[ CAS No. 1101120-05-1 ] {[proInfo.proName]}

Name: 1101120-05-1|3-Formylpyrazolo[1,5-a]pyridine-5-carbonitrile|97%
Brand: Ambeed
SKU: A275693
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Quality Control of [ 1101120-05-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1101120-05-1 ]

Product Details of [ 1101120-05-1 ]

CAS No. :	1101120-05-1	MDL No. :	MFCD22067049
Formula :	C₉H₅N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AWKQMXSIHPOEGN-UHFFFAOYSA-N
M.W :	171.16	Pubchem ID :	25171436
Synonyms :

Calculated chemistry of [ 1101120-05-1 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	45.29
TPSA :	58.16 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) :	-7.17 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.21
Log Po/w (XLOGP3) :	0.24
Log Po/w (WLOGP) :	1.02
Log Po/w (MLOGP) :	0.15
Log Po/w (SILICOS-IT) :	1.02
Consensus Log Po/w :	0.73

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.5
Solubility :	5.43 mg/ml ; 0.0317 mol/l
Class :	Very soluble
Log S (Ali) :	-1.02
Solubility :	16.3 mg/ml ; 0.0951 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.12
Solubility :	1.31 mg/ml ; 0.00767 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.67

Safety of [ 1101120-05-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1101120-05-1 ]

* 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 [ 1101120-05-1 ]
Downstream synthetic route of [ 1101120-05-1 ]

[ 1101120-05-1 ] Synthesis Path-Upstream 1~4

1
[ 1101120-03-9 ]
[ 68-12-2 ]
[ 1101120-05-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: at 20℃; for 2 h; Inert atmosphere Stage #2: With sodium hydroxide In water	General procedure: These were made by decarboxylation/Vilsmeier or hydrolysis/reduction/reoxidation as detailed below, unless otherwise stated.Decarboxylation was carried out by refluxing a solution of the ester (1 equiv) in 40percent aqueous H₂SO₄ (3 mL) for 18 h. The solution was then cooled in ice and neutralised to pH 7 with 6 M NaOH, then extracted twice with CH₂Cl₂. The combined extracts were dried (Na₂SO₄) and the solvent removed in vacuo to leave the decarboxylated material. The pyrazolo[1,5-a]pyridine was then reacted under Vilsmeier conditions in dry DMF (2 mL) with POCl₃ (3 equiv) at 0 °C under an atmosphere of N₂. The reaction mixture was then warmed to room temperature and stirred for 2 h. The solution was poured onto ice, basified to pH 10 with 1 M NaOH, stirred for 1 h then extracted twice with CH₂Cl₂. The combined extracts were washed twice with water, dried (Na₂SO₄) and the solvent removed in vacuo to leave the aldehyde.Alternatively, the ester was hydrolysed by refluxing a solution of the ester (1 equiv) in 1 M NaOH (3 equiv) and EtOH (5 mL) for 6 h. The EtOH was removed in vacuo, and then the aqueous residue acidified to pH 1 with 1 M HCl. The precipitated carboxylic acid was filtered off, washed with water and dried. The carboxylic acid was reduced by adding CDI (1.5 equiv) to a suspension of carboxylic acid (1 equiv) in dry THF (10 mL) under an atmosphere of N₂. After stirring for 18 h, the resulting solution was added dropwise to a solution of NaBH₄ (5 equiv) in H₂O (10 mL) and stirred for 30 min. The reaction was then quenched by the addition of 1 M HCl and stirred for a further 30 min. The solution was neutralised with saturated aqueous NaHCO₃ and extracted twice with CH₂Cl₂. The combined organic layers were dried (Na₂SO₄) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient) gave the alcohol. Reoxidation was carried out by stirring a suspension of the pyrazolo[1,5-a]pyridine-3-methanol (1 equiv) and MnO₂ (10 equiv) in CH₂Cl₂ (2 mL) at room temperature for 4 days. The reaction mixture was then filtered through celite, washed with CH₂Cl₂, and the solvent removed from the filtrate in vacuo to leave the aldehyde.

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 69 - 85
[2] Patent: WO2009/8748, 2009, A1, . Location in patent: Page/Page column 43; 60

2
[ 1101120-00-6 ]
[ 1101120-05-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 69 - 85
[2] Patent: WO2009/8748, 2009, A1,

3
[ 104468-87-3 ]
[ 1101120-05-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 69 - 85
[2] Patent: WO2009/8748, 2009, A1,

4
[ 2459-09-8 ]
[ 1101120-05-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 69 - 85

[ 1101120-05-1 ] Synthesis Path-Downstream 1~78

1
[ 1101120-03-9 ]
[ 68-12-2 ]
[ 1101120-05-1 ]

Yield	Reaction Conditions	Operation in experiment
77%		General procedure: These were made by decarboxylation/Vilsmeier or hydrolysis/reduction/reoxidation as detailed below, unless otherwise stated.Decarboxylation was carried out by refluxing a solution of the ester (1 equiv) in 40% aqueous H2SO4 (3 mL) for 18 h. The solution was then cooled in ice and neutralised to pH 7 with 6 M NaOH, then extracted twice with CH2Cl2. The combined extracts were dried (Na2SO4) and the solvent removed in vacuo to leave the decarboxylated material. The pyrazolo[1,5-a]pyridine was then reacted under Vilsmeier conditions in dry DMF (2 mL) with POCl3 (3 equiv) at 0 C under an atmosphere of N2. The reaction mixture was then warmed to room temperature and stirred for 2 h. The solution was poured onto ice, basified to pH 10 with 1 M NaOH, stirred for 1 h then extracted twice with CH2Cl2. The combined extracts were washed twice with water, dried (Na2SO4) and the solvent removed in vacuo to leave the aldehyde.Alternatively, the ester was hydrolysed by refluxing a solution of the ester (1 equiv) in 1 M NaOH (3 equiv) and EtOH (5 mL) for 6 h. The EtOH was removed in vacuo, and then the aqueous residue acidified to pH 1 with 1 M HCl. The precipitated carboxylic acid was filtered off, washed with water and dried. The carboxylic acid was reduced by adding CDI (1.5 equiv) to a suspension of carboxylic acid (1 equiv) in dry THF (10 mL) under an atmosphere of N2. After stirring for 18 h, the resulting solution was added dropwise to a solution of NaBH4 (5 equiv) in H2O (10 mL) and stirred for 30 min. The reaction was then quenched by the addition of 1 M HCl and stirred for a further 30 min. The solution was neutralised with saturated aqueous NaHCO3 and extracted twice with CH2Cl2. The combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient) gave the alcohol. Reoxidation was carried out by stirring a suspension of the pyrazolo[1,5-a]pyridine-3-methanol (1 equiv) and MnO2 (10 equiv) in CH2Cl2 (2 mL) at room temperature for 4 days. The reaction mixture was then filtered through celite, washed with CH2Cl2, and the solvent removed from the filtrate in vacuo to leave the aldehyde.
		Step 5.3: 1 ,1 '-Carbonyldiimidazole (2.40 g, 14.8 mmol) was added to a suspension of 15 (1.60 g, 9.9 mmol)in dry THF (50 mL) under an atmosphere of N2 and stirred for 18 h. The solution was then poured into concentrated NH3 (30 mL) at 0 0C and stirred for 2 h. After 2 h, the solvent was removed in vacuo. The crude pyrazolo[1 ,5-a]pyridine-5- carboxamide (16) was taken up in dry DMF (50 mL) and cooled to 00C, then POCI3 (17.5 mL, 0.19 mol) was added. After 30 min the ice bath was removed and the reaction stirred for a further 18 h at room temperature. The solution was then poured onto ice, basified to pH 10 with 6M NaOH, stirred for 1 h and extracted twice with CH2CI2. The combined extracts were washed twice with water, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with hexanes: EtOAc 3:1 to 2:1 to 1 :1) gave 3-formylpyrazolo- [1 ,5-a]pyridine-5-carbonitrile (17) as a pale yellow solid (927 mg, 55%). 1H NMR delta (400 MHz, CDCI3) 10.12 (s, 1H), 8.70 (m, 1 H), 8.66 (d, J 7.1 Hz, 1 H), 8.52 (s, 1H), 7.19 (dd, J 7.1 , 1.7 Hz, 1H). LCMS (APCI+) 172 (MH+, 100%).

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85
[2]Patent: WO2009/8748,2009,A1 .Location in patent: Page/Page column 43; 60

2
[ 1101120-05-1 ]
[ 302-15-8 ]
2-fluoro-5-nitrobenzene-1-sulfonyl chloride [ No CAS ]
[ 1101118-97-1 ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.
82%		Example 55: lambdaT-((5-Cyanopyrazolo[1 ,5-a]pyridin-3-yl)methylene)-2-fluoro-W-methyl- 5-nitrobenzenesulfonohydrazide (E55). A suspension of 3-formylpyrazolo[1 ,5-a]pyridine-5-carbonitrile (17) (250 mg, 1.46 mmol), methylhydrazine sulfate (200 mg, 1.75 mmol) and 2,6-lutidine (1.02 mL, 8.76 mmol) in MeOH (30 mL) was stirred for 1h until all solid had dissolved. A solution of 2-fluoro-5- nitrobenzenesulfonyl chloride (455 mg, 1.90 mmol) [A. Courtin, HeIv. Chim. Acta 1982, 65(2), 546] in CH2CI2 (2 mL) was added, and the reaction stirred for a further 2h. The precipitate was filtered off, washed with a little MeOH and dried to leave lambdaT-((5- cyanopyrazolo[1 ,5-a]pyridin-3-yl)methylene)-2-fluoro-lambda/-methyl-5- <n="87"/>nitrobenzenesulfonohydrazide (E55) as a yellow solid (485 mg, 82%). 1H NMR delta (400 MHz, CDCI3) 8.93 (dd, J 5.8, 2.9 Hz, 1 H), 8.53 (dd, J 7.2, 1.0 Hz, 1 H), 8.49 (ddd, J 9.0, 4.0, 2.9 Hz, 1 H), 8.30 (dd, J 1.8, 1.0 Hz, 1 H), 8.19 (s, 1 H), 7.98 (s, 1 H), 7.40 (t, J 8.9 Hz, 1 H), 7.01 (dd, J 7.2, 1.8 Hz, 1 H), 3.46 (d, J 1.6 Hz, 3H). LCMS (APCI+) 403 (MH+, 100%). Anal. Calcd for C16H11FN6O4S: C, 47.76; H, 2.76; N, 20.89. Found C, 48.04; H, 2.97; N, 20.69.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68
[2]Patent: WO2009/8748,2009,A1 .Location in patent: Page/Page column 85-86

3
[ 109-84-2 ]
[ 1101120-05-1 ]
[ 121-02-8 ]
[ 1101118-62-0 ]

Yield	Reaction Conditions	Operation in experiment
60%		2-Hydroxyethylhydrazine (134 mg, 1.76 mmol) was added to a solution of aldehyde 2 (200 mg, 1.17 mmol) in MeOH (30 mL). After 1 h, 2,6-lutidine (0.27 mL, 2.3 mmol) and 2-methyl-5-nitrobenzenesulfonyl chloride (413 mg, 1.75 mmol) were added and the reaction mixture stirred for a further 1.5 h. The precipitated product was filtered off, washed with a little MeOH and dried to leave 5 as a yellow solid (302 mg, 60%). 1H NMR delta (400 MHz, d6-DMSO) 8.96 (dd, J = 7.2, 1.0 Hz, 1H), 8.73 (d, J = 2.5 Hz, 1H), 8.45-8.38 (m, 3H), 8.08 (dd, J = 1.9, 1.0 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.32 (dd, J = 7.2, 1.9 Hz, 1H), 5.05 (t, J = 5.8 Hz, 1H), 3.99 (t, J = 5.8 Hz, 2H), 3.68 (q, J = 5.8 Hz, 2H), 2.69 (s, 3H). LC-MS (APCI+) 429 (MH+, 100%). Anal. Calcd for C18H16N6O5S: C, 50.46; H, 3.76; N, 19.62. Found C, 50.09; H, 3.86; N, 19.27.
55%		Example 38: lambdaT-((5-Cyanopyrazolo[1 ,5-a]pyridin-3-yl)methylene)-/V-(2-hydroxyethyl)-2-methyl-5-nitrobenzenesulfonohydrazide (E38).2-Hydroxyethylhydrazine (27 mg, 0.35 mmol) was added to a solution of 3-formylpyrazolo-[1 ,5-a]pyridine-5-carbonitrile (17) (30 mg, 0.18 mmol) in MeOH (10 ml_). After 2 h, NaHCO3 (59 mg, 0.70 mmol) and 2-methyl-5-nitrobenzenesulfonyl chloride (83 mg, 0.35 mmol) were added and the reaction mixture stirred for a further 3 h. The solvent was removed in vacuo and the residue taken up in CH2CI2 and water. The layers were separated and the aqueous phase extracted with CH2CI2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with hexanes: EtOAc 2:1 to 1 :1 to EtOAc) gave /V-((5-cyanopyrazolo[1 ,5-a]pyridin-3- yl)methylene)-lambda/-(2-hydroxyethyl)-2-methyl-5-nitrobenzenesulfonohydrazide (E38) as a yellow solid (41 mg, 55%). 1H NMR delta (400 MHz, d6-DMSO) 8.96 (dd, J 7.2, 1.0 Hz, 1 H), 8.73 (d, J 2.5 Hz, 1 H), 8.45 - 8.38 (m, 3H), 8.08 (dd, J 1.9, 1.0 Hz, 1 H), 7.77 (d, J 8.4 Hz, 1 H), 7.32 (dd, J 7.2, 1.9 Hz, 1 H), 5.05 (t, J 5.8 Hz, 1 H), 3.99 (t, J 5.8 Hz, 2H), 3.68 (q, J 5.8 Hz, 2H), 2.69 (s, 3H). LCMS (APCI+) 429 (MH+, 100%). Anal. Calcd for C18H16N6O5S: C, 50.46; H, 3.76; N, 19.62. Found C, 50.09; H, 3.86; N, 19.27.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68
[2]Patent: WO2009/8748,2009,A1 .Location in patent: Page/Page column 79

4
[ 1101120-05-1 ]
[ 53516-95-3 ]
[ 1101118-71-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	In methanol; at 20℃; for 18h;	General procedure: A solution of the aldehyde or ketone (1 equiv) and 2-methyl-5-nitrobenzenesulfonohydrazide (1.1 equiv) in MeOH (5 mL) was refluxed for 18 h unless otherwise stated. After cooling to room temperature, the precipitated solid was filtered off, washed with a little MeOH and dried.
91%	In methanol; for 18h;	Example 42: lambdaT-((5-Cyanopyrazolo[1 ,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitro- benzenesulfonohydrazide (E42). 3-Formylpyrazolo[1 ,5-a]pyridine-5-carbonitrile (17) (150 mg, 0.88 mmol) and 2-methyl-5- nitrobenzenesulfonohydrazide (45) (213 mg, 0.92 mmol) were stirred in MeOH (30 mL) for <n="82"/>18h. The precipitate was filtered off and dried to leave /V-((5-cyanopyrazolo[1 ,5-a]pyridin- 3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide (E42) as a yellow solid (305 mg, 91%). 1H NMR delta (400 MHz, d6-DMSO) 11.99 (s, 1 H), 8.94 (dd, J 7.2, 0.9 Hz, 1H), 8.72 (d, J 2.5 Hz, 1 H), 8.42 (s, 1 H), 8.38 (dd, J 8.4, 2.5 Hz, 1 H), 8.20 (s, 1H), 8.10 (dd, J 1.9, 0.9 Hz, 1 H), 7.73 (d, J 8.4 Hz, 1 H), 7.31 (dd, J 7.2, 1.9 Hz, 1 H), 2.77 (s, 3H). LCMS (APCI+) 385 (MH+, 100%). Anal. Calcd for C16H12N6O4S: C, 50.00; H, 3.15; N, 21.86. Found C, 50.21 ; H, 3.15; N, 21.80.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85
[2]Patent: WO2009/8748,2009,A1 .Location in patent: Page/Page column 80-81
[3]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

5
[ 1101120-05-1 ]
[ 1101120-82-4 ]
[ 1101119-63-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	In methanol; for 72h;	A solution of 2-(chloromethyl)-1-methyl-4-nitrobenzene20 (7) (200 mg, 1.08 mmol) and methylhydrazine (0.28 mL, 5.3 mmol) in EtOH (6 mL) was refluxed for 1 h. The solvent was removed in vacuo, then taken up in CH2Cl2, washed with 1 M aqueous NaOH, dried (Na2SO4) and the solvent removed in vacuo to leave 1-methyl-1-(2-methyl-5-nitrobenzyl)hydrazine (8) as a yellow oil (210 mg, 100%). 1H NMR delta (400 MHz, CDCl3) 8.20 (d, J = 2.5 Hz, 1H), 8.04 (dd, J = 8.3, 2.5 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H), 3.65 (s, 2H), 3.00 (br s, 2H), 2.57 (s, 3H), 2.47 (s, 3H). LC-MS (APCI+) 196 (MH+, 100%). A suspension of 2 (30 mg, 0.18 mmol) and 8 (35 mg, 0.18 mmol) was stirred in MeOH (10 mL) for 3 days. The precipitate was filtered off and dried to leave 9 as a yellow solid (40 mg, 66%). 1H NMR delta (400 MHz, CDCl3) 8.45 (dd, J = 7.2, 0.9 Hz, 1H), 8.27 (dd, J = 1.8, 0.9 Hz, 1H), 8.18 (d, J = 2.4 Hz, 1H), 8.12 (dd, J = 8.3, 2.4 Hz, 1H), 8.07 (s, 1H), 7.49 (s, 1H), 7.41 (d, J = 8.3 Hz, 1H), 6.86 (dd, J = 7.2, 1.8 Hz, 1H), 4.50 (s, 2H), 2.95 (s, 3H), 2.51 (s, 3H). LC-MS (APCI+) 349 (MH+, 100%). Anal. Calcd for C18H16N6O2: C, 62.06; H, 4.63; N, 24.12. Found C, 61.76; H, 4.57; N, 24.06.
66%	In methanol; for 72h;	Step 84.2: A suspension of 17 (30 mg, 0.18 mmol) and 64 (Z = 2-Me, 5-NO2) (35 mg, 0.18 mmol) was stirred in MeOH (10 mL) for 3 days. The precipitate was filtered off and dried to leave 3-((2-methyl-2-(2-methyl-5-nitrobenzyl)hydrazono)methyl)pyrazolo[1 ,5-a]pyridine- 5-carbonitrile (E84) as a yellow solid (40 mg, 66%). 1H NMR delta (400 MHz, CDCI3) 8.45 (dd, J 7.2, 0.9 Hz, 1 H), 8.27 (dd, J 1.8, 0.9 Hz, 1 H), 8.18 (d, J 2.4 Hz, 1 H), 8.12 (dd, J 8.3, 2.4 Hz, 1 H), 8.07 (s, 1 H), 7.49 (s, 1 H), 7.41 (d, J 8.3 Hz, 1 H), 6.86 (dd, J 7.2, 1.8 Hz, 1 H), 4.50 (s, 2H), 2.95 (s, 3H), 2.51 (s, 3H). LCMS (APCI+) 349 (MH+, 100%). Anal. Calcd for C18H16N6O2: C, 62.06; H, 4.63; N, 24.12. Found C, 61.76; H, 4.57; N, 24.06.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68
[2]Patent: WO2009/8748,2009,A1 .Location in patent: Page/Page column 96

6
[ 1101120-05-1 ]
[ 1101118-73-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68
[2]Patent: WO2009/8748,2009,A1

7
[ 1101120-05-1 ]
[ 1101118-79-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

8
[ 1101120-05-1 ]
[ 1101118-77-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68
[2]Patent: WO2009/8748,2009,A1

9
[ 1101120-05-1 ]
[ 1101118-81-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

10
[ 1101120-05-1 ]
[ 1101118-83-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

11
[ 1101120-05-1 ]
[ 1101118-75-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

12
[ 1101120-05-1 ]
[ 1353889-44-7 ]
[ 1353889-36-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

13
[ 1101120-05-1 ]
[ 1353889-44-7 ]
[ 302-15-8 ]
[ 1353889-35-6 ]

Yield	Reaction Conditions	Operation in experiment
69%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

14
[ 1101120-05-1 ]
[ 372198-41-9 ]
[ 302-15-8 ]
[ 1101118-46-0 ]

Yield	Reaction Conditions	Operation in experiment
74%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

15
[ 1101120-05-1 ]
[ 372198-49-7 ]
[ 302-15-8 ]
[ 1101118-28-8 ]

Yield	Reaction Conditions	Operation in experiment
48%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of 3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

16
[ 1101120-05-1 ]
[ 491850-53-4 ]
[ 302-15-8 ]
[ 1101118-32-4 ]

Yield	Reaction Conditions	Operation in experiment
49%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

17
[ 1101120-05-1 ]
[ 34981-38-9 ]
[ 302-15-8 ]
[ 1353889-40-3 ]

Yield	Reaction Conditions	Operation in experiment
46%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

18
[ 1101120-05-1 ]
[ 69321-56-8 ]
[ 302-15-8 ]
[ 1101118-42-6 ]

Yield	Reaction Conditions	Operation in experiment
62%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

19
[ 1101120-05-1 ]
[ 2548-29-0 ]
[ 302-15-8 ]
[ 1353889-37-8 ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of 3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

20
[ 1101120-05-1 ]
[ 21320-90-1 ]
[ 302-15-8 ]
[ 1101118-38-0 ]

Yield	Reaction Conditions	Operation in experiment
59%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

21
[ 1101120-05-1 ]
[ 2224-67-1 ]
[ 302-15-8 ]
[ 1101118-48-2 ]

Yield	Reaction Conditions	Operation in experiment
87%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

22
[ 1101120-05-1 ]
[ 19040-62-1 ]
[ 302-15-8 ]
[ 1353889-39-0 ]

Yield	Reaction Conditions	Operation in experiment
70%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

23
[ 1101120-05-1 ]
[ 445-05-6 ]
[ 302-15-8 ]
[ 1101118-40-4 ]

Yield	Reaction Conditions	Operation in experiment
78%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

24
[ 1101120-05-1 ]
[ 81118-92-5 ]
[ 302-15-8 ]
[ 1101118-56-2 ]

Yield	Reaction Conditions	Operation in experiment
77%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

25
[ 1101120-05-1 ]
[ 56682-04-3 ]
[ 302-15-8 ]
[ 1353889-32-3 ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

26
[ 1101120-05-1 ]
[ 56202-22-3 ]
[ 302-15-8 ]
[ 1353889-33-4 ]

Yield	Reaction Conditions	Operation in experiment
45%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

27
[ 1101120-05-1 ]
[ 13632-07-0 ]
[ 302-15-8 ]
[ 1353889-34-5 ]

Yield	Reaction Conditions	Operation in experiment
67%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

28
[ 1101120-05-1 ]
[ 62533-48-6 ]
[ 302-15-8 ]
[ 1101118-58-4 ]

Yield	Reaction Conditions	Operation in experiment
29%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

29
[ 1101120-05-1 ]
[ 64688-68-2 ]
[ 302-15-8 ]
[ 1101119-61-2 ]

Yield	Reaction Conditions	Operation in experiment
63%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

30
[ 1101120-05-1 ]
2-isopropyl-5-nitrobenzenesulfonyl chloride [ No CAS ]
[ 302-15-8 ]
[ 1101118-52-8 ]

Yield	Reaction Conditions	Operation in experiment
55%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

31
[ 1101120-05-1 ]
[ 302-15-8 ]
[ 89189-34-4 ]
[ 1101118-50-6 ]

Yield	Reaction Conditions	Operation in experiment
92%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

32
[ 1101120-05-1 ]
[ 302-15-8 ]
[ 4533-95-3 ]
[ 1101118-54-0 ]

Yield	Reaction Conditions	Operation in experiment
27%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

33
[ 1101120-05-1 ]
[ 302-15-8 ]
[ 121-51-7 ]
[ 1101118-24-4 ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

34
[ 1101120-05-1 ]
[ 302-15-8 ]
[ 121-90-4 ]
[ 1101119-59-8 ]

Yield	Reaction Conditions	Operation in experiment
90%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

35
[ 1101120-05-1 ]
[ 302-15-8 ]
[ 133-59-5 ]
[ 1101118-34-6 ]

Yield	Reaction Conditions	Operation in experiment
81%		General procedure: These were made using NaHCO3 or 2,6-lutidine as detailed below, unless otherwise stated. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of <strong>[1101120-05-1]3-formylpyrazolo[1,5-a]pyridine-5-carbonitrile</strong> (2) (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography or trituration then afforded the hydrazides. Alternatively, methylhydrazine sulfate (1.2 equiv) and 2,6-lutidine (5 equiv) were added to a solution of 2 (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, sulfonyl chloride or acyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The hydrazide was then filtered off, washed with MeOH and dried.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 58 - 68

36
[ 2459-09-8 ]
[ 1101120-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85

37
[ 1101120-05-1 ]
[ 1101118-09-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85

38
[ 1101120-05-1 ]
[ 302-15-8 ]
C₁₀H₉N₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In methanol;	General procedure: Unless otherwise stated, sulfonohydrazides 5 were made by the following method. Methylhydrazine sulfate (1.2 equiv) and NaHCO3 (5 equiv) were added to a solution of aldehyde (1 equiv) in MeOH (5 mL). After all of the aldehyde was consumed, 2-methyl-5-nitrobenzenesulfonyl chloride (1.3 equiv) was added and the reaction mixture stirred for a further 30 min. The solvent was removed in vacuo and the residue taken up in CH2Cl2 and water. The layers were separated and the aqueous phase extracted with CH2Cl2, then the combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient, unless otherwise stated) afforded 5.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85

39
[ 1101120-00-6 ]
[ 1101120-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85
[2]Patent: WO2009/8748,2009,A1

40
[ 104468-87-3 ]
[ 1101120-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85
[2]Patent: WO2009/8748,2009,A1

41
[ 1101120-05-1 ]
[ 91188-13-5 ]
tert-butyl 1-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methyl)azetidin-3-ylcarbamate [ No CAS ]