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Chemical Structure| 875781-17-2
Chemical Structure| 875781-17-2
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Product Details of [ 875781-17-2 ]

CAS No. :875781-17-2 MDL No. :MFCD05663982
Formula : C6H4BrN3 Boiling Point : -
Linear Structure Formula :- InChI Key :BASYLPMLKGQZOG-UHFFFAOYSA-N
M.W : 198.02 Pubchem ID :40427454
Synonyms :

Calculated chemistry of [ 875781-17-2 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 10
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 : 41.59
TPSA : 41.57 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
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) : 1.13
Log Po/w (XLOGP3) : 1.51
Log Po/w (WLOGP) : 1.72
Log Po/w (MLOGP) : 1.35
Log Po/w (SILICOS-IT) : 2.28
Consensus Log Po/w : 1.6

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.69
Solubility : 0.409 mg/ml ; 0.00207 mol/l
Class : Soluble
Log S (Ali) : -1.99
Solubility : 2.02 mg/ml ; 0.0102 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.4
Solubility : 0.0797 mg/ml ; 0.000403 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.68

Safety of [ 875781-17-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 875781-17-2 ]

* 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 [ 875781-17-2 ]
  • Downstream synthetic route of [ 875781-17-2 ]

[ 875781-17-2 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 875781-17-2 ]
  • [ 875781-18-3 ]
YieldReaction ConditionsOperation in experiment
97%
Stage #1: With iodine; potassium hydroxide In N,N-dimethyl-formamide for 3.5 h;
Stage #2: With iodine; sodium hydroxide In 1,4-dioxane at 40℃; for 23 h;
5-bromo-3 -iodo- 1 H-pyrazolo [3 ,4-bipyridine ( IV-A-I); To a stirred solution of the bromo-diazaindole III- A-I (1 g, 5.05 mmol) in DMF (14 mL) was added crushed KOH pellets (1.06 g, 19.03 mmol) in one portion. After 11 min, I2 (1.15 g, 4.54 mmol) was added and the mixture stirred vigorously for 3.5 h. The mixture was then partially concentrated in vacuo, diluted with EtOAc (40 mL): saturated NaHCO3 solution (20 mL) and partitioned. The aqueous layer was extracted with EtOAc (2 x 20 mL). The combined organic layers were dried (MgSO4), filtered and concentrated to afford a 1 :1 mixture of III-A-1 and IV-A-I (1.377 g). This mixture was re-dissolved in 1,4-dioxane (14 mL) and treated with solid NaOH (0.7 g). The mixture was stirred for 5 min at RT and I2 (0.7 g) was added. The mixture was stirred at 40 0C for 23 h, diluted with EtOAc (50 mL) and washed with saturated aqueous Na2S2O3 solution (30 mL). The aqueous layer was extracted with EtOAc (2 x 30 mL) and the combined organic extracts were dried (MgSO4), filtered and concentrated to afford azaindazole IV-A-I (1.585 g, 97percent). 1H NMR (400 MHz; CDCl3) δ 7.94 (d, J2.1, IH), 8.55 (d, J2.1, IH), 10.85 (brs, NH).
91% With iodine; sodium hydroxide In 1,4-dioxane; water at 60℃; To a solution of 5-bromo-lH-pyrazolo[3,4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in 1,4- dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The reaction mixture was extracted with EtOAc (100 ml x 2). The combined organic extracts were washed with saturated aqueous NaHS03 solution (100 mL x 3) and brine (50 mL), dried over Na2S04, filtered, and concentrated to give the title compound 5-bromo-3-iodo-lH- pyrazolo[3,4-b]pyridine as an off-white solid (7.5 g , yield:91percent).
91% With iodine; sodium hydroxide In 1,4-dioxane; water at 60℃; [0116] To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in a mixture of 1 ,4-dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The resulting mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The resulting mixture was extracted with EtOAc (100 ml x 2). The combined organic layers were washed with saturated aqueous NaHSO3 (100 mL x 3) and brine (50 mL), dried over Na2504, and concentrated to give the title compound 5-bromo-3-iodo-JH- pyrazolo[3,4-b]pyridine (II) as an off-white solid (7.5 g , yield:91percent), which was used in the next step without any further purification.
91% With iodine; sodium hydroxide In 1,4-dioxane; water at 60℃; To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in 1,4-dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The reaction mixture was extracted with EtOAc (100 ml x 2). The combined organics were washed with saturated aqueous NaHSO3 (100 mL x 3) and brine (50 mL), dried over Na2SO4, and concentrated to give the title compound 5-bromo-3-iodo-JH-pyrazolo[3,4- b]pyridine (II) as an off-white solid (7.5 g , yield:91percent), which was used in the next step without any further purification.
85.6%
Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 25℃; for 0.166667 h; Inert atmosphere
Stage #2: With iodine In N,N-dimethyl-formamide at 25℃; for 4 h; Inert atmosphere
To a solution of 5-Bromo-1H-pyrazolo[3,4-b]pyridine (2.0 g, 10.1 mmol) in DMF (20 mL) Potassium hydroxide (KOH, 1.2 g, 21.4 mmol) was added at 25 °C.
After stirring for 10 min, Iodine (2.8 g, 11.1 mmol) was added and stirred at 25 °C for 4 h.
The resulting mixture was diluted with water (30 mL), extracted with EtOAc (20 mL * 3).
The organic phase was washed with sat. Na2S2O3 solution (30 mL * 2), brine (30 mL * 2), dried over Na2SO4, and concentrated to give compound 39 as a brown solid (2.8 g, 85.6percent yield).
1H NMR (400 MHz, DMSO-d6) δ 14.30 (s, 1H, NH), 8.65 (s, 1H, Ar-H), 8.21 (s, 1H, Ar-H).
85.6%
Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.166667 h;
Stage #2: With iodine In N,N-dimethyl-formamide at 20℃; for 4 h;
The 5-bromo -1H-pyrazolo [3,4-b] pyridine (2.0g, 10 . 1mmol) adding 20mLN, in N-dimethyl formamide, stirring to dissolve, then adding flaky potassium hydroxide (1.2g, 21 . 4mmol), stir at room temperature the reaction 10 minutes, and then added with the solid iodine (2.8g, 11 . 1mmol), stir at room temperature the reaction 4 experimental, then water (30 ml) dilution, ethyl acetate (3×20 ml) extraction, then with saturated sodium thiosulfate solution (2×30 ml) and saturated salt water (2×30 ml) washing, the organic phase is dried with anhydrous sodium sulfate, concentrated. Then the solid plus dioxane (30 ml) is dissolved, add potassium hydroxide (1.2g, 21 . 4mmol), stir to react under room temperature for 10 minutes, then adding solid iodine (2.8g, 11 . 1mmol), stir at room temperature reaction sleepovers, water reaction is ended (30 ml) dilution, ethyl acetate (3×20 ml) extraction, then with saturated sodium thiosulfate solution (2×30 ml) and saturated salt water (2×30 ml) washing, the organic phase is dried with anhydrous sodium sulfate, concentrated to obtain pale brown solid (2.8g, 85.6percent).
77% With N-iodo-succinimide In 1,2-dichloro-ethane for 6 h; Heating / reflux Step 4: Synthesis of 5-bromo-3-iodo-lH-pyrazolo[3,4-b]pyridine.[0220] 5-bromo-17J-pyrazolo[3,4-b]pyridine (3.00 g, 15.2 mmol) and A'-iodosuccinimide(3.60 g, 16.0 mmol) were dissolved in anhydrous dichloroethane (100 mL). The resultingmixture was stirred under reflux conditions for 6 h, cooled to room temperature and dilutedwith THF (300 mL). The resulting solution was washed with a saturated aqueous solutionof sodium thiosulfate (100 mL) and brine, then dried over magnesium sulfate, filtered andconcentrated. The residue was titurated with a 1:1 mixture of dichloromethane and etherand then ether before being dried in vacuum to afford 5-bromo-3-iodo-l//-pyrazolo[3,4-bjpyridine (3.795 g, 77percent yield) as a beige-brown solid. ^-NMR (500 MHz, 6-DMSO) S14.31 (s, 1H), 8.65 (d, 1H), 8.20 (d, 1H). MS: m/z 323, 325 [MH+].
77% With N-iodo-succinimide In 1,2-dichloro-ethane for 6 h; Heating / reflux 5-bromo-1H-pyrazolo[3,4-b]pyridine (3.00 g, 15.2 mmol) and N-iodosuccinimide (3.60 g, 16.0 mmol) were dissolved in anhydrous dichloroethane (100 mL). The resulting mixture was stirred under reflux conditions for 6 h, cooled to room temperature and diluted with THF (300 mL). The resulting solution was washed with a saturated aqueous solution of sodium thiosulfate (100 mL) and brine, then dried over magnesium sulfate, filtered and concentrated. The residue was titurated with a 1:1 mixture of dichloromethane and ether and then ether before being dried in vacuum to afford 5-bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine (3.795 g, 77percent yield) as a beige-brown solid. 1H-NMR (500 MHz, d6-DMSO) δ 14.31 (s, 1H), 8.65 (d, 1H), 8.20 (d, 1H). MS: m/z 323, 325 [MH+].
75% With N-iodo-succinimide In 1,1-dichloroethaneHeating; Reflux N-Iodosuccinimide (8.1 g, 34.1 mmol) was added to a solution of 5- bromo-lH-pyrazolo[3,4-b]pyridine (4.5 g, 22.7 mmol) in dichloroethane (100 mL), and the reaction mixture was heated to reflux overnight. The reaction mixture was cooled to room temperature and diluted with THF (300 mL). The organic layers were washed with saturated Na2S2O3 (100 mL) and brine (100 mL). The organic layers were dried, filtered and concentrated to a solid. The crude product was triturated with DCM and ethyl acetate to give 5-bromo-3-iodo-lH-pyrazolo[3,4-b]pyridine (5.5 g, 75percent) as a solid.
70% With N-iodo-succinimide In 1,2-dichloro-ethaneReflux 5-Bromo-1H-pyrazolo[3,4-b]pyridine (19.7 g, 100 mmol) was dissolved in 150 mL of 1,2-dichloroethane, and N-iodosuccinimide (24.8 g) was added. , 110 mmol), heated to reflux overnight.After the reaction was completed, the sodium thiosulfate solution was added and stirred for 20 min, and a yellow solid was charged and analyzed, and the mixture was filtered under reduced pressure. The filter cake was washed thoroughly with petroleum ether and dried in vacuo.A yellow solid was obtained 22.7 g (Yield: 70percent).
41.3%
Stage #1: With iodine In N,N-dimethyl-formamide at 20℃; for 0.0833333 h;
Stage #2: With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 3 h;
Four grams of compound d and 10.25 g of iodine were dissolved into 50 ml N,N-dimethylformamide, stirred for 5 minutes at room temperature. Slowly, 2.83 g of potassium hydroxide was added into the above solution, and further stirred at room temperature for 3 hours, the reaction was completed. The reactant liquid was poured into 1000 ml water, solid was precipitated, filtered, the filter cake was washed three times by water immersion, vacuum dried to obtain compound e (m=1.35 g, yield: 41.3percent). (0183) 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=2.1 Hz, 1H), 7.93 (d, J=2.1 Hz, 1H).

Reference: [1] Patent: WO2010/15803, 2010, A1, . Location in patent: Page/Page column 43
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 5, p. 2513 - 2529
[3] Patent: WO2016/26078, 2016, A1, . Location in patent: Paragraph 065
[4] Patent: WO2016/192063, 2016, A1, . Location in patent: Paragraph 0112; 0115; 0116
[5] Patent: WO2017/28314, 2017, A1, . Location in patent: Paragraph 0125
[6] Bioorganic Chemistry, 2016, vol. 65, p. 146 - 158
[7] Patent: CN103613591, 2016, B, . Location in patent: Paragraph 0342-0344
[8] Patent: WO2006/15124, 2006, A2, . Location in patent: Page/Page column 59
[9] Patent: US2008/261921, 2008, A1, . Location in patent: Page/Page column 73-74
[10] Patent: WO2009/111279, 2009, A1, . Location in patent: Page/Page column 83
[11] Patent: CN108117553, 2018, A, . Location in patent: Paragraph 0278; 0279; 0280-0282
[12] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 5, p. 543 - 547
[13] Patent: US2016/137640, 2016, A1, . Location in patent: Paragraph 0181; 0182
[14] Patent: WO2015/25025, 2015, A1, . Location in patent: Page/Page column 130
[15] Patent: WO2016/192064, 2016, A1, . Location in patent: Paragraph 0118-0119
  • 2
  • [ 516-12-1 ]
  • [ 875781-17-2 ]
  • [ 875781-18-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 3, p. 879 - 894
  • 3
  • [ 2065-75-0 ]
  • [ 1225387-53-0 ]
  • [ 705263-10-1 ]
  • [ 875781-17-2 ]
YieldReaction ConditionsOperation in experiment
2.1% at 20℃; Heating / reflux A solution of 1 H-pyrazol-5-amine x79 (25 g, 1 eq, 0.3 mol) and bromomalonaldehyde x9 (45.4 g, 1 eq, 0.3 mol) ethanol (250 ml) is refluxed for 2 hours. After cooling, the reaction mixture is stirred at room temperature overnight. The solvent is removed under reduced pressure and the crude is purified using chiral chromatography affording 5-bromo-1H-pyrazolo[3,4-b]pyridine x80 (yield: 2.1 percent; LC-MS (MH+): 198/200) and 6-bromopyrazolo[1 ,5-a]pyrimidine x81 (yield: 13.8 percent; LC-MS (MH+): 198/200).
Reference: [1] Patent: WO2006/128692, 2006, A2, . Location in patent: Page/Page column 86
  • 4
  • [ 875781-15-0 ]
  • [ 875781-17-2 ]
YieldReaction ConditionsOperation in experiment
46% With hydrazine In ethanolHeating / reflux Preparation of 5-bromo-1H-pyrazolo[3,4-b]pyridine (D-1-3). <n="101"/>D-1-2 D"1-3A solution of compound D-1-2 (20 g, 0.1 mol) and anhydrous hydrazine (18 g, 0.56 mol) in ethanol was heated to reflux overnight. TLC (petroleum ether/EtOAc 2:1 ) indicated complete consumption of starting material. The reaction mixture was concentrated in vacuo to a volume of about 50 ml_ and poured into water (500 ml_), the resulting mixture was filtered. The cake was washed with water (50 ml_χ3) and ether (20 ml_χ3), then dried in vacuo to yield compound D-1-3 (9.0 g, 46percent) as a yellow solid.
40% With hydrazine hydrate In ethanol at 100℃; for 8 h; 5-Bromo-2-fluoro-pyridine-3-carbaldehyde (4.1g, 20mmol) obtained from Preparation Example 129-1 was dissolved in ethanol (50ml). After adding hydrazine hydrate (5.0ml, 100mmol), the mixture was stirred for 8 hours at 100 and then distilled under reduced pressure. Water was added thereto and the residue was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and filtered. Filtrate was distilled under reduced pressure and separated by column chromatography to obtain the title compound (1.8g, 40percent).[1499] NMR:1H-NMR(400HMz, CDCl3); δ 11.29 (br s, 1H), 8.63 (s, 1H), 8.26 (s, 1H), 8.07 (s, 1H)
135 g With hydrazine hydrate In ethanol at 75 - 80℃; for 12 h; To a stirred solution of 5-bromo-2-fluoronicotinaldehyde (XV) (250 g, 1.23 mol, 1.0 eq) in EtOH (2.50 L) was added hydrazine hydrate (221 g, 4.41 mol, 3.6 eq) at 25°C. The reaction was then heated to 75~80°C and stirred for 12 h. The solvent was removed under reduced pressure at 45°C. The residual crude solid was triturated in water (750 mL) and EtOH (250 mL). The resultant suspension was filtered and washed with ethanol to give 5 -bromo- lH-pyrazolo[3,4- b]pyridine (XVI) (135 g, 0.68 mol, 55.4percent yield) as yellowish solid which was used directly for the next step without further purification. ESIMS found for CeLLtBrNs mlz 199.1 (M+H).
135 g With hydrazine hydrate In ethanol at 25 - 80℃; for 12 h; To a stirred solution of 5-bromo-2-fluoronicotinaldehyde (XV) (250 g, 1.23mol, 1.0 eq) in EtOH (2.50 L) was added hydrazine hydrate (221 g, 4.41 mol, 3.6 eq) at 25°C. The reaction was then heated to 7580°C and stirred for 12 h. The solvent was removed under reduced pressure at 45°C. The residual crude solid was triturated in water (750 mL) and EtOH (250 mL). The resultant suspension was filtered and washed with ethanol to give 5-bromo-1H- pyrazolo[3,4-bjpyridine (XVI) (135 g, 0.68 mol, 55.4percent yield) as yellowish solid which was used directly for the next step without further purification. ESIMS found for C6H4BrN3 mlz 199.1 (M+H).

Reference: [1] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7420 - 7427
[2] Patent: WO2009/16460, 2009, A2, . Location in patent: Page/Page column 99-100
[3] Patent: WO2014/73904, 2014, A1, . Location in patent: Paragraph 1496-1499
[4] Patent: CN103980272, 2016, B, . Location in patent: Paragraph 0031; 0033
[5] Patent: WO2017/23987, 2017, A1, . Location in patent: Paragraph 0610; 0612
[6] Patent: WO2017/23981, 2017, A1, . Location in patent: Paragraph 0610; 0612
[7] Patent: WO2017/23973, 2017, A1, . Location in patent: Paragraph 0633
[8] Patent: WO2017/23996, 2017, A1, . Location in patent: Paragraph 0612
  • 5
  • [ 875781-16-1 ]
  • [ 875781-17-2 ]
Reference: [1] Patent: US2008/261921, 2008, A1, . Location in patent: Page/Page column 73-74
  • 6
  • [ 1083326-08-2 ]
  • [ 875781-17-2 ]
Reference: [1] Patent: US2008/293706, 2008, A1, . Location in patent: Page/Page column 85
  • 7
  • [ 2065-75-0 ]
  • [ 1225387-53-0 ]
  • [ 705263-10-1 ]
  • [ 875781-17-2 ]
YieldReaction ConditionsOperation in experiment
2.1% at 20℃; Heating / reflux A solution of 1 H-pyrazol-5-amine x79 (25 g, 1 eq, 0.3 mol) and bromomalonaldehyde x9 (45.4 g, 1 eq, 0.3 mol) ethanol (250 ml) is refluxed for 2 hours. After cooling, the reaction mixture is stirred at room temperature overnight. The solvent is removed under reduced pressure and the crude is purified using chiral chromatography affording 5-bromo-1H-pyrazolo[3,4-b]pyridine x80 (yield: 2.1 percent; LC-MS (MH+): 198/200) and 6-bromopyrazolo[1 ,5-a]pyrimidine x81 (yield: 13.8 percent; LC-MS (MH+): 198/200).
Reference: [1] Patent: WO2006/128692, 2006, A2, . Location in patent: Page/Page column 86
  • 8
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  • [ 1225387-53-0 ]
  • [ 875781-17-2 ]
YieldReaction ConditionsOperation in experiment
25% for 6 h; Heating; Reflux; Inert atmosphere of N2 lH-Pyrazol-5-amine (5.3 g, 64 mmol) and 2-bromomalonaldehyde(9.9 g, 64 mmol) were suspended in acetic acid (100 mL). The reaction mixture was heated <n="82"/>to reflux under N2 for 6 hours. The reaction mixture was cooled to room temperature and concentrated to give a solid. The crude solids were suspended in MeOH (200 mL) and absorbed onto silica gel (200 g). The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1), hexanes/ethyl acetate (2:1) to give 5-bromo-lH- pyrazolo[3,4-b]pyridine as a solid (3.1 g, 25percent).
Reference: [1] Patent: WO2009/111279, 2009, A1, . Location in patent: Page/Page column 79-80
  • 9
  • [ 1820-80-0 ]
  • [ 2065-75-0 ]
  • [ 875781-17-2 ]
YieldReaction ConditionsOperation in experiment
11% for 2 h; Heating / reflux Preparation 6; 5 -Bromo- 1 H-pyrazolo [3 ,4-b] pyridine; Dissolve 2-bromomalonaldehyde (Aldrich; 2.5 g, 16.5 mmol) and3-aminopyrazole (Aldrich; 1.38 g, 16.5 mmol) in glacial acetic acid (25 mL) and reflux under nitrogen for 2 h. Concentrate under reduced pressure and dissolve the residue in absolute methanol (150 mL), vacuum filter through a pad of diatomaceous earth and concentrate under reduced pressure. Purify via chromatography (silica gel, hexane to 50percent ethyl acetate/50percent hexane) to obtain 365 mg (11percent) of the title compound as a light EPO <DP n="25"/>yellow solid. TOF MS ES+ exact mass calculated for C6H5N3Br (p+H): m/z =197.9667, Found: 197.9674.
Reference: [1] Patent: WO2006/52568, 2006, A2, . Location in patent: Page/Page column 23-24
  • 10
  • [ 766-11-0 ]
  • [ 875781-17-2 ]
Reference: [1] Patent: WO2014/73904, 2014, A1,
[2] Patent: CN103980272, 2016, B,
[3] Patent: WO2017/23987, 2017, A1,
[4] Patent: WO2017/23981, 2017, A1,
[5] Patent: WO2017/23973, 2017, A1,
[6] Patent: WO2017/23996, 2017, A1,
  • 11
  • [ 875781-17-2 ]
  • [ 74-88-4 ]
  • [ 887115-56-2 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 0.5 h; Inert atmosphere
Stage #2: at 25℃; Inert atmosphere
Step 1
5-bromo-1-methyl-1H-pyrazolo[3,4-b]pyridine (Compound 4-2)
Sodium hydride (720 mg, 30 mmol) was added into a 100 ml reaction flask, and anhydrous THF (40 mL) was added to the reaction flask.
After stirring at 0° C. for 5 min, the reaction substrate 5-bromo-1H-pyrazolo[3,4-b]pyridine (4.0 g, 20 mmol, commercially available) was dissolved in THF (20 ml), and the resulting solution was slowly added dropwise to the reaction flask through the constant pressure funnel, and stirred for 30 min.
Afterwards, iodomethane (1.6 ml, 26 mmol) was added dropwise to the reaction system.
After completion of the addition, the reaction solution was slowly warmed to room temperature and stirred overnight.
The reaction progress was monitored by TLC.
After completion of the reaction, 10 ml of ice water was added to the reaction system to quench the reaction, THF was removed by concentration under reduced pressure, and the residue was extracted with dichloromethane (60 ml) and water (20 ml*3).
The organic layer was dried over anhydrous Na2SO4, and concentrated under reduced pressure to give 4.1 g brown solid, which was separated and purified by Combi-flash chromatography [PE:EA=10:90-40:60] to give the title compound 4-2 (3.1 g, 73percent). MS m/z (ESI): 211.9 [M+H]+.
Reference: [1] Patent: US2017/8889, 2017, A1, . Location in patent: Paragraph 0165; 0166
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  • [ 875781-17-2 ]
  • [ 74-88-4 ]
  • [ 887115-56-2 ]
Reference: [1] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6334 - 6353
[2] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6334 - 6353
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  • [ 875781-17-2 ]
  • [ 952182-02-4 ]
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2692 - 2703
[2] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7420 - 7427
  • 14
  • [ 875781-17-2 ]
  • [ 1257628-77-5 ]
Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 3, p. 879 - 894
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Chemical Structure| 916326-37-9

[ 916326-37-9 ]

5-Bromo-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde

Similarity: 0.83

Related Parent Nucleus of
[ 875781-17-2 ]

Other Aromatic Heterocycles

Chemical Structure| 405224-24-0

[ 405224-24-0 ]

5-Bromo-1H-pyrazolo[3,4-b]pyridin-3-amine

Similarity: 0.94

Chemical Structure| 885223-65-4

[ 885223-65-4 ]

5-Bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine

Similarity: 0.90

Chemical Structure| 856859-49-9

[ 856859-49-9 ]

4-Bromo-1H-pyrazolo[3,4-b]pyridine

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Chemical Structure| 887115-56-2

[ 887115-56-2 ]

5-Bromo-1-methyl-1H-pyrazolo[3,4-b]pyridine

Similarity: 0.87

Chemical Structure| 271-73-8

[ 271-73-8 ]

1H-Pyrazolo[3,4-b]pyridine

Similarity: 0.85