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[ CAS No. 271-73-8 ] {[proInfo.proName]}

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Chemical Structure| 271-73-8
Chemical Structure| 271-73-8
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Product Details of [ 271-73-8 ]

CAS No. :271-73-8 MDL No. :MFCD05663981
Formula : C6H5N3 Boiling Point : -
Linear Structure Formula :- InChI Key :GVLRTOYGRNLSDW-UHFFFAOYSA-N
M.W : 119.12 Pubchem ID :2755850
Synonyms :
Chemical Name :1H-Pyrazolo[3,4-b]pyridine

Calculated chemistry of [ 271-73-8 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 33.89
TPSA : 41.57 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.44 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.79
Log Po/w (XLOGP3) : 0.82
Log Po/w (WLOGP) : 0.96
Log Po/w (MLOGP) : 0.56
Log Po/w (SILICOS-IT) : 1.67
Consensus Log Po/w : 0.96

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.84
Solubility : 1.74 mg/ml ; 0.0146 mol/l
Class : Very soluble
Log S (Ali) : -1.28
Solubility : 6.32 mg/ml ; 0.0531 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.49
Solubility : 0.387 mg/ml ; 0.00325 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.43

Safety of [ 271-73-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 271-73-8 ]

* 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 [ 271-73-8 ]
  • Downstream synthetic route of [ 271-73-8 ]

[ 271-73-8 ] Synthesis Path-Upstream   1~18

  • 1
  • [ 271-73-8 ]
  • [ 68618-36-0 ]
YieldReaction ConditionsOperation in experiment
86% With bromine In chloroform at 20℃; 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 ]
YieldReaction ConditionsOperation 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 ]
YieldReaction ConditionsOperation 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] Patent: WO2012/83117, 2012, A1, . Location in patent: Page/Page column 126
  • 4
  • [ 63682-46-2 ]
  • [ 271-73-8 ]
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
  • 5
  • [ 6752-16-5 ]
  • [ 271-73-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 13, p. 4763 - 4772
[2] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
  • 6
  • [ 63682-42-8 ]
  • [ 271-73-8 ]
Reference: [1] Monatshefte fuer Chemie, 1988, vol. 119, p. 597 - 604
  • 7
  • [ 36404-88-3 ]
  • [ 116854-97-8 ]
  • [ 271-73-8 ]
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 ]
YieldReaction ConditionsOperation 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
  • 17
  • [ 271-73-8 ]
  • [ 875781-18-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1243 - 1245
[2] Patent: WO2006/130673, 2006, A1,
  • 18
  • [ 271-73-8 ]
  • [ 956010-88-1 ]
Reference: [1] Patent: WO2011/149921, 2011, A1,
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