[ CAS No. 19798-77-7 ]

Name: 19798-77-7|4-Amino-3-chloropyridine|97%
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Quality Control of [ 19798-77-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 19798-77-7 ]

SDS Specification

Alternatived Products of [ 19798-77-7 ]

Product Details of [ 19798-77-7 ]

CAS No. :	19798-77-7	MDL No. :	MFCD03984473
Formula :	C₅H₅ClN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KJBKPRMEMJKXDV-UHFFFAOYSA-N
M.W :	128.56	Pubchem ID :	581853
Synonyms :

Calculated chemistry of [ 19798-77-7 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	33.65
TPSA :	38.91 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.52 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.27
Log Po/w (XLOGP3) :	0.8
Log Po/w (WLOGP) :	1.33
Log Po/w (MLOGP) :	0.4
Log Po/w (SILICOS-IT) :	1.37
Consensus Log Po/w :	1.03

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.7
Solubility :	2.59 mg/ml ; 0.0201 mol/l
Class :	Very soluble
Log S (Ali) :	-1.2
Solubility :	8.14 mg/ml ; 0.0633 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.24
Solubility :	0.735 mg/ml ; 0.00571 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.29

Safety of [ 19798-77-7 ]

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

Application In Synthesis of [ 19798-77-7 ]

* 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 [ 19798-77-7 ]
Downstream synthetic route of [ 19798-77-7 ]

[ 19798-77-7 ] Synthesis Path-Upstream 1~11

1
[ 504-24-5 ]
[ 19798-77-7 ]

Reference： [1] Organic Process Research and Development, 1998, vol. 2, # 3, p. 157 - 168

2
[ 78-95-5 ]
[ 17758-33-7 ]
[ 19798-77-7 ]

Reference： [1] Chemical Communications, 2002, # 18, p. 2170 - 2171

3
[ 13194-60-0 ]
[ 19798-77-7 ]

Reference： [1] Bulletin des Societes Chimiques Belges, 1988, vol. 97, # 1, p. 51 - 54

4
[ 55934-00-4 ]
[ 19798-77-7 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690

5
[ 76439-45-7 ]
[ 19798-77-7 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1988, vol. 330, # 1, p. 154 - 158

6
[ 20511-15-3 ]
[ 19798-77-7 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690

7
[ 55934-00-4 ]
[ 19798-77-7 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690

8
[ 19798-77-7 ]
[ 22889-78-7 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690

9
[ 19798-77-7 ]
[ 52334-38-0 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1765 - 1770

10
[ 936-61-8 ]
[ 19798-77-7 ]
[ 52334-38-0 ]
[ 116608-23-2 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1765 - 1770

11
[ 19798-77-7 ]
[ 1300750-79-1 ]

Reference： [1] Journal of Organic Chemistry, 2012, vol. 77, # 11, p. 5006 - 5016

[ 19798-77-7 ] Synthesis Path-Downstream 1~68

1
[ 936-61-8 ]
[ 19798-77-7 ]
[ 52334-38-0 ]
[ 116608-23-2 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

2
[ 19798-77-7 ]
[ 13749-75-2 ]
[ 116608-26-5 ]
[ 116608-25-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

3
[ 19798-77-7 ]
[ 926-67-0 ]
[ 98383-10-9 ]
[ 116608-24-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

4
[ 19798-77-7 ]
[ 144036-19-1 ]
N-(3-chloropyrid-4-yl)-3-(cyclopentyloxy)-4-methoxybenzamide [ No CAS ]

Reference： [1]Organic Process Research and Development,1998,vol. 2,p. 157 - 168
[2]Journal of Medicinal Chemistry,1994,vol. 37,p. 1696 - 1703

5
[ 13194-60-0 ]
[ 19798-77-7 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1988,vol. 97,p. 51 - 54

6
[ 19798-77-7 ]
[ 98383-10-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

7
[ 19798-77-7 ]
[ 52334-38-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

8
[ 19798-77-7 ]
[ 116608-26-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1765 - 1770

9
[ 20511-15-3 ]
[ 19798-77-7 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1950,vol. 69,p. 673,690

10
[ 19798-77-7 ]
[ 75-26-3 ]
[ 823189-19-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	at 100 - 110℃;	Combine 3-CHLORO-4-AMINOPYRIDINE (3.00 g, 14.6 mmol) and 2-bromopropane (2.20 mL, 23.4 mmol) in a sealed tube and heat the mixture overnight at 100-110 C. Cool the mixture to RT, add aqueous NaHC03, and extract with EtOAc. Dry the combined extracts over NA2SO4, filter, and concentrate. Purify the residue by chromatography over silica gel using CH2CI2 to provide the title compound (1.72 g, 69 %) as a light oil. MS (ES) 170.2 (M+L) + ; RF= 0. 71 (25% EtOAc/hexanes).

Reference： [1]Patent: WO2005/821,2005,A1 .Location in patent: Page 40

11
[ 19798-77-7 ]
2-(2-FURYL)OXAZOLO[5,4-c]PYRIDINE [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 31: 2-(2-FURYL)OXAZOLO[5,4-c]PYRIDINE Using the procedure described in Example 7, but replacing 3-amino-2-chloropyridine by <strong>[19798-77-7]4-amino-3-chloropyridine</strong>.

Reference： [1]Patent: US5077408,1991,A

12
[ 19798-77-7 ]
[ 252029-82-6 ]
2-ethyl-7-methoxyfuro[2,3-c]pyridine-4-carboxylic acid (3-chloropyridin-4-yl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethyl acetate;	EXAMPLE 3 2-Ethyl-7-methoxyfuro[2,3-c]pyridine-4-carboxylic acid (3-chloropyridin-4-yl)amide Starting from 2-ethyl-7-methoxyfuro[2,3-c]pyridine-4-carboxylic acid 4-nitrophenyl ester (0.20 g) and <strong>[19798-77-7]4-amino-3-chloropyridine</strong> (0.15 g). Purification by column chromatography on silica eluding with 50% hexane in ethyl acetate gave the title compound (0.14 g) as a white solid. TLC Rf 0.42 (50% hexane in ethyl acetate) m.p. 172-3 C.

Reference： [1]Patent: US6169090,2001,A

13
[ 19798-77-7 ]
[ 1137671-27-2 ]
[ 6160-65-2 ]
[ 1137670-96-2 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1-43; (2-Chloro-pyridin-4-yl)-{5-[2-(2,6-dichloro-phenyl)-3H-benzoimidazol-5-yl]- [1 ,3,4]oxadiazol-2-yl}-amine.; Combine 4-amino-3-chloro-pyridine (78 mg, 0.606 mmol) and di-imidazol-1-yl- methanethione (108 mg, 0.606 mmol) in DMF (1.5 mL) and stir overnight. Add 2-(2,6- dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (150 mg, 0.466 mmol) and DMF (1.5 mL). Heat to 80 C for 1 hr. Add EDCI (179 mg, 0.932 mmol) and heat to 80 C for 1 hr. Upon cooling, dilute the reaction with EtOAc (75 mL) and extract with water (15 mL). Dry the organic phase over Na2SO4 and concentrate. Purify the concentrate by reverse-phase HPLC (25 - 40 % ACN / H2O + 5 mM NH4OH) to afford the title compound as a yellow solid: 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.51 (d, J=4.17 Hz, 1 H) 7.62 - 7.68 (m, 1 H) 7.70 (s, 1 H) 7.73 (dd, J=7.39, 1.96 Hz, 2 H) 7.75 - 7.87 (m, 1 H) 7.87 - 7.95 (m, 1 H) 8.07 (tautomer, br. s., 1 H) 8.19 (tautomer, br. s., 1 H) 8.29 (d, J=5.68 Hz, 1 H) 11.58 (br. s., 1 H) 13.32 (br. s., 1 H); MS m/z = 456.9 (M+1).

Reference： [1]Patent: WO2009/40410,2009,A1 .Location in patent: Page/Page column 89

14
[ 19798-77-7 ]
[ 1122-17-4 ]
[ 1258283-37-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6560 - 6564

15
[ 19798-77-7 ]
[ 463-71-8 ]
[ 337533-50-3 ]

Yield	Reaction Conditions	Operation in experiment
34%	In toluene; at 0℃;Reflux;	Compound 1 (200 mg, 1.56 mmol) was dissolved in toluene (70 mL) at 00C and compound 3(0.16 mL, 2.03 mmol) was added. The reaction mixture was stirred at reflux for 6 hours and the reaction was cooled to 00C. The residue was washed with aqueous KHCO3 (15 mL) and H2O(20 mL). The mixture was extracted with DCM (50 mL x 4), the organic layer was washed with brine (15 mL) and dried (MgSO4), and concentrated to give crude product which was purified by column chromatography on silica gel eluting with EA: PE=IO: 1 to give compound 4 (90 mg)(also confirmed by LC-MS). Yield: 34%.1HNMR (400 MHz, CDCl3): delta (ppm): 8.62 (IH, s, Py-H), 8.45-8.47 (IH, d, Py-H), 7.11-7.12(lH,d, Py-H)

Reference： [1]Patent: WO2010/139966,2010,A1 .Location in patent: Page/Page column 128

16
[ 19798-77-7 ]
[ 1256374-56-7 ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

17
[ 19798-77-7 ]
C₄₁H₅₆ClN₃O₆ [ No CAS ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

18
[ 19798-77-7 ]
C₁₇H₁₈ClN₃O₃ [ No CAS ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

19
[ 19798-77-7 ]
[ 892403-44-0 ]
[ 1256374-56-7 ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

20
[ 19798-77-7 ]
[ 892403-44-0 ]
C₄₁H₅₆ClN₃O₆ [ No CAS ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

21
[ 19798-77-7 ]
[ 30924-93-7 ]
C₂₂H₂₆ClN₃O₅ [ No CAS ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 2038 - 2048

22
[ 19798-77-7 ]
[ 77412-96-5 ]
[ 1314090-47-5 ]

Yield	Reaction Conditions	Operation in experiment
28%	With potassium carbonate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tert-butyl XPhos; In tert-butyl alcohol; at 80 - 85℃; for 43h;Inert atmosphere; Sealed tube;	Step 2: 8-tert-But l-6,7,8,9-tetrahydro-5H-pyrido[4,3-b]indole<strong>[19798-77-7]4-Amino-3-chloropyridine</strong> (8.0 g, 62 mmol) and K2CO3 (19.56 g, 142 mmol) were added into a round bottom pressure vessel, followed by addition of t-BuOH (100 ml). The mixture was stirred at room temperature and purged with N2 for 10min. Pd2(dba)3CHCI3 (2.929 g, 2.83 mmol) and 2-di-tert-butylphosphino-2',4',6'- triisopropylbiphenyl (4.807 g, 1 1 .32 mmol) were added. The mixture was stirred at room temperature for another 10 min before trifluoromethanesulfonic acid 4-tert-butyl- cyclohex-1 -enyl ester (16.209 g, 56.6 mmol) was added. The pressure vessel was sealed under N2 and heated at 80~85C for 43 hours. The reaction mixture was cooled, diluted with EtOAc and filtered through Celite. The filtrate was concentrated and triturated with DCM/EtOAc. The resulting solid was filtered and washed with DCM and H2O, respectively. The beige solid was dried under vacuum and afforded 3.07g of the title compound. The filtrate was concentrated, and the residue was subjected to chromatography (silica gel treated with Et3N, eluting with MeOH in DCM). Another 0.50g of 8-tert-butyl-6,7,8,9-tetrahydro-5H-pyrido[4,3-b]indole was obtained as a beige solid (total yield: 28%).

Reference： [1]Patent: WO2011/84439,2011,A1 .Location in patent: Page/Page column 34

23
[ 19798-77-7 ]
[ 1300750-84-8 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 5006 - 5016

24
[ 19798-77-7 ]
[ 1300750-79-1 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 5006 - 5016

25
[ 19798-77-7 ]
[ 1300750-89-3 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 5006 - 5016

26
[ 19798-77-7 ]
[ 1390656-84-4 ]
[ 1390657-26-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tert-butyl alcohol; at 100℃; for 18h;Inert atmosphere;	EXAMPLE 60 7-[(3-chloropyridin-4-yl)amino]-5-[2-metlioxy-4-(piperazin-l -yl)phenyl]amino}pyrid d]pyridazin-4(3H)-one EXAMPLE 60A tert-butyl 4-(4-(7-(3 hloropyridin-4-ylamino)-4-oxo-3,4-dihydropyrido\|3,4-i ]pyridazin-5- ylamino)-3-methoxyphenyl)piperazine- l -carboxylate A mixture of EXAMPLE 24A (160 mg, 0.33 mmol), <strong>[19798-77-7]3-chloropyridin-4-amine</strong> (65 mg, 0.45 mmol), tris(dibenzylideneacetone)dipalladium (30 mg, 0.03 mmol),dimethylbisdiphenyl phosphinoxanthene (20 mg, 0.03 mmol), potassium r/-butoxide (1 12 mg, 1 mmol) and /erf-butanol (2 mL) was bubbled with nitrogen and heated at 100C for 18 hours. The mixture was concentrated and the residue was dissolved in dichloromethane, washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 98/2 dichloromethane/methanol to give the title compound. MS : 579 (M + H+).

Reference： [1]Patent: WO2012/97682,2012,A1 .Location in patent: Page/Page column 119

27
[ 19798-77-7 ]
[ 25145-43-1 ]
C₁₄H₁₃ClN₂O [ No CAS ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10957 - 10959

28
[ 19798-77-7 ]
[ 1003579-29-0 ]
[ 1421917-38-5 ]

Reference： [1]Molecules,2012,vol. 17,p. 14205 - 14218

29
[ 19798-77-7 ]
[ 613-45-6 ]
[ 1436852-89-9 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

30
[ 19798-77-7 ]
[ 830-79-5 ]
[ 1436852-97-9 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

31
[ 19798-77-7 ]
[ 135-02-4 ]
[ 1436852-98-0 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

32
[ 19798-77-7 ]
[ 555-16-8 ]
[ 1436852-99-1 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

33
[ 19798-77-7 ]
[ 104-88-1 ]
[ 1436853-00-7 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

34
[ 19798-77-7 ]
[ 100-52-7 ]
[ 1353101-72-0 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

35
[ 19798-77-7 ]
[ 123-38-6 ]
[ 1436853-01-8 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5705 - 5710

36
[ 19798-77-7 ]
4-amino-3-bromo-5-chloropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With N-Bromosuccinimide;	Step 1: 3-bromo-5-chloropyridin-4-amine To a solution of <strong>[19798-77-7]3-chloropyridin-4-amine</strong> (10 g, 77.78 mmol) in acetonitrile (100 ml) was added N-bromosuccinimide (14.5 g, 81.67 mmol) at room temperature, and the resulting mixture was stirred at 60 C. for overnight under nitrogen. The reaction mixture was quenched with water (50 ml) and extracted with ethyl acetate (50 ml2). The combined organic layers were washed with brine (50 ml2), dried over anhydrous sodium sulfate, and concentrated to give a residue which was purified by silica gel flash chromatography (eluted with 20-50% ethyl acetate in hexane) to afford 3-bromo-5-chloropyridin-4-amine (8.8 g, yield 54%) as white solid.

Reference： [1]Organic Process Research and Development,1998,vol. 2,p. 157 - 168
[2]Patent: US2018/125821,2018,A1

37
[ 19798-77-7 ]
N-(3-bromo-5-chloropyrid-4-yl)-3-(cyclopentyloxy)-4-methoxybenzamide [ No CAS ]

Reference： [1]Organic Process Research and Development,1998,vol. 2,p. 157 - 168

38
[ 504-24-5 ]
[ 19798-77-7 ]

Reference： [1]Organic Process Research and Development,1998,vol. 2,p. 157 - 168

39
[ 19798-77-7 ]
[ 5538-53-4 ]
5-chloro-N-(2-chloropyridine-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22.5 mg		To a solution of 2- acetoxy-5-chlorobenzoyl chloride [Example 51, step 1] (0.65g, 0.0028 mol) in chloroform (15 mL) was added triethylamine (0.27g, 0.0027 mol) and the mixture was chilled to 0 C. 4- Amino-3-chloropyridine (0.35g, 0.0027 mol) was added portionwise over 5 min. The resulting mixture was stirred at 0 C until all of the <strong>[19798-77-7]4-amino-3-chloropyridine</strong> had dissolved. The mixture was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched by addition of 2M aqueous hydrogen chloride (1 mL). The mixture was stirred for 30 min., then extracted with 10% aqueous hydrogen chloride (2 X 50 mL). The pH of the combined aqueous extracts was adjusted to ~8 with saturated aqueous sodium bicarbonate solution and the mixture was stirred for several hours at ambient temperature. The resulting solid was filtered, washed several times with water and air dried to give 46.6 mgs of crude product. Attempts to recrystallize the product from ethanol failed. The recovered crude product was dissolved in a dichloromethane/MeOH mixture, silica gel was added and the mixture was concentrated in vacuo. The residue was transferred to a pre-column and purified by chromatography using a gradient as follows: initially dichloromethane (1 min.), then the eluent was modified to 2% MeOH/dichloro methane over a 15 min. period and kept at 2% MeOH/dichloromethane for the remainder of the purification. The fractions containing the pure major component were combined and concentrated in vacuo to give 22.5 mg (2.9% yield) of 5-chloro-N-(3-chloropyridin-4-yl)-2-hydroxybenzamide as an off-white solid. MS: m/z 281.1 (MH") and m/z 283 (MH?). 1H NMR (500 MHz, DMSO-d6): delta 7.109 (d, 1H), 7.552 (dd, 1H), 7.970 (d, 1H), 8.512 (m, 2H), 8.671 (s, 1H).
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Patent: WO2014/165816,2014,A1 .Location in patent: Page/Page column 86-87
[2]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

40
[ 19798-77-7 ]
[ 5538-51-2 ]
N-(3-chloropyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

41
[ 19798-77-7 ]
[ 54223-77-7 ]
3,5-dichloro-N-(3-chloropyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

42
[ 19798-77-7 ]
[ 780771-73-5 ]
3-chloro-N-(3-chloropyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

43
[ 19798-77-7 ]
[ 5485-91-6 ]
5-bromo-N-(3-chloropyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

44
[ 19798-77-7 ]
Acetic acid 2-chlorocarbonyl-4-trifluoromethyl-phenyl ester [ No CAS ]
N-(3-chloropyridin-4-yl)-5-(trifluoromethyl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

45
[ 19798-77-7 ]
C₁₀H₈Cl₂O₄ [ No CAS ]
5-chloro-N-(3-chloropyridin-4-yl)-2-hydroxy-4-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

46
[ 19798-77-7 ]
[ 19202-27-8 ]
N-(3-chloropyridin-4-yl)-2-hydroxy-4-methoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

47
[ 19798-77-7 ]
[ 850142-79-9 ]
N-(3-chloropyridin-4-yl)-6-propoxypyridin-3-amine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10705 - 10715

48
[ 19798-77-7 ]
[ 850142-79-9 ]
[ 1196699-80-5 ]
2-propoxy-5H-pyrrolo[3,2-b:4,5-c']dipyridine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10705 - 10715

49
[ 19798-77-7 ]
[ 870521-31-6 ]
N-(3-chloropyridin-4-yl)-6-isopropoxypyridin-3-amine [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10705 - 10715

50
[ 19798-77-7 ]
[ 32315-10-9 ]
(S)-tert-butyl (1-(3-(3-aminophenyl)-5-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate [ No CAS ]
(S)-tert-butyl (1-(5-chloro-3-(3-(3-(3-chloropyridin-4-yl)ureido)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		G. Preparation of a compound of formula (2b) where W2 is CH, n is 1, R1 is chloro, m is 0, R3 is methyl, R6 is 3-chloro-4-pyridinyl, and R5 is hydrogen Triethylamine (0.68 mL, 4.9 mmol) was added to a nearly homogeneous mixture of <strong>[19798-77-7]4-amino-3-chloropyridine</strong> (0.21 g, 1.6 mmol) in benzene (16 mL). Triphosgene (0.24 g, 0.80 mmol) was added quickly, dropwise as a solution in benzene (3 mL). The mixture was heated overnight at 100 C. (S)-tert-butyl(1-(3-(3-aminophenyl)-5-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate (0.37 g, 0.89 mmol) was added dropwise as a solution in dichloromethane (3 mL) to the isocyanate mixture at room temperature. The mixture was stirred for 2 hours at room temperature before the addition of ethanolamine (0.20 mL) and concentration under reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous phase was extracted twice with dichloromethane and twice with 10% methanol/dichloromethane. The combined extracts were concentrated to dryness under reduced pressure. The residue was purified by column chromatography on SiO2, eluting with methanol/ethyl acetate in hexanes to provide (S)-tert-butyl(1-(5-chloro-3-(3-(3-(3-chloropyridin-4-yl)ureido)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate. ES/MS m/z=569.1 (M+H+).

Reference： [1]Patent: US2015/361095,2015,A1 .Location in patent: Paragraph 0878; 0879

51
[ 19798-77-7 ]
5-{(benzyloxy)methyl}isoxazol-3-carboxylic acid [ No CAS ]
N-(3-chloropyridin-4-yl)-5-benzyloxymethylisoxazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.26 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃;	5-benzyloxy-methyl - isoxazole-3-carboxylic acid (0.24g, 1.0mmol), 4- amino-3-chloro-pyridine (0.16g, 1.2mmol), 1- hydroxybenzotriazole (0.01g, 0.1mmol) was added to the chloroform (amylene addition of goods) (2.5mL). To the mixture, it was added at room temperature 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol), and stirred at room temperature overnight. Then, dilute hydrochloric acid was added to the reaction mixture, and the mixture was extracted twice with chloroform. After removing impurities through the organic layer to a short column which was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, represented by the following formula N-(3- chloro-pyridin-4-yl) -5-benzyloxymethyl - isoxazole-3-carboxamide (hereinafter, the present invention compound (35) referred to.) was obtained 0.26g.

Reference： [1]Patent: JP2016/30727,2016,A .Location in patent: Paragraph 0181

52
[ 19798-77-7 ]
5-(biphenyl-4-ylcarbamoyl)-2-methoxybenzoic acid [ No CAS ]
N’-(biphenyl-4-yl)-N3-(3-chloropyridin-4-yl)-4-methoxyisophthalamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	Under argon 100.0 mg (0.29 mmol) of 5-(biphenyl-4-ylcarbamoyl)-2-methoxybenzoic acid(intermediate 14) were dissolved in 6.0 mL of anh DMF. 44.4 mg (0.35 mmol) of <strong>[19798-77-7]3-chloropyridin-4-amine</strong>, 0.06 mL (0.35 mmol) of N-ethyl-N-isopropylpropan-2-amine and 179.8 mg (0.35 mmol) ofPYBOP were added and it was stirred over night at rt. It was concentrated on a rotavap and theresidue was purified by HPLC (method 5) yielding 23 mg (17% of theory) of the title compound.?H-NMR (300 MHz, DMSO-d6) 6 [ppm]: 1.131 (0.48), 1.155 (1.00), 1.179 (0.52), 2.270 (0.47), 2.727(0.50), 2.906 (0.43), 3.910 (1.39), 3.949 (0.75), 4.208 (16.00), 7.318 (0.80), 7.336 (1.06), 7.343 (2.30),7.349 (0.91), 7.363 (1.25), 7.367 (1.73), 7.371 (1.03), 7.430 (1.09), 7.436 (2.82), 7.457 (2.90), 7.462(4.57), 7.486 (4.66), 7.516 (2.78), 7.661 (2.13), 7.668 (4.85), 7.673 (7.49), 7.695 (5.40), 7.703 (6.72),7.864 (0.71), 7.888 (5.62), 7.895 (2.39), 7.911 (1.73), 7.918 (4.03), 8.276 (1.69), 8.285 (1.83), 8.305(1.76), 8.314 (1.82), 8.522 (10.34), 8.692 (4.86), 8.742 (3.56), 8.750 (3.55), 10.477 (3.48), 10.799(3.68).LC-MS (Method 3): R = 1.35 mm; MS (ESIpos): m/z = 458 [M+H].

Reference： [1]Patent: WO2016/131794,2016,A1 .Location in patent: Page/Page column 76

53
[ 19798-77-7 ]
5-[(biphenyl-4-ylcarbonyl)amino]-2-methoxybenzoic acid [ No CAS ]
N-{3-[(3-chloropyridin-4-yl)carbamoyl]-4-methoxyphenyl}biphenyl-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To a solution of the compound of intermediate 3 (150 mg, 0.43 mmol, 1.0 equiv.) and 3- chloropyridin-4-amine (83.3 mg, 0.65 mmol, 1.5 equiv.) in DMF (10 mL) was added (1H-benzotriazol- 1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 337 mg, 0.65 mmol, 1.5 equiv.) and diisopropylethylamine (0.30 mL, 1.73 mmol, 4.0 equiv.). The resulting mixture was stirred atroom temperature over night. 3-Chloropyridin-4-amine (55.5 mg, 0.43 mmol, 1.0 equiv.), (1H- benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 225 mg, 0.43 mmol, 1.0 equiv.) and diisopropylethylamine (0.15 mL, 0.87 mmol, 2.0 equiv.) were added and the resulting mixture was stirred at room temperature over night. After concentration, purification by HPLC(Waters Autopurificationsystem, column: XBrigde C18 5jim 100x30 mm, solvent: water / acetonitrile+ 0.2% ammonia (32%) gradient, rate: 50 mL/min, temperature: room temperature) yielded 21.0 mg (10% of theory) of the title compound.?H-NMR (300 MHz, DMSO-d6) 6 [ppm]: 1.107 (0.92), 1.224 (0.70), 1.646 (0.79), 2.074 (0.84), 2.084 (0.89), 2.525 (3.17), 2.540 (1.36), 4.131 (16.00), 7.360 (2.98), 7.379 (1.11), 7.391 (3.29), 7.405 (1.00),7.421 (0.62), 7.429 (2.23), 7.437 (0.80), 7.448 (1.16), 7.453 (1.97), 7.458 (1.19), 7.494 (2.98), 7.514(2.33), 7.519 (4.32), 7.536 (0.90), 7.543 (1.87), 7.547 (1.31), 7.759 (3.48), 7.762 (4.18), 7.767 (2.28),7.779 (1.35), 7.786 (3.64), 7.791 (2.69), 7.838 (4.26), 7.845 (1.81), 7.860 (2.09), 7.867 (5.24), 8.092(5.16), 8.099 (1.93), 8.113 (1.65), 8.120 (4.18), 8.137 (1.84), 8.146 (1.80), 8.167 (1.52), 8.176 (1.60),8.492 (1.91), 8.510 (3.84), 8.539 (7.01), 8.548 (3.87), 8.559 (2.33), 8.679 (5.59), 10.466 (3.53), 10.958(3.67).LC-MS (Method 1): R = 1.33 mm; MS (ESIpos): m/z = 458 [M+H]

Reference： [1]Patent: WO2016/131794,2016,A1 .Location in patent: Page/Page column 71; 72

54
[ 19798-77-7 ]
trans-4-([4-(phenoxycarbonyl)-1H-imidazol-5-yl]carbonyl}amino)cyclohexanecarboxylic acid [ No CAS ]
phenyl 5-({trans-4-[(3-chloropyridin-4-yI)carbamoyl]cyclohexyl}carbamoyl)-1H-imidazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
390 mg		To a suspension of 250 mg (0.70 mmol) trans-4-([4-(phenoxycarbonyl)-1 H-imidazol-5- yl]carbonyl}amino)cyclohexane-carboxylic acid in 20 ml dichloromethane 195 p1(1.40 mmol) 1-chloro-N,N,2-trimethylprop-1-en-1 -amine were added and the mixture was stirred at roomtemperature for 1 hour. 170 p1 (2.10 mmol) pyridine and 92.7 mg (0.70 mmol) 3- chloropyridin-4-amine were added and the reaction was stirred at room temperature for 24 hours. The reaction mixture was concentrated in vacuo to obtain the crude product. Another batch was prepared accordingly (1 .4 mmol of the starting material) and the combined crude products were purified by flash column chromatography (dichloromethane/methanol10 gradient) to give 390 mg of the title compound as a solid material.

Reference： [1]Patent: WO2016/177658,2016,A1 .Location in patent: Page/Page column 188; 189

55
[ 19798-77-7 ]
[ 321-14-2 ]
5-chloro-N-(2-chloropyridine-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With phosphorus trichloride; In 5,5-dimethyl-1,3-cyclohexadiene; for 1h;Molecular sieve; Inert atmosphere; Reflux;	Example 1. Comp [00153] General method: To a 100 mL flask equipped with a reflux condenser was added 5-chloro-2-hydroxybenzoic acid (1 equiv.), the aminoheteroaryl derivative NH2-Q (1 equiv.), and dry xylenes (stored over 3A molecular sieves, 40 mL per gram of 5-chloro-2- hydroxybenzoic acid) under an atmosphere of argon. The mixture was heated to reflux, and PCI3 (0.4 equiv.) was added rapidly via syringe. The mixture was heated at reflux for 1 hour and cooled to room temperature. Water (40 mL per gram of 5-chloro-2-hydroxybenzoic acid) was added and the resultant heterogeneous mixture stirred rapidly for 1 hour. Saturated sodium bicarbonate was added to a final pH of 3-4, and the mixture stirred rapidly overnight. The solids were filtered and washed sequentially with water, toluene and hexane. Samples were analyzed by NMR, HPLC/mass spectrometry and TLC. Purification by crystallization or column chromatography on silica gel was performed when purity was less than 95% by LC. HPLC/MS was accomplished using an Agilent spectrometer - 6310 Ion trap. Mass ions (m/z) detected in positive ionization mode are M+ ; in negative ionization mode, mass ions (m/z) are M-.

Reference： [1]Patent: WO2016/210247,2016,A1 .Location in patent: Paragraph 00153-00154

56
[ 19798-77-7 ]
[ 87-51-4 ]
N-(3-chloropyridin-4-yl)-2-(1H-indol-3-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 3h;	first step,Indole acetic acid (1.05 g)Was added to dichloromethane (20 mL) and stirred and stirred,EDCI (1.27 g) was added at room temperature,<strong>[19798-77-7]3-chloro-4-aminopyridine</strong> (0.85 g), DMAP (0.15 g),The reaction was stirred at room temperature for 3 h.Add deionized water (20 mL) for 10 min,The organic phase was stirred for 10 min with saturated brine (10 mL)The organic phase was removed at 40 C under reduced pressure to give the crude N- (3-chloropyridin-4-yl) -2- (1H-indol-3-yl) acetamide as a pale reddish brown oil.
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 3h;	Indole acetic acid (1.05 g)Was added to dichloromethane (20 mL) and stirred at room temperature. EDCI (1.27 g) was added at room temperature and stirred and dissolved.3-Chloro-4-aminopyridine (0.85 g) was added,DMAP (0.15 g), stirred at room temperature for 3 h;(10 mL) was stirred for 10 min, and the organic phase was added to the saturated salt (10 mL) for 10 min.The organic phase was removed at 40 C under reduced pressure to give the crude product as a pale reddish brown oilN- (3-chloropyridin-4-yl) -2- (1H-indol-3-yl) acetamide.

Reference： [1]Patent: CN107149603,2017,A .Location in patent: Paragraph 0436; 0438
[2]Patent: CN107176921,2017,A .Location in patent: Paragraph 0438

57
[ 19798-77-7 ]
N-(3-chloropyridin-4-yl)-2-(indolin-3-yl)acetamide [ No CAS ]