[ CAS No. 63725-51-9 ] {[proInfo.proName]}

Name: 63725-51-9|6-Chloro-1H-pyrazolo[3,4-b]pyridine|98%
Brand: Ambeed
SKU: A182275
Price: 8.0 USD
Availability: InStock
Rating: 91 (30 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 63725-51-9

Structure of 63725-51-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 63725-51-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 63725-51-9 ]

SDS Specification

Alternatived Products of [ 63725-51-9 ]

Product Details of [ 63725-51-9 ]

CAS No. :	63725-51-9	MDL No. :	MFCD09832900
Formula :	C₆H₄ClN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NWYLBGYCSAJFCB-UHFFFAOYSA-N
M.W :	153.57	Pubchem ID :	45480283
Synonyms :

Calculated chemistry of [ 63725-51-9 ]

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 :	38.9
TPSA :	41.57 Å²

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) :	-5.97 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.09
Log Po/w (XLOGP3) :	1.78
Log Po/w (WLOGP) :	1.61
Log Po/w (MLOGP) :	1.18
Log Po/w (SILICOS-IT) :	2.24
Consensus Log Po/w :	1.58

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.58
Solubility :	0.404 mg/ml ; 0.00263 mol/l
Class :	Soluble
Log S (Ali) :	-2.27
Solubility :	0.822 mg/ml ; 0.00535 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.14
Solubility :	0.112 mg/ml ; 0.000728 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.63

Safety of [ 63725-51-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 63725-51-9 ]

* 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 [ 63725-51-9 ]
Downstream synthetic route of [ 63725-51-9 ]

[ 63725-51-9 ] Synthesis Path-Upstream 1~7

1
[ 924909-11-5 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Reference： [1] Patent: WO2016/4272, 2016, A1, . Location in patent: Paragraph 00851

2
[ 271-73-8 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Reference： [1] Patent: WO2016/4272, 2016, A1,

3
[ 1093880-37-5 ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With hydrazine hydrate In tetrahydrofuran at 60℃; for 5 h;	To the solution of 6-chloro-2-fluoropyridine-3-carboxaldehyde (4gm, 25.lmmol) in THF (30mL), was added hydrazine hydrate (2.5 15gm, 56.3mmol) and the reaction mixture was heated60°C for 5h. The reaction mixture was concentrated and quenched with ice water. The solid was filtered and dried under vacuum to obtain the title compound (3.5gm, 92percent).‘HNMR (DMSO-d6, 300MHz): ö 13.8 (s, 1H), 8.32-8.29 (d, 1H), 8.20 (s, 1H), 7.27-7.24 (d,1H). LCMS: 89.96percent, mlz = 153.9 (M+1).

Reference： [1] Patent: WO2017/9798, 2017, A1, . Location in patent: Page/Page column 66

4
[ 55304-73-9 ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrazine hydrate In butan-1-ol for 16.5 h; Reflux; Industrial scale	In n-butanol (6 L), 2,6-dichloro-3-pyridinecarboxaldehyde (1056 g, 6.0 mol, 1 eq.) was added and hydrazine hydrate (1060g, 18.0mol, 3eq., 85percent), stirred at room temperature for 0.5h. The mixture was warmed to reflux overnight (16 h), filtered and evaporated. The crude product is then beaten with water/isopropyl alcohol (ν/ν = 7:1), filtered and dried. The product 6-chloro-1 hydrogen-pyrazolo[3,4-B]pyridine (774 g, 5.0 mol) was obtained as a yellow powdery solid. The yield was 84percent and the purity was 98percent.

Reference： [1] Patent: CN108570049, 2018, A, . Location in patent: Paragraph 0022; 0023; 0025-0036
[2] Patent: WO2013/169964, 2013, A1,

5
[ 924909-11-5 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Reference： [1] Patent: WO2016/4272, 2016, A1, . Location in patent: Paragraph 00851

6
[ 2402-78-0 ]
[ 63725-51-9 ]

Reference： [1] Patent: WO2013/169964, 2013, A1,

7
[ 271-73-8 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Reference： [1] Patent: WO2016/4272, 2016, A1,

[ 63725-51-9 ] Synthesis Path-Downstream 1~88

1
1-[1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-(trifluoromethyl)-1H-benzimidazole [ No CAS ]
[ 63725-51-9 ]
6-{4-[1-[1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-(trifluoromethyl)-1H-benzimidazol-2-yl]phenyl}-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃;Inert atmosphere; Sealed vial;	Example 1606-{4-[l-[(3S)-l-(Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-(trifluoromethyl)- lH-benzimidazol-2-yl] phenyl}-lH-pyrazolo [3,4-6] pyridine1 - { [(3 S)- 1 -(Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -2-[4-(4,4, 5 ,5-tetramethyl- 1,3,2- dioxaborolan-2-yl)phenyl]-5-(trifluoromethyl)-lH-benzimidazole (120 mg, 0.167 mmol) was dissolved in 1,4-dioxane (1.5 mL) in a 5-mL microwave vial. 6-Chloro-lH- pyrazolo[3,4-b]pyridine (25.6 mg, 0.167 mmol), PdCi2(dppf)-CH2Ci2 adduct (6.81 mg, 8.34 umol), and potassium carbonate (0.250 mL, 0.501 mmol) were added with stirring. The vial was purged with nitrogen, sealed and heated at 100 C for 2 hours. An addtional aliquot of PdCl2(dppf)-CH2Cl2 adduct (6.81 mg, 8.34 umol) were added and the vial was again purged with nitrogen, sealed, and heated at 100 C overnight. The reaction mixture was allowed to cool to RT, and was diluted with water (50mL) and acidified to pH 7 with IN HC1. The reaction mixture was extracted with DCM (3 x 50mL), and the combined DCM layers were dried over MgSC^, filtered and evaporated to dryness. The crude product was purified by silica gel column chromatography using a gradient of 0-10% MeOH/DCM, followed by preparative reverse phase hplc using a gradient of 1%NH40H(aq)/acetonitrile to afford 15 mg of the titled compound as an off-white solid. (LCMS m/z 530.9, M+H).

Reference： [1]Patent: WO2011/56635,2011,A1 .Location in patent: Page/Page column 140-141

Yield	Reaction Conditions	Operation in experiment
40%	With hydrazine; In butan-1-ol; at 110℃;	General procedure: Hydrazine hydrate (4.7 mL, 97 mmol) was added to a solution of 2-fluoro-4-methoxy benzonitrile (2.9 g, 19.2 mmol) in n-butanol (120 mL). The resulting mixture was heated at 110ºC overnight. After cooling the reaction mixture in an ice-water bath, the resulting precipitate was filtered, washed with diethyl ether and dried to provide the title compound (2.88 g, 93%) as a white solid. LRMS (m/z): 164 (M+1)+. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.76 (s, 3 H), 5.20 (s, 2 H), 6.51 (dd, J=8.99, 1.95 Hz, 1 H), 6.62 (s, 1 H), 7.52 (d, J=8.60 Hz, 1 H), 11.13 (bs, 1 H).

3
[ 63725-51-9 ]
[ 1357946-70-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	N-Chlorosuccinimide (1.05 g, 5.93 mmol) was added to a solution of <strong>[63725-51-9]6-chloro-1H-pyrazolo[3,4-b]pyridine</strong> (example 91 a, 827 mg, 5.39 mmol) in DMF (19 mL). The mixture was stirred at room temperature. After 1 hour, water and ice were added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated. Purification of the residue by flash chromatography (8:2 hexanes/ethyl acetate) gave the title compound (0.86 g, 55%). LRMS (m/z): 232/234 (M+1)+, 230/232 (M-1)-. 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 7.27 (d, J=8.51 Hz, 1 H), 7.97 (d, J=8.51 Hz, 1 H), 11.05 (br. s., 1 H).

Reference： [1]Patent: EP2489663,2012,A1 .Location in patent: Paragraph 0772; 0773; 0774

4
[ 824-94-2 ]
[ 63725-51-9 ]
6-chloro-1-[(4-methoxyphenyl)methyl]pyrazolo[3,4-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In acetonitrile; at 60℃; for 1h;	6-Chloro-lH-pyrazolo[3,4-b]pyridine (1.05 g, 6.82 mmol) was dissolved in MeCN (25 ml) at rt. 4-Methoxybenzylchloride (1.69 ml, 11.6 mmol) was added followed by K2CO3 (2.83 g, 20.5 mmol) and the resulting mixture was stirred at 60 C for 1 h. Sat. aq. NaHCCb (30 ml) was added and the mixture extracted with DCM (3 x 30 ml). The combined organics were dried over Na2S04, filtered, concentrated and purified on a silica gel column eluted with 0-100% EtOAc in Heptane to give the product as a solid (1.9 g, quant.). MS ES+ m/z 274 [M+H]+.
57%	With potassium carbonate; In acetonitrile; at 60℃; for 1h;	A mixture of compound 1-4 (600 mg, 3.92 mmol, 1.0 eq.), l-(chloromethyl)-4- methoxybenzene (1044 mg, 6.67 mmol, 1.7 eq.), and potassium carbonate (1624 mg, 11.76 mmol, 3.0 eq) in acetonitrile (15 mL) was stirred at 60 C for 1 h. The mixture was diluted with aq. sodium bicarbonate (30 mL) and extracted with dichloromethane (3 x 30 mL). The combined organic phase was dried, concentrated and purified by flash column chromatography (petroleum ether : ethyl acetate = 5: 1) to provide compound 1-5 as a pale yellow oil (610 mg, yield: 57%). MS (ESI) m/z 274.0 [M+H]+.
44%	With potassium carbonate; In acetonitrile; at 60℃;	To a mixture of 6-chloro-1H-pyrazolo[3,4-bjpyridine (6.00 g, 39.1 mmol) and K2C03 (16.2 g,117 mmol) in CH3CN (30 mL) was added PMB-CI (10.4 g, 66.5 mmol). The mixture was heated to 60 C and stirred overnight. The mixture was directly concentrated in vacuum. The residue was purified by silica column (PE: EtOAc = 15:1)to give the desired product (4.8 g, yield 44%) as a yellow solid.D475 1H NMR (300 MHz, CDCI3): oe 7.99 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.33 (d, J 8.7 Hz,2H), 7.13(d, J 8.4 Hz, 1H), 6.84(d, J 8.7 Hz, 2H), 5.59 (s, 2H), 3.76 (s, 3H).LCMS: [mobile phase: 10-95% Acetonitrile +0.02% NH4OAc in 4 mm] Rt = 2.518 mm; MSCalcd.: 273; MS Found: 274 [M÷1].

Reference： [1]Patent: WO2019/126733,2019,A1 .Location in patent: Paragraph 0393
[2]Patent: WO2013/169964,2013,A1 .Location in patent: Paragraph 00254; 00258
[3]Patent: WO2017/12576,2017,A1 .Location in patent: Page/Page column 305

5
[ 2402-78-0 ]
[ 63725-51-9 ]

Reference： [1]Patent: WO2013/169964,2013,A1

6
[ 55304-73-9 ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrazine hydrate; In butan-1-ol; for 16.5h;Reflux; Industrial scale;	In n-butanol (6 L), 2,6-dichloro-3-pyridinecarboxaldehyde (1056 g, 6.0 mol, 1 eq.) was added and hydrazine hydrate (1060g, 18.0mol, 3eq., 85%), stirred at room temperature for 0.5h. The mixture was warmed to reflux overnight (16 h), filtered and evaporated. The crude product is then beaten with water/isopropyl alcohol (nu/nu = 7:1), filtered and dried. The product 6-chloro-1 hydrogen-pyrazolo[3,4-B]pyridine (774 g, 5.0 mol) was obtained as a yellow powdery solid. The yield was 84% and the purity was 98%.
21%	With hydrazine hydrate; In tert-butyl alcohol; at 120℃; for 8h;Inert atmosphere;	Compound 2,6-dichloronicotal aldehyde at room temperature50a (4.0g, 22.86mmol)To a solution of n-butanol (100 mL) was added hydrazine hydrate (3.3 mL, 68.57 mmol).Heat to 120 C and stir for 8 hours.The mixture was diluted with EtOAc (EtOAc) (EtOAc (EtOAc)The organic phase is dried over anhydrous sodium sulfate, and the desiccant is removed by filtration.Decomposition under reduced pressure to give crude product by flash column chromatography ( petroleum ether / ethyl acetate =100:0-7:1) get the target product6-Chloro-1H-pyrazolo[3,4-b]pyridine 50b (0.75 g, 4.90 mmol, yellow solid).Yield: 21%.

Reference： [1]Patent: CN108570049,2018,A .Location in patent: Paragraph 0022; 0023; 0025-0036
[2]Patent: CN109020957,2018,A .Location in patent: Paragraph 0214
[3]Patent: WO2013/169964,2013,A1

7
2,6-dichloro-3-(1,3-dioxolan-2-yl)pyridine [ No CAS ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
28.6%	With hydrazine hydrate; In butan-1-ol; at 150℃; for 1h;Sealed tube;	To a solution of compound 1-3 (3.0 g, 13.70 mmol, 1.0 eq) in butan-l-ol (8 mL) was added hydrazine hydrate (1.48 g, 24.66 mmol, 1.8 eq). The mixture was heated to 150 C and stirred for 1 h in a sealed tube. After cooling, the mixture was filtered and evaporated to give crude product, which was purified by silica gel column chromatography (dichloromethane: methanol = 10:1) to provide compound 1-4 as a yellow solid (600 mg, yield: 28.6%). MS (ESI) m/z 154[M+H]+.

Reference： [1]Patent: WO2013/169964,2013,A1 .Location in patent: Paragraph 00254; 00257

8
[ 63725-51-9 ]
4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-yloxy)butan-1-ol [ No CAS ]

Reference： [1]Patent: WO2013/169964,2013,A1

9
[ 63725-51-9 ]
4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-yloxy)butyl 4-methylbenzenesulfonate [ No CAS ]

Reference： [1]Patent: WO2013/169964,2013,A1

10
[ 63725-51-9 ]
6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3 ,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2013/169964,2013,A1

11
[ 63725-51-9 ]
6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1H-pyrazolo[3 ,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2013/169964,2013,A1

12
[ 63725-51-9 ]
[ 1259223-95-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-iodo-succinimide; In N,N-dimethyl-formamide; at 110℃; for 12h;	To a mixture of 6-chl oro-li-pyrazolo[3,4-/>]pyri dine (350.0 mg, 2.3 mmol, CAS 63725-51-9) in DMF (15.0 mL) was added NIS (764.0 mg, 3.4 mmol), and the resulting mixture was stirred at 110 C for 12 hours. The reaction mixture was then quenched with sat. Na2S03 (15.0 mL) and sat. NaHC03 (15.0 mL), stirred for 10 min, then H20 (15.0 mL) was added and the mixture was stirred for 5 min. The solid was then collected by filtration, washed with H20 (50.0 mL) and dried under reduced pressure to afford 6-chl oro-3 -i odo- 1 H- pyrazolo[3,4-/>]pyridine (580.0 mg, 91% yield) as a yellow solid. LC-MS (ESI+) m/z 279.8 (M+H)+.
0.7 g	With N-iodo-succinimide; In dichloromethane; acetonitrile; at 70℃; for 3h;	A mixture of <strong>[63725-51-9]6-chloro-1H-pyrazolo[3,4-b]pyridine</strong> (0.40 g, 2.6 mmol)(Ark Pharm Cat. No. AK-32412) and N-iodosuccinimide (0.64 g, 2.9 mmol) in methylene chloride (6 mL) and acetonitrile (3 mL) was stirred at 70 C. for 3 h. After cooling it was concentrated and the residue was treated with water. The precipitate was collected by filtration to afford the desired product (0.70 g). LCMS (M+H)+=279.9.
	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 3h;	Intermediate Gen-21-a: 6-Chloro-3-iodo-l-(4-methoxy-benzyl)-lH-pyrazolo [3, 4-bj 1 pyridine Step i: 6-Chloro-3-iodo-lH-pyrazolo[3,4-b]pyridine (Intermediate Gen-20-a) Intermediate Gen-19-a (5 g, 32.6 mmol, 1 eq) is dissolved in DMF (30 mL). I2 (16.4 g, 64.6 mol, 2 eq) and KOH (6.8 g, 121 mmol, 3.7 eq) are added. The reaction mixture is stirred at rt for 3h. Then the reaction is quenched with a 10% solution of Na2S203. The aqueous layer is extracted four times with 50 mL Et20, three times with DCM and three times with DCM/MeOH 9: 1. The combined organic layers are dried over Na2SO (, after washing with brine (50 mL), filtered and concentrated to afford Gen-20-a.

With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 3h;

Intermediate Gen-19-a (5 g, 32.6 mmol, 1 eq) is dissolved in DMF (30 mL). I2 (16.4 g, 64.6 mol, 2 eq) and KOH (6.8 g, 121 mmol, 3.7 eq) are added. The reaction mixture is stirred at rt for 3 h. Then the reaction is quenched with a 10% solution of Na2S2O3. The aqueous layer is extracted four times with 50 mL Et2O, three times with DCM and three times with DCM/ MeOH 9:1. The combined organic layers are dried over Na2SO4, after washing with brine (50 mL), filtered and concentrated to afford Gen-20-a.

Reference： [1]Patent: WO2019/183367,2019,A1 .Location in patent: Paragraph 0331
[2]Patent: US2014/171405,2014,A1 .Location in patent: Paragraph 0454
[3]Patent: WO2015/24905,2015,A1 .Location in patent: Paragraph 00300
[4]Patent: US2015/80391,2015,A1 .Location in patent: Paragraph 0582; 0583

13
[ 63725-51-9 ]
[ 1416714-43-6 ]

Reference： [1]Patent: US2014/171405,2014,A1
[2]Patent: WO2019/183367,2019,A1

14
[ 63725-51-9 ]
[ 1614234-26-2 ]

Reference： [1]Patent: US2014/171405,2014,A1

15
[ 63725-51-9 ]
[ 1614234-27-3 ]

Reference： [1]Patent: US2014/171405,2014,A1

16
[ 63725-51-9 ]
[ 1614233-32-7 ]

Reference： [1]Patent: US2014/171405,2014,A1

17
[ 63725-51-9 ]
C₂₃H₂₃F₂N₅O₃ [ No CAS ]

Reference： [1]Patent: US2014/171405,2014,A1

18
[ 63725-51-9 ]
6-chloro-3-iodo-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

19
[ 63725-51-9 ]
6-chloro-1-(4-methoxy-benzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

20
[ 63725-51-9 ]
6-chloro-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

21
[ 63725-51-9 ]
6-chloro-1-(4-methoxy-benzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

22
[ 63725-51-9 ]
2-bromo-1-[6-chloro-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-ethanol [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

23
[ 63725-51-9 ]
6-chloro-3-ethyl-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

24
[ 63725-51-9 ]
1-[6-chloro-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-ethanone [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

25
[ 63725-51-9 ]
3-trifluoromethyl-N-{3-[3-(1-hydroxy-2-morpholin-4-yl-ethyl)-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-benzamide [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1

26
[ 63725-51-9 ]
N-{3-[3-(1-hydroxy-2-morpholin-4-yl-ethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1

27
[ 63725-51-9 ]
3-dimethylamino-N-{3-[3-(1-hydroxy-2-morpholin-4-yl-ethyl)-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-benzamide [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

28
[ 63725-51-9 ]
1-[6-chloro-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-2-morpholin-4-yl-ethanol [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

29
[ 63725-51-9 ]
3-dimethylamino-N-{3-[3-(1-hydroxy-2-morpholin-4-yl-ethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-benzamide [ No CAS ]

Reference： [1]Patent: WO2015/24905,2015,A1
[2]Patent: US2015/80391,2015,A1

30
[ 63725-51-9 ]
N-{3-[3-(1-hydroxy-ethyl)-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-3,5-dimethoxy-benzamide [ No CAS ]

Reference： [1]Patent: US2015/80391,2015,A1

31
[ 63725-51-9 ]
N-{3-[3-acetyl-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-phenyl}-3,5-dimethoxy-benzamide [ No CAS ]

Reference： [1]Patent: US2015/80391,2015,A1

32
[ 63725-51-9 ]
N-[3-(3-ethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-4-methyl-phenyl]-3,5-dimethoxy-benzamide [ No CAS ]

Reference： [1]Patent: US2015/80391,2015,A1

33
[ 63725-51-9 ]
N-(3,5-dimethyl-phenyl)-3-[3-(1-hydroxy-2-morpholin-4-yl-ethyl)-1-(4-methoxy-benzyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-4-methyl-benzamide [ No CAS ]

Reference： [1]Patent: US2015/80391,2015,A1

34
[ 271-73-8 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Reference： [1]Patent: WO2016/4272,2016,A1

35
[ 924909-11-5 ]
[ 29274-28-0 ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; at 20 - 30℃; for 3h;	To a solution of lH-pyrazolo[3,4-Z?]pyridine 7-oxide (47.3 g, 0.31 mol) in ACN (250 mL) was added POCl3 (130 mL, 1.41 mol) dropwise to maintain the temperature below 30C. Stirred at r.t. for 3 hrs, the reaction mixture was quenched carefully with 20% NaOH aqueous solution (300 mL). The precipitate was collected by filtration and washed with H20, dried under high vacuum to give the crude product (a mixture of 4-Cl and 6-Cl isomers) (50 g) as a white solid. LC-MS (ESI): mlz (M+H)+, 154.1.

Reference： [1]Patent: WO2016/4272,2016,A1 .Location in patent: Paragraph 00851

36
[ 110-87-2 ]
[ 63725-51-9 ]
6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 4h;	Added to the dried 250mL round bottom flask 56 (10.00g, 51.0mmol), p-TSA (1.75g, 10.2mmol) and methylene chloride (100.0mL), was slowly added dropwise DHP (8.56g, 102.0mmol), room temperature stirring 4.0h. After completion of the reaction, the reaction solution was diluted with 100.0mL of water, 200 mL of dichloromethane and extracted two times the combined organic phase was dried over anhydrous sodium sulfate, the solvent was spin-dry the compound 57 (8.90g, 62%).
	With toluene-4-sulfonic acid; In dichloromethane; at 30℃; for 3h;	To a solution of <strong>[63725-51-9]6-chloro-1H-pyrazolo[3,4-b]pyridine</strong> (10 g, 65.1 mmol, 1.00 eq) in DCM (200 mL) was added 3,4-dihydro-2H-pyran (6.57 g, 78.1 mmol, 7.14 mL, 1.20 eq) followed by p-toluenesulfonic acid monohydrate (1.24 g, 6.51 mmol, 0.10 eq) and the reaction mixture was then stirred at 30C for 3 hrs. TLC (Petroleum ether: EtOAc = 1:1, Rf = 0.43) showed one new spot formed. The mixture was washed with sat.NaHCO3 (100 mL x2) and brine (100 mL), dried over Na2SO4, filtered and the filtrate was evaporated to give 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine (15 g, crude) as a yellow oil.

Reference： [1]Patent: CN105524048,2016,A .Location in patent: Paragraph 0363; 0364
[2]Patent: WO2018/13867,2018,A1 .Location in patent: Paragraph 567

37
[ 63725-51-9 ]
C₁₉H₂₁N₃O₃ [ No CAS ]

Reference： [1]Patent: CN105524048,2016,A

38
[ 63725-51-9 ]
C₁₉H₁₉Cl₂N₃O₃ [ No CAS ]

Reference： [1]Patent: CN105524048,2016,A

39
[ 63725-51-9 ]
[ 74-88-4 ]
[ 63725-52-0 ]
[ 1616099-29-6 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[63725-51-9]6-chloro-1H-pyrazolo[3,4-b]pyridine</strong> (1gm, 6.8 mmol) in THF (l0mL)added sodium hydride (65 8mg, l3mmol) and the mixturewas stined for 30mm at RT. Thereaction mixture was then cooled to 0C and methyl iodide (3.712gm, 26.lmmol) was addedwise into it and the reaction mixture was stined at room temperature for lh. The reactionquenched with ice water, extracted with EtOAc, washed with brine and dried over anhydrous Na2SO4. After concentration, the residue was purified by 60-120 silica gel columnchromatography and compound eluted using 40% ethyl acetate in hexane to give the title compound (800mg, 80%) along with 6-chloro- 1 -methyl-2H-pyrazolo[3 ,4-b]pyridine.?HNMR (400MHz, DMSO-d6): oe 8.49 (s, 1H), 8.29-8.26 (d, 1H), 7.13-7.11 (d, 1H), 4.18 (s, 3H).

Reference： [1]Patent: WO2017/9798,2017,A1 .Location in patent: Page/Page column 66

40
[ 1093880-37-5 ]
[ 63725-51-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With hydrazine hydrate; In tetrahydrofuran; at 60℃; for 5h;	To the solution of 6-chloro-2-fluoropyridine-3-carboxaldehyde (4gm, 25.lmmol) in THF (30mL), was added hydrazine hydrate (2.5 15gm, 56.3mmol) and the reaction mixture was heated60C for 5h. The reaction mixture was concentrated and quenched with ice water. The solid was filtered and dried under vacuum to obtain the title compound (3.5gm, 92%).?HNMR (DMSO-d6, 300MHz): oe 13.8 (s, 1H), 8.32-8.29 (d, 1H), 8.20 (s, 1H), 7.27-7.24 (d,1H). LCMS: 89.96%, mlz = 153.9 (M+1).

Reference： [1]Patent: WO2017/9798,2017,A1 .Location in patent: Page/Page column 66

41
[ 63725-51-9 ]
N-(2-methyl-2H-pyrazolo[3,4-b]pyridin-6-yl)acetamide [ No CAS ]