[ CAS No. 4139-61-1 ] {[proInfo.proName]}

Name: 4139-61-1|6-Bromo-4-hydroxycoumarin|95%
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SKU: A526974
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Quality Control of [ 4139-61-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4139-61-1 ]

SDS Specification

Alternatived Products of [ 4139-61-1 ]

Product Details of [ 4139-61-1 ]

CAS No. :	4139-61-1	MDL No. :	MFCD00239372
Formula :	C₉H₅BrO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KNMCTCABMSGXGR-UHFFFAOYSA-N
M.W :	241.04	Pubchem ID :	54691404
Synonyms :

Calculated chemistry of [ 4139-61-1 ] Expand+

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	52.21
TPSA :	50.44 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) :	-6.38 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.71
Log Po/w (XLOGP3) :	1.96
Log Po/w (WLOGP) :	2.26
Log Po/w (MLOGP) :	1.76
Log Po/w (SILICOS-IT) :	2.62
Consensus Log Po/w :	2.06

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.14
Solubility :	0.175 mg/ml ; 0.000727 mol/l
Class :	Soluble
Log S (Ali) :	-2.64
Solubility :	0.547 mg/ml ; 0.00227 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.9
Solubility :	0.0307 mg/ml ; 0.000127 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.57

Safety of [ 4139-61-1 ]

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 [ 4139-61-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 4139-61-1 ]

[ 4139-61-1 ] Synthesis Path-Downstream 1~109

1
[ 50-00-0 ]
[ 4139-61-1 ]
bis-(6-bromo-2,4-dioxo-chroman-3-yl)-methane [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1944,vol. 66,p. 656

2
[ 4139-61-1 ]
[ 141-82-2 ]
9-bromo-pyrano[3,2-c]chromene-2,4,5-trione [ No CAS ]

Reference： [1]Monatshefte fur Chemie,1956,vol. 87,p. 386,390

3
[ 1121-60-4 ]
[ 4139-61-1 ]
[ 95943-30-9 ]

Reference： [1]Journal of Medicinal Chemistry,1964,vol. 7,p. 284 - 288

4
[ 4139-61-1 ]
2-[4-(N-acetyl-anilino)-buta-1,3-dienyl]-3-methyl-benzooxazolium; iodide [ No CAS ]
[ 4699-04-1 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

5
[ 4139-61-1 ]
[ 71467-45-3 ]
[ 5003-07-6 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

6
[ 4139-61-1 ]
[ 24136-78-5 ]
[ 5002-76-6 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

7
[ 4139-61-1 ]
[ 62148-33-8 ]
[ 5002-79-9 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

8
[ 4139-61-1 ]
[ 62196-30-9 ]
[ 4699-03-0 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

9
[ 4139-61-1 ]
2-[4t-(N-acetyl-anilino)-buta-1,3-dien-t-yl]-1-methyl-quinolinium; iodide [ No CAS ]
[ 4699-07-4 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

10
[ 4139-61-1 ]
[ 41682-06-8 ]
[ 5002-77-7 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

11
[ 4139-61-1 ]
[ 112658-19-2 ]
[ 4699-06-3 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

12
[ 4139-61-1 ]
[ 135692-19-2 ]
[ 5002-78-8 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

13
[ 4139-61-1 ]
[ 111065-21-5 ]
[ 4699-05-2 ]

Reference： [1]Indian Journal of Chemistry,1965,vol. 3,p. 461 - 462

14
[ 4139-61-1 ]
[ 34173-12-1 ]

Reference： [1]Phytochemistry,1971,vol. 10,p. 539 - 544

15
[ 4139-61-1 ]
[ 120-80-9 ]
[ 21523-53-5 ]

Reference： [1]Synthetic Communications,1989,vol. 19,p. 1303 - 1308
[2]Tetrahedron,1989,vol. 45,p. 6867 - 6874

16
[ 4139-61-1 ]
[ 106-95-6 ]
[ 129206-55-9 ]

Reference： [1]Synthesis,1990,p. 535 - 538
[2]Journal of Heterocyclic Chemistry,2015,vol. 52,p. 1014 - 1018

17
[ 4139-61-1 ]
[ 137-07-5 ]
2-Bromo-12H-5-oxa-7-thia-12-aza-benzo[a]anthracen-6-one [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1985,vol. 62,p. 377 - 379
[2]European Journal of Medicinal Chemistry,2001,vol. 36,p. 127 - 136

18
[ 4139-61-1 ]
[ 57584-95-9 ]
3-benzoyl-9-bromo-3,4-dihydro-2H-pyrano[3,2-c]chromen-5-one [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1998,vol. 35,p. 1455 - 1460

19
[ 4139-61-1 ]
1-(3,4-Dimethoxy-phenyl)-2-dimethylaminomethyl-propenone [ No CAS ]
9-bromo-3-(3,4-dimethoxy-benzoyl)-3,4-dihydro-2H-pyrano[3,2-c]chromen-5-one [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1998,vol. 35,p. 1455 - 1460

20
[ 4139-61-1 ]
[ 75318-43-3 ]
(E)-6-bromo-3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-6-methyl-2H-1-benzopyran-2,4-dione [ No CAS ]

Reference： [1]Tetrahedron,1999,vol. 55,p. 9651 - 9667

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydride; In toluene; mineral oil; for 1h;Reflux;	General procedure: Using method B,200 mg NaH (5 eq, 60% dispersion in solid oil)Was added to 30 ml of anhydrous toluene in phaseThe acetophenone analogue (8 mmol, leq) was then added,Then, 0.18 ml of diethyl carbonate (1.5 eq) was slowly added dropwise, and the mixture was refluxed for 1 hour.After cooling to room temperature, the reaction was quenched by slow addition of cold water under an ice bath and 1 N hydrochloric acid was adjusted to acidity. Ethyl acetate extraction three times, each 20 ml, the combined organic phase, 20 ml of saturated brine washed once, evaporated under vacuum, column purification. (Intermediate 3a, 1.18 g, 75%; intermediate 4a, 1.45 g, 75%; intermediate 5b, 1.65 g, 93%; intermediate 6b, 1.82g, 91% , intermediate 8b, 1.40g, 91%; intermediate 9b, 1.55g, 94%; intermediate 10c, 1.70g, 87%; intermediate 11c, 1.54g, 89%; intermediate 13b, 1.55g, 89%

23
[ 4139-61-1 ]
[ 50609-85-3 ]
4-bromo-2-(3-methylamino-5-phenyl-2-thenoyl)phenol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3690 - 3699

24
[ 4139-61-1 ]
[ 58885-58-8 ]
[3-(6-bromo-2-oxo-2H-chromen-4-yloxy)-propyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 2723 - 2739

25
[ 4139-61-1 ]
[ 109384-19-2 ]
4-(6-bromo-2-oxo-2H-chromen-4-yloxy)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 2723 - 2739

26
[ 4139-61-1 ]
3,6-dibromo-4-hydroxy-chromen-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; ammonium acetate; In acetonitrile; at 20℃; for 3h;	General procedure: Bromination of 4-hydroxycoumarin (5 g, 30.8 mmol) was carried out in acetonitrile (100 mL) with the addition of N-bromosuccinimide (5.7 g, 32.34 mmol) followed by ammonium acetate (0.237 g, 3.08 mmol). The reaction mixture was stirred at rt for 3 h. After the reaction time, organic solvent was evaporated and the crude was treated with ethyl acetate and water mixture (50 mL, 1:1). The organic layer was extracted with ethyl acetate (3×20 mL), treated with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude product was purified by crystallization to obtain 3-bromo-4-hydroxycoumarin as light yellow solid (6.5 g, 88%). It was used directly in the next step.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 6181 - 6184
[2]Tetrahedron,2015,vol. 71,p. 5137 - 5147

27
[ 4139-61-1 ]
[ 1896-62-4 ]
6-bromo-4-hydroxy-3-(3-oxo-1-phenylbutyl)chromen-2-one [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 413 - 415

28
[ 4139-61-1 ]
2-bromo-7,12-dihydro-chromeno[3,4-b]quinoxalin-6-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 6181 - 6184

29
[ 4139-61-1 ]
2-bromo-9,10-dimethyl-7,12-dihydro-chromeno[3,4-b]quinoxalin-6-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 6181 - 6184

30
[ 4139-61-1 ]
4-(3-aminopropoxy)-6-bromo-1-benzopyran-2-one trifluoroacetate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 2723 - 2739

31
[ 4139-61-1 ]
6-bromo-4-(piperidin-4-yloxy)-1-benzopyran-2-one trifluoroacetate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 2723 - 2739

32
[ 4139-61-1 ]
[ 129206-59-3 ]

Reference： [1]Synthesis,1990,p. 535 - 538
[2]Journal of Heterocyclic Chemistry,2015,vol. 52,p. 1014 - 1018

33
[ 4139-61-1 ]
[ 358-23-6 ]
[ 638191-63-6 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In dichloromethane; at -10℃; for 2.16667h;	[[00124]] To a cooled (-10 [C)] solution of 6-bromo-4- hydroxycoumarin (1.8 g, 7.5 mmol) and dry triethylamine (2.1 mL, 15 mmol) in dry CH2Cl2 was added trifluoromethane sulfonic anhydride (1.5 mL, 9 mmol) dropwise over 10 minutes. The solution was allowed to stir for 2 hrs at-10 [C] and was warmed to room temperature and diluted with 100 mL of 1: 1 hexane: diethylether solution. The reddish brown solution was filtered through silica gel aided by another 300 mL of 1: 1 hexane: diethylether solution and was concentrated to give 2.4g (86%) of a pure yellow solid. 1H NMR (300 MHz, DMSO) 8 ppm 6.97 (s, 1H), 7.57 (d, 1H), 7.80 (d, 1H), 7. 98 (dd, 1H).
60%	With triethylamine; In dichloromethane; at -15℃; for 2h;Inert atmosphere;	Tf2O (0.41 mL, 2.43 mmol) was added at -15 C to a solution of 1 (0.45 g, 1.87 mmol) and triethylamine (0.5 mL, 3.74 mmol) in CH2Cl2 (15 mL) and the reaction mixture was stirred at the same temperature under argon atmosphere for 2 h. To the reaction mixture was added toluene (10 mL) and the solution was concentrated in vacuo. The residue was chromatographed (EtOAc/Heptanes: 9/300) without aqueous work up to yield 2 as a white solid (0.42 g, 60%), mp 110-112 C. 1H NMR (300 MHz, CDCl3): delta = 6.47 (s, 1H, CCH), 7.25 (d, 1H, J = 8.9 Hz, ArH), 7.69-7.73 (m, 2H, ArH). 19F NMR (282.4 MHz, CDCl3): delta = -72.5. 13C NMR (75.5 MHz, CDCl3): delta = 105.5 (CH), 114.4, 117.1 (C), 118.1 (CH), 118.3 (q, JC,F = 320.6 Hz, CF3), 124.0, 136.0 (CH), 151.2, 154.8, (C), 157.8 (CO). IR (KBr): v = 3119, 3087, 3054, 2918, (w), 1727 (s), 1628, 1599, 1562, 1473 (m), 1436, 1418, 1349 (s), 1307, 1266 (w), 1250 (m), 1213, 1184 (s), 1170 (m), 1041 (s), 937 (w), 876, 852, 825, 826, 808, 788, 759 (m), 741, 712, 696, 653, 633 (w) cm-1. GC-MS (EI, 70 eV): m/z (%) = 374 ([M, 81Br]+, 100), 372 ([M, 79Br]+, 97), 282 (29), 280 (29), 213 (51), 211 (53). HRMS (EI, 70 eV): calcd for C10H4BrF3O5S [M, 79Br]+: 371.89094; found 371.89097, calcd for C10H4BrF3O5S ([M, 81Br]+: 373.88890; found 373.88890.
	With triethylamine; In dichloromethane; for 3h;Cooling with ice;	Step one: the 6 - bromo -4 - hydroxy coumarin (1 mmol) with triethylamine (1.5 mmol) dissolved in 10 ml dichloromethane after, cold water bath cooling, trifluoromethyl sulfonic acid anhydride (1.5 mmol) is added slowly dropping in the reaction system, the reaction 3 hours later, and steaming and to remove the solvent, after concentrating column separation (petroleum ether and ethyl acetate to the volume proportion 4:1) to obtain 6 - bromo -4 - trifluoromethanesulfonic acid ester - coumarin.

Reference： [1]Patent: WO2003/106452,2003,A2 .Location in patent: Page 88
[2]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209
[3]Patent: CN107629050,2018,A .Location in patent: Paragraph 0248; 0249

34
[ 33821-94-2 ]
[ 4139-61-1 ]
6-Bromo-4-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-1-benzopyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%		EXAMPLE 50 6-Bromo-4-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-1-benzopyran-2-one 6-Bromo-4-hydroxycoumarin (1.19 mmol, 0.287 g), K2CO3 (3.57 mmol, 0.493 g) and 2-3-(bromopropoxy)tetrahydro-2H-pyran (1.19 mmol, 0.264 g) is suspended in 10 mL of acetone, and is heated to 55 C. for 24 hrs at which time the reaction is not complete. Cs2CO3 (1.54 mmol, 0.5 g) and 5 mL of DMF are added and the reaction is heated for an additional 2 hrs. Twenty-five percent of the crude THP protected material is purified by HPLC to afford the title compound (70.8 mg, 62%); 1H NMR (CDCl3, 300 MHz) delta 7.91 (1H, d, J=2.25 Hz), 7.82 (1H, dd, J=2.5, 9 Hz), 7.39 (1H, d, J=9 Hz), 5.98 (1H, s), 4.59 (1H, m), 4.31 (2H, t, J=6 Hz), 3.83 (1H, m), 3.72 (1H, m), 3.55 (2H, m), 2.09 (2H, m), 1.65 (2H, m), 1.45 (4H, m); MS (ESI, Pos.) calcd for C17H19BrO5 m/z [M+H]=383.0, found 383.1.

Reference： [1]Patent: US2005/54681,2005,A1 .Location in patent: Page/Page column 25

35
[ 4139-61-1 ]
[ 131543-46-9 ]
8-bromo-3-(6-bromo-4-hydroxy-2-oxo-2H-chromene-3-yl)-2-hydroxy-2,3-dihydro-4H-furo[3,2-c]chromene-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	In water; acetonitrile; for 4h;Heating / reflux;	Compound 33: 8-BROMO-3- (6-BROMO-4-HYDROXY-2-OXO-2H-CHROMENE-3-YL)-2- hydroxy-2,3-dihydro-4H-furo [3,2-c]chromene-4-one; Example 33; 6-BROMO-4-HYDROXYCOUMARIN (120 mg; 0.5 mmole) was mixed with a 40 % aqueous solution of glyoxal (288 muL ; 2.5 mmole). Acetonitrile (5 mL) was added thereto and the reaction mixture was refluxed for 4 hours. By cooling the solution to room temperature a white precipitate was precipitated, which was filtered and washed with acetonitrile. There were obtained 20 mg (24%) of compound 33, which did not need additional purification. 1H-NMR (300 MHz, DMSO-D6) RPPM : 4.82 (bs, 1H); 5.34 (bs, 1H, aldehyde form); 6.33 (bs, 1H); 7.25-7. 40 (m, 2H); 7.72-7. 88 (m, 3H); 8. 19 (bs, 1H); 9.26 (bs, 1H, aldehyde form); 13C-NMR (75.4 MHz, DMSO-D6) No./PPM : 42.7 ; 101.1 ; 101.6 ; 108. 6; 112.7 ; 114.7 ; 115.0 ; 116.7 ; 117.6 ; 117.9 ; 122.9 ; 124.2 ; 133. 8 ; 134.2 ; 149.7 ; 152.3 ; 156.7 ; 160.0 ; 162.6 ; 164.9 ; MS M/Z : ES- (acetonitrile: water) [M-H]- : 518. 6,520. 6; 522.6.

Reference： [1]Patent: WO2005/10006,2005,A1 .Location in patent: Page/Page column 47-48

36
[ 4139-61-1 ]
[ 33209-75-5 ]
6-Bromo-4-hydroxy-3-[4-(2-methoxyphenyl)butyl]-2H-1-benzopyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%		EXAMPLE 27 6-Bromo-4-hydroxy-3-[4-(2-methoxyphenyl)butyl]-2H-1-benzopyran-2-one The title compound was prepared from <strong>[4139-61-1]4-hydroxy-6-bromo-2H-1-benzopyran-2-one</strong>, and 4-(2-methoxyphenyl)butanoic acid using the procedure described in Example 13. A 55% yield of the title compound was obtained, m.p. 147.5-148.5 C.

Reference： [1]Patent: US5510375,1996,A

37
[ 4139-61-1 ]
o-methylsulfonyliodosobenzene [ No CAS ]
((2-Methylsulfonyl)phenyl)-iodonium 6-bromo-3,4-dihydro-2,4-dioxo-2H-benzopyran-3-ylide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	EXAMPLE 30 ((2-Methylsulfonyl)phenyl)-iodonium 6-bromo-3,4-dihydro-2,4-dioxo-2H-benzopyran-3-ylide STR45 To a solution of O-methylsulfonyliodosobenzene (0.5 mol, 150 mg) and 10 mL of hot methanol was added to a solution consisting of <strong>[4139-61-1]6-bromo-4-hydroxycoumarin</strong> (0.5 mmol, 120 mg) and 15 mL of hot methanol. The resultant solution was cooled to give a precipitate which was filtered, dried under vacuum, and determined by PMR, CMR and MS to be the desired product: yield, 180 mg: m.p. 285-287 C. (dec.).

Reference： [1]Patent: US5106407,1992,A

38
[ 4139-61-1 ]
[ 69180-53-6 ]
(2-Nitrophenyl)-iodonium 6-bromo-3,4-dihydro-2,4-dioxo-2H-benzopyran-3-ylide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	EXAMPLE 23 (2-Nitrophenyl)-iodonium 6-bromo-3,4-dihydro-2,4-dioxo-2H-benzopyran-3-ylide STR38 6-Bromo-4-hydroxycoumarin (1 mmol, 240 mg) was dissolved in 10 mL of hot methanol and to it was added a solution of 2-nitroiodosobenzene (1 mmol, 265 mg) in 15 mL of hot methanol. The resultant solution was allowed to cool and a precipitate was formed which was filtered, dried under vacuum and determined by both PMR and MS to be the desired product; yield, 390 mg; m.p. 288-290 C. (dec.).

Reference： [1]Patent: US5106407,1992,A

Yield	Reaction Conditions	Operation in experiment
		(i) 6-Bromo-4-hydroxy-3-nitrocoumarin Fuming nitric acid (17 ml) was added to a stirred suspension of 6-bromo-4-hydroxycoumarin (m.p. 275-7; 3.25g) in chloroform (200 ml) at room temperature over 1.5 hours. After a further 2 hours, the solvent was removed in vacuo at room temperature and 6N hydrochloric acid (100 ml) added to the residue. Filtration gave the product, m.p. 161-4(d), (C9 H4 NO5 Br requires C, 37.79; H, 1.41; N, 4.90; Br, 27.94. Found: C, 37.86; H, 1.63; N, 5.05; Br, 27.64).

40
[ 4139-61-1 ]
[ 87120-72-7 ]
[ 638192-59-3 ]

Yield	Reaction Conditions	Operation in experiment
		[[00187]] To an oven dried 250 mL round bottom flask with a stir bar was added 3.00 g (12.4 mmol) of 4-hydroxy-6- bromocoumarin and 25.0 mL of dry [CH2C12. TO] this was added 2.25 mL (16.1 mmol) of triethylamine, and the resultant solution cooled to-10 [C] in an ice/sat NaCl bath. Triflic anhydride was then added dropwise (2.80 mL, 16.6 mmol) and the reaction. stirred at this temp under N2 for 2 h. After this time, the reaction solution was allowed to warm to rt, and was then diluted with 120 mL of 1: 1 [ETHER/HEXANE.] The mixture was then poured over a bed of silica gel to remove the fine white precipitate and the cake rinsed with 1: 1 ether/hexane. Evaporation of the filtrate afforded 4.30 g of a yellow solid. This material was then added to a 500 mL rb flask with a stir bar and 100 mL THF was added. To this was added 2.40 g (12.0 mmol) of [4-AMINO-PIPERIDINE-1-CARBOXYLIC] acid tert-butyl ester and the reaction mixture allowed to stir for 5 h. After this time the solvent was evaporated down and the resultant material taken up in 1: 1 EtOAc/hexanes and loaded onto a plug of silica gel. Elution with the same mixture afforded the title product as a white [SOLID. 1H] NMR (300 MHz, [DMSO-D6)] ppm 1.42 (m, 11 H) 1.89 (s, 2 H) 2.89 (m, 2 H) 3.75 (m, [1] H) 3.99 (m, 2 H) 5.37 (m, [1] H) 7.29 (m, 2 H) 7.74 (m, [1] H) 8.40 (m, 1 H); MS (DCI/NH3) m/z 425 [M+H] [+.]

Reference： [1]Patent: WO2003/106452,2003,A2 .Location in patent: Page 127-128

41
[ 6553-96-4 ]
[ 4139-61-1 ]
6-bromo-2-oxo-2H-chromen-4-yl 2,4,6-triisopropylbenzenesulfonate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3649 - 3653

42
[ 1450-75-5 ]
[ 105-58-8 ]
[ 4139-61-1 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydride; In toluene; at 100℃; for 4.5h;Cooling with ice;	2 (74 mmol) and diethyl carbonate (111 mmol) in toluene (160 mL) were added dropwise to sodium hydride (369 mmol) in toluene (50 mL) in ice-water bath. The mixture was stirred at ice bath for 30 min and at 100C for 4 h. The sodium hydride was quenched with water, acidized with hydrochloric acid and then the suspension was filtered separately, and the solid collected from this filtration was washed with toluene and water for three times. The solid dried at room temperature with phosphorus pentoxide. 3: yield 71%. 1H NMR (400MHz, CDCl3): delta 12.17 (s, 1H), 7.83 (d, J=2.45, 1H), 7.55 (dd, J=2.4Hz, 8.8Hz, 1H), 6.90 (d, J=9.2Hz, 1H), 2.63 (s, 3H) ppm.
70%	With sodium hydride; In toluene; at 100℃; for 4.5h;Cooling with ice;	General procedure: 2a-2c (23.1 mmol) and diethyl carbonate (34.7 mmol, 4.14 g) in toluene (10 mL) were added dropwise to sodium hydride (115 mmol, 4.7 g) in toluene (50 mL) in ice-water bath. The mixture was stirred at ice bath for 30 min and at 100 ? for 4 h. The sodium hydride was quenched with water, acidized with hydrochloric acid and then the suspension was filtered separately, and the solid collected from this filtration was washed with toluene and water for three times. The solid dried at room temperature with phosphorus pentoxide. 3a: yield 70%. HPLC purity: 96.9%.1H NMR (400 MHz, d6-DMSO): delta 5.62 (s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.81 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.90 (d, J = 2.0 Hz, 1H), 12.51 (br s, 1H). 3b: yield 67%. HPLC purity: 96.9%. 3c: yield 86%. HPLC purity: 98.2%.1H NMR (400 MHz, d6-DMSO): delta 3.83 (s, 3H), 5.51 (s, 1H), 6.92-6.96 (m, 2H), 7.71 (d, J = 8.4 Hz, 1H), 12.51 (br s, 1H).
69%	With sodium hydride; In toluene; at 0℃; for 4.5h;Reflux;	General procedure: To a stirred mixture of 5a-f (1.15 mmol) and sodium hydride (138 mg, 5.75 mmol) in 5 ml dry toluene, a solution of the diethyl carbonate (1.15 mmol) in dry toluene was dropped. The mixture was reacted at 0C for 30 min, then heated to reflux and reacted for another 4 h. The reaction mixture was quenched with water (20 mL) at ice bath and neutralized to pH 7 with 2 N HCl. The precipitate was filtered, washed with cold water and dried to get 6a-f.

		General procedure: Preparation of 4-hydroxycoumarin (step 1)9aA solution of 2-hydroxy-5-methoxyacetophenone (9 mmol,1.5 g) in toluene (15 mL) was added dropwise to a dry three-neckround-bottom flask containing sodium hydride (60% w/w suspension,45 mmol, 1.8 g) in toluene (10 mL). This was done under N2atmosphere at ice bath temperature. The mixturewas stirred at thesame temperature for 15 min and followed by the dropwise additionof diethylcarbonate (13.5 mmol, 1.6 g) in toluene (10 mL). Aftercomplete addition, the reaction mixturewas stirred at rt for 30 minand refluxed for five more hours. The reaction mixture wasquenched at ice bath temperature by slow addition of water(20 mL) and acidified with 2 N HCl. The product obtained as a solidprecipitate was filtered, washed with water, and dried under vacuumto get 4-hydroxy-6-methoxy-2H-chromen-2-one as a whitesolid (1.4 g, 82%). This product was directly used in step 2.
	With sodium hydride; In mineral oil; at 100℃; for 4h;	A mixture of 2-hydroxy-5-bromoacetophenone (5g, 23.1mmol) and diethyl carbonate (4.14g, 34.7mmol) were combined then added toluene (10ml) was dissolved. Sodium hydride (4.7g, mass fraction of 60%, 115mmol) and toluene (50ml) After mixing, the toluene was dissolved 2-hydroxy-5-bromoacetophenone and diethyl carbonate mixed solution was slowly added dropwise under ice bath among them. After dropping about 20min,The reaction temperature was raised to 100 deg.] C for 4 hours. After completion of the reaction, insolubles were filtered off the solid, the filter cake washed with toluene, repeating the first layer, followed by two to three times a small amount of water. With phosphorus pentoxide at room temperature under reduced pressure and dried to give a yellow solid (3.9g, 70% crude yield).
		In a 250 mL two-neck round-bottom flask, 9 mmol of ohydroxyacetophenonein 15 mL toluene was slowly added to sodiumhydride (60% w/w suspension, 5 equiv, 45 mmol, 1.8 g) intoluene (10 mL) under N2 atmosphere at 0 C. After 15 min,13.5 mmol of diethyl carbonate in 10 mL toluene was added dropwise,and the mixture was stirred at room temperature for 30 minand refluxed until the reaction finished (monitored by TLC (ThinLayer Chromatography)). After the mixture cooled to room temperature,the reaction was quenched by slowly addition of 2 N hydrochloricacid. The resulting precipitate was further purified by ashort silica gel column chromatography to give a white solid.

Reference： [1]New Journal of Chemistry,2018,vol. 42,p. 13985 - 13997
[2]European Journal of Medicinal Chemistry,2016,vol. 114,p. 232 - 243
[3]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807
[4]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 2129 - 2135
[5]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3649 - 3653
[6]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2550 - 2557
[7]Tetrahedron,2014,vol. 70,p. 6995 - 7005
[8]Journal of Heterocyclic Chemistry,2015,vol. 52,p. 1014 - 1018
[9]Patent: CN103254203,2016,B .Location in patent: Paragraph 0062; 0072; 0073
[10]Tetrahedron,2018,vol. 74,p. 970 - 974
[11]Bioorganic and medicinal chemistry letters,2020

43
[ 4139-61-1 ]
[ 60438-50-8 ]
[ 1262056-70-1 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 9708 - 9713

44
[ 4139-61-1 ]
[ 501-65-5 ]
[ 1309855-04-6 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 5422 - 5424

45
[ 930-68-7 ]
[ 4139-61-1 ]
[ 1316832-95-7 ]
[ 1316832-31-1 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 4382 - 4385

46
[ 4139-61-1 ]
[ 1380599-62-1 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

47
[ 4139-61-1 ]
[ 1380599-63-2 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209
[2]Tetrahedron,2014,vol. 70,p. 6995 - 7005

48
[ 4139-61-1 ]
[ 1380599-64-3 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

49
[ 4139-61-1 ]
[ 1380599-65-4 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

50
[ 4139-61-1 ]
[ 1380599-66-5 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

51
[ 4139-61-1 ]
[ 1380599-67-6 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

52
[ 4139-61-1 ]
[ 1380599-68-7 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

53
[ 4139-61-1 ]
[ 1380599-70-1 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

54
[ 4139-61-1 ]
[ 1380599-71-2 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

55
[ 4139-61-1 ]
[ 1380599-72-3 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

56
[ 4139-61-1 ]
[ 1380599-73-4 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

57
[ 4139-61-1 ]
[ 1380599-74-5 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

58
[ 4139-61-1 ]
[ 1380599-57-4 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209
[2]Tetrahedron,2014,vol. 70,p. 6995 - 7005

59
[ 4139-61-1 ]
[ 1380599-58-5 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

60
[ 4139-61-1 ]
[ 1380599-59-6 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

61
[ 4139-61-1 ]
[ 1380599-60-9 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

62
[ 4139-61-1 ]
[ 1380599-61-0 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3206 - 3209

63
[ 4139-61-1 ]
[ 18315-80-5 ]
[ 1399075-94-5 ]

Reference： [1]Chemistry Letters,2012,vol. 41,p. 777 - 779

64
[ 4139-61-1 ]
[ 119-67-5 ]
[ 1443462-17-6 ]

Reference： [1]Synthesis,2013,vol. 45,p. 1181 - 1190

65
[ 4139-61-1 ]
[ 119-67-5 ]
[ 1428965-46-1 ]

Reference： [1]Green Chemistry,2013,vol. 15,p. 896 - 900

66
[ 4139-61-1 ]
[ 94-41-7 ]
[ 1450853-42-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With iodine; acetic acid; at 100℃; for 0.833333h;	General procedure: A mixture of a selected chalcone (0.5 mmol), 4-hydroxycoumarin (0.5 mmol),and iodine (0.5 mmol) was dissolved in 2-3mL acetic acid. Then, the mixture was stirred under reflux at 100 C for the time indicated in Table 1. The reaction mixture was cooled to room temperature and diluted with water, followed by Na2S2O3*H2O solution to quench excess iodine. The reaction mixture was filtered invacuo, and the residue was purified by column chromatography on silica gel (100-200mesh) usingh exane=EtOAc (10:2 to 10:1, v=v) as eluent to give the pure product.

Reference： [1]Synthetic Communications,2013,vol. 43,p. 3044 - 3053

67
[ 956-04-7 ]
[ 4139-61-1 ]
[ 1450853-43-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With iodine; acetic acid; at 100℃; for 0.916667h;	General procedure: A mixture of a selected chalcone (0.5 mmol), 4-hydroxycoumarin (0.5 mmol),and iodine (0.5 mmol) was dissolved in 2-3mL acetic acid. Then, the mixture was stirred under reflux at 100 C for the time indicated in Table 1. The reaction mixture was cooled to room temperature and diluted with water, followed by Na2S2O3*H2O solution to quench excess iodine. The reaction mixture was filtered invacuo, and the residue was purified by column chromatography on silica gel (100-200mesh) usingh exane=EtOAc (10:2 to 10:1, v=v) as eluent to give the pure product.

Reference： [1]Synthetic Communications,2013,vol. 43,p. 3044 - 3053

68
[ 4139-61-1 ]
[ 57077-29-9 ]
[ 1450853-45-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With iodine; acetic acid; at 100℃; for 1.58333h;	General procedure: A mixture of a selected chalcone (0.5 mmol), 4-hydroxycoumarin (0.5 mmol),and iodine (0.5 mmol) was dissolved in 2-3mL acetic acid. Then, the mixture was stirred under reflux at 100 C for the time indicated in Table 1. The reaction mixture was cooled to room temperature and diluted with water, followed by Na2S2O3*H2O solution to quench excess iodine. The reaction mixture was filtered invacuo, and the residue was purified by column chromatography on silica gel (100-200mesh) usingh exane=EtOAc (10:2 to 10:1, v=v) as eluent to give the pure product.

Reference： [1]Synthetic Communications,2013,vol. 43,p. 3044 - 3053

69
[ 4139-61-1 ]
[ 33868-40-5 ]
[ 1450853-44-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With iodine; acetic acid; at 100℃; for 1.58333h;	General procedure: A mixture of a selected chalcone (0.5 mmol), 4-hydroxycoumarin (0.5 mmol),and iodine (0.5 mmol) was dissolved in 2-3mL acetic acid. Then, the mixture was stirred under reflux at 100 C for the time indicated in Table 1. The reaction mixture was cooled to room temperature and diluted with water, followed by Na2S2O3*H2O solution to quench excess iodine. The reaction mixture was filtered invacuo, and the residue was purified by column chromatography on silica gel (100-200mesh) usingh exane=EtOAc (10:2 to 10:1, v=v) as eluent to give the pure product.

Reference： [1]Synthetic Communications,2013,vol. 43,p. 3044 - 3053

70
[ 4139-61-1 ]
[ 1449795-80-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9014 - 9025
[2]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2550 - 2557
[3]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 2129 - 2135

71
[ 4139-61-1 ]
[ 1449795-47-4 ]

Reference： [1]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2550 - 2557

72
[ 3731-51-9 ]
[ 4139-61-1 ]
[ 16231-98-4 ]
6-(5-bromo-2-hydroxybenzoyl)-2,7-bis(4-chlorophenyl)-1-picolinoyl-3,8a-di(pyridin-2-yl)hexahydroindolizin-5(1H)-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 11414 - 11420

73
[ 3731-51-9 ]
[ 4139-61-1 ]
[ 24582-66-9 ]
6-(5-bromo-2-hydroxybenzoyl)-1-picolinoyl-3,8a-di(pyridin-2-yl)-2,7-di-p-tolylhexahydroindolizin-5(1H)-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 11414 - 11420

74
[ 3731-51-9 ]
[ 4139-61-1 ]
[ 18451-44-0 ]
6-(5-bromo-2-hydroxybenzoyl)-2,7-bis(4-methoxyphenyl)-1-picolinoyl-3,8a-di(pyridin-2-yl)hexahydroindolizin-5(1H)-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 11414 - 11420

75
[ 3731-51-9 ]
[ 4139-61-1 ]
[ 24582-72-7 ]
6-(5-bromo-2-hydroxybenzoyl)-2,7-bis(4-fluorophenyl)-1-picolinoyl-3,8a-di(pyridin-2-yl)hexahydroindolizin-5(1H)-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 11414 - 11420

76
[ 4139-61-1 ]
[ 51069-81-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; trichlorophosphate; at 0℃; for 4.66667h;Reflux;	General procedure: To a stirred mixture of 6a-f (1 mmol) and phosphorus oxychloride (4 ml) at ice bath, triethylamine (0.2 ml) was added drop by drop. The reaction mixture was stirred at 0C for 10 min, then stirred at 40C for 30 min and heated under reflux for 4 h. The reaction mixture was quenched by slow addition of cold water (10 mL) at ice bath. The product obtained as a solid precipitate was filtered, dissolved with ethyl acetate (10 mL), dried over anhydrous Na2SO4 and evaporated in vacuo. The residue was separated by column chromatography on silica gel with petroleum ether-ethyl acetate to afford compound 9af as brown solid.
75%	With triethylamine; trichlorophosphate; for 1.5h;Reflux;	To a suspension of 3a-3c and 4-hydroxycoumarin (10 mmol) in phosphorus oxychloride (15 mL) was added triethylamine slowly. The mixture was stirred and refluxed for 1.5 h. The phosphorus oxychloride was quenched with water carefully, then the suspension was filtered and the decolorized solid was recrystallized with ethyl acetate and petroleum ether. 4a: yield 75%. HPLC purity: 98.0%. 1H NMR (400 MHz, d6-DMSO): delta 6.65 (s, 1H), 7.26 (d, J = 4.4 Hz, 1H), 7.71 (dd, J = 2.0 Hz, 8.8 Hz, 1H), 8.00 (q, J = 1.2 Hz, 1H). 4b: yield 80%. HPLC purity: 97.9%. 4c: yield 70%. HPLC purity: 95.8%. 1H NMR (400 MHz, d6-DMSO): delta 3.83 (s, 3H), 6.47 (s, 1H), 6.81-6.86 (m, 2H), 7.59 (d, J = 8.4 Hz, 1H). 4f: yield 85%. HPLC purity: 99.4%. 1H NMR (400 MHz, d6-DMSO): delta 6.54 (s, 1H), 7.19-7.29 (m, 2H), 7.54-7.57 (m, 1H), 7.69 (dd, J = 1.2 Hz, 8.0 Hz, 1H).
66%	With triethylamine; trichlorophosphate; for 2h;Reflux;	General procedure: Preparation of 1d (step 2)9bTo an oven-dried two-neck round-bottom flask, 4-hydroxy-6-methoxycoumarin (8 mmol, 1.53 g) was charged in phosphorusoxychloride (20 mL). To this mixture, triethylamine (12 mmol,1.6 mL) was added slowly in a period of 5e10 min and the mixturewas refluxed for 2 h. After the reaction time, it was cooled to rt andquenched slowly by pouring into ice-cold water and extracted withdichloromethane. The organic extract was washed with water,brine, dried over anhydrous MgSO4, and concentrated under reducedpressure. The crude was purified by silica gel column chromatography(5% EtOAc/petroleum ether) to obtain 4-chloro-6-methoxy-2H-chromen-2-one (1d) as gray solid (1.15 g, 70% yield)and it was identified by spectroscopic analysis and in comparisonwith the literature data.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 2129 - 2135
[2]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807
[3]Tetrahedron,2014,vol. 70,p. 6995 - 7005

77
[ 4139-61-1 ]
[ 1404189-38-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807
[2]European Journal of Organic Chemistry,2019,vol. 2019,p. 5610 - 5623

78
[ 4139-61-1 ]
[ 1404189-34-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

79
[ 4139-61-1 ]
[ 1404189-21-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

80
[ 4139-61-1 ]
[ 1404189-26-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

81
[ 4139-61-1 ]
[ 1404189-25-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

82
[ 4139-61-1 ]
[ 1404189-29-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

83
[ 4139-61-1 ]
[ 1551217-01-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

84
[ 4139-61-1 ]
[ 1404189-16-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

85
[ 4139-61-1 ]
[ 1404189-18-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

86
[ 4139-61-1 ]
[ 1404189-19-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

87
[ 4139-61-1 ]
[ 1404189-20-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

88
[ 4139-61-1 ]
[ 1404189-28-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

89
[ 4139-61-1 ]
[ 1404189-22-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

90
[ 4139-61-1 ]
[ 1551217-24-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

91
[ 4139-61-1 ]
[ 1404189-17-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

92
[ 4139-61-1 ]
[ 1551217-28-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807

93
[ 106-41-2 ]
[ 4139-61-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807
[2]European Journal of Medicinal Chemistry,2016,vol. 114,p. 232 - 243
[3]Patent: CN103254203,2016,B

94
[ 1927-95-3 ]
[ 4139-61-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 799 - 807
[2]European Journal of Medicinal Chemistry,2016,vol. 114,p. 232 - 243
[3]Patent: CN103254203,2016,B

95
[ 4139-61-1 ]
[ 82100-23-0 ]
[ 122-51-0 ]
[ 1634693-12-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	In neat (no solvent); at 50℃; for 0.166667h;Green chemistry;	General procedure: HKA 1-3 (0.5 mmol), triethoxymethane 4 (1.0 mmol) and 4-hydroxycoumarin derivatives 5 (0.6 mmol) were charged into a 25 mL round-bottom flask and the mixture was heated to 50 C for about 10 minutes and monitored by TLC. Until the substrate HKA had been used up. Then reaction mixture was cooled to room temperature, filtered and washed with 95% EtOH to give the pure product in 83-95% yield. The products were further identified by FTIR, NMR and HRMS, and were in good agreemen twith the assigned structures.