[ CAS No. 72990-37-5 ] {[proInfo.proName]}

Name: 72990-37-5|3-Chloroisonicotinaldehyde|97%
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Quality Control of [ 72990-37-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 72990-37-5 ]

CAS No. :	72990-37-5	MDL No. :	MFCD06200712
Formula :	C₆H₄ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZVGDKOQPJCOCLI-UHFFFAOYSA-N
M.W :	141.56	Pubchem ID :	2762995
Synonyms :

Calculated chemistry of [ 72990-37-5 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	34.63
TPSA :	29.96 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) :	-6.5 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.25
Log Po/w (XLOGP3) :	0.94
Log Po/w (WLOGP) :	1.55
Log Po/w (MLOGP) :	0.4
Log Po/w (SILICOS-IT) :	2.16
Consensus Log Po/w :	1.26

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.74
Solubility :	2.59 mg/ml ; 0.0183 mol/l
Class :	Very soluble
Log S (Ali) :	-1.16
Solubility :	9.89 mg/ml ; 0.0699 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.56
Solubility :	0.387 mg/ml ; 0.00274 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.14

Safety of [ 72990-37-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H317-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 72990-37-5 ]

* 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 [ 72990-37-5 ]
Downstream synthetic route of [ 72990-37-5 ]

[ 72990-37-5 ] Synthesis Path-Upstream 1~5

1
[ 72990-37-5 ]
[ 68325-15-5 ]

Reference： [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 15, p. 2466 - 2472

2
[ 626-60-8 ]
[ 68-12-2 ]
[ 72990-37-5 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -78℃; Stage #2: at 20℃; for 1 h;	Preparatio example 411·^' 3-chloroi son i cot inaldehyde To a 250 ml round-bottomed flask, LDA (11ml, 22.02mmol) was added to 3- chloropyr icli edg, 8.80mmol) in THF(20 ml) dropwise at -78 ^°C and stirred at same temperature for l~2hr. Then DMF(822//.P, , 10.56mmol )was added and stirred at room temperature for Ihr. EA (Ethyl acetate) and water were added to the reaction mixture, and after the separation of the layers, the aqueous phase was further extracted with the organic solvent. The combined organic extracts were dried over anhydrous Sodium sulfate (Na₂S0₄), filtered and concentrated under vacuum. The crude compound was purified by. a silica gel column, to produce the title compound (0.33g, 30~65percent) NMR (400MHz, CDC 13 ) δ 7.73 (d, J = 8.0, 1H) 8.71 (cl, J = 4.0, 1H) 8.81 (s, 1H) 10.52 (s, 1H)

Reference： [1] Heterocycles, 2006, vol. 67, # 2, p. 543 - 547
[2] Patent: WO2015/88271, 2015, A1, . Location in patent: Page/Page column 208

3
[ 626-60-8 ]
[ 109-94-4 ]
[ 72990-37-5 ]

Reference： [1] Patent: US2003/45540, 2003, A1,

4
[ 626-60-8 ]
[ 541-41-3 ]
[ 72990-37-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 14, p. 4425 - 4433

5
[ 626-60-8 ]
[ 109-94-4 ]
[ 72990-37-5 ]

Reference： [1] Journal of Organometallic Chemistry, 1981, vol. 216, # 2, p. 139 - 147

[ 72990-37-5 ] Synthesis Path-Downstream 1~88

1
[ 626-60-8 ]
[ 72990-37-5 ]
Bis-(3-chloro-pyridin-4-yl)-methanol [ No CAS ]

Reference： [1]Journal of Organometallic Chemistry,1981,vol. 216,p. 139 - 147

2
[ 626-60-8 ]
[ 109-94-4 ]
[ 72990-37-5 ]

Reference： [1]Journal of Organometallic Chemistry,1981,vol. 216,p. 139 - 147

3
[ 626-60-8 ]
[ 541-41-3 ]
[ 72990-37-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 4425 - 4433

4
[ 72990-37-5 ]
[ 65399-19-1 ]
3-(3-chloropyridin-4-ylmethylene)-6-methoxy-3H-isobenzofuran-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With acetic anhydride; In toluene;	EXAMPLE 4 Preparation of 3-[(3-chloro-4-pyridinyl)methylen]-6-methoxy-1-(3H)-isobenzofuranone A mixture of 5-methoxy-3-oxo-1,3-dihydro-1-isobenzofurancarboxylic acid (0.7 g; 3.4 mmoles) and <strong>[72990-37-5]3-chloro-4-pyridinecarboxaldehyde</strong> (0.52 g; 3.7 mmoles), prepared as described in J. Organometallic Chem. (1981), 216, 139, in toluene (5 ml) and acetic anhydride (1 ml) was refluxed, under stirring, for 10 hours. The mixture was cooled at 0 C. and filtered. The filtrate was washed with hexane. The compound 3-[(3-chloro-4-pyridinyl)methylen]-6-methoxy-1-(3H)-isobenzofuranone was obtained (680 mg) as yellow solid. Yield 70% 1H-NMR (200 MHz, CDCl3) delta (ppm): 8.58 (s 1H ClC=CH-N); 8.47 (d, 1H, JHH=5.3 Hz, N-CH=CH), 8.11 (d, 1H, N-CH=CH); 7.74 (d, 1H, JHH=8.5 Hz, CH=CH-OMe); 7.35-7.28 (m, 2H, Ar); 6.61 (s, 1H, CH-Py); 3.90 (s, 3H, CH3-O).

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 4425 - 4433
[2]Patent: US2003/23094,2003,A1

5
[ 626-60-8 ]
[ 68-12-2 ]
[ 72990-37-5 ]

Yield	Reaction Conditions	Operation in experiment
65%		Preparatio example 411·' 3-chloroi son i cot inaldehyde To a 250 ml round-bottomed flask, LDA (11ml, 22.02mmol) was added to 3- chloropyr icli edg, 8.80mmol) in THF(20 ml) dropwise at -78 C and stirred at same temperature for l~2hr. Then DMF(822//.P, , 10.56mmol )was added and stirred at room temperature for Ihr. EA (Ethyl acetate) and water were added to the reaction mixture, and after the separation of the layers, the aqueous phase was further extracted with the organic solvent. The combined organic extracts were dried over anhydrous Sodium sulfate (Na2S04), filtered and concentrated under vacuum. The crude compound was purified by. a silica gel column, to produce the title compound (0.33g, 30~65%) NMR (400MHz, CDC 13 ) delta 7.73 (d, J = 8.0, 1H) 8.71 (cl, J = 4.0, 1H) 8.81 (s, 1H) 10.52 (s, 1H)

Reference： [1]Heterocycles,2006,vol. 67,p. 543 - 547
[2]Patent: WO2015/88271,2015,A1 .Location in patent: Page/Page column 208

6
[ 72990-37-5 ]
C₆H₄Cl₂N₂O [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 67,p. 543 - 547

7
[ 72990-37-5 ]
[ 74-89-5 ]
[ 823189-17-9 ]

Reference： [1]Heterocycles,2006,vol. 67,p. 543 - 547

8
[ 72990-37-5 ]
3,3'-bipyridine-4,4'-diyldimethanol [ No CAS ]

Reference： [1]Synlett,2007,p. 2101 - 2105
[2]Tetrahedron,2008,vol. 64,p. 9906 - 9910

9
[ 72990-37-5 ]
N-(3-chloropyridin-4-ylmethyl)-N-methyl-1-(3,5-bis-trifluoromethylbenzyl)-5-phenyl-1H-[1,2,3]triazole-4-carboxamide [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 67,p. 543 - 547

10
[ 72990-37-5 ]
[ 1122-97-0 ]
[ 662150-31-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 62℃; for 2h;	3-Chloroisonicotinaldehyde prepared according to R. B. Moffett et al., J. Heterocycl. Chem. 1979,16, 1459] (550 mg, 3.9 mmol), 4-methylsulfanyl-benzenethiol (732 mg, 4,7 mmol) potassium carbonate (700 mg, 5.1 mmol) and DMF (10 mL) were combined and the mixture was heated together at 65C for 2 h. The solvent was removed in vacuo and the residue was partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine, dried (MgS04) and evaporated to give the title compound (1.124 g) as a yellow oil. 1H NMR spectrum showed the material to be of sufficient purity (90-95%) to be used without further purification; & delta H (CDCl3, 300 MHz) 2.52 (3H, s), 7.28 (2H, d), 7.40 (2H, d), 7.64 (1H, d), 8.39 (1H, s), 8.61 (1H, d), 10.42 (1H, s); MS m/z (ES-) 260 (M-H+)

Reference： [1]Patent: WO2004/16593,2004,A1 .Location in patent: Page 31

11
[ 3120-74-9 ]
[ 72990-37-5 ]
C₁₄H₁₃NO₂S [ No CAS ]

Reference： [1]Patent: WO2006/8635,2006,A1 .Location in patent: Page/Page column 8

12
[ 626-60-8 ]
[ 109-94-4 ]
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]thieno[2,3-c]pyridine-2-carboxamide Dihydrochloride [ No CAS ]
[ 72990-37-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	In tetrahydrofuran; diisopropylamine;	EXAMPLE 17 N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]thieno[2,3-c]pyridine-2-carboxamide Dihydrochloride Preparation of the Acid: THF (200 mL) is chilled to -70 C. in a dry flask under N2, and N-butyllithium (24.4 mL, 55.0 mmol) is added drop-wise. The reaction is placed in an ice bath and diisopropyl amine (7.71 mL, 55.0 mmol) in THF (20 mL) is added drop-wise. The solution is again chilled to -70 C., and 3-chloropyridine (4.75 mL, 50.0 mmol) in THF (20 mL) is added drop-wise. The reaction is allowed to stir for 4 h at -70 C. and ethyl formate (4.44 mL, 55.0 mmol) in THF (20 mL) is added. The reaction is stirred for an additional 3 h at -70 C. and quenched with H2O (500 mL). The layers are allowed to separate, and the aqueous layer is extracted with EtOAc (3*250 mL). The combined organic layer is dried over MgSO4, filtered, and concentrated to a dark brown solid. The crude material is chromatographed over 250 g slurry-packed silica, eluding with 50% EtOAc/hexane. The fractions with the desired compound are collected and concentrated to give 3-chloroisonicotinaldehyde (C120) as an off-white solid (55% yield). MS (EI) for C6H4ClNO, m/z: 141 (M)+.

Reference： [1]Patent: US2003/45540,2003,A1

13
[ 72990-37-5 ]
[ 2365-48-2 ]
[ 478148-99-1 ]

Yield	Reaction Conditions	Operation in experiment
22%	With potassium carbonate; In water; N,N-dimethyl-formamide;	C120 (2.12 g, 14.9 mmol) is dissolved in DMF (75 mL) with a small amount of H2O (7.5 mL). Methyl thioglycolate (1.67 mL, 18.7 mmol) and K2CO3 (2.59 g, 18.7 mmol) are added portionwise, and the mixture is stirred at 45 C. for 24 h. The reaction is quenched with cold H2O (200 mL) and extracted with EtOAc (3150 mL). The combined organic layer is washed with 50% NaCl solution (3150 mL), dried over MgSO4, filtered, and concentrated to an orange solid. The crude material is chromatographed over 40 g slurry-packed silica, eluding with 50% EtOAc/hexane. The fractions with the desired compound are collected and concentrated, affording ethyl thieno[2,3-c]pyridine-2-carboxylate (C121) as a pale yellow solid (22% yield).

Reference： [1]Patent: US2003/45540,2003,A1

14
[ 72990-37-5 ]
[ 57663-18-0 ]
[ 206066-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylsilane; trifluoroacetic acid;	EXAMPLE 38 Production of 3-((3-chloropyridin-4-yl)methyl)-5-(methoxycarbonyl)-2-methylindole (67) According to the method of Example 33, obtained is 3-((3-chloropyridin-4-yl)methyl)-5-(methoxycarbonyl)-2-methylindole (67) (0.355 g) from 5-(methoxycarbonyl)-2-methylindole (0.486 g), 3-chloropyridine-4-carboxyaldehyde (0.40 g), triethylsilane (0.896 g) and trifluoroacetic acid (0.439 g). 1H-NMR (CDCl3, delta ppm): 2.38 (3H, s), 3.89 (3H, s), 4.16 (2H, s), 6.82 (1H, d, J=5.0 Hz), 7.33 (1H, d, J=8.5 Hz), 7.87 (1H, d, J=8.7 Hz), 8.08 (1H, s), 8.20 (1H, brs), 8.25 (1H, d, J=5.0 Hz), 8.57 (1H, s).

Reference： [1]Patent: US6410584,2002,B1

15
potassium 1-(trifluoroboratomethyl)piperidine [ No CAS ]
[ 72990-37-5 ]
[ 1014990-21-6 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 2052 - 2057

16
[ 72990-37-5 ]
[ 1065010-87-8 ]
[ 1063960-86-0 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 7481 - 7485

17
[ 72990-37-5 ]
[ 14220-21-4 ]
[ 115-77-5 ]
[ 30418-59-8 ]
(ReBr(CO)3C₅H₃N(Cl)CHNC₆H₄B(OCH₂)2C(CH₂O)2BC₆H₄NCHC₅H₃N(Cl))2 [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 1848 - 1852

18
[ 72990-37-5 ]
[ 620535-14-0 ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 10753 - 10766
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 3951 - 3963
[3]Organic and Biomolecular Chemistry,2013,vol. 11,p. 2466 - 2472
[4]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5209 - 5212

19
[ 72990-37-5 ]
[ 823-96-1 ]
[ 74663-96-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 3h;	3-Chloropyridine-4-carbaldehyde (141.6 mg, 1.00 mmol) , trimethylboroxine (278.4 mul 2.00 mmol) , [1,1'- bis (diphenylphosphino) ferrocene] dichloropalladium (II) dichloromethane complex (81.6 mg, 0.10 mmol) and potassium carbonate (414.6 mg, 3.00 mmol) were mixed with water (0.2 mL) and 1,4-dioxane (1.8 mL) and stirred at 100C for 3 hours. After completion of the reaction, the reaction solution was allowed to cool, and the solvent was removed by vacuum distillation. The resulting crude reaction product containing the desired product was used <n="210"/>for the next step (594.7 mg)
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;	(a) 3-Methylisonicotinaidehyde: PdC12(dppfyCH2Cl2 (220mg, 0.27mmol) and K2C03 (745mg. 5.4mmoi) were added to a solution of 3-chioroisomcotinaidehyde (382mg, 2.7mmoi) and 2,4.6-triniethyi-1.3,5,2,4,6-trioxatriborinane (680mg, 5Ammol) in 5 mL of dioxane and 0.6 niL of water, and the mixture was stirred at 100 C for 3h, At that point, solvent was removed under reduced pressure, and water (15 nI) was added to the mixture. The mixture was then extractedwith EtOAc (3 x 15 mL). The combined organic extracts were washed with brine (30 mL), dried over Na2SO4,, and filtered. The filtrate was concentrated unde reduced pressure to obtain crude 3- methylisonieotinaldehyde (680mg, crude) as a dark brown solid, which was carried through without thither purification. LCiV[SAOI2: 122.1 [M-i-Hit it, = 0.906 mm Purity : 30.1% (254nm).

Reference： [1]Patent: WO2009/57827,2009,A1 .Location in patent: Page/Page column 207
[2]Patent: WO2013/19626,2013,A1 .Location in patent: Page/Page column 46

20
[ 72990-37-5 ]
[ 2065-66-9 ]
[ 1168722-58-4 ]

Yield	Reaction Conditions	Operation in experiment
55%		A dry round-bottom flask containing with methyltriphenylphosphonium iodide (632 mg, 1.77 mmol) and THF (25 mL) was cooled with an ice-water bath and the suspension treated with w-BuLi (1.0 mL of a 1.6M solution in hexanes) and the reaction stirred for 0.5 hours. The solution was cooled to -78 0C and 3- chloroisonicotinaldehyde (250 mg, 1.77 mmol) was added portion-wise and then the reaction was allowed to warm to room temperature over 4 hours. The reaction was quenched with AcOH (0.10 mL) and the THF removed in vacuo. The residue was dissolved in EtOAc and then washed with water (2X), and brine (2X), the organic layer dried (MgSO4) and the EtOAc was removed. The residue was purified by column chromatography, silica gel (99:1 to 98:2 CH2Cl2 / MeOH) to give the title compound (135 mg, 55 %) as a yellow oil. MS ESI 140.0 [M + H]+, calcd for [C7H6ClN+ H]+ 140.03.

Reference： [1]Patent: WO2009/79767,2009,A1 .Location in patent: Page/Page column 182

21
potassium (4-(benzoyloxy)butyl)trifluoroborate [ No CAS ]
[ 72990-37-5 ]
[ 1137726-29-4 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 3626 - 3631

22
[ 72990-37-5 ]
[ 333-27-7 ]
[ 1201000-46-5 ]

Reference： [1]Dalton Transactions,2009,p. 9123 - 9125

23
[ 72990-37-5 ]
[ 74-89-5 ]
C₇H₇ClN₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 4053 - 4057

24
[ 72990-37-5 ]
3-chloro-4-(hydroxymethyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1.5h;	To a solution of <strong>[72990-37-5]3-chloropyridine-4-carbaldehyde</strong> (3.58 g, 25.3 mmol) in MeOH(150 mL) at 0 C was added NaBH4 (1.91 g, 50.6 mmol) portion wise. The mixture was stirred at this temperature for 5 min then allowed to warm up to rt and stirred at this temperature for 1.5 h. The reaction mixture was quenched with saturated aqueous solution of NH4Cl. Volatiles were removed in vacuo and the aqueous layer was extracted with EtOAc (150 mL). The organic layer was washed successively with water (150 mL) and brine (150 mL), dried over Na2SO4, filtered and concentrated in vacuo to give chloropyridine 33 (3.58 g, 99%) as a white solid which was used in the next step without further purification.
90%	With methanol; sodium tetrahydroborate; at 0 - 20℃; for 1h;	To a solution of sodium borohydride (601 mg, 15.9 mmol) in anhydrous methanol (25 mL) was added a solution of <strong>[72990-37-5]3-chloropyridine-4-carbaldehyde</strong> (1.5 g, 10.6 mmol) in anhydrous methanol (5 mL) at O0C. The mixture was stirred for 1 hour at room temperature. Water was added and extracted 3 times with ethyl acetate. The combined organic phase was washed with brine and dried over sodium sulfate. After evaporation of the solvent, (3-chloropyridin-4-yl)methanol was obtained as a white solid (1.4 g, 90% yield) and used for next step without further purification; 1H NMR (400 MHz, CDCl3): delta 2.41 (t, J = 5.9 Hz, IH), 4.83 (dd, J = 0.8 Hz, J = 5.9 Hz, 2H), 7.52-7.55 (m, IH), 8.51 (m, 2H).
1.40 g	With sodium tetrahydroborate; ethanol; at 20℃; for 2h;Cooling with ice;	Reference Production Example 4 To a mixture of 1.53 g of <strong>[72990-37-5]3-chloroisonicotinaldehyde</strong> and 5 ml of ethanol was gradually added 0.40 g of sodium borohydride under ice-cooling, and the mixture was stirred under ice-cooling for 1 hour, and subsequently at room temperature for 1 hour. Saturated brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layers were combined and dried over magnesium sulfate. The resulting mixture was concentrated under reduced pressure to obtain 1.40 g of (3-chloropyridin-4-yl)methanol. 1H-NMR (CDCl3) delta: 8.54-8.49 (m, 2H), 7.55-7.51 (m, 1H), 4.83 (d, J=4.4 Hz, 2H), 2.34-2.29 (br m, 1H)

Reference： [1]Beilstein Journal of Organic Chemistry,2017,vol. 13,p. 988 - 994
[2]Patent: WO2010/132999,2010,A1 .Location in patent: Page/Page column 88
[3]Chemical Communications,2018,vol. 54,p. 11805 - 11808
[4]Patent: US2013/90353,2013,A1 .Location in patent: Paragraph 0754; 0755

25
[ 72990-37-5 ]
[ 454-81-9 ]
[ 1192021-01-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 3h;Reflux;	Reference Production Example 12 A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of <strong>[72990-37-5]3-chloro-4-pyridinecarboxyaldehyde</strong> and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-(trifluoromethyl)phenol. [Show Image] 1H-NMR (CDCl3) delta: 9.14 (s, 1H), 8.76 (s, 1H), 8.65 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.62 (m, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.35 (br s, 1H), 7.14 (d, J=8.6 Hz, 1H)
	In ethanol; for 3h;Reflux;	Reference Production Example 12A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of <strong>[72990-37-5]3-chloro-4-pyridinecarboxyaldehyde</strong> and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-(trifluoromethyl)phenol.1H-NMR (CDCl3) delta: 9.14 (s, 1H), 8.76 (s, 1H), 8.65 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.62 (m, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.35 (br s, 1H), 7.14 (d, J=8.6 Hz, 1H)
	In ethanol; for 3h;Reflux;	Reference Production Example 12A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of 3-chloro-4- pyridinecarboxyaldehyde and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4- (trifluoromethyl)phenol.-NMR (CDC13) delta: 9.14 (s, 1H), 8.76 (s, 1H), 8.65 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, IH), 7.62 (m, IH), 7.56 (d, J=8.6 Hz, IH), 7.35 (br s, IH), 7.14 (d, J=8.6 Hz, IH)

	With ethanol; for 3h;Reflux;	A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of 3-chloro-4- pyridinecarboxyaldehyde and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4- (trifluoromethyl)phenol .1H-NMR (CDC13) delta: 9.14 (s, IH), 8.76 (s, IH), 8.65 (d, J=5.1 Hz, IH), 8.01 (d, J=5.1 Hz, IH), 7.62 (m, IH), 7.56 (d, J=8.6 Hz, IH), 7.35 (br s, IH), 7.14 (d, J=8.6 Hz, IH)
	In ethanol; for 3h;Reflux;	A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of 3-chloro-4- pyridinecarboxyaldehyde and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4- (trifluoromethyl)phenol.1 H-NMR (CDC13) delta: 9.14 (s, IH), 8.76 (s, IH), 8.65 (d, J=5.1 Hz, IH), 8.01 (d, J=5.1 Hz, IH), 7.62 (m, IH), 7.56 (d, J=8.6 Hz, IH), 7.35 (br s, IH), 7.14 (d, J=8.6 Hz, IH)
	In ethanol; for 3h;Reflux;	Reference Production Example 12A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of 3-chloro-4- pyridinecarboxyaldehyde and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4- (trifluoromethyl)phenol.1H-NMR (CDC13) delta: 9.14 (s, IH), 8.76 (s, IH), 8.65 (d, J=5.1 Hz, IH), 8.01 (d, J=5.1 Hz, IH), 7.62 (m, IH), 7.56 (d, J=8.6 Hz, IH), 7.35 (br s, IH), 7.14 (d, J=8.6 Hz, IH)
	In ethanol; for 3h;Reflux;	Reference Production Example 12A mixture of 0.89 g of 2-amino-4-(trifluoromethyl)phenol, 0.71 g of 3-chloro-4- pyridinecarboxyaldehyde and 5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated and the residue was washed with an ethyl acetate-hexane mixture solvent to give 0.71 g of 2-(3-chloropyridin-4-yl)methylideneamino-4- (trifluoromethyl)phenol .1 H-NMR (CDC13) delta: 9.14 (s, IH), 8.76 (s, IH), 8.65 (d, J=5.1 Hz, IH), 8.01 (d, J=5.1 Hz, IH), 7.62 (m, IH), 7.56 (d, J=8.6 Hz, IH), 7.35 (br s, IH), 7.14 (d, J=8.6 Hz, IH)

Reference： [1]Patent: EP2274983,2011,A1 .Location in patent: Page/Page column 124
[2]Patent: US2011/39843,2011,A1 .Location in patent: Page/Page column 78
[3]Patent: WO2011/40629,2011,A1 .Location in patent: Page/Page column 206-207
[4]Patent: WO2011/49220,2011,A1 .Location in patent: Page/Page column 205-206
[5]Patent: WO2011/49221,2011,A1 .Location in patent: Page/Page column 207
[6]Patent: WO2011/49223,2011,A1 .Location in patent: Page/Page column 205-206
[7]Patent: WO2011/49222,2011,A1 .Location in patent: Page/Page column 210

26
[ 72990-37-5 ]
[ 1199-46-8 ]
[ 1192021-40-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 3h;Reflux;	Reference Production Example 29 A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of <strong>[72990-37-5]3-chloro-4-pyridinecarboxyaldehyde</strong> and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert-butylphenol. [Show Image] 1H-NMR (CDCl3) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)
	In ethanol; for 3h;Reflux;	Reference Production Example 29A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of <strong>[72990-37-5]3-chloro-4-pyridinecarboxyaldehyde</strong> and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert-butylphenol.1H-NMR (CDCl3) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)
	In ethanol; for 3h;Reflux;	Reference Production Example 29A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of 3-chloro-4- pyridinecarboxyaldehyde and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert- butylphenol.1H-NMR (CDC13) delta: 9.07 (s, IH), 8.71 (s, IH), 8.60 (d, J=5.1 Hz, IH), 8.01 (d, J=5.1 Hz, IH), 7.36-7.33 (m, 2H), 7.02 (s, IH), 7.00-6.97 (m, IH), 1.35 (s, 9H)

	In ethanol; for 3h;Reflux;	A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of 3-chloro-4- pyridinecarboxyaldehyde and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert- butylphenol.1H-NMR (CDC13) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)
	In ethanol; for 3h;Reflux;	A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of 3-chloro-4- pyridinecarboxyaldehyde and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert- butylphenol.1 H-NMR (CDC13) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)
	In ethanol; for 3h;Reflux;	Reference Production Example 29A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of 3-chloro-4- pyridinecarboxyaldehyde and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert- butylphenol.1 H-NMR (CDC13) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)
	In ethanol; for 3h;Reflux;	Reference Production Example 29A mixture of 0.41 g of 2-amino-4-tert-butylphenol, 0.35 g of 3-chloro-4- pyridinecarboxyaldehyde and 2.5 ml of ethanol was heated to reflux for three hours. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 0.50 g of 2-(3-chloropyridin-4-yl)methylideneamino-4-tert- butylphenol.1 H-NMR (CDC13) delta: 9.07 (s, 1H), 8.71 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.36-7.33 (m, 2H), 7.02 (s, 1H), 7.00-6.97 (m, 1H), 1.35 (s, 9H)

Reference： [1]Patent: EP2274983,2011,A1 .Location in patent: Page/Page column 133
[2]Patent: US2011/39843,2011,A1 .Location in patent: Page/Page column 85
[3]Patent: WO2011/40629,2011,A1 .Location in patent: Page/Page column 222
[4]Patent: WO2011/49220,2011,A1 .Location in patent: Page/Page column 221
[5]Patent: WO2011/49221,2011,A1 .Location in patent: Page/Page column 222
[6]Patent: WO2011/49223,2011,A1 .Location in patent: Page/Page column 221
[7]Patent: WO2011/49222,2011,A1 .Location in patent: Page/Page column 225

27
[ 72990-37-5 ]
[ 1192019-05-8 ]

Reference： [1]Patent: WO2011/49220,2011,A1
[2]Patent: US2011/39843,2011,A1

28
[ 72990-37-5 ]
[ 1192019-06-9 ]

Reference： [1]Patent: WO2011/49220,2011,A1
[2]Patent: WO2011/49221,2011,A1
[3]Patent: US2011/39843,2011,A1

29
[ 72990-37-5 ]
[ 1199-46-8 ]
[ 1192019-07-0 ]

Reference： [1]Patent: US2011/39843,2011,A1

30
[ 72990-37-5 ]
[ 1318898-56-4 ]
[ 20439-47-8 ]
[ 1318898-25-7 ]

Reference： [1]Advanced Synthesis and Catalysis,2011,vol. 353,p. 1797 - 1806

31
[ 72990-37-5 ]
[ 1318898-57-5 ]
[ 20439-47-8 ]
[ 1318898-32-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2011,vol. 353,p. 1797 - 1806

32
[ 72990-37-5 ]
[ 20439-47-8 ]
[ 231963-91-0 ]
[ 1318898-28-0 ]

Reference： [1]Advanced Synthesis and Catalysis,2011,vol. 353,p. 1797 - 1806

33
[ 72990-37-5 ]
[ 1334713-66-4 ]

Reference： [1]Patent: WO2011/113798,2011,A2
[2]Patent: US2013/102587,2013,A1

34
[ 72990-37-5 ]
[ 1334712-60-5 ]

Reference： [1]Patent: WO2011/113798,2011,A2
[2]Patent: US2013/102587,2013,A1

35
[ 25637-16-5 ]
[ 72990-37-5 ]
[ 1334713-65-3 ]

Yield	Reaction Conditions	Operation in experiment
		Magnesium (86.5 mg, 3.60 mmol) was stirred vigorously under nitrogen for 30 min. THF (2 mL) and dibromoethane (2 drops) were added and the reaction mixture was warmed to 50 C. A solution of 4-bromotetrahydropyran (495 mg, 3.00 mmol) in THF (4 mL) was added drop-wise over 5 min and the reaction mixture was heated at reflux for 2 h. A solution of 3-chloro-4-pyridaldehyde (170 mg, 1.20 mmol) in THF (4 mL) was added drop-wise over 5 min and the reaction mixture was heated at reflux for 6 h, stirred at room temperature overnight and heated at reflux for 8 h. The reaction mixture was cooled to 0 C and quenched with sat aq NH4C1 (10 mL). The reaction mixture was diluted with EtOAc (40 mL) and the aqueous fraction was extracted with EtOAc (3 x 40 mL). The combined organic fractions were washed with sat aq Na2C03 (20 mL), dried (MgS04) and concentrated in vacuo. The residue was purified by normal phase column chromatography to give the crude title compound as a pale yellow gum (69.0 mg, 25%). LCMS (ES+): 228.2 (M+H)+.
		Magnesium (86.5 mg, 3.60 mmol) was stirred vigorously under nitrogen for 30 min. THF (2 mL) and dibromoethane (2 drops) were added and the reaction mixture was warmed to 50 C. A solution of 4-bromotetrahydropyran (495 mg, 3.00 mmol) in THF (4 mL) was added drop-wise over 5 min and the reaction mixture was heated at reflux for 2 h. A solution of 3-chloro-4-pyridaldehyde (170 mg, 1.20 mmol) in THF (4 mL) was added drop-wise over 5 min and the reaction mixture was heated at reflux for 6 h, stirred at room temperature overnight and heated at reflux for 8 h. The reaction mixture was cooled to 0 C. and quenched with sat aq NH4Cl (10 mL). The reaction mixture was diluted with EtOAc (40 mL) and the aqueous fraction was extracted with EtOAc (3*40 mL). The combined organic fractions were washed with sat aq Na2CO3 (20 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography to give the crude title compound as a pale yellow gum (69.0 mg, 25%). LCMS (ES+): 228.2 (M+H)+.

Reference： [1]Patent: WO2011/113798,2011,A2 .Location in patent: Page/Page column 55-56
[2]Patent: US2013/102587,2013,A1 .Location in patent: Paragraph 0256; 0257

36
[ 1122-54-9 ]
[ 72990-37-5 ]
[ 1346704-75-3 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 6864 - 6870

37
[ 72990-37-5 ]
[ 1382094-12-3 ]

Reference： [1]Patent: WO2012/87630,2012,A1

38
[ 72990-37-5 ]
[ 1382294-52-1 ]

Reference： [1]Patent: WO2012/87630,2012,A1

39
[ 72990-37-5 ]
[ 63488-10-8 ]
[ 1383429-42-2 ]

Yield	Reaction Conditions	Operation in experiment
		SYNTHESIS EXAMPLE 1Preparation of 3-chloro-4-[[4-(l, l-dimethylethyl)phenyl]fluoromethyl]pyridine (compound number 7)and 3-chloro-4-[[4-(l,l-dimethylethyl)phenyl]difluoromethyl]pyridine (compound number 9)Step A: Preparation of 3-chloro-a-[4-(l, l-dimethylethyl)phenyl]-4-pyridinemethanolTo a stirred solution of <strong>[72990-37-5]3-chloro-4-pyridinecarboxaldehyde</strong> (1.10 g, 7.8 mmol) in tetrahydrofuran (20 mL) was added a solution of 4-tert-butylphenylmagnesium bromide (4.68 mL, 2.0 M in diethyl ether) at 0 C. After stirring for 2 hrs, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (50:50 to 5:95) as eluent to afford the title product as a pale yellow solid (1.08 g).lH NMR (CDC13) delta 8.52 (d, 1H), 8.47 (s, 1H), 7.71 (d, 1H), 7.36 (d, 2H), 7.29 (d, 2H), 6.10 (d, 1H), 2.58 (s, br. 1H), 1.30 (s, 9H).

Reference： [1]Patent: WO2012/87630,2012,A1 .Location in patent: Page/Page column 46

40
[ 95-16-9 ]
[ 72990-37-5 ]
[ 1383429-43-3 ]

Yield	Reaction Conditions	Operation in experiment
		SYNTHESIS EXAMPLE 5Preparation of 2-[(3-chloro-4-pyridinyl)fluoromethyl]benzothiazole (compound number 4) Step A: Preparation of a-(3-chloro-4-pyridinyl)-2-benzothiazolemethanolTo a stirred solution of benzothiazole (780 mg, 5.78 mmol) in tetrahydrofuran (25 mL) was added w-butyllithium (3.6 mL, 2.0 M in hexanes) dropwise at -78 C. After stirring at -78 C for 0.5 hr, a solution of <strong>[72990-37-5]3-chloro-4-pyridinecarboxaldehyde</strong> (900 mg, 6.36 mmol) in tetrahydrofuran (5 mL) was added slowly at -78 C to the reaction mixture. The reaction mixture was stirred for another 5 hrs at -78 C, then was treated with water and extracted with ethyl acetate. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (60:40 to 10:90) as eluent to afford the title product as a pale yellow solid (120 mg)..H NMR (CDCI3) delta 8.62 (s, 1H), 8.55 (d, 1H), 8.06 (d, 1H), 7.88 (d, 1H), 7.60 (d, 1H), 7.24 (m, 2H), 6.32 (s, 1H).

Reference： [1]Patent: WO2012/87630,2012,A1 .Location in patent: Page/Page column 48

41
[ 95-16-9 ]
[ 72990-37-5 ]
[ 1383428-91-8 ]

Reference： [1]Patent: WO2012/87630,2012,A1

42
[ 72990-37-5 ]
[ 485828-89-5 ]

Reference： [1]Patent: US2013/90353,2013,A1

43
[ 72990-37-5 ]
[ 1352748-22-1 ]

Reference： [1]Patent: US2013/90353,2013,A1

44
[ 72990-37-5 ]
[ 1352748-23-2 ]

Reference： [1]Patent: US2013/90353,2013,A1

45
[ 72990-37-5 ]
[ 68325-15-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 2466 - 2472

46
[ 72990-37-5 ]
[ 147123-47-5 ]
[ 1438887-39-8 ]

Yield	Reaction Conditions	Operation in experiment
47%	With hydrogenchloride; In ethanol; at 140℃; for 0.333333h;Microwave irradiation;	2-(3-Chloro-pyridin-4-yl)-thieno[3,2-d]pyrimidin-4-ol [BB-15b] A microwave vial was charged with 3-amino-thiophene-2-carboxylic acid amide (1 g, 7.03 mmol), 3-Chloro-pyridine-4-carbaldehyde (0.6 g, 4.24 mmol), 2.5 N hydrogen chloride in ethanol (0.56 mL, 1.4 mmol) and ethanol (10 ml). The reaction mixture was heated to 140 C for 20 minutes under microwave irradiation. After completion, the precipitate formed was filtered and washed with DCM then methanol. The residue was purified by flash column chromatography (Si02, MeOH : DCM elution) to five the title compound (0.52g, 47% yield). LCMS method: 10, MI: 264 [M+l].

Reference： [1]Patent: WO2013/78126,2013,A1 .Location in patent: Page/Page column 245

47
[ 625-82-1 ]
[ 72990-37-5 ]
(1,3,5,7-tetramethyl-8-(2-chloro-4-pyridyl)-4,4’-difluoroboradiazaindacene) [ No CAS ]

Reference： [1]New Journal of Chemistry,2013,vol. 37,p. 2663 - 2668

48
[ 72990-37-5 ]
[ 22382-97-4 ]

Reference： [1]Patent: WO2013/19626,2013,A1

49
[ 72990-37-5 ]
[ 13575-75-2 ]
[ 1620646-28-7 ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium hydroxide; In ethanol; at 20℃; for 4h;	At room temperature, a mixture of 6,7-dimethoxy- 1 -tetralone (1.44 g, 7 mmol) and 3 -chloro-4- pyridinecarboxaldehyde (1.0 g, 7 mmol) was added in one portion to a solution of sodium hydroxide (280 mg, 1 equiv) in ethanol (7 mL). After being stirred at room temperature for 4h, thesolid obtained was filtered and rinsed with ethanol then diethyl ether to give the title compound 85 (Yield 932 mg, 44%),?H NMR (300 Mhz, CDC13, 6): 2.87-2.95 (m, 4H), 3.95 (s, 6H), 6.68 (s, 1H), 7.21 (d, 1H, J 5.1 Hz), 7.63 (s, 1H), 7.70 (s, 1H), 8.54 (d, 1H, J 4.8 Hz), 8.66 (s, 111).MS (ESr): 330.09 (M+Hj

Reference： [1]Patent: WO2014/114742,2014,A1 .Location in patent: Page/Page column 68; 69

50
[ 72990-37-5 ]
N²-(1-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)sulfonyl)piperidin-4-yl)-6-methylpyridine-2,3-diamine [ No CAS ]
2-(3-chloropyridin-4-yl)-3-(1-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)sulfonyl)piperidin-4-yl)-5-methyl-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.015 g	With acetic acid; for 6h;Reflux;	2-(3-Chloropyridin-4-yl)-3-(l-((2,2-difluorobenzo[< ] [l,3]dioxol-5-yl)sulfonyl)piperidin- 4-yl)-5-methyl-3H-imidazo[4,5-6]pyridine (51). A solution of 49 (0.100 g, 0.234 mmol) and 50 (0.0332 g, 0.2343 mmol) in HOAc (3 mL) was heated refluxed for 6 hr. After the reaction was complete, the reaction mixture was cooled to rt basified with saturated aHC03 solution. The resulting mixture was extracted with EtOAc and the organic layer was dried over anhydrous Na2S04 then concentrated in vacuo to give the crude product as a yellow solid. This was purified by flash column chromatography using 100-200 mesh silica gel. The desired product was eluted in 50% EtOAc in pet-ether to obtain 0.015 g (12%) of pure 51 as an off white solid. XH NMR (DMSO-d6) delta 8.88 - 8.85 (d, J = 9.9 Hz, 1H), 8.73 - 8.71 (d, J = 4.8 Hz, 1H), 8.04 - 8.01 (d, J = 8.1 Hz, 1H), 7.85 (s, 1H), 7.76 - 7.65 (m, 3H), 7.25 - 7.23 (d, J = 8.1 Hz, 1H), 3.98 - 3.87 (m,lH), 3.77 - 3.73 (d, J = 11.1 Hz, 2H), 2.96 - 288 (t, J = 11.4 Hz, 2H), 2.63 - 2.62 (d, J = 4.8 Hz, 2H), 2.42 (s, 3H), 1.96 - 1.89 (t, J = 10.8 Hz, 2H). LCMS m/z 548 [M + H - 1], 550 [M + H + 1].

Reference： [1]Patent: WO2014/160478,2014,A1 .Location in patent: Page/Page column 73

51
[ 72990-37-5 ]
N²-(1-(benzo[d][1,3]dioxol-5-ylsulfonyl)piperidin-4-yl)-6-methylpyridine-2,3-diamine [ No CAS ]
3-(1-(benzo[d][1,3]dioxol-5-ylsulfonyl)piperidin-4-yl)-2-(3-chloropydridin-4-yl)-5-methyl-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.011 g	With acetic acid; for 6h;Reflux;	3-(l-(Benzo [d] [1,3] dioxol-5-ylsulfonyl)piperidin-4-yl)-2-(3-chloropydridin-4-yl)-5- methyl-3H-imidazo[4,5-Z>]pyridine (56). A solution of 55 (0.075 g, 0.192 mmol) and 50 (0.0272 g, 0.192 mmol) in HOAc (3 mL) was heated refluxed for 6 hr. After the reaction was complete, the reaction mixture was cooled to rt basified with saturated aHC03 solution. The resulting mixture was extracted with EtOAc and the organic layer was dried over anhydrous Na2S04 then concentrated in vacuo to give the crude product as a yellow solid. This was purified by flash column chromatography using 100-200 mesh silica gel. The desired product was eluted in 50% EtOAc in pet-ether to obtain 0.011 g (11%) of pure 56 as a pale yellow solid. XH NMR (DMSO-d6) delta 8.84 (s, 1H), 8.70 - 8.68 (d, J = 4.8 Hz, 1H), 8.03 - 8.01 (d, J = 8.1 Hz, 1H), 7.68 - 7.66 (d, J = 4.8 Hz, 1H), 7.29 - 7.21 (m, 3H), 7.13 - 7.10 (d, J = 8.4 Hz, 1H), 6.17 (s, 2H), 3.98 (br s, 1H), 3.73 - 3.69 (d, J = 11.1 Hz, 2H), 2.86 (br s, 2H), 2.64 (s, 3H), 2.38 - 2.26 (m, 2H), 1.91 - 1.88 (d, J = 11.4 Hz, 2H). LCMS m/z 512 [M + H - 1], 514 [M + H + 1].

Reference： [1]Patent: WO2014/160478,2014,A1 .Location in patent: Page/Page column 76

52
[ 72990-37-5 ]
[ 7498-57-9 ]
3-(3-chloropyridin-4-yl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]
3-(3-chloropyridin-4-yl)-3-hydroxy-2-(naphthalen-2-yl)propanenitrile [ No CAS ]