* 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.
Bromine (1.91 mL, 37.1 mmol) was added dropwise to a solution of lH-pyrazolo[3,4-b]pyridine (2.6 g, 21.8 mmol) in CHCl3 (100 mL), and the reaction mixture was left at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was taken up in ethyl acetate (200 mL) and saturated NaHCO3 (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were dried, filtered and concentrated to give 3-bromo-lH-pyrazolo[3,4-b]pyridine (3.7 g, 86percent) as a solid.
65%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 44℃; for 1.66667 h;
Formation of 3-bromo-lH-pyrazolo[3,4-b]pyridine (43)To a solution of 1H -pyrazolo[3,4-b]pyridine, 42, (0.21 kg, 1.79 mol) in DMF (2 L) was added NBS (0.34 kg, 1.07 eq) portionwise over 1 hour. The temperature reached 44 °C during addition. The reaction mixture was stirred for 40 minutes. Ice water (3L total volume) was added and the resulting precipitate was collected by filtration. The product was washed with Η20 (3 x 2L) and left on the filter over 3 days. The product was washed with heptanes (lx) and dissolved in EtOAc (4 L). The aqueous phase was separated and the remaining organic layer was washed with brine and concentrated to dryness to afford the product (229 g, 65percent yield) as a light-yellow solid: NMR (CDC13, 300 MHz) δ 8.71 -8.64 (m, 1 H); 8.08-8.02 (m, 1 H); 7.30- 7.24 m, 1 H) ppm.
1.2 g
With N-Bromosuccinimide In N,N-dimethyl-formamide at 50℃; for 16 h;
To a solution of 1H-pyrazolo[3,4-b]pyridine (1.10 g, 9.23 mmol, 1.00 eq) in DMF (2.00 mL) was added NBS (2.46 g, 13.85 mmol, 1.50 eq). The mixture was stirred at 50 C for 16 h. The reaction mixture was poured into water 100 mL, and then extracted with EtOAc (30 mL * 3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE/EtOAc=10:1 to 3:1) to afford the title compound (1.2 g) as a white solid. (Note: Combined purification with another batch: SM scale: 200 mg).
Reference：
[1] Patent: WO2009/111279, 2009, A1, . Location in patent: Page/Page column 81
[2] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
[3] Patent: WO2012/83117, 2012, A1, . Location in patent: Page/Page column 126-127
[4] Patent: WO2018/13867, 2018, A1, . Location in patent: Paragraph 506
2
[ 36404-88-3 ]
[ 271-73-8 ]
Yield
Reaction Conditions
Operation in experiment
87%
at 130℃; for 3 h; Inert atmosphere
Hydrazine hydrate (10 mL) was added to a mixture of 2-chloro-3-formylpyridine 1 (5.00 g, 35 mmol) and p-TsOH (3.50 g, 18 mmol). The reaction mixture was stirred for 3 h at 130 °C. Upon cooling with cold water, the mixture was extracted with EtOAc. The combined organic extracts were dried over anhydrous MgSO4. After filtration, the solvent was removed in vacuum and gave compound 2 (3.65 g, 87percent) as a yellow solid; mp 88‑90 °C(97-98 °C);34 FTIR (KBr) νmax/cm-1 3450 (N-H), 3089, 3026 (C-H Ar), 2958, 2915 (C-H), 1606, 1588, 1509, 1470, 1429 (C=N, C=C); 1H NMR (300 MHz, CDCl3) δ/ppm 1.69 (s, 1H, N-H), 7.19 (dd, 1H, J 4.7 and 7.5, ArH, 5-H), 8.12 (s, 1H, ArH, 3-H), 8.15 (d, 1H, J 8.1, ArH, 4-H), 8.63 (d, 1H, J 4.5, ArH, 6-H).
62%
Stage #1: at 120℃; for 0.166667 h; Microwave heating Stage #2: With sodium hydrogencarbonate In water
Preparation of 1H-pyrazolo[3,4-b]pyridine 2-Chloro-3-pyridinecarboxyaldehyde (1.0 g, 7.0 mmol) and p-toluenesulfonic acid monohydrate (700 mg) were dissolved in hydrazine monohydrate (1.4 mL, 28.0 mmol). The resulting mixture was heated at 120°C for 10 minutes in a sealed tube under irradiation with a macrowave of 100 watts. After cooled to room temperature, the mixture was neutralized with a saturated sodium bicarbonate aqueous solution and extracted with DCM (50 mL) three times. The organic layer was dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel (Fuji Silysia, BW300, 30 g, n-hexane: ethyl acetate = 1:1) to give 1H-pyrazolo[3,4-b]pyridine (513 mg, yield: 62percent). 1H-NMR (270MHz, CDCl3) δ (ppm): 7.16 (1H, dd, J=4.6, 8.1Hz), 8.08 (1H, d, J=2.0Hz), 8.10 (1H, d, J=1.5Hz), 8.60 (1H, d, J=4.6Hz) ESI (LC-MS positive mode) m/z 120 (M+H).
4 g
With hydrazine In ethanol for 24 h; Reflux
A stirred solution of 2-chloronicotinaldehyde (I-5) (5.1 g, 36 mmol) in EtOH (100 mL) and NH2NH2 (85 percent in H20, 50 mL) was heated to reflux for 24 hr. TLC (petroleum ether/ EtOAc = 1 :1) showed the reaction was complete. The mixture was concentrated and separated between H20 (100 mL) and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na2S04 and concentrated in vacuo to give 1 H-pyrazolo[3,4-b]pyridine (I-6) (4 g, 93percent) as a yellow solid.
Reference：
[1] European Journal of Medicinal Chemistry, 2012, vol. 57, p. 311 - 322
[2] Journal of Organic Chemistry, 2017, vol. 82, # 23, p. 12300 - 12306
[3] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 8, p. 1295 - 1306
[4] Patent: EP1921078, 2008, A1, . Location in patent: Page/Page column 32
[5] Patent: US2007/21442, 2007, A1, . Location in patent: Page/Page column 56
[6] Patent: WO2011/149921, 2011, A1, . Location in patent: Page/Page column 98
[7] Patent: US2012/16117, 2012, A1, . Location in patent: Page/Page column 28
[8] Heteroatom Chemistry, 2016, vol. 27, # 1, p. 3 - 11
[9] Patent: WO2016/97918, 2016, A1, . Location in patent: Page/Page column 51
[10] Patent: WO2018/13867, 2018, A1, . Location in patent: Paragraph 505
3
[ 36404-90-7 ]
[ 271-73-8 ]
Yield
Reaction Conditions
Operation in experiment
90%
With hydrazine hydrate In ethanol at 80℃; for 1 h;
Formation of lH-pyrazolo[3,4-b]pyridine (42)Hydrazine hydrate (64percent, 0.29 L, 5.99 mol hydrazine, 3 eq) was added dropwise to a solution of 2-fluoropyridine-3-carboxylaldehyde (0.25 kg, 1.99 mol) in EtOH (600 mL) over lhr. During the addition, a thick suspension formed, which turned into a clear red solution towards the end of the addition. The reaction mixture was heated to 80 °C overnight. The reaction mixture was cooled to room temperature, quenched with H20/aqueous saturated NaHC03 (1/1 mixture, 600mL) and extracted with EtOAc (2x 800 mL, lx 500 mL). The combined organic layers were washed with brine (400 mL), dried over Na2S04 and concentrated in vacuo. The resulting solid was washed with heptanes (3x 800 mL), dried under reduced pressure and stripped twice with heptanes. The product (214 g, 90percent yield) was obtained as a light-yellow solid: NMR (CDC13, 300 MHz) δ 8.65-8.64 (m, 1 H); 8.14-8.10 (m, 2H); 7.17-7.12(m, 1 H) ppm.
Reference：
[1] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
8
[ 75427-09-7 ]
[ 271-73-8 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 938 - 942
9
[ 6602-54-6 ]
[ 271-73-8 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
10
[ 109-09-1 ]
[ 271-73-8 ]
Reference：
[1] Patent: WO2016/97918, 2016, A1,
11
[ 75427-06-4 ]
[ 271-73-8 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 938 - 942
12
[ 75427-15-5 ]
[ 271-73-8 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 938 - 942
13
[ 271-73-8 ]
[ 29274-28-0 ]
Reference：
[1] Patent: EP1921078, 2008, A1,
14
[ 271-73-8 ]
[ 29274-28-0 ]
[ 63725-51-9 ]
Reference：
[1] Patent: WO2016/4272, 2016, A1,
15
[ 271-73-8 ]
[ 29274-28-0 ]
[ 63725-51-9 ]
Reference：
[1] Patent: WO2016/4272, 2016, A1,
16
[ 271-73-8 ]
[ 117007-52-0 ]
Yield
Reaction Conditions
Operation in experiment
90%
With sodium hydroxide; water; iodine In 1,4-dioxane at 55℃;
lΗ-pyrazolo[3,4-b]pyridine Compound 4a (0.50 g, 4.2 mmol), iodine (2.1 g, 8.3 mmol), 3M aqueous NaOH (20 mL) and 1,4-dioxane (20 mL) were added to a flask and the mixture was heated to 55 0C overnight. The organic solvent was removed in vacuo and acetic acid was added dropwise to adjust the solution pH to 5. A yellow solid was . precipitated, 'cqllected by filtration and air-dried to afford Compound 4b (0.93 g, 90percent). 1H NMR (400 MHz, CDCl3) δ 13.80 (br, s, 1 H), 8.66 (d, J = 4.8 Hz, IH), 7.88 (d, / = 7.2 Hz, IH), 7.26 (dd, /= 7.2, 4.8 Hz, IH); MS (ESI) m/z: 246 (M+H)+.
84%
Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 0 - 20℃; for 0.5 h; Stage #2: With iodine In N,N-dimethyl-formamide at 0 - 20℃;
To a solution of 1 H-pyrazolo[3,4-b]pyridine (I-6) (4 g, 34 mmol) in DMF (150 mL) was added KOH (7.6 g, 136 mmol) at 0 °C. The mixture was stirred at room temperature for 30 min. To the resulting mixture was added iodine (15 g, 61 mmol) in portions at 0°C and the mixture was stirred at room temperature overnight. TLC (petroleum ether/ EtOAc = 1 :1) showed the reaction was complete. The reaction mixture was poured into ice water and extracted with CH2CI2 (300 mL x 2). The combined organic layers were washed with sat. aq.Na2S03 (300 mL χ 2), brine (200 mL x 3), dried over Na2S04 and concentrated in vacuo to give 3-iodo-1 H-pyrazolo[3,4-b]pyridine (I-7) (7 g, 84percent) as a yellow solid.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1243 - 1245
[2] Patent: WO2006/130673, 2006, A1, . Location in patent: Page/Page column 86
[3] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
[4] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 13, p. 4763 - 4772
[5] Patent: WO2016/97918, 2016, A1, . Location in patent: Page/Page column 51-52
[6] Patent: US2007/21442, 2007, A1, . Location in patent: Page/Page column 56
[7] Journal of Medicinal Chemistry, 2010, vol. 53, # 23, p. 8368 - 8375
[8] Patent: WO2011/149921, 2011, A1, . Location in patent: Page/Page column 98
[9] Patent: US2012/16117, 2012, A1, . Location in patent: Page/Page column 28
[10] Patent: WO2014/2057, 2014, A1, . Location in patent: Page/Page column 52
[11] Patent: EP3351533, 2018, A1, . Location in patent: Paragraph 0201; 0202
[12] Patent: JP2018/145180, 2018, A, . Location in patent: Paragraph 0210; 0211; 0212
With pyridine; Iodine monochloride; In dichloromethane; at 0℃; for 0.833333h;
lH-Pyrazolo[3,4-b]pyridine (0.225 g, 0.00189 mol) was dissolved in pyridine (2.0 mL, 0.025 mol; Acros) and cooled in an ice bath. A solution of 1.00 M of iodine monochloride in methylene chloride (2.1 mL; Aldrich) was added over 5 min. After 15 min the cooling bath was removed, and after another 30 min the solution was diluted with 200 mL of ethyl acetate. The organic solution was washed sequentially with 1 N hydrogen chloride and 1 N sodium hydroxide, dried over magnesium sulfate, and concentrated. The residue was taken up in DMF and purified by preparative HPLC to yield the desired product as TFA salt in 55.5 mg yield (8percent). MS m/z = 245.87 (M+l). IH NMR (400 MHz, DMSO-d6) .(TM). ppm 14.070 (s(br), IH) 8.564 (dd, J= 4.5, 1.6Hz, IH) 7.917 (d, J=8.0Hz, IH) 7.253 (dd, J=8.1, 4.5Hz, IH).
With toluene-4-sulfonic acid; hydrazine hydrate; at 130℃; for 3h;Inert atmosphere;
Hydrazine hydrate (10 mL) was added to a mixture of 2-chloro-3-formylpyridine 1 (5.00 g, 35 mmol) and p-TsOH (3.50 g, 18 mmol). The reaction mixture was stirred for 3 h at 130 °C. Upon cooling with cold water, the mixture was extracted with EtOAc. The combined organic extracts were dried over anhydrous MgSO4. After filtration, the solvent was removed in vacuum and gave compound 2 (3.65 g, 87percent) as a yellow solid; mp 88?90 °C(97-98 °C);34 FTIR (KBr) numax/cm-1 3450 (N-H), 3089, 3026 (C-H Ar), 2958, 2915 (C-H), 1606, 1588, 1509, 1470, 1429 (C=N, C=C); 1H NMR (300 MHz, CDCl3) delta/ppm 1.69 (s, 1H, N-H), 7.19 (dd, 1H, J 4.7 and 7.5, ArH, 5-H), 8.12 (s, 1H, ArH, 3-H), 8.15 (d, 1H, J 8.1, ArH, 4-H), 8.63 (d, 1H, J 4.5, ArH, 6-H).
62%
Preparation of 1H-pyrazolo[3,4-b]pyridine 2-Chloro-3-pyridinecarboxyaldehyde (1.0 g, 7.0 mmol) and p-toluenesulfonic acid monohydrate (700 mg) were dissolved in hydrazine monohydrate (1.4 mL, 28.0 mmol). The resulting mixture was heated at 120°C for 10 minutes in a sealed tube under irradiation with a macrowave of 100 watts. After cooled to room temperature, the mixture was neutralized with a saturated sodium bicarbonate aqueous solution and extracted with DCM (50 mL) three times. The organic layer was dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel (Fuji Silysia, BW300, 30 g, n-hexane: ethyl acetate = 1:1) to give 1H-pyrazolo[3,4-b]pyridine (513 mg, yield: 62percent). 1H-NMR (270MHz, CDCl3) delta (ppm): 7.16 (1H, dd, J=4.6, 8.1Hz), 8.08 (1H, d, J=2.0Hz), 8.10 (1H, d, J=1.5Hz), 8.60 (1H, d, J=4.6Hz) ESI (LC-MS positive mode) m/z 120 (M+H).
With hydrazine; In ethanol; water; for 24h;Heating / reflux;
EXAMPLE 49; 3-Chloro-5-{2-chloro-5-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]phenoxy}benzonitrile (49-9); Step 1: 1H-pyrazolo[3,4-b]pyridine (49-2) A mixture of 10.00 g (70.65 mmol) of 2-chloro-3-formylpyridine(49-1) in 225 mL of absolute ethanol/100 mL of hydrazine hydrate was heated at reflux for 24 hours. The reaction mixture was then cooled to room temperature and concentrated in vacuo to a brown oil-solid. The crude product was chromatographed over silica gel with 2.5percent methanol/chloroform to give the desired product as a yellow oil that slowly crystallized to a yellow solid. 1H NMR (CDCl3): 7.20(m,1H), 8.15(m,2H), 8.66 (dd,1H), 12.49 (br s, 1H).
With hydrazine hydrate; In water; at 100℃; for 72h;Inert atmosphere;
A solution of 2-chloropyridine-3-carbaldehyde (20g, 141mmol) and hydrazine monohydrate(60percent in water, 1 13g, 2.1 mol) in 140 mL water was heated at 100 °C for 72 hours. The reaction mixture was cooled to room temperature and diluted with 200 mL of EtOAc. The aqueous layer was separated and extracted with EtOAc (3x). The combined organics were dried over MgS04, filtered and concentrated in vacuo to give a light orange solid which was crystallized from hexanes to give the title compound as an off-white solid. NMR (400 MHz, CH3CN-d3): delta11.56 (s, 1 H); 8.51 (dd, J = 4.52, 1.56 Hz, 1 H); 8.17 (dd, J = 8.05, 1.58 Hz, 1 H); 8.05 (s, 1H); 7.17 (dd, J = 8.05, 4.51 Hz, 1 H).
Reference Example 1; (1); According to the method of Chemical Communications 293-294 (1966), to a mixture of Compound 1 (20.0 g) and p-toluenesulfonic acid monohydrate (15.6 g) was added slowly hydrazine monohydrate (26.6 ml) with stirring under ice-cooling. The mixture was heated to stir at 130° C. for 21 hours. The reaction mixture was let stand to cool, and then poured into 25percent aqueous potassium carbonate solution, and extracted with ethyl acetate. The extracted layer was combined, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate 2:1 to 1:1). The resulting solid was triturated by hexane-ethyl acetate (1:1) to give Compound 2 (12.27 g) as colorless powdery crystals.MS (APCI) 120 [M+H]+
4 g
With hydrazine; In ethanol; for 24h;Reflux;
A stirred solution of 2-chloronicotinaldehyde (I-5) (5.1 g, 36 mmol) in EtOH (100 mL) and NH2NH2 (85 percent in H20, 50 mL) was heated to reflux for 24 hr. TLC (petroleum ether/ EtOAc = 1 :1) showed the reaction was complete. The mixture was concentrated and separated between H20 (100 mL) and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na2S04 and concentrated in vacuo to give 1 H-pyrazolo[3,4-b]pyridine (I-6) (4 g, 93percent) as a yellow solid.
With toluene-4-sulfonic acid; hydrazine hydrate; at 130℃; for 16h;
To a solution of 2-chloropyridine-3-carbaldehyde (3.00 g, 21.19 mmol, 1.00 eq) in hydrazine; hydrate (6.36 g, 127.14 mmol, 6.18 mL, 6.00 eq) was added PTSA (1.82 g, 10.60 mmol, 0.50 eq). The mixture was stirred at 130 C for 16 h. It was concentrated. The residue was purified by column chromatography to afford the title compound (1.50 g, 11.33 mmol, 53.48percent yield, 90percent purity) as a white solid.
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃;Product distribution / selectivity;
Example 36 3-(3-Chloro-2-methyl-phenyl)-1-(2-pyrazolo[3,4-b]pyridin-1-yl-acetyl)-imidazolidin-4-one A mixture of 1-(2-Chloro-acetyl)-3-(3-chloro-2-methyl-phenyl)-imidazolidin-4-one (230 mg, 0.8 mmol, 1 eq), <strong>[271-73-8]1H-Pyrazolo[3,4-b]pyridine</strong> (96 mg, 0.8 mmol, 1 eq), Cesium carbonate (653 mg, 2.0 mmol, 2.5 eq) in DMF (6 ml) was stirred at room temperature overnight. It was diluted with ethyl acetate, washed with water and purified with HPLC to give the desired product. LCMS observed for (M+H)+: 370.1 Example 37; 3-(3-Chloro-2-methyl-phenyl)-1-(2-pyrazolo[3,4-b]pyridin-2-yl-acetyl)-imidazolidin-4-one; A mixture of 1-(2-Chloro-acetyl)-3-(3-chloro-2-methyl-phenyl)-imidazolidin-4-one (230 mg, 0.8 mmol, 1 eq), <strong>[271-73-8]1H-Pyrazolo[3,4-b]pyridine</strong> (96 mg, 0.8 mmol, 1 eq), Cesium carbonate (653 mg, 2.0 mmol, 2.5 eq) in DMF (6 ml) was stirred at room temperature overnight. It was diluted with ethyl acetate, washed with water and purified with HPLC to give the desired product. LCMS observed for (M+H)+: 370.1
l-(2-TrimethylsilanylethoxymethylV4,5,6,7-tetrahvdro-lH-pyrazolor3,4-b1pyridine To a solution of lH-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong> (380 mg, 3.2 mmol) in DMF (5 mL) was added NaH (60percent dispersion in mineral oil, 153 mg, 3.8 mmol). After stirring for 20 min, the mixture was heated with a heat gun and then allowed to cool to rt. SEM-Cl (647 muL, 3.8 mmol) was added dropwise and stirring continued for 2 h. The resulting mixture was partitioned between water and ethyl acetate. The organic layer was separated and concentrated, and the residue was purified by flash column chromatography (silica gel, eluting with 0-50percent ethyl acetate in hexanes) to provide l-(2-trimethylsilanylethoxymethyl)-lH-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong>, which was dissolved in ethanol (30 mL) and flushed with a nitrogen stream. Palladium on charcoal (5percent wet on carbon, -50 mg) was added and the mixture was placed under hydrogen (50 psi) for 2 days. The reaction mixture was filtered, and the filtrate was concentrated to provide the title compound: 1H NMR (500 MHz, CDCl3) delta 7.13 (s, IH), 5.24 (s, 2H), 3.68 (br, IH), 3.54 (t, J = 8.2 Hz, 2H), 3.28 (m, 2H), 2.51 (t, J = 6.1, 2H), 1.81 (m, 2H), 0.89 (t, J = 8.2 Hz, 2H), -0.01 (s, 9H).
Preparation of <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> 7N-oxide m-chlorobenzoate <strong>[271-73-8]1H-Pyrazolo[3,4-b]pyridine</strong> (1.0 g, 8.48 mmol) was dissolved in ethyl acetate (8.5 mL), and an ethyl acetate (8 mL) solution of m-CPBA (65percent, 2.8 g, 10.6 mmol) was dropwise added thereto under ice-cooling. The resulting mixture was stirred at room temperature for 13 hours. The precipitated solid was collected by filtration under reduced pressure, washed with ethyl acetate, and dried under reduced pressure to give <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> 7N-oxide m-chlorobenzoate (1.25 g) containing m-chlorobenzoic acid in a molar ratio of 20percent (yield: 85percent).
Example 12; 1-Ethyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-1-yl)phenyl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 12a) 1-(4-nitrophenyl)-<strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> To a stirred solution of <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> (300 mg) in DMF (3.0 mL) was added sodium hydride (101 mg) (60percent in mineral oil) with ice-cooling. The mixture was stirred at room temperature for 30 min, and then 1-fluoro-4-nitrobenzene (355 mg) was added. After stirring at room temperature for 2 h, the mixture was warmed up to 50° C. The mixture was stirred at 50° C. for 12 h. Cesium carbonate (821 mg) was added and the mixture was stirred at 100° C. for 12 h, and treated with water and AcOEt. The insoluble material was filtered off. The organic layer was separated and the aqueous layer was extracted with AcOEt. The organic layer was combined, dried over MgSO4 and concentrated in vacuo. The residue was used for the next reaction.
N'-acetyl-4-amino-5-methyl-6-oxo-2-[1-(3,3,4.4.4-pentafluorobutyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carbohydrazide[ No CAS ]
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