-ethoxyprop-1-ene (141.3 g, 0.39 mol) in toluene (2 L) was added Pd(PPh3J2CI2 (11.4 g, 16.3 mmol) under N2. The mixture was refluxed overnight. TLC (petroleum ether/EtOAc 5:1 ) showed the reaction was complete. The reaction mixture was directly used in next step.

References: [1]Patent: WO2009/16460,2009,A2 .Location in patent: Page/Page column 116.

4
[ 98-09-9 ]
[ 183208-35-7 ]
[ 1001070-33-2 ]

Yield	Reaction Conditions	Operation in experiment
100%		5-Bromo-li/-pyrrolo[2,3-6]pyridine (1 g, 5.075 mmol) was dissolved in DMF (8 mL) and cooled to 0 C. Then NaH (300 mg, 7.51 mmol, 60 % dispersion in mineral oil) was added, and the mixture was stirred for 20 minutes at room temperature. After cooling the mixture to 0 C, benzenesulfonyl chloride (0.78 mL, 6.09 mmol) was added dropwise, and allowed to warm to room temperature. After 2 hours reaction time, the mixture was treated with saturated NH4CI, extracted with CH2CI2 (2x). The combined organic layers were washed with water (2x) and brine, dried over NazSCL, and evaporated to dryness to give 1.71 g (100 %) of i-(benzenesulfonyl)-5-bromo-i//-pyrrolo[2,3-6]pyridine.
99.6%		To a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine 17 (5 g, 25 mmol) in N,N-Dimethylformamide (DMF, 40 mL) Sodium hydride (NaH, 0.91 g, 37 mmol) was added at 0 C and stirred at 25 C for 20 min. To the mixture Benzenesulfonyl chloride (5.37 g, 30 mmol) was added dropwise at 0 C and stirred at 25 C for 1 h. The mixture was quenched with Ammonium chloride (NH4Cl) solution, extracted with Bichloromethane (DCM, 50 mL * 2). The organic phase was washed with water (50 mL * 2), brine (50 mL * 2), dried over Sodium sulfate (Na2SO4). After filtering, the organic phase was concentrated to give compound 18 as a white solid (8.5 g, 99.6% yield). 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H, Ar-H), 8.18-8.16 (d, J = 7.8 Hz, 2H, Ar-H), 7.96 (s, 1H, Ar-H), 7.74-7.73 (m, J = 4.0 Hz, 1H, Ar-H), 7.59-7.50 (t, J = 7.4 Hz, 1H, Ar-H), 7.47-7.38 (t, 2H, Ar-H), 6.55-6.54 (d, J = 4.0 Hz, 1H, Ar-H).
95%		A solution of 5-bromo- lH-pyrrolo[2,3-b]pyridine 8 (196 g, 994 mmol) in anhydrous tetrahydrofuran (2 L) was cooled to 0 C and treated with sodium hydride (60% in mineral oil, 49.3 g 1233 mmol) over 30 minutes. After two hours, benzenesulfonyl chloride 9 (153 mL, 1 193 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The reaction was quenched with brine (1 L). The layers were separated and the aqueous phase was extracted with ethyl acetate (2 x 500 mL). The organic layers were combined, dried with sodium sulfate, filtered and concentrated under reduced pressure. The product was triturated with methyl tert-butyl ether to give compound 10 as a tan solid (319 g, 95%). The data from the lH NMR spectrum were consistent with the structure of the compound.

94.3 - 94.8%		Preparation of 5-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (B-7-4)B-7-3 B-7-4To a suspension of 5-bromo-1 H-pyrrolo[2,3-b]pyridine (B-7-3) (6.2 g, 0.031 mol) in THF (100 mL) was added NaH (1.51 g, 0.037 mol) under N2. BsCI (3.58 g, 0.035mol) was added 30 minutes later. The mixture was stirred at room temperature overnight. TLC (Petroleum ether: EtOAc = 5:1 ) showed that the reaction was complete. Water (200 mL) and EtOAc (50 mLchi3) were added into the mixture. The organic layer was separated and concentrated to give 5-bromo-1-(phenylsulfonyl)-1 H-pyrrolo[2,3-b]pyridine (B-7- 4) (10 g, 94.3%) as a light yellow solid. 1HNMR (400 MHz, CDCI3): delta 8.465 (s, 1 H), 8.141-8.114 (d, 2H), 7.905 (s, 1 H), 7.679-7.669 (d, 1 H), 7.586-7.529 (m, 1 H), 7.430-7.351 (2, 1 H), 6.458-6.475 (d, 1 H). Example H-1 : 4-(3-(3-chloro-1 H-pyrrolo[2,3-b]pyridin-5-yl)-1 -isopropyl-1 H-pyrazol-4-yl)pyridin-2- aminePreparation of 5-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (H-1 -2)H-1-1 H-1 -2To a suspension of NaH (87 g, 2.18 mol, 60% in oil) in dry THF (1 L) was added dropwise a solution of 5- bromo-1 H-pyrrolo[2,3-b]pyridine H-1-1 (120 g, 0.62 mol) in dry THF (1 L) at O0C. After addition, the mixture was stirred at O0C under N2 for 0.5 h. To the mixture was added dropwise BsCI (219.5 g, 1.24 mol) at 50C. After the addition, the mixture was stirred at room temperature overnight. TLC (Petroleum ether/EtOAc 5:1 ) showed the reaction was complete. The reaction mixture was poured slowly into ice-cold saturated NH4CI (500 mL). The mixture was extracted with EtOAc (600 mLchi2). The combined organic layers were washed with saturated aqueous NaCI (700 mL), dried over Na2SO4 and concentrated in vacuo. The residue was washed with Petroleum ether/EtOAc (15:1 , 1.5 L) to give compound H-1-2 (198 g, 94.8%) as an off-white solid.
92.2%	With pyridine; at 85℃; for 4h;	Compound numbers 1 to 7 recited in Example 4 apply only to Example 4. To a solution of 5-bromo-lH-pyrrolo[2,3-b]pyridine(50 g, 0.254 mol) in pyridine (300 mL) was added benzene sulfonyl chloride (224 g, 1.27 mol). The resulted mixture was heated at 85 C for 4 hours and then concentrated under vacuum. The residue was diluted with EtOAc (1500 mL). The pH of the solution was adjusted to 3 with 1M HC1, and the resulted mixture was washed with NaHC03 and water. The organic layer was washed with water and brine, dried (Na2S04) and concentrated. The residue was purified by a silica gel column to afford (85 g, 99.2 %) of the title compound as a slightly yellow solid
76%		5-Bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine To a well stirred solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (10.0 g, 50.7 mmol) in dry THF (100 mL) was added NaH (60% oil suspension; 3.0 g, 75 mmol) at 0 C. and stirred for 30 min. Phenylsulfonyl chloride (10.7 g, 60 mmol) was added slowly and the mixture was stirred at ambient temperature for 16 h (TLC monitoring: 60% ethyl acetate in hexanes). Solvent was removed under reduced pressure, water (25 mL) was added to the residue, and the mixture was extracted with dichloromethane (3*100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue thus obtained was crystallized from dichloromethane to yield the title compound (13.0 g, 76%). 1H NMR (CDCl3, 300 MHz): delta=6.55 (d, J=4.2 Hz, 1H), 7.46-7.62 (m, 3H), 7.74 (d, J=4.0 Hz, 1H), 7.97 (d, J=2.1 Hz, 1H), 8.15-8.18 (m, 2H), 8.44 (d, J=2.1 Hz, 1H).
75%	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; at 0℃; for 2h;	Preparation of Method A Intermediate 2: l-Benzenesulfonyl-5-bromo-lH-pyrrolo[2,3- b] pyridine[0425] 5-Bromoazaindole (1, 2.00 g, 10.1 mmol), tetrabutylammonium bromide (0.03 eq, 0.25 mmol, 82 mg) and powdered NaOH (3 eq, 30.45 mmol, 1.22 g) are combined in DCM (100 ml) and cooled to 0C. Phenylsulfonyl chloride (1.25 eq, 12.69 mmol, 1.62 mL) is added dropwise. After the addition is completed the mixture is stirred for 2h at 0C. The mixture is filtered, absorbed on Celite and purified by silica gel chromatography with a 40 to 60% gradient of EtOAc in hexane. 2.58 g (7.65 mmol, 75% yield) of 2 is obtained. 1H NMR (CDC13, 300 MHz): delta 8.45 (d, J= 1.8 Hz, 1H), 8.17 (m, 2 H), 7.98 (d, J= 2.1 Hz, 1H), 7.74 (d, J= 3.9 Hz, 1H), 7.60 (m, 1H), 7.50 (m, 2H), 6.55 (d, J= 3.9 Hz, 1H). MS (m/z): 338 (M+H).
75%	With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; at 0℃; for 2h;	5-Bromoazaindole (1, 2.00 g, 10.1 mmol), tetrabutylammonium bromide (0.03 eq, 0.25 mmol, 82 mg) and powdered NaOH (3 eq, 30.45 mmol, 1.22 g) are combined in DCM (100 ml) and cooled to 0C. Phenylsulfonyl chloride (1.25 eq, 12.69 mmol, 1.62 mL) is added dropwise. After the addition is completed the mixture is stirred for 2h at 0C. The mixture is filtered, absorbed on Celite and purified by silica gel chromatography with a 40 to 60% gradient of EtOAc in hexane. 2.58 g (7.65 mmol, 75% yield) of 2 is obtained. XH NMR (CDC13, 300 MHz): delta 8.45 (d, J= 1.8 Hz, 1H), 8.17 (m, 2 H), 7.98 (d, J= 2.1 Hz, 1H), 7.74 (d, J= 3.9 Hz, 1H), 7.60 (m, 1H), 7.50 (m, 2H), 6.55 (d, J= 3.9 Hz, 1H). MS (m/z): 338 (M+H).
55.46%		To a mixture of 5-bromo-7-azaindole (1.00 g, 5.08 mmol) and DMF (3 ml) was added 60% NaH (0.13 g, 5.59 mmol). The mixture was stirred for 10 minutes, and, after addition of benzenesulfonyl chloride (0.71 ml, 5.59 mmol), was stirred again overnight at room temperature. The reaction was quenched with water and the mixture was extracted with ethyl acetate (30ml x 3). The organic layer was collected, dried over anhydrous MgS04, and concentrated in vacuo to yield a brown residue, which was purified by a flash column over silica gel (ethyl acetate: n-hexane = 1 : 1, Rf = 0.40) to afford 11a (0.95 g, 55.46%) as a yellow solid. *H-NMR (500MHZ, CDCI3 ): delta 6.55 (d, /= 4.5 Hz, 1H), 7.50 (t, /= 8.0 Hz, 2H), 7.59(t, /= 7.5 Hz, 1H), 7.74 (d, /= 4.0 Hz, 1H), 7.97 (d, /= 2.0Hz, 1H), 8.17 (t, /= 8.0 Hz, 2H), 8.45 (d, /= 2.0Hz, 1H).
		EXAMPLE 1; Compound 1-1; 5-?-methyl-lH-pyrazol-4-yl)-3-(6-piperazin-l-ylpyrazin-2-v?-lH-pyrrolor2,3-b1pyridine; Step 1 : 5-bromo-l-(phenylsulfonylMH-pyrrolo[2,3-fr]rhoyridine; To a stirred solution of 5-bromo-lH-pyrrolo[2,3-Z>]pyridine (20.0 g, 102 mmol) in DMF (400 ml) at 0 0C was added NaH (60% mineral oil dispersion; 4.87 g, 122 mmol) slowly (CAUTION: GAS EVOLUTION). The reaction mixture was stirred at 0 C for 2 h. Benzenesulfonyl chloride (17.0 ml, 132 mmol) was added dropwise, and the reaction mixture was allowed to warm to ambient. After 1 hour the reaction mixture was cooled in an ice bath, and 100 mL of water was added slowly (CAUTION: GAS EVOLUTION, EXOTHERM). The reaction mixture was partitioned between ethyl acetate (500 mL) and brine (600 mL). The organic layer was washed with additional brine (500 mL), followed by saturated aqueous ammonium chloride (250 mL). The first and 3rd aqueous layers were combined and back- extracted with ethyl acetate (500 mL). The combined organics were dried over sodium sulfate, filtered and concentrated to a thick slurry. EtOAc (100 mL) was added, followed by hexanes (100 mL). The mixture was filtered, and the filter cake was rinsed with 1 :1 EtOAc/Hexanes (50 mL) to afford 5-bromo-l-(phenylsulfonyl)-lH-pyrrolo[2,3-£]pyridine as a grey solid. The filtrate can be concentrated and purified by silica gel chromatography (EtOAc/etaexanes gradient) to afford additional product. LRMS (ESI) calculated for C13H9BrN2O2S [M+H]+, 337.0; found 336.9.

References: [1]Patent: WO2020/12424,2020,A1 .Location in patent: Page/Page column 84.
[2]Bioorganic Chemistry,2016,vol. 65,p. 146 - 158.
[3]Patent: WO2014/100620,2014,A2 .Location in patent: Paragraph 0285.
[4]Patent: WO2009/16460,2009,A2 .Location in patent: Page/Page column 73.
[5]Patent: WO2016/210296,2016,A1 .Location in patent: Page/Page column 164.
[6]Patent: US2011/281888,2011,A1 .Location in patent: Page/Page column 66.
[7]Patent: WO2011/149950,2011,A2 .Location in patent: Page/Page column 151.
[8]Patent: WO2014/85795,2014,A1 .Location in patent: Paragraph 0392.
[9]Patent: WO2015/157504,2015,A1 .Location in patent: Page/Page column 75.
[10]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 582 - 586.
[11]Patent: WO2009/54941,2009,A1 .Location in patent: Page/Page column 44-45.
[12]Drug Development Research,2019,vol. 80,p. 617 - 628.

5
[ 552846-17-0 ]
[ 1001070-33-2 ]
[ 1147998-27-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 1.08h;	EXAMPLE 2; Compound 2-1; 3-r6-(piperidin-4-yloxy)rhoyrazin-2-yll-5-(lH-pyrazol-4-yl)-lH-pyrrolor2,3-blPvridine; )h 1 -(phenylsulfonylV5-(lH-pwazol-4-vD-lH-pyrrolor2, 3-fr\|pyridine; To a degassed (sparging with argon for 5 minutes), stirred solution of 4-(4 ,4,5,5- tetramethyl-l,3,2-dioxaborolan-2yl)-pyrazole-l-carboxylic acid tert-butyl ester (1.31 g, 4.45 mmol) and 5-bromo-l-(phenylsulfonyl)-lH-pyrrolo[2,3->]pyridine (1.00 g, 2.97 mmol) in dioxane (12.0 ml) was added Pd(Ph3P)4 (0.171 g, 0.148 mmol), followed by a degassed aqueous <n="51"/>solution of sodium carbonate (4.45 ml, 8.90 mmol). The reaction mixture was stirred under nitrogen at 100 0C for 1 hour. The reaction mixture was cooled to room temperature and partitioned between EtOAc (50 mL) and saturated aqueous ammonium chloride (50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude residue. The residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford 1 - (phenylsulfonyl)-5-(l/-/-pyrazol-4-yl)-lH-pyrrolo[2, 3-£]pyridine as a yellow solid. LRMS (ESI) calculated for C16HnN4O2S [M+H]+, 325.1; found 325.0.

References: [1]Patent: WO2009/54941,2009,A1 .Location in patent: Page/Page column 49-50.

6
[ 1001070-33-2 ]
[ 761446-44-0 ]
[ 1147998-19-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2h;	Step 2: 5-(l-methyl-lH-rhoyrazol-4-yl)-l-(phenylsulfonvn-lH-pyrrolor2,3-felpyridine; To a degassed (sparging with argon for 5 minutes), stirred solution of 1 -methyl-4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-leta-pyrazole (0.617 g, 2.97 mmol) and 5-bromo-l- (phenylsulfonyl)-lH-pyrrolo[2,3-6]pyridine (1.00 g, 2.97 mmol) in dioxane (12.0 ml) was added Pd(Ph3P)4 (0.171 g, 0.148 mmol), followed by a degassed aqueous solution of sodium carbonate (4.45 ml, 8.90 mmol). The reaction mixture was stirred under nitrogen at 100 0C for 2 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (25 mL) and saturated aqueous ammonium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude residue. The residue was purified by silica gel chromatography (EtOAc/etaexanes gradient) to afford 5-(l-methyl-l//-pyrazol-4-yl)-l- (rhohenylsulfonyl)-lH-pyrrolo[2,3-b]pyridine as a white solid. LRMS (ESI) calculated for Ci7Hi4N4O2S [M+H]+, 339.1 ; found 339.1.

References: [1]Patent: WO2009/54941,2009,A1 .Location in patent: Page/Page column 45.

7
[ 1001070-33-2 ]
[ 24850-33-7 ]
[ 1312018-04-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 20 - 80℃; for 12h;	To a solution of <strong>[1001070-33-2]1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridine</strong> (prepared as in Example 7) (10 g, 29.7 mmol) in N,N-dimethylformamide (20 mL) was added allyltributylstannane (14 mL, 44.51 mmol), and tetrakis(triphenylphosphine)palladium(0) (1.72 g, 1.49 mmol) at room temperature and then stirred at 80 C. for 12 h. The mixture was cooled to room temperature and extracted with ethyl acetate (2×250 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 33% ethyl acetate/hexanes) afforded 5-allyl-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine as a white solid (5.3 g, 60%): LC/MS m/e calcd for C16H14N2O2S [M+H]+ 299.37, observed 299.1.

References: [1]Patent: US2011/144105,2011,A1 .Location in patent: Page/Page column 21.

8
1-(tert-butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
[ 1001070-33-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

9
5-bromo-1-(tert-butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
[ 1001070-33-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

10
[ 10592-27-5 ]
[ 1001070-33-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

11
[ 1001070-33-2 ]
[ 7486-35-3 ]
[ 1312017-88-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 85℃; for 15h;	A mixture of <strong>[1001070-33-2]1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridine</strong> (3.0 g, 8.9 mmol), tributyl-vinyl-stannane (3.9 mL, 13.55 mmol) and tetrakis(triphenylphosphine)palladium(0) (514 mg, 0.445 mmol) in N,N-dimethylformamide (10 mL) was stirred at 85 C. for 15 h. The mixture was cooled to 25 C., extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, hexanes to 15% ethyl acetate/hexanes) to afford 1-benzenesulfonyl-5-vinyl -1H-pyrrolo[2,3-b]pyridine (2.2 g, 87%) as a white solid: LC/MS m/e calcd for C15H13N2SO2 [M+H]+ 285.34, observed 285.2; 1H NMR (400 MHz, CDCl3) delta ppm 5.32 (d, J=11.0 Hz, 1H), 5.78 (d, J=17.6 Hz, 1H), 6.59 (d, J=4.0 Hz, 1H), 6.77 (dd, J=11.0 Hz, J=17.6 Hz, 1H), 7.49 (m, 2H), 7.58 (m, 1H), 7.74 (d, J=4.0 Hz, 1H), 7.88 (d, J=2.0 Hz, 1H), 8.19 (m, 2H), 8.46 (d, J=2.0 Hz, 1H).

References: [1]Patent: US2011/144105,2011,A1 .Location in patent: Page/Page column 16.

12
[ 754214-54-5 ]
[ 98-09-9 ]
[ 1001070-33-2 ]

Yield	Reaction Conditions	Operation in experiment
100%		Sodium hydroxide (4.1 g, 102.8 mmol) was added to a solution of tetrabutylammonium bromide (331 mg, 1.0 mmol) and 5-bromo-1H-pyrrolo[2,3-b]pyridine (6.7 g, 34.7 mmol) in dichloromethane (80 mL) at 0 C. The mixture was stirred at 0 C. for 5 min. Benzene sulfonyl chloride (5.7 mL, 44.5 mmol) was added to the above mixture slowly at 0 C. The resulting mixture was stirred at 0 C. for 15 min before it was warmed to 25 C. and kept stirring at that temperature for 12 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo and then washed with hexanes to afford 1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridine as a white solid (11.8 g, 100%): LC/MS m/e calcd for C13H10BrN2O2S [M+H]+ 338.20, observed 337.1, 339.1; 1H NMR (400 MHz, CDCl3) delta ppm 6.56 (d, J=4.0 Hz, 1H), 7.51 (m, 2H), 7.60 (m, 1H), 7.75 (d, J=4.0 Hz, 1H), 7.98 (d, J=2.1 Hz, 1H), 8.18 (m, 2H), 8.45 (d, J=2.0 Hz, 1H).

References: [1]Patent: US2011/144105,2011,A1 .Location in patent: Page/Page column 16.

13
[ 271-63-6 ]
[ 1001070-33-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

14
[ 1001070-33-2 ]
[ 627-41-8 ]
[ 1254568-11-0 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	With copper(l) iodide; triethylamine;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 20 - 85℃; for 12h;	To a solution of <strong>[1001070-33-2]1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridine</strong> (prepared as in Example 7, 6.5 g, 19.3 mmol) in N,N-dimethylformamide (30 mL) was added 3-methoxy-propyne (5 mL, 57.9 mmol), tetrakis(triphenylphosphine)palladium(0) (2.2 g, 1.93 mmol), copper (I) iodide (735 mg, 3.85 mmol) and triethylamine (8.1 mL, 57.9 mmol) at room temperature. The mixture was then heated at 85 C. and stirred for 12 h. The resulting mixture was cooled to room temperature, extracted with ethyl acetate (2×250 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-5-(3-methoxy-prop-1-ynyl)-1H-pyrrolo[2,3-b]pyridine as a light yellow solid (5 g, 89.1%): LC/MS m/e calcd for C17H14N2O3S [M+H]+ 327.38, observed 327.0.

References: [1]Patent: US2011/144105,2011,A1 .Location in patent: Page/Page column 40.

15
[ 1001070-33-2 ]
[ 1312016-01-5 ]

References: [1]Patent: US2011/144105,2011,A1 .

16
[ 1001070-33-2 ]
[ 1312016-04-8 ]

References: [1]Patent: US2011/144105,2011,A1 .

17
[ 1001070-33-2 ]
[ 1312016-06-0 ]

References: [1]Patent: US2011/144105,2011,A1 .

18
[ 1001070-33-2 ]
[ 1312016-11-7 ]

References: [1]Patent: US2011/144105,2011,A1 .

19
[ 1001070-33-2 ]
[ 1312016-67-3 ]

References: [1]Patent: US2011/144105,2011,A1 .

20
[ 1001070-33-2 ]
[ 1312016-69-5 ]

References: [1]Patent: US2011/144105,2011,A1 .

21
[ 1001070-33-2 ]
[ 1312016-70-8 ]

References: [1]Patent: US2011/144105,2011,A1 .

22
[ 1001070-33-2 ]
[ 1312016-71-9 ]

References: [1]Patent: US2011/144105,2011,A1 .

23
[ 1001070-33-2 ]
[ 1312016-72-0 ]

References: [1]Patent: US2011/144105,2011,A1 .

24
[ 1001070-33-2 ]
[ 1312016-76-4 ]

References: [1]Patent: US2011/144105,2011,A1 .

25
[ 1001070-33-2 ]
[ 1312016-77-5 ]

References: [1]Patent: US2011/144105,2011,A1 .

26
[ 1001070-33-2 ]
[ 1312017-89-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

27
[ 1001070-33-2 ]
[ 1312017-90-5 ]

References: [1]Patent: US2011/144105,2011,A1 .

28
[ 1001070-33-2 ]
[ 1312017-91-6 ]

References: [1]Patent: US2011/144105,2011,A1 .

29
[ 1001070-33-2 ]
[ 1312017-92-7 ]

References: [1]Patent: US2011/144105,2011,A1 .

30
[ 1001070-33-2 ]
[ 1312017-97-2 ]

References: [1]Patent: US2011/144105,2011,A1 .

31
[ 1001070-33-2 ]
[ 1312018-05-5 ]

References: [1]Patent: US2011/144105,2011,A1 .

32
[ 1001070-33-2 ]
[ 1312018-06-6 ]

References: [1]Patent: US2011/144105,2011,A1 .

33
[ 1001070-33-2 ]
[ 1312018-07-7 ]

References: [1]Patent: US2011/144105,2011,A1 .

34
[ 1001070-33-2 ]
[ 1312018-08-8 ]

References: [1]Patent: US2011/144105,2011,A1 .

35
[ 1001070-33-2 ]
[ 1312018-12-4 ]

References: [1]Patent: US2011/144105,2011,A1 .

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Preparation of Alkylbenzene • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Vilsmeier-Haack Reaction

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P378
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P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
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P401
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Code	Phrase
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H250	Catches fire spontaneously if exposed to air
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H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
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Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
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H310	Fatal in contact with skin
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H312	Harmful in contact with skin
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H314	Causes severe skin burns and eye damage
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Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 1001070-33-2

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CAS No.: 1001070-33-2

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[ 1001070-33-2 ] Synthesis Path-Downstream 1~35

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