[ CAS No. 4494-18-2 ] {[proInfo.proName]}

Name: 4494-18-2|Isoquinoline-1-carbaldehyde|97%
Brand: Ambeed
SKU: A159977
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Quality Control of [ 4494-18-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4494-18-2 ]

SDS Specification

Alternatived Products of [ 4494-18-2 ]

Product Details of [ 4494-18-2 ]

CAS No. :	4494-18-2	MDL No. :	MFCD06738864
Formula :	C₁₀H₇NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HORFVOWTVOJVAN-UHFFFAOYSA-N
M.W :	157.16	Pubchem ID :	265306
Synonyms :

Calculated chemistry of [ 4494-18-2 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.13
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) :	-5.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.23
Log Po/w (XLOGP3) :	2.04
Log Po/w (WLOGP) :	2.05
Log Po/w (MLOGP) :	0.87
Log Po/w (SILICOS-IT) :	2.62
Consensus Log Po/w :	1.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.65
Solubility :	0.352 mg/ml ; 0.00224 mol/l
Class :	Soluble
Log S (Ali) :	-2.3
Solubility :	0.793 mg/ml ; 0.00504 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.63
Solubility :	0.0364 mg/ml ; 0.000232 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.01

Safety of [ 4494-18-2 ]

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

Application In Synthesis of [ 4494-18-2 ]

* 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 [ 4494-18-2 ]
Downstream synthetic route of [ 4494-18-2 ]

[ 4494-18-2 ] Synthesis Path-Upstream 1~12

1
[ 1721-93-3 ]
[ 4494-18-2 ]

Yield	Reaction Conditions	Operation in experiment
77%	With selenium(IV) oxide In 1,4-dioxane; hexane; ethyl acetate	(Step 1) Synthesis of 1-isoquinolinecarbaldehyde In 1,4-dioxane (20 ml) was dissolved 1-methylisoquinoline (300 mg, 2.10 mmol). To the resulting solution was added selenium dioxide (323 mg, 2.91 mmol), followed by heating under reflux for 1.5 hours under a nitrogen gas stream. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (5:1, v/v) eluate fractions, 1-isoquinolinecarbaldehyde (252 mg, 77percent) was obtained as a white solid. ¹H-NMR (CDCl₃) δ: 7.73-7.79 (m, 2H), 7.88-7.93 (m, 2H), 8.74-8.76 (m, 1H), 9.30-9.33 (m, 1H), 10.39 (s, 1H). MS (ESI) m/z 158 (M⁺+1).
77%	With selenium(IV) oxide In 1,4-dioxane for 1.5 h; Reflux; Inert atmosphere	To a stirred solution of 1-methylisoquinoline (12g) (300 mg, 2.10 mmol) in dioxane (20 ml) was added SeO₂ (323 mg, 2.91 mmol), and the reaction mixture was refluxed for 1.5 h under N₂ atmosphere. After cooled to room temperature, the mixture was filtered through a celite pad, and the filtrate was evaporated. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (5:1, v/v) as eluent to give the title compound (252 mg, 77percent) as a white solid. ¹H NMR (CDCl₃) δ 7.73-7.79 (m, 2H), 7.88-7.93 (m, 2H), 8.74-8.76 (m, 1H), 9.30-9.33 (m, 1H), 10.39 (s, 1H); MS (ESI), m/z 158 [M+H]⁺.
63%	With selenium(IV) oxide In 1,4-dioxane for 16 h; Reflux	SeO2 (757 mg, 6.82 mmol) and 1-methylisoquinoline (698 mg, 4.87 mmol) were dissolved in dioxane (10 mL) and the mixture was stirred at reflux for 16 h, cooled and filtered. The filtrate was concentrated and the residue was column chromatographed. The compound was a white solid (485 mg, yield 63percent).

Reference： [1] Patent: EP1346982, 2003, A1,
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 3, p. 1201 - 1212
[3] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2753 - 2775
[4] Organic and Biomolecular Chemistry, 2012, vol. 10, # 6, p. 1239 - 1245
[5] Patent: CN103570683, 2018, B, . Location in patent: Paragraph 0221; 0226-0228
[6] Journal of Medicinal Chemistry, 1985, vol. 28, # 8, p. 1103 - 1106
[7] Journal of the American Chemical Society, 1942, vol. 64, p. 2430

2
[ 27104-72-9 ]
[ 4494-18-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	With lithium aluminium tetrahydride In tetrahydrofuran	(b) 1-Isoquinolinecarboxaldehyde (7.3 g, 64percent) was prepared from 1-isoquinolinecarboxylic acid methyl ester (13.6 g, 0.073 mol) and 1M LAH (36.6 ml in THF) in 300 ml of dry THF (J. Org. Chem., vol 28, p 1898, 1963) to afford 7.3 g (64percent) of 1-isoquinolinecarboxaldehyde.
33%	With lithium aluminium tetrahydride; sodium hydroxide In tetrahydrofuran at -70℃; for 0.25 h;	A solution of methyl 1-isoquinolinecarboxylate (1.00 g, 5.34 mmol) in dry THF (30 mL) was cooled to -70 °C in a dry ice/MeOH bath. To that solution was added a suspension of LiAlH₄ (0.10 g, 2.67 mmol) in THF (10 mL). The resulting brown reaction mixture was stirred for 15 min followed by a quench with glacial acetic acid (1.3 mL). Once the mixture warmed to RT the aluminum salts were precipitated with a few drops 1 N NaOH. The heterogeneous mixture was filtered, and the solvent was removed under vacuum. The residue was dissolved into a small portion of CH₂Cl₂ and chromatographed on silica (1:1 hexanes: EtOAc, R_f = 0.79) affording 1-isoquinolinecarboxaldehyde (0.28 g, 33percent) as a crystalline white solid. ¹H NMR (CDCl₃): 10.40 ppm (1H, s); 9.33 ppm (1H, m); 8.76 ppm (1H, d, J = 5.6 Hz); 7.91 ppm (2H, m); 7.77 ppm (2H, m). ¹³C NMR (CDCl₃): 195.63, 149.79, 142.41, 136.85, 130.74, 130.01, 126.91, 126.31, 125.70, 125.45 ppm. IR (KBr pellet): 3033, 2844, 1703 cm^-1.

Reference： [1] Patent: US5554620, 1996, A,
[2] Polyhedron, 2016, vol. 109, p. 147 - 153

3
[ 119-65-3 ]
[ 20461-86-3 ]
[ 4494-18-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With ammonium peroxydisulfate; caesium carbonate In dimethyl sulfoxide at 20℃; for 24 h; Inert atmosphere; Irradiation; Green chemistry	General procedure: Heterocycle (0.10mmol,1equiv)ammonium persulfate (0.30 mmol, 3 equiv), Cs2CO3(0.20mmol,2 equiv)were placed in a dry glass tube.Then, anhydrous DMSO1 mL) and2,2-diethoxyacetic acid (0.7mmol7equiv), wereinjected into the tube by syringe under a N2atmosphere.The solution was then stirred at roomtemperature under the irradiation of 15W blueLEDs strip for 24h.After completion of the reaction,the mixture was quenched by addition of1.2mL of 3.0 M HCl, stirred for 20hthen saturated Na2CO3solution was added to adjust pH tobasicextract with CH2Cl2,the combined organic layers was washed with brine, then dry overanhydrous Na2SO4. The desired products were obtained in thecorresponding yields afterpurification by flashchromatography on silica gel eluting with petroleum and ethylacetate.

Reference： [1] Synlett, 2018, vol. 29, # 14, p. 1881 - 1886

4
[ 27311-63-3 ]
[ 4494-18-2 ]

Reference： [1] Patent: EP1550657, 2005, A1, . Location in patent: Page/Page column 68

5
[ 1532-71-4 ]
[ 68-12-2 ]
[ 4494-18-2 ]

Reference： [1] ChemMedChem, 2016, vol. 11, # 4, p. 403 - 419

6
[ 88237-16-5 ]
[ 4494-18-2 ]

Reference： [1] Russian Journal of Organic Chemistry, 2010, vol. 46, # 5, p. 706 - 708

7
[ 119-65-3 ]
[ 4494-18-2 ]

Reference： [1] Organic Letters, 2018, vol. 20, # 18, p. 5752 - 5756

8
[ 2412-58-0 ]
[ 4494-18-2 ]

Reference： [1] Journal of the American Chemical Society, 1942, vol. 64, p. 2430

9
[ 486-73-7 ]
[ 4494-18-2 ]

Reference： [1] Patent: US5554620, 1996, A,
[2] Polyhedron, 2016, vol. 109, p. 147 - 153

10
[ 110-88-3 ]
[ 119-65-3 ]
[ 4494-18-2 ]

Reference： [1] Journal of Organic Chemistry, 1986, vol. 51, # 4, p. 536 - 537

11
[ 1721-93-3 ]
[ 540-80-7 ]
[ 4494-18-2 ]
[ 126921-66-2 ]

Reference： [1] Chemische Berichte, 1975, vol. 108, p. 3771,3778

12
[ 4494-18-2 ]
[ 74417-44-0 ]

Reference： [1] Journal of the Chemical Society, 1951, p. 1145,1147

[ 4494-18-2 ] Synthesis Path-Downstream 1~88

1
[ 110-88-3 ]
[ 119-65-3 ]
[ 4494-18-2 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 536 - 537

2
[ 4930-98-7 ]
[ 4494-18-2 ]
[ 92096-92-9 ]

Reference： [1]Analytical Chemistry,1984,vol. 56,p. 2860 - 2862

3
[ 4494-18-2 ]
[ 15793-77-8 ]
[ 92096-93-0 ]

Reference： [1]Analytical Chemistry,1984,vol. 56,p. 2860 - 2862

4
[ 4494-18-2 ]
[ 15793-94-9 ]
[ 103851-10-1 ]

Reference： [1]Journal of Chemical and Engineering Data,1986,vol. 31,p. 503 - 504

5
[ 4494-18-2 ]
[ 61645-34-9 ]
[ 92096-89-4 ]

Reference： [1]Analytical Chemistry,1984,vol. 56,p. 2860 - 2862

6
[ 4494-18-2 ]
[ 952-92-1 ]
Isoquinolin-1-yl-methanolate1-benzyl-3-carbamoyl-pyridinium; [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 2651 - 2654

7
[ 4494-18-2 ]
[ 36826-58-1 ]
1-<(1-isoquinolylmethylene)amino>-3-hydroxyguanidine tosylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 1103 - 1106

8
[ 4494-18-2 ]
[ 3086-29-1 ]
1-Oxiranyl-isoquinoline [ No CAS ]

Reference： [1]Heterocycles,1984,vol. 22,p. 2517 - 2522

9
[ 4494-18-2 ]
[ 80414-62-6 ]
C₁₉H₂₃N₃O [ No CAS ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1983,vol. 325,p. 205 - 210

10
[ 4494-18-2 ]
[ 70775-39-2 ]
1-Oxiranyl-isoquinoline [ No CAS ]

Reference： [1]Heterocycles,1984,vol. 22,p. 2517 - 2522

11
[ 4494-18-2 ]
[ 162256-49-7 ]
3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4-isoquinolin-1-ylmethyl-5-(4-methoxy-phenyl)-5H-furan-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1063 - 1074

12
4,4'-methylenedianiline [ No CAS ]
[ 4494-18-2 ]
C₃₃H₂₄N₄ [ No CAS ]

Reference： [1]Dalton Transactions,2006,p. 2635 - 2642

13
[ 4494-18-2 ]
[ 4301-14-8 ]
[ 912964-99-9 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 12050 - 12051
[2]Tetrahedron,2008,vol. 64,p. 6876 - 6883

14
[ 4494-18-2 ]
[ 912964-85-3 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 12050 - 12051

15
[ 4494-18-2 ]
1-((tert-butyldimethyl)-silanyloxy)pyrrolo[2,1-a]isoquinoline [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 12050 - 12051

16
[ 4494-18-2 ]
1-Thiiranyl-isoquinoline [ No CAS ]

Reference： [1]Heterocycles,1984,vol. 22,p. 2517 - 2522
[2]Heterocycles,1984,vol. 22,p. 2517 - 2522

17
[ 2412-58-0 ]
[ 4494-18-2 ]

Reference： [1]Journal of the American Chemical Society,1942,vol. 64,p. 2430

18
[ 4494-18-2 ]
[ 74417-44-0 ]

Reference： [1]Journal of the Chemical Society,1951,p. 1145,1147

19
[ 27311-63-3 ]
[ 4494-18-2 ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide; In chloroform; at 20℃; for 0.5h;	Isoquinolin-1-yl-methanol (123.7 mg) was dissolved in chloroform (6.2 ml) and then added with manganese dioxide (chemically processed product) (1.24 g), followed by stirring at room temperature for 30 minutes. The reaction solution was filtrated through Celite and the solvent was then distilled off. The residue was dried under vacuum, thereby obtaining the subject compound (103.9 mg) as a brown solid. 1H-NMR(500MHz,CDCl3):delta=7.72-7.80(2H,m),7.88-7.96(2H,m),8.77(1H,d,J=5.4Hz),9.30-9.36(1H,m),10.3(1H,s).

Reference： [1]Patent: EP1550657,2005,A1 .Location in patent: Page/Page column 68

20
[ 4494-18-2 ]
[ 101-77-9 ]
[ 849661-91-2 ]

Yield	Reaction Conditions	Operation in experiment
69%	In ethanol; at 20℃; for 24h;	To a stirred solution of isoquinaldaldehyde (0.314g, 2 mmol) in ethanol (30 ml) at room temperature was added dropwise an ethanolic solution of bis (4-aminophenyl) methane (0.198g, 1 mmol). After the addition was complete, the reaction mixture was stirred at room temperature for 24 hours. The resultant precipitate was filtered off, washed with ethanol and dried in vacuo under P4O10 to afford 0.33g (69%) of yellow solid. Mass spectrum (FAB): m/z = 477 [M+H]+ Elemental analysis calculated (%) for C33H24N4.0.25H2O : C: 82.4, H: 5.1, N: 11.6 ; found: C: 82.6, H: 5.1, N: 11.6. 1H NMR (400MHz, CDCl3, 298 K): delta = 9.67 (1H, d, J = 7.7 Hz, H9), 9.09 (1H, s, H1), 8.66 (1H, d, J = 5.8 Hz, H3), 7.90 (1H, d, J = 7.5 Hz, H6), 7.75 (3H, m, H4, H7, H8), 7.35 (4H, m, H11, H12), 4.09 (1H, s, H13). IR: nu=3048 (s), 1620 (m), 1582 (m), 1550 (s), 1500 (s), 1388 (m), 1347 (m), 1312 (m), 1140 (m), 1111 (w), 1061 (w), 1011 (w), 966 (m), 905 (m), 866 (w), 847 (w), 823 (vs), 799 (m), 781 (s) 641 (s) cm-1

Reference： [1]Patent: WO2005/33119,2005,A1 .Location in patent: Page/Page column 70

21
[ 4494-18-2 ]
[ 675137-32-3 ]
N-(4-dipropylaminomethylphenyl)-4-[(1H-imidazol-2-ylmethyl)-isoquinolin-1-ylmethylamino]-methyl}-benzamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium cyanoborohydride; acetic acid; In methanol; at 20℃; for 14h;pH ~ 5;	The compound (80 mg) obtained in Example 47-3 was dissolved in methanol (5.0 ml) and added with the compound (59.9 mg) obtained in Example 63-1, followed by the addition of sodium cyanoborohydride (35.9 mg). Then, the reaction solution was adjusted to about pH 5 with acetic acid, followed by stirring at room temperature for 14 hours. The reaction solution was added with a saturated aqueous sodium bicarbonate solution and then extracted with chloroform. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate. Subsequently, the solvent was distilled off. The resulting crude product was purified through silica gel column chromatography (chloroform/methanol) and treated with hydrochloric acid, thereby obtaining hydrochloride (97.1 mg) of the subject compound as a white solid. MS(FAB,Pos.):m/z=561[M+H]+1H-NMR(500MHz,DMSO-d6):delta=0.87(6H,t,J=7.4Hz),1.67-1.78(4H,m),2.86-2.93(4H,m),3.92(2H,s),4.25-4.26(2H,m),4.36(2H,s),4.78(2H,brs),7.57-7.65(6H,m),7.81-7.86(4H,m),7.95(1H,brs),8.11(1H,brs),8.23(1H,brs),8.48-8.52(1H,m),8.62(1H,d,J=6.2Hz),10.34(1H,s),10.48(1H,brs).

Reference： [1]Patent: EP1550657,2005,A1 .Location in patent: Page/Page column 69

22
[ 27104-72-9 ]
[ 4494-18-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	With lithium aluminium tetrahydride; In tetrahydrofuran;	(b) 1-Isoquinolinecarboxaldehyde (7.3 g, 64%) was prepared from 1-isoquinolinecarboxylic acid methyl ester (13.6 g, 0.073 mol) and 1M LAH (36.6 ml in THF) in 300 ml of dry THF (J. Org. Chem., vol 28, p 1898, 1963) to afford 7.3 g (64%) of 1-isoquinolinecarboxaldehyde.
33%	With lithium aluminium tetrahydride; sodium hydroxide; In tetrahydrofuran; at -70℃; for 0.25h;	A solution of methyl 1-isoquinolinecarboxylate (1.00 g, 5.34 mmol) in dry THF (30 mL) was cooled to -70 C in a dry ice/MeOH bath. To that solution was added a suspension of LiAlH4 (0.10 g, 2.67 mmol) in THF (10 mL). The resulting brown reaction mixture was stirred for 15 min followed by a quench with glacial acetic acid (1.3 mL). Once the mixture warmed to RT the aluminum salts were precipitated with a few drops 1 N NaOH. The heterogeneous mixture was filtered, and the solvent was removed under vacuum. The residue was dissolved into a small portion of CH2Cl2 and chromatographed on silica (1:1 hexanes: EtOAc, Rf = 0.79) affording 1-isoquinolinecarboxaldehyde (0.28 g, 33%) as a crystalline white solid. 1H NMR (CDCl3): 10.40 ppm (1H, s); 9.33 ppm (1H, m); 8.76 ppm (1H, d, J = 5.6 Hz); 7.91 ppm (2H, m); 7.77 ppm (2H, m). 13C NMR (CDCl3): 195.63, 149.79, 142.41, 136.85, 130.74, 130.01, 126.91, 126.31, 125.70, 125.45 ppm. IR (KBr pellet): 3033, 2844, 1703 cm-1.

Reference： [1]Patent: US5554620,1996,A
[2]Polyhedron,2016,vol. 109,p. 147 - 153

23
[ 4494-18-2 ]
[ 6343-98-2 ]
[ 173213-26-8 ]

Yield	Reaction Conditions	Operation in experiment
83%		EXAMPLE 22 Synthesis of <strong>[4494-18-2]1-isoquinolinecarbaldehyde</strong>-(5-nitro-2-pyridyl)hydrazone (compound 22) A desired product was obtained in the same manner as in Example 1 by using 3.20 g (20.8 mmol) of 5-nitro-2-pyridylhydrazine and 3.10 g (19.7 mmol) of <strong>[4494-18-2]1-isoquinolinecarbaldehyde</strong>. Yield: 4.80 g (16.4 mmol) [yield rate: 83%] Melting point: 303 to 304 C.

Reference： [1]Patent: US5569763,1996,A

24
[ 4494-18-2 ]
[ 170486-98-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; toluene-4-sulfonic acid; In water; ethylene glycol; toluene;	(c) A mixture of <strong>[4494-18-2]1-isoquinolinecarboxaldehyde</strong> (7.2 g, 46 mmol), 5.7 g (92 mmol) of ethylene glycol, 200 ml of toluene and 2.3 g (12 mmol) of p-toluenesulfonic acid under argon in a 3 neck-flask equipped with a Dean-Stark Trap was refluxed for 6 h separating the water. The mixture was cooled to room temperature, and poured into an ice-cold 10% sodium carbonate solution. The aqueous layer was extracted with ether, the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford 9.3 g of 1-(1,3-dioxolan-2-yl)isoquinoline.

Reference： [1]Patent: US5554620,1996,A

25
[ 4494-18-2 ]
[ 353525-11-8 ]
methyl (2-(1-isoquinolinyl)-6-benzoxazolyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With iodobenzene diacetic acid; In ethanol; hexane; ethyl acetate;	(Step 2) Synthesis of methyl (2-(1-isoquinolinyl)-6-benzoxazolyl)acetate In ethanol (5 ml), <strong>[4494-18-2]1-isoquinolinecarbaldehyde</strong> (252 mg, 1.60 mmol) and methyl 4-amino-3-hydroxyphenylacetate (349 mg, 1.93 mmol) were stirred at room temperature for 12 hours. Iodobenzene diacetate (619 mg, 1.92 mmol) was added and the reaction mixture was stirred further at room temperature for 15 minutes. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (4:1 to 3:1, v/v) eluate fractions, methyl (2-(1-isoquinolinyl)-6-benzoxazolyl)acetate (166 mg, 33%) was obtained as a yellow amorphous substance. 1H-NMR (CDCl3) delta: 3.73 (s, 3H), 3.82 (s, 2H), 7.35-7.38 (m, 1H), 7.68 (m, 1H), 7.75-7.95 (m, 5H), 8.77-8.78 (m, 1H), 9.67-9.70 (m, 1H). MS (ESI) m/z 319 (M++1).
		General procedure: A mixture of 6-fluoro-1-methylindole-3-carbaldehyde (13a) (500 mg, 2.82 mmol) and methyl 4-amino-3-hydroxyphenylacetate (11a) (767 mg, 4.23 mmol) in EtOH (15 ml) was stirred for 22 h, and iodobenzene diacetate (1.09 g, 3.38 mmol) was added portionwise to the mixture. After being stirred for 1 h, the mixture was concentrated, and the residue was purified column chromatography with n-hexane-AcOEt (1:1, v/v) as eluent to give methyl [2-(6-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl]acetate (889 mg, 93%) as a brown solid.

Reference： [1]Patent: EP1346982,2003,A1
[2]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 1201 - 1212

26
[ 4494-18-2 ]
[ 441713-62-8 ]
methyl (7-fluoro-2-(1-isoquinolinyl)-6-benzoxazolyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With iodobenzene diacetic acid; In ethanol; hexane; ethyl acetate;	(Step 1) Synthesis of methyl (7-fluoro-2-(1-isoquinolinyl)-6-benzoxazolyl)acetate In ethanol (13 ml), <strong>[4494-18-2]isoquinoline-1-carbaldehyde</strong> (500 mg, 3.18 mmol) and methyl 4-amino-2-fluoro-3-hydroxyphenylacetate (632 mg, 3.17 mmol) were stirred at room temperature for 2 days. Iodobenzene diacetate (1.23 g, 3.82 mmol) was added, and the reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (3:1, v/v) eluate fractions, methyl (7-fluoro-2-(1-isoquinolinyl)-6-benzoxazolyl)acetate (155 mg, 14%) was obtained as a red brown solid. 1H-NMR (CDCl3) delta: 3.74 (s, 3H), 3.87 (s, 2H), 7.30-7.33 (m, 1H), 7.66-7.94 (m, 5H), 8.78-8.79 (m, 1H), 9.58 (m, 1H). MS (ESI) m/z 337 (M++1).

Reference： [1]Patent: EP1346982,2003,A1

27
[ 4494-18-2 ]
nickel(II) perchlorate hexahydrate [ No CAS ]
[ 154778-71-9 ]
Ni(C₁₈H₂₀N₃O)⁽¹⁺⁾*ClO₄^(1-)=[Ni(C₁₈H₂₀N₃O)]ClO₄ [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1999,vol. 293,p. 115 - 122

28
[ 4494-18-2 ]
[ 32566-01-1 ]
N-[2-(1H-2-indolyl)phenyl]-N-[(E)-1-(1-isoquinolyl)methylidene]amine [ No CAS ]

Reference： [1]Archiv der Pharmazie,2009,vol. 342,p. 533 - 540

29
[ 928632-96-6 ]
[ 4494-18-2 ]
[ 1201913-96-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6441 - 6446

30
[ 4494-18-2 ]
[ 558446-23-4 ]
C₂₈H₃₆N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3026 - 3030

31
[ 4494-18-2 ]
[ 5805-39-0 ]
N₁-[(E)-1-(1-isoquinolyl)methylidene]-2-(1H-benzo[d]imidazol-2-yl)aniline [ No CAS ]

Reference： [1]Journal of the Brazilian Chemical Society,2010,vol. 21,p. 49 - 57

32
[ 4494-18-2 ]
[ 536-74-3 ]
C₁₈H₁₃NO [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3242 - 3245
[2]Organic Letters,2016,vol. 18,p. 2204 - 2207

33
[ 4494-18-2 ]
[ 693-02-7 ]
[ 1256744-35-0 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3242 - 3245
[2]Organic Letters,2010,vol. 12,p. 5558 - 5560

34
[ 88237-16-5 ]
[ 4494-18-2 ]

Reference： [1]Russian Journal of Organic Chemistry,2010,vol. 46,p. 706 - 708

35
[ 4494-18-2 ]
[ 343338-28-3 ]
C₁₄H₁₆N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	copper(II) sulfate; In dichloromethane; at 90℃; for 0.0833333h;	General Procedure F(S)-2-Methyl-propane-2-sulfinic acid amide (1 equiv) was taken up in DCM (2 mL/mmol) in a MW vial, then copper sulphate (2.2 equiv) and aldehyde (1.1 equiv) was added and the vial capped. Heated at 90 0C for 5 min, then filtered and cooled under argon to -50 0C before slow addition of methyl magnesium bromide (2 equiv). The reaction mixture was allowed to warm to r.t. over night. Quenched with ammonium chloride (aq) and extracted with EtOAc, then dried over Na2SO4 and concentrated in vacuo. The intermediate was purified by flash chromatography. Taken up in methanol (1 mL/mmol), then HCI in dioxane (4M, 1 mL/mmol) was added and the reaction mixture stirred at r.t. for 30 min. The methanol was evaporated and the product precipitated with ether. The title compound was collected by filtration and dried in vacuo.; Preparation 21. (R)-l-Isoquinolin-l-yl-ethylamine dihydrochlorideGeneral procedure F was followed using <strong>[4494-18-2]isoquinoline-1-carbaldehyde</strong> as the aldehyde. 1H NMR (300 MHz, DMSO) delta 8.68 (s, 3H), 8.55 (d, J = 5.7, IH), 8.36 (d, J = 7.9, IH), 8.08 (d, J = 7.9, IH), 7.88 (ddd, J = 3.4, 8.4, 9.3, 2H), 7.77 (ddd, J = 1.3, 6.9, 8.2, IH), 5.64 - 5.08 (m, 7H), 1.59 (d, J = 6.8, 3H).

Reference： [1]Patent: WO2010/136037,2010,A1 .Location in patent: Page/Page column 52; 59

36
[ 4494-18-2 ]
[ 109-77-3 ]
[ 1284237-36-0 ]

Yield	Reaction Conditions	Operation in experiment
31%	With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; piperdinium acetate; In toluene; at 105℃; for 3h;Inert atmosphere;	The general procedure for the synthesis of the 3-aminoindolizine derivatives 1a-e, 6a-g, and uncyclized product 8a-c is described below: To a reaction mixture of cyano substrate 3 (2.0 mmol), 2-carbonyl pyridine derivative (2.0 mmol), and piperidinium acetate (15 mg, 0.10 mmol) in toluene (6 ml), was added diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (9) (Hantzsch ester, 557 mg, 2.2 mmol) in one portion at room temperature. The resulting mixture was degassed with a stream of nitrogen and then stirred at 105 C for 3 h. After cooling to room temperature, a minimum amount (ca 0.3-0.5 mL) of DMSO was added to the reaction mixture and the resulting solution was directly loaded to a silica gel column and purified by column chromatography using Teledyne Isco Combiflash system.

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 1392 - 1394

37
[ 4494-18-2 ]
C₅₂H₇₂N₂O₇S₄ [ No CAS ]
25,27-bis[2-(quinoline)iminoethoxy]thiacalix[4]crown-5 [ No CAS ]

Reference： [1]Dalton Transactions,2010,vol. 39,p. 10122 - 10127

38
[ 4494-18-2 ]
C₅₀H₇₀N₂O₄S₄ [ No CAS ]
C₇₀H₈₀N₄O₄S₄ [ No CAS ]

Reference： [1]Dalton Transactions,2010,vol. 39,p. 10122 - 10127

39
[ 4494-18-2 ]
[ 67-64-1 ]
[ 1357287-85-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 1239 - 1245

40
[ 4494-18-2 ]
[ 441712-74-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 1201 - 1212

41
[ 4494-18-2 ]
[ 441716-04-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 1201 - 1212

42
[ 4494-18-2 ]
[2-(1-isoquinolinyl)-6-benzoxazolyl]acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 1201 - 1212

43
[ 4494-18-2 ]
[ 2835-06-5 ]
[ 19382-37-7 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 11161 - 11166

44
[ 4494-18-2 ]
[ 591-87-7 ]
[ 1610596-33-2 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 6168 - 6170

45
[ 4494-18-2 ]
[ 104-94-9 ]
[ 1588480-68-5 ]

Reference： [1]Organometallics,2014,vol. 33,p. 1820 - 1833

46
[ 4494-18-2 ]
(±)-cis-4-(isoquinolin-1-yl)-3-phenoxyazetidin-2-one [ No CAS ]

Reference： [1]Organometallics,2014,vol. 33,p. 1820 - 1833

47
[ 4494-18-2 ]
(±)-cis-4-(isoquinolin-1-yl)-1-(4-methoxyphenyl)-3-phenoxyazetidin-2-one [ No CAS ]

Reference： [1]Organometallics,2014,vol. 33,p. 1820 - 1833

48
[ 4494-18-2 ]
[ 107-15-3 ]
[ 1167511-25-2 ]

Reference： [1]Dalton Transactions,2014,vol. 43,p. 10013 - 10022

49
[ 4494-18-2 ]
[ 1615717-31-1 ]

Reference： [1]Dalton Transactions,2014,vol. 43,p. 10013 - 10022

50
[ 4494-18-2 ]
[ 1615717-10-6 ]

Reference： [1]Dalton Transactions,2014,vol. 43,p. 10013 - 10022

51
[ 4494-18-2 ]
[ 170486-99-4 ]

Reference： [1]Patent: US5554620,1996,A

52
[ 4494-18-2 ]
[ 170487-00-0 ]

Reference： [1]Patent: US5554620,1996,A

53
[ 486-73-7 ]
[ 4494-18-2 ]

Reference： [1]Patent: US5554620,1996,A
[2]Polyhedron,2016,vol. 109,p. 147 - 153

54
[ 4494-18-2 ]
[ 1323988-51-7 ]
isoquinolin-1-yl((4aR,8aS)-2-(4-methoxyphenyl)-4,4a,8,8a-tetrahydropyrano[3,2-d][1,3]dioxin-6-yl)methanone [ No CAS ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 13391 - 13393

55
[ 4494-18-2 ]
[ 1067-71-6 ]
4-(isoquinolin-1-yl)but-3-en-2-one [ No CAS ]