[ CAS No. 101820-69-3 ] {[proInfo.proName]}

Name: 101820-69-3|Ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate|97%
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Quality Control of [ 101820-69-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 101820-69-3 ]

CAS No. :	101820-69-3	MDL No. :	MFCD13183145
Formula :	C₁₁H₁₂N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SFCNXCZZKZRJLZ-UHFFFAOYSA-N
M.W :	204.23	Pubchem ID :	11171725
Synonyms :

Calculated chemistry of [ 101820-69-3 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.27
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	55.86
TPSA :	43.6 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) :	-6.16 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.26
Log Po/w (XLOGP3) :	1.95
Log Po/w (WLOGP) :	1.44
Log Po/w (MLOGP) :	0.96
Log Po/w (SILICOS-IT) :	1.44
Consensus Log Po/w :	1.61

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.51
Solubility :	0.624 mg/ml ; 0.00306 mol/l
Class :	Soluble
Log S (Ali) :	-2.49
Solubility :	0.66 mg/ml ; 0.00323 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.98
Solubility :	0.215 mg/ml ; 0.00105 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.2

Safety of [ 101820-69-3 ]

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 [ 101820-69-3 ]

* 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 [ 101820-69-3 ]
Downstream synthetic route of [ 101820-69-3 ]

[ 101820-69-3 ] Synthesis Path-Upstream 1~8

1
[ 504-29-0 ]
[ 13176-46-0 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
94.1%	at 20 - 70℃; for 3.5 h;	(1) 10.83 g (51.8 mmol) of 4-bromo-acetoacetic acid ethyl ester and 0.97 g of a reaction accelerator M were placed in a 100 ml three-necked flask equipped with a mixed solvent of water and 1,4-dioxane and stirred at room temperature for 15 Minute, then 2-aminopyridine5.36 g (57 mmol) was stirred at 70 ° C for 3.5 hours. TLC was monitored until ethyl 4-bromo-acetoacetate was complete, filtered,The mixture was concentrated under reduced pressure, extracted with water (50 mL × 3 times) and washed with saturated brine (50 mL × 3 times). The combined organic phases were reducedThe solvent was removed by pressure and dried to give 10.17 g of a pale yellow oil, which was obtained as ethyl 2- (imidazo [1,2-a] pyridin-3-yl) acetate in a yield of 94.1percent and a purity of 97.9percent The agent M consists of zinc nitrate and glycine in a weight ratio of 7: 1, mixed and dissolvedA mixture of 10 ml of water and 20 ml of 1,4-dioxane.

Reference： [1] Patent: CN105175446, 2017, B, . Location in patent: Paragraph 0038; 0039; 0040; 0045; 0050; 0055; 0064; 0066

2
[ 504-29-0 ]
[ 638-07-3 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
92.8%	With copper(I) triflate; triethylamine In ethanol at 55 - 60℃;	Dissolve 23.5 g (250 mmol) of 2-aminopyridine with 100 mL of absolute ethanol, add 35.4 g of triethylamine, 2.4 g of copper trifluoromethanesulfonate to the solution, and add dropwise 100 mL of absolute ethanol to the solution 47.3 while stirring. g ethyl 4-chloroacetoacetate, heated to 55-60° C., reacted for 4-5 hours, TLC (developer: chloroform:methanol=2:1) was used to monitor the reaction solution to 2-aminopyridine.The spots disappeared, and 1percent citric acid solution was added to the solution until the pH of the solution was 7.6. The insolubles were removed by filtration and the filtrate was extracted with ethyl acetate. The organic layer was collected, dried, filtered and concentrated to give a pale yellow viscous liquid. 47.4 g, yield 92.8percent (calculated as 2-aminopyridine), purity 97.57percent, impurity 2-(imidazo[1,2-a]pyridin-2-yl)acetic acid ethyl ester 0.43percent (HPLC normalization method) .

Reference： [1] Patent: CN104945436, 2017, B, . Location in patent: Paragraph 0035; 0036; 0037; 0038; 0039; 0040; 0041; 0042

3
[ 504-29-0 ]
[ 59006-06-3 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
94.7%	Stage #1: With zinc(II) nitrate; glycine In 1,4-dioxane; water at 20℃; for 0.25 h; Stage #2: at 85℃; for 5 h;	(1) 14.19 g of ethyl 3,4-dibromo-butyrate (51.8 mmol) and 1.14 g of a reaction accelerator A were added to a 100 ml three-necked flask containing a mixed solvent of water and 1,4-dioxane. After stirring at room temperature for 15 minutes, 6.43 g (67.34 mmol) of 2-aminopyridine was added and the reaction was stirred at 85°C for 5 hours. TLC monitored that the reaction was complete with ethyl 3,4-dibromo-butyrate, filtered, and concentrated under reduced pressure. Water was added and the mixture was extracted with ethyl acetate (50 mL×3 times). The organic phases were combined and the solvent was removed under reduced pressure. The resulting mixture was dried to give 10.2 g of a pale yellow oil, which was 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid. The ethyl ester has a yield of 94.7percent and a purity of 98.2percent. Among them, the reaction accelerator A consists of zinc nitrate and glycine in a weight ratio of 4.5:1. The mixed solvent is a mixture of 15 ml of water and 30 ml of 1,4-dioxane

Reference： [1] Patent: CN105153232, 2017, B, . Location in patent: Paragraph 0040; 0043-0045; 0050; 0055; 0060

4
[ 504-29-0 ]
[ 19255-60-8 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With toluene-4-sulfonic acid In water; acetonitrile for 2 h; Reflux Stage #2: for 16 h; Reflux	Imidazo[1,2-α]pyridin-3-yl-acetic acid ethyl ester (0038) Heat a mixture of 4,4-dimethoxy-but-2-enoic acid ethyl ester (43.5 g, 250 mmol) and p-toluenesulfonic acid (4.75 g, 25 mmol) in acetonitrile (240 mL) and water (15 mL) at reflux for 2 hours. Cool the reaction mixture to room temperature and add 2-aminopyridine (18.8 g, 200 mmol). Heat the mixture at reflux for 16 hours then cool to room temperature. Dilute the reaction mixture with ethyl acetate (1200 mL) and wash sequentially with saturated aqueous sodium bicarbonate (600 mL×3) and saturated aqueous sodium chloride (600 mL×2). Dry the organic phase over sodium sulfate and concentrate under reduced pressure to provide the desired compound as a brown oil (30 g, 73percent). ¹H-NMR(300 MHz, CDCl₃): δ 8.06 (d, J= 6.6 Hz, 1H), 7.63 (d, J= 9.1 Hz, 1H), 7.56 (s, 1H), 7.20 (dd, J= 8.9, 6.8 Hz, 1H), 6.84 (t, J= 6.7 Hz, 1H), 4.17 (q, J= 7.3 Hz, 2H), 3.93 (s, 2H), 1.25 (t, J= 7.3 Hz, 3H).

Reference： [1] Patent: EP2173348, 2015, B1, . Location in patent: Paragraph 0038

5
[ 2568-30-1 ]
[ 504-29-0 ]
[ 75-05-8 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
82.9%	Stage #1: With triethylamine In tetrahydrofuranReflux	This Comparative Example was prepared according to the method provided in CN102875602B Preparation of 2- (imidazo [1,2-a] pyridin-3-yl)Ethyl acetate. details as follows: will2-Chloromethyl- [l, 3] -dioxlopentan-2-yl(51.8 mmol) and 6.72 g of 2-aminopyridine were dissolved in tetrahydrofuran, stirred well, and 8.4 g of triethylamine was slowly added dropwise. The mixture was heated to reflux and the reaction mixture was checked by TLC (ethyl acetate: methanol = 70: 30) - chloromethyl- [1,3] -dioxlopentan-2-yl disappeared,50ml of water was added, and then the reaction solution was adjusted to pH 3.0 with 1N hydrochloric acid, the reaction was stirred at room temperature for 1 hour,Then warmed to reflux for 3 hours, then the reaction solution was concentrated under reduced pressure to dryness,The concentrate was dissolved in 500 ml of ethyl acetate,Then, the organic material was washed with 25 ml × 3 water, the organic matter was concentrated,The concentrate was refluxed with 25 ml of acetonitrile, filtered, and crystallized at 0 ° C to give 9.11 g of pale yellow needle crystal, namely ethyl 2- (imidazo [1,2-a] pyridin-3-yl) acetate, yield 82.9 percent, Purity 96.3percent.

Reference： [1] Patent: CN105175446, 2017, B, . Location in patent: Paragraph 0073; 0074; 0075

6
[ 504-29-0 ]
[ 2960-66-9 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	at 80℃; for 6 h;	Preparation 109; 2-(Imidazo [1, 2-a] pyridin-3-yl) acetamide; Add ethyl (E) -oxybutenoate (14.3g, 111.66 mmol) to 2-aminopyridine (10.0 g, 106.4 mmol) in acetonitrile (270 ml). Heat the reaction at 80°C for 6 hours. Concentrate the reaction mixture under reduced pressure. Purify the resulting oil by flash chromatography, eluting with a gradient of 100percent hexane to 95percent ethyl acetate: methanol to provide imidazo [1, 2-a] pyridin-3-yl-acetic acid ethyl ester (10.95g, 50.0percent) as a brown solid. lH-NMR (400 MHz, DMSO-d6): S 8.3 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H) Bubble ammonia through a solution of (imidazo [1, 2-a] pyridin-3-yl) acetic acid ethyl ester (10.0 g, 48.96 mmol) in methanol (30 ml) at 0°C. Heat the reaction mixture in a sealed tube at 100°C for 2 hours. Concentrate the reaction mixture under reduced pressure. Triturate with ethyl acetate to give the title compound as a white solid. ESMS: m/z = 176.1 (M++1)
50 %Spectr.	at 80℃; for 6 h;	PREPARATION 85; 2- (Imidazo [1, 2-a] pyridin-3-yl) acetamide; a) Imidazo [1, 2-a] pyridin-3-ylacetic acid ethyl ester; Add ethyl (E) oxybutenoate (14.3g, 111.66 mmol) to 2-amino pyridine (10.0 g, 106.4 mmol) in acetonitrile (270 ml). Heat the reaction at 80°C for 6 hours. Concentrate the reaction mixture under reduced pressure. Purification of the resulting oil by flash chromatography and eluting with a gradient from 100percent hexane to 95percent ethyl acetate: methanol gives the title compound, Imidazo [1, 2-a] pyridin-3-ylacetic acid ethyl ester (10.95g, 50.0percent-determined by NMR) and 2-aminopyridine (co-elution), as a brown solid. 1H NMR (400 MHz, DMSO-d6) 83 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H).

Reference： [1] Patent: WO2003/76442, 2003, A1, . Location in patent: Page/Page column 53-54
[2] Journal of Medicinal Chemistry, 2004, vol. 47, # 16, p. 3934 - 3937
[3] Patent: WO2003/76398, 2003, A2, . Location in patent: Page/Page column 34
[4] Patent: CN106831873, 2017, A, . Location in patent: Paragraph 0021-0023; 0026-0028; 0031-0033
[5] Patent: US2018/214458, 2018, A1, . Location in patent: Paragraph 0326-0327
[6] Patent: CN104725422, 2018, B, . Location in patent: Paragraph 0017; 0027-0030
[7] Patent: WO2018/125746, 2018, A1, . Location in patent: Paragraph 0239

7
[ 504-29-0 ]
[ 101820-69-3 ]

Reference： [1] Patent: WO2003/76442, 2003, A1, . Location in patent: Page/Page column 77

8
[ 504-29-0 ]
[ 19255-60-8 ]
[ 101820-69-3 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 4, p. 899 - 903

[ 101820-69-3 ] Synthesis Path-Downstream 1~57

1
[ 504-29-0 ]
[ 2960-66-9 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
50.0%	In acetonitrile; at 80℃; for 6h;Product distribution / selectivity;	Preparation 109; 2-(Imidazo [1, 2-a] pyridin-3-yl) acetamide; Add ethyl (E) -oxybutenoate (14.3g, 111.66 mmol) to 2-aminopyridine (10.0 g, 106.4 mmol) in acetonitrile (270 ml). Heat the reaction at 80C for 6 hours. Concentrate the reaction mixture under reduced pressure. Purify the resulting oil by flash chromatography, eluting with a gradient of 100% hexane to 95% ethyl acetate: methanol to provide imidazo [1, 2-a] pyridin-3-yl-acetic acid ethyl ester (10.95g, 50.0%) as a brown solid. lH-NMR (400 MHz, DMSO-d6): S 8.3 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H) Bubble ammonia through a solution of (imidazo [1, 2-a] pyridin-3-yl) acetic acid ethyl ester (10.0 g, 48.96 mmol) in methanol (30 ml) at 0C. Heat the reaction mixture in a sealed tube at 100C for 2 hours. Concentrate the reaction mixture under reduced pressure. Triturate with ethyl acetate to give the title compound as a white solid. ESMS: m/z = 176.1 (M++1)
50%Spectr.	In acetonitrile; at 80℃; for 6h;	PREPARATION 85; 2- (Imidazo [1, 2-a] pyridin-3-yl) acetamide; a) Imidazo [1, 2-a] pyridin-3-ylacetic acid ethyl ester; Add ethyl (E) oxybutenoate (14.3g, 111.66 mmol) to 2-amino pyridine (10.0 g, 106.4 mmol) in acetonitrile (270 ml). Heat the reaction at 80C for 6 hours. Concentrate the reaction mixture under reduced pressure. Purification of the resulting oil by flash chromatography and eluting with a gradient from 100% hexane to 95% ethyl acetate: methanol gives the title compound, Imidazo [1, 2-a] pyridin-3-ylacetic acid ethyl ester (10.95g, 50.0%-determined by NMR) and 2-aminopyridine (co-elution), as a brown solid. 1H NMR (400 MHz, DMSO-d6) 83 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H).
	In methanol; at 85℃; for 0.5h;	(1) 92 g of 2-aminopyridine was added to 1000 g of anhydrous ethanol, and 110 g of trans-4-oxy-2-butenoic acid ethyl ester was added dropwise to carry out the reaction. After about 30 minutes, the mixture was heated to 85±5C. The reaction is completed and the reaction is completed. After cooling to room temperature, ethyl 2-(imidazo[1,2-a]-3-yl)acetate is formed and hydrolyzed by adding 1000 g of 10% NaOH to obtain 2-(imidazo[1,2]). -a]-3-yl) acetic acid;

	In acetonitrile; at 80℃; for 6h;	To a solution of intermediate 1 (20 g, 213 mmol) in MeCN (540 ml) was ethyl (E)-4-oxo-butenoate (28.6 g, 223 mmol). The reaction mixture was heated to 80 C. and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Dichloromethane/MeOH from 1:0 to 200:1) to give the crude intermediate 2 (25 g) as brown solid.
	at 60 - 80℃;	2-aminopyridine 100.0gMix with 70.0 g of trans-4-oxo-2-butenoic acid ethyl ester,Stirring, temperature control 60~80C reaction for 6-8h, TLC detection of the end of the reaction,Cool down to room temperature, add 600.0ml of 10% potassium hydroxide aqueous solution, warm to 40~50 C, stir the reaction for 1-2 hours, cool to 25 C, slowly add 5% hydrochloric acid about 50ml, adjust PH6-7, stir Crystal 2-4h,After suction filtration, the filter cake was dissolved in 300 ml of 10% potassium hydroxide solution at room temperature, and dilute hydrochloric acid was added to adjust PH6-7 to stir and crystallize.Filter by suction, filter cake 50~60. (: Vacuum drying for 3-6 h gave 70.0 g of a white solid, yield 72.0%.
	In acetonitrile; at 80℃; for 6h;	To a solution of intermediate 1 (20 g, 213 mnmoi) in MeCN (540 ml) was ethyl (E)-4. oxobutenoate (28.6 g, 22.3 mmol). The reaction mixture was heated to 80 C and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Dichloromethane/MeOH from 1:0 to 200:1) to give the crude intermediate 2 (25 g) as brown solid.
	In acetonitrile; at 80℃; for 6h;	j0285j To a solution of intermediate 1 (20 g, 213 mmol) in MeCN (540 mL) was ethyl (E)-4-oxo-butenoate (28.6 g, 223 mmol). The reaction mixture was heated to 80 C and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Dichloromethane/MeOH from 1:0 to 200:1) to give the cmde intermediate 2 (25 g) as brown solid.
	In acetonitrile; at 80℃; for 6h;	To a solution of 2-aminopyridine (20 g, 213 mmol) in acetonitrile (540 mL) was ethyl (E)-4-oxo-butenoate (28.6 g, 223 mmol). The reaction mixture was heated to 80 C and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Diehl oromethane/MeOH from 1 :0 to 200: 1) to give the crude ethyl 2-(imidazo[l,2-a]pyridin-3- yl)acetate (25 g) as brown solid.
	In acetonitrile; at 80℃; for 6h;	To a solution of intermediate 1 (20 g, 213 mmol) in MeCN (540 mL) was ethyl (E)-4-oxo-butenoate (28.6 g, 223 mmol). The reaction mixture was heated to 80C. and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Dichloromethane/MeOH from 1:0 to 200:1) to give the crude intermediate 2 (25 g) as brown solid.
	In acetonitrile; at 80℃; for 6h;	To a solution of 2-aminopyridine (20 g, 213 mmol) in acetonitrile (540 mL) was ethyl (E)-4-oxo-butenoate (28.6 g, 223 mmol). The reaction mixture was heated to 80 C. and stirred for 6 hrs. The reaction mixture was concentrated under reduced pressure, the residue was purified by flash column chromatography (eluted with Dichloromethane/MeOH from 1:0 to 200:1) to give the crude ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate (25 g) as brown solid. To a solution of intermediate 23 (1.8 g, 5.2 mmol) in DMF (18 mL) was added CDI (0.9 g, 5.5 mmol), the mixture was stirred at 50 C. for 16 hrs. The reaction was cooled to 0 C., ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate (1.1 g, 5.5 mmol) and NaH (0.6 g, 15.6 mmol) were added, and the reaction was stirred at 30 C. for 6 hrs. The mixture was poured into water and the product extracted into ethyl acetate. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The crude product was purified by silica gel chromatography to give intermediate 24 (0.7 g, 25.9%) as pink solid. 1HNMR (DMSO-d6, 400 MHz): δ (ppm) 8.65 (s, 1H), 8.468.48 (d, 1H, J=6.8 Hz), 7.737.76 (m, 1H), 7.62 (s, 1H), 7.56-7.58 (d, 1H, J=9.2 Hz), 7.257.29 (m, 1H), 7.09 (dd, 1H, J=2.4 Hz, J=9.6 Hz), 6.97 (t, 1H), 6.37 (s, 1H), 4.734.64 (ab quart, 2H), 4.50 (t, 2H, J=5.2 Hz), 4.174.23 (m, 2H), 3.843.90 (m, 2H), 3.02 (bs, 4H), 1.49 (bs, 6H), 1.18 (t, 3H, J=7.2 Hz).

Reference： [1]Patent: WO2003/76442,2003,A1 .Location in patent: Page/Page column 53-54
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937
[3]Patent: WO2003/76398,2003,A2 .Location in patent: Page/Page column 34
[4]Patent: CN106831873,2017,A .Location in patent: Paragraph 0021-0023; 0026-0028; 0031-0033
[5]Patent: US2018/214458,2018,A1 .Location in patent: Paragraph 0326-0327
[6]Patent: CN104725422,2018,B .Location in patent: Paragraph 0017; 0027-0030
[7]Patent: WO2018/125746,2018,A1 .Location in patent: Paragraph 0239
[8]Patent: WO2018/191350,2018,A1 .Location in patent: Paragraph 0274; 0284; 0285
[9]Patent: WO2019/126686,2019,A1 .Location in patent: Paragraph 0300
[10]Patent: US2020/121681,2020,A1 .Location in patent: Paragraph 0349; 0359-0360
[11]Patent: US2020/316089,2020,A1 .Location in patent: Paragraph 0341; 0350

2
[ 101820-69-3 ]
[ 21801-86-5 ]

Yield	Reaction Conditions	Operation in experiment
58.2%	With ammonia; In methanol; at 0 - 100℃; for 2h;	b) 2-(Imidazo [1, 2-a] pyridin-3-yl) acetamide Bubble ammonia through a solution of (Imidazo [1, 2-a] pyridin-3-yl) acetic acid ethyl ester (10.0 g, 48.96 mmol) in methanol (30 ml) at 0C. Heat the reaction mixture in a sealed tube at 100C for 2 hours. Concentrate the reaction mixture under reduced pressure. Tituration in ethyl acetate to gives the title compound (5. 0g, 58. 2%), as a white solid. ESMS (M++1) : 176.1 m/z.
35%	In NH3/MeOH;	Amide Formation Heat a solution of imidazo[1,2-a]pyridin-3-yl-acetic acid ethyl ester (30 g, 147 mmol) in NH3/MeOH (7 N solution, 250 mL) at 85 C. in a sealed tube for 15 hours. Cool the reaction mixture to room temperature and concentrate under reduced pressure. Treat the residue with dichloromethane, sonicate, and filter the resulting precipitate to provide the desired compound as a yellow solid (8.9 g, 35%). 1H-NMR (300 MHz, DMSO): δ 8.30 (d, J=6.9 Hz, 1H), 7.62 (br s, 1H), 7.54 (d, J=9.0 Hz, 1H), 7.42 (s, 1H), 7.21 (dd, J=7.7, 6.7 Hz, 1H), 7.18 (br s, 1H), 6.91 (t, J=6.8 Hz, 1H), 3.81 (s, 2H).
35%	With ammonia; In methanol; at 85℃; for 15h;Sealed tube;	Amide Formation (0039) Heat a solution of imidazo[1,2-α]pyridin-3-yl-acetic acid ethyl ester (30 g, 147 mmol) in NH3/MeOH (7 N solution, 250 mL) at 85 C in a sealed tube for 15 hours. Cool the reaction mixture to room temperature and concentrate under reduced pressure. Treat the residue with dichloromethane, sonicate, and filter the resulting precipitate to provide the desired compound as a yellow solid (8.9 g, 35%). 1H-NMR(300 MHz, DMSO): δ 8.30 (d, J= 6.9 Hz, 1H), 7.62 (br s, 1H), 7.54 (d, J= 9.0 Hz, 1H), 7.42 (s, 1H), 7.21 (dd, J = 7.7, 6.7 Hz, 1H), 7.18 (br s, 1H), 6.91(t, J = 6.8 Hz, 1H), 3.81 (s, 2H).

	With ammonia; In methanol; at 0 - 100℃; for 2h;Heating in sealed tube;Product distribution / selectivity;	Preparation 109; 2-(Imidazo [1, 2-a] pyridin-3-yl) acetamide; Add ethyl (E) -oxybutenoate (14.3g, 111.66 mmol) to 2-aminopyridine (10.0 g, 106.4 mmol) in acetonitrile (270 ml). Heat the reaction at 80C for 6 hours. Concentrate the reaction mixture under reduced pressure. Purify the resulting oil by flash chromatography, eluting with a gradient of 100% hexane to 95% ethyl acetate: methanol to provide imidazo [1, 2-a] pyridin-3-yl-acetic acid ethyl ester (10.95g, 50.0%) as a brown solid. lH-NMR (400 MHz, DMSO-d6): S 8.3 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H) Bubble ammonia through a solution of (imidazo [1, 2-a] pyridin-3-yl) acetic acid ethyl ester (10.0 g, 48.96 mmol) in methanol (30 ml) at 0C. Heat the reaction mixture in a sealed tube at 100C for 2 hours. Concentrate the reaction mixture under reduced pressure. Triturate with ethyl acetate to give the title compound as a white solid. ESMS: m/z = 176.1 (M++1); Amide formation; Bubble ammonia through a solution of ethyl 2-(imidazol[1, 2-a] pyridin-3-yl) acetate (10.0 g, 48.96 mmol) in methanol (30 ml) at 0C. Heat the reaction mixture in a sealed tube at 100C for 2 hours. Concentrate the reaction mixture under reduced pressure. Add ethyl acetate to the residue to provide the title compound as a white solid. ESMS: m/z = 176.1 (M++1)
13 g	With ammonia; In methanol; at 20℃;	To a solution of crude intermediate 2 (25 g) in MeOH (100 ml) was added NH3/MeOH (6 M, 100 ml). The reaction mixture was stirred at room temperature overnight. The mixture was poured into EtOAc (500 ml), and then filtered. The filter cake was dried in vacuo to give intermediate 3 (13 g, 35% for two steps) as a brown solid. (0332) 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 8.30 (d, J=6.8 Hz, 1H), 7.60 (s br, 1H), 7.54 (d, J=5.2 Hz, 1H), 7.41 (s, 1H), 7.19-7.23 (m, 1H), 7.06 (s br, 1H), 6.89-6.93 (m, 1H), 3.80 (s, 2H).
13 g	With ammonia; In methanol; at 20℃;	To a solution of crude intermediate 2 (25 g) in MeOH (100 ml) was added MI3IMeOH (6 M. 100 ml), The reaction mixture was stirred at room temperature overnight. The mixture was poured into EtOAc (500 ml), and then filtered. The filter cake was dried in vacuo to give intermediate 3 (13 g, 35% for two steps) as a brown solid.‘H N14R DMSOd6, 400 MHz): 3 (ppm) 8.30 (d, J=6.8Hz, 1H), 760 (s br, IH), 7.54 (d, J::::5.2f1z, 1H), 7.41 (s, 1H), 7.i97.23 (m, 1H), 7.06 (s br, IFI), 6.89-6.93 (ni, 1H), 3.80 (s, 2H).
13 g	With ammonia; In methanol; at 20℃;	j0286j To a solution of crude intermediate 2 (25 g) in MeOH (100 mL) was added NH3/MeOH (6 M, 100 mL). The reaction mixture was stirred at room temperature overnight. The mixture was poured into EtOAc (500 mL), and then filtered. The filter cake was dried in vacuo to give intermediate 3 (13 g, 35% for two steps) as a brown solid.j0287j ‘H NMR (DMSO-d6, 400 MHz): ö (ppm) 8.30 (d, J=6.8Hz, 1H), 7.60 (s br, 1H),7.54 (d, J=5.2Hz, 1H), 7.41 (s, 1H), 7.19-7.23 (m, 1H), 7.06 (s br, 1H), 6.89-6.93 (m, 1H),3.80 (s, 2H).
13 g	With ammonia; In methanol; at 20℃;	To a solution of crude intermediate 2 (25 g) in MeOH (100 mL) was added NH3/MeOH (6 M, 100 mL). The reaction mixture was stirred at room temperature overnight. The mixture was poured into EtOAc (500 mL), and then filtered. The filter cake was dried in vacuo to give intermediate 3 (13 g, 35% for two steps) as a brown solid. [0363] 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 8.30 (d, J=6.8 Hz, 1H), 7.60 (s br, 1H), 7.54 (d, J=5.2 Hz, 1H), 7.41 (s, 1H), 7.19-7.23 (m, 1H), 7.06 (s br, 1H), 6.89-6.93 (m, 1H), 3.80 (s, 2H).

Reference： [1]Patent: WO2003/76398,2003,A2 .Location in patent: Page/Page column 34
[2]Patent: US2010/261712,2010,A1
[3]Patent: EP2173348,2015,B1 .Location in patent: Paragraph 0039
[4]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937
[5]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903
[6]Patent: WO2003/76442,2003,A1 .Location in patent: Page/Page column 53-54
[7]Patent: US2018/214458,2018,A1 .Location in patent: Paragraph 0330-0332
[8]Patent: WO2018/125746,2018,A1 .Location in patent: Paragraph 0240; 0241
[9]Patent: WO2018/191350,2018,A1 .Location in patent: Paragraph 0274; 0284; 0286; 0287
[10]Patent: US2020/121681,2020,A1 .Location in patent: Paragraph 0349; 0361-0363

3
[ 504-29-0 ]
(E)-4,4-dimethoxy-but-2-enoic acid ethyl ester [ No CAS ]
[ 101820-69-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903

4
[ 101820-69-3 ]
3-(2-acetyl-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-imidazo[1,2-a]pyridin-3-yl-pyrrole-2,5-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903

5
[ 101820-69-3 ]
3-imidazo[1,2-a]pyridin-3-yl-4-(2-isobutyryl-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-pyrrole-2,5-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903

6
[ 101820-69-3 ]
3-imidazo[1,2-a]pyridin-3-yl-4-[2-(tetrahydro-pyran-4-carbonyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl]-pyrrole-2,5-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903

7
[ 101820-69-3 ]
[ 603310-08-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903

8
[ 101820-69-3 ]
7-(4-imidazo[1,2-a]pyridin-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-3,4-dihydro-1H-[1,4]diazepino[6,7,1-hi]indole-2-carboxylic acid dimethylamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

9
[ 101820-69-3 ]
[ 848483-50-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

10
[ 101820-69-3 ]
3-imidazo[1,2-a]pyridin-3-yl-4-[2-(morpholine-4-carbonyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl]-pyrrole-2,5-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

11
[ 101820-69-3 ]
L⁽⁹⁰³⁾Y₂₀₁₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 899 - 903
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

12
[ 101820-69-3 ]
7-(4-imidazo[1,2-a]pyridin-3-yl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-3,4-dihydro-1H-[1,4]diazepino[6,7,1-hi]indole-2-carboxylic acid isopropyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

13
[ 101820-69-3 ]
[ 1027312-01-1 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937
[2]Patent: US2018/214458,2018,A1
[3]Patent: WO2018/191350,2018,A1
[4]Patent: US2020/121681,2020,A1

14
[ 101820-69-3 ]
7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

15
[ 101820-69-3 ]
3-imidazo[1,2-a]pyridin-3-yl-4-(1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)pyrrole-2,5-dione dihydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937

16
[ 101820-69-3 ]
3-(9-fluoro-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-imidazo[1,2-a]pyridin-3-yl-pyrrole-2,5-dione hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3934 - 3937
[2]Patent: US2018/214458,2018,A1
[3]Patent: WO2018/191350,2018,A1
[4]Patent: US2020/121681,2020,A1

17
[ 504-29-0 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
		Ethyl 2- (imidazorl, 2-alpyridin-3-yl; Add ethyl 4,4-dimethoxybut-2-enoate (2. 0g, 11.48 mmol) and p-toluenesulfonic acid (catalytic) to 4: 1 acetonitrile : water. Reflux for 1 hour and add 2-aminopyridine (1.08 g, 11.48 mmol). Reflux for lhour, dilute with ethyl acetate, and wash saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride. Concentrate under reduced pressure to provide the desired compound as a brown oil. 'H-NMR (400 MHz, DMSO-d6) : 8 8.3 (m, 1H), 7.53 (m, 1H), 7.46 (s, 1H), 6.9 (m, 1H), 6.42 (m, 1H), 4.1 (q, J = 7Hz, 2H), 1.15 (t, J = 7Hz, 3H)

Reference： [1]Patent: WO2003/76442,2003,A1 .Location in patent: Page/Page column 77

18
[ 504-29-0 ]
[ 19255-60-8 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
73%		Imidazo[1,2-α]pyridin-3-yl-acetic acid ethyl ester (0038) Heat a mixture of 4,4-dimethoxy-but-2-enoic acid ethyl ester (43.5 g, 250 mmol) and p-toluenesulfonic acid (4.75 g, 25 mmol) in acetonitrile (240 mL) and water (15 mL) at reflux for 2 hours. Cool the reaction mixture to room temperature and add 2-aminopyridine (18.8 g, 200 mmol). Heat the mixture at reflux for 16 hours then cool to room temperature. Dilute the reaction mixture with ethyl acetate (1200 mL) and wash sequentially with saturated aqueous sodium bicarbonate (600 mL×3) and saturated aqueous sodium chloride (600 mL×2). Dry the organic phase over sodium sulfate and concentrate under reduced pressure to provide the desired compound as a brown oil (30 g, 73%). 1H-NMR(300 MHz, CDCl3): δ 8.06 (d, J= 6.6 Hz, 1H), 7.63 (d, J= 9.1 Hz, 1H), 7.56 (s, 1H), 7.20 (dd, J= 8.9, 6.8 Hz, 1H), 6.84 (t, J= 6.7 Hz, 1H), 4.17 (q, J= 7.3 Hz, 2H), 3.93 (s, 2H), 1.25 (t, J= 7.3 Hz, 3H).

Reference： [1]Patent: EP2173348,2015,B1 .Location in patent: Paragraph 0038

19
[ 101820-69-3 ]
3-(9-fluoro-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-imidazo[1,2-a]-pyridin-3-yl-pyrrole-2,5-dione dihydrochloride [ No CAS ]

Reference： [1]Patent: EP2173348,2015,B1

20
[ 2568-30-1 ]
[ 504-29-0 ]
[ 75-05-8 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
82.9%		This Comparative Example was prepared according to the method provided in CN102875602B Preparation of 2- (imidazo [1,2-a] pyridin-3-yl)Ethyl acetate. details as follows: will2-Chloromethyl- [l, 3] -dioxlopentan-2-yl(51.8 mmol) and 6.72 g of 2-aminopyridine were dissolved in tetrahydrofuran, stirred well, and 8.4 g of triethylamine was slowly added dropwise. The mixture was heated to reflux and the reaction mixture was checked by TLC (ethyl acetate: methanol = 70: 30) - chloromethyl- [1,3] -dioxlopentan-2-yl disappeared,50ml of water was added, and then the reaction solution was adjusted to pH 3.0 with 1N hydrochloric acid, the reaction was stirred at room temperature for 1 hour,Then warmed to reflux for 3 hours, then the reaction solution was concentrated under reduced pressure to dryness,The concentrate was dissolved in 500 ml of ethyl acetate,Then, the organic material was washed with 25 ml × 3 water, the organic matter was concentrated,The concentrate was refluxed with 25 ml of acetonitrile, filtered, and crystallized at 0 C to give 9.11 g of pale yellow needle crystal, namely ethyl 2- (imidazo [1,2-a] pyridin-3-yl) acetate, yield 82.9 %, Purity 96.3%.

Reference： [1]Patent: CN105175446,2017,B .Location in patent: Paragraph 0073; 0074; 0075

21
[ 504-29-0 ]
[ 13176-46-0 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
94.1%	In 1,4-dioxane; water; at 20 - 70℃; for 3.5h;	(1) 10.83 g (51.8 mmol) of 4-bromo-acetoacetic acid ethyl ester and 0.97 g of a reaction accelerator M were placed in a 100 ml three-necked flask equipped with a mixed solvent of water and 1,4-dioxane and stirred at room temperature for 15 Minute, then 2-aminopyridine5.36 g (57 mmol) was stirred at 70 C for 3.5 hours. TLC was monitored until ethyl 4-bromo-acetoacetate was complete, filtered,The mixture was concentrated under reduced pressure, extracted with water (50 mL × 3 times) and washed with saturated brine (50 mL × 3 times). The combined organic phases were reducedThe solvent was removed by pressure and dried to give 10.17 g of a pale yellow oil, which was obtained as ethyl 2- (imidazo [1,2-a] pyridin-3-yl) acetate in a yield of 94.1% and a purity of 97.9% The agent M consists of zinc nitrate and glycine in a weight ratio of 7: 1, mixed and dissolvedA mixture of 10 ml of water and 20 ml of 1,4-dioxane.

Reference： [1]Patent: CN105175446,2017,B .Location in patent: Paragraph 0038; 0039; 0040; 0045; 0050; 0055; 0064; 0066

22
[ 101820-69-3 ]
minodronic acid [ No CAS ]

Reference： [1]Patent: CN105175446,2017,B

23
[ 101820-69-3 ]
[ 17745-04-9 ]

Yield	Reaction Conditions	Operation in experiment
93.5%	With sodium hydroxide; In ethanol; water; at 40 - 50℃;	Ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate was used for 20.4 g.Add 50mL of ethanol to dissolve,Add 2mol/L sodium hydroxide aqueous solution 100mL, and stir at 40-50C for 1.5-2 hours. TLC monitors the reaction. After the reaction is completed, the reaction solution is extracted once with 200 mL of dichloromethane. The aqueous layer is collected and neutralized with hydrochloric acid solution. Extract three times with 500mL of methylene chloride, combine the organic phases and wash them with water, dry them, and concentrate under reduced pressure. Heat and reflux with anhydrous ethanol to dissolve the concentrates. Cool naturally, filter and dry to obtain 16.5g of white solids. Yield: 93.5%.
92%	With sodium hydroxide; In water; at 50℃; for 1h;	(2) The ethyl 2- (imidazo [1,2-a] pyridin-3-yl) acetate obtained in the step (1) was mixed with 5.97 g of sodium hydroxide and added to 100 mL of water and the mixture was stirred at 50 C for 1 hour The reaction solution was then adjusted to pH = 5 with HCl (1 M), filtered,Washed with water (30mL × 3 times) to obtain 8.16g of a yellow solid,That is, 2- (imidazo [1,2-a] pyridin-3-yl) acetic acid, yield92%, purity 96.8%.
91.1%	With water; sodium hydroxide; at 60℃; for 1h;	(2) Ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate obtained in step (1) was mixed with 3.86 g of sodium hydroxide, 100 mL of water was added, and the reaction was stirred at 60 C. for 1 hour, and then used. The reaction solution was adjusted to rhoEta=4 by HC1 (1M), filtered, and washed with water (30 mL×3 times) to give 8.26 g of a yellow solid, namely 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid. The yield was 91.1% and the purity was 94.9%

	With sodium hydroxide; In water;	(1) 92 g of 2-aminopyridine was added to 1000 g of anhydrous ethanol, and 110 g of trans-4-oxy-2-butenoic acid ethyl ester was added dropwise to carry out the reaction. After about 30 minutes, the mixture was heated to 85±5C. The reaction is completed and the reaction is completed. After cooling to room temperature, ethyl 2-(imidazo[1,2-a]-3-yl)acetate is formed and hydrolyzed by adding 1000 g of 10% NaOH to obtain 2-(imidazo[1,2]). -a]-3-yl) acetic acid;
	With water; sodium hydroxide; In ethanol; at 20℃;	To a solution of intermediate 2 (1 g, 4.9 mmol) in EtOH (6 ml) was added NaOH (0.6 g, 14.7 mmol) in H2O (6 ml). The mixture was stirred at room temperature for overnight. The solvent was concentrated in vacuum, the residue was dissolved in EtOH, filtered. The solvent was concentrated in vacuum again to give intermediate 3A as a brown solid (1 g, crude).
70 g	With water; potassium hydroxide;	2-aminopyridine 100.0gMix with 70.0 g of trans-4-oxo-2-butenoic acid ethyl ester,Stirring, temperature control 60~80C reaction for 6-8h, TLC detection of the end of the reaction,Cool down to room temperature, add 600.0ml of 10% potassium hydroxide aqueous solution, warm to 40~50 C, stir the reaction for 1-2 hours, cool to 25 C, slowly add 5% hydrochloric acid about 50ml, adjust PH6-7, stir Crystal 2-4h,After suction filtration, the filter cake was dissolved in 300 ml of 10% potassium hydroxide solution at room temperature, and dilute hydrochloric acid was added to adjust PH6-7 to stir and crystallize.Filter by suction, filter cake 50~60. (: Vacuum drying for 3-6 h gave 70.0 g of a white solid, yield 72.0%.

Reference： [1]Patent: CN104945436,2017,B .Location in patent: Paragraph 0045; 0046
[2]Patent: CN105175446,2017,B .Location in patent: Paragraph 0038; 0041; 0046; 0051; 0056; 0061
[3]Patent: CN105153232,2017,B .Location in patent: Paragraph 0048; 0051
[4]Patent: CN106831873,2017,A .Location in patent: Paragraph 0021-0023; 0026-0028; 0031-0033
[5]Patent: US2018/214458,2018,A1 .Location in patent: Paragraph 0328-0329
[6]Patent: CN104725422,2018,B .Location in patent: Paragraph 0017; 0027-0030

24
[ 504-29-0 ]
[ 638-07-3 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
92.8%	With copper(I) triflate; triethylamine; In ethanol; at 55 - 60℃;	Dissolve 23.5 g (250 mmol) of 2-aminopyridine with 100 mL of absolute ethanol, add 35.4 g of triethylamine, 2.4 g of copper trifluoromethanesulfonate to the solution, and add dropwise 100 mL of absolute ethanol to the solution 47.3 while stirring. g ethyl 4-chloroacetoacetate, heated to 55-60 C., reacted for 4-5 hours, TLC (developer: chloroform:methanol=2:1) was used to monitor the reaction solution to 2-aminopyridine.The spots disappeared, and 1% citric acid solution was added to the solution until the pH of the solution was 7.6. The insolubles were removed by filtration and the filtrate was extracted with ethyl acetate. The organic layer was collected, dried, filtered and concentrated to give a pale yellow viscous liquid. 47.4 g, yield 92.8% (calculated as 2-aminopyridine), purity 97.57%, impurity 2-(imidazo[1,2-a]pyridin-2-yl)acetic acid ethyl ester 0.43% (HPLC normalization method) .

Reference： [1]Patent: CN104945436,2017,B .Location in patent: Paragraph 0035; 0036; 0037; 0038; 0039; 0040; 0041; 0042

25
[ 504-29-0 ]
[ 59006-06-3 ]
[ 101820-69-3 ]

Yield	Reaction Conditions	Operation in experiment
94.7%		(1) 14.19 g of ethyl 3,4-dibromo-butyrate (51.8 mmol) and 1.14 g of a reaction accelerator A were added to a 100 ml three-necked flask containing a mixed solvent of water and 1,4-dioxane. After stirring at room temperature for 15 minutes, 6.43 g (67.34 mmol) of 2-aminopyridine was added and the reaction was stirred at 85C for 5 hours. TLC monitored that the reaction was complete with ethyl 3,4-dibromo-butyrate, filtered, and concentrated under reduced pressure. Water was added and the mixture was extracted with ethyl acetate (50 mL×3 times). The organic phases were combined and the solvent was removed under reduced pressure. The resulting mixture was dried to give 10.2 g of a pale yellow oil, which was 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid. The ethyl ester has a yield of 94.7% and a purity of 98.2%. Among them, the reaction accelerator A consists of zinc nitrate and glycine in a weight ratio of 4.5:1. The mixed solvent is a mixture of 15 ml of water and 30 ml of 1,4-dioxane

Reference： [1]Patent: CN105153232,2017,B .Location in patent: Paragraph 0040; 0043-0045; 0050; 0055; 0060

26
[ 101820-69-3 ]
C₂₈H₂₉FN₆O₃ [ No CAS ]

Reference： [1]Patent: US2018/214458,2018,A1

27
[ 101820-69-3 ]
C₃₀H₂₉FN₆O₃ [ No CAS ]

Reference： [1]Patent: US2018/214458,2018,A1

28
[ 101820-69-3 ]
C₂₈H₂₇FN₆O₂ [ No CAS ]

Reference： [1]Patent: US2018/214458,2018,A1

29
[ 101820-69-3 ]
3-(imidazo[1,2-a]pyridin-3-yl)-4-(2-(piperidine-1-carbonyl)-9-(trifluoromethyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-1H-pyrrole-2,5-dione [ No CAS ]