[ CAS No. 34259-99-9 ] {[proInfo.proName]}

Name: 34259-99-9|4-Bromothiazole|98%
Brand: Ambeed
SKU: A172160
Rating: 99 (30 reviews)

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Quality Control of [ 34259-99-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 34259-99-9 ]

CAS No. :	34259-99-9	MDL No. :	MFCD06657592
Formula :	C₃H₂BrNS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VDTIGYKLTROQAH-UHFFFAOYSA-N
M.W :	164.02	Pubchem ID :	2763218
Synonyms :

Calculated chemistry of [ 34259-99-9 ]

Physicochemical Properties

Num. heavy atoms :	6
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	29.81
TPSA :	41.13 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.7
Log Po/w (XLOGP3) :	1.98
Log Po/w (WLOGP) :	1.91
Log Po/w (MLOGP) :	0.53
Log Po/w (SILICOS-IT) :	3.07
Consensus Log Po/w :	1.84

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.72
Solubility :	0.312 mg/ml ; 0.0019 mol/l
Class :	Soluble
Log S (Ali) :	-2.47
Solubility :	0.556 mg/ml ; 0.00339 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.14
Solubility :	1.2 mg/ml ; 0.00729 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.5

Safety of [ 34259-99-9 ]

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 [ 34259-99-9 ]

* 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 [ 34259-99-9 ]
Downstream synthetic route of [ 34259-99-9 ]

[ 34259-99-9 ] Synthesis Path-Upstream 1~9

1
[ 557-21-1 ]
[ 34259-99-9 ]
[ 1452-15-9 ]

Reference： [1] Organic Letters, 2015, vol. 17, # 2, p. 202 - 205

2
[ 34259-99-9 ]
[ 1452-15-9 ]

Reference： [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 38, p. 10035 - 10039[2] Angew. Chem., 2013, vol. 125, # 38, p. 10219 - 10223

3
[ 14904-70-2 ]
[ 34259-99-9 ]
[ 1452-15-9 ]

Reference： [1] Journal of the American Chemical Society, 2015, vol. 137, # 2, p. 648 - 651

4
[ 4175-77-3 ]
[ 34259-99-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.5 h; Stage #2: With methanol In diethyl ether; hexane at -78 - 20℃; for 16 h;	a) Synthesis of 4-bromothiazol A solution of 10.0 g (41.2 mmol) 2,4-dibromothiazol in ether (210 ml) was cooled to -78° C. and 28.3 ml (45.3 mmol, 15percent in hexane) n-butyllithium was added in drops at this temperature. After 30 min of stirring, 3.3 ml (82.3 mmol) methanol was added at -78° C. to the reaction mixture. Heating was subsequently performed to RT over a period of 16 h. The reaction mixture was filtered over silica gel and washed with a n-hexane/AE mixture (2:1). The filtrate was concentrated in a vacuum, whereby 6.7 g (40.9 mmol, 99percent) 4-bromothiazol was obtained.

Reference： [1] Patent: US2008/261996, 2008, A1, . Location in patent: Page/Page column 44
[2] Journal of Materials Chemistry C, 2017, vol. 5, # 45, p. 11927 - 11936
[3] Journal of Organic Chemistry, 2006, vol. 71, # 10, p. 3754 - 3761
[4] Tetrahedron Letters, 1995, vol. 36, # 51, p. 9293 - 9296
[5] Patent: US4990520, 1991, A,
[6] Patent: WO2008/94737, 2008, A2, . Location in patent: Page/Page column 41-42
[7] Journal of Organic Chemistry, 2017, vol. 82, # 11, p. 5947 - 5951

5
[ 173978-99-9 ]
[ 34259-99-9 ]

Reference： [1] Patent: US2005/124637, 2005, A1, . Location in patent: Page/Page column 16-18

6
[ 20731-74-2 ]
[ 34259-99-9 ]

Reference： [1] Patent: US5025099, 1991, A,

7
[ 57314-13-3 ]
[ 34259-99-9 ]
[ 4175-77-3 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 2, p. 215 - 219
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 2, p. 215 - 219

8
[ 108306-53-2 ]
[ 108306-56-5 ]
[ 34259-99-9 ]

Reference： [1] Synthesis, 1986, # 9, p. 757 - 760

9
[ 57314-13-3 ]
[ 34259-99-9 ]
[ 4175-77-3 ]

[ 34259-99-9 ] Synthesis Path-Downstream 1~88

1
[ 140-29-4 ]
[ 34259-99-9 ]
[ 130161-31-8 ]

Reference： [1]Heterocycles,1990,vol. 31,p. 1115 - 1127

2
[ 108306-53-2 ]
[ 108306-56-5 ]
[ 34259-99-9 ]

Reference： [1]Synthesis,1986,p. 757 - 760

3
[ 292638-84-7 ]
[ 34259-99-9 ]
[ 111601-03-7 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 823 - 828

4
[ 75-77-4 ]
[ 34259-99-9 ]
[ 108306-53-2 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 1748 - 1761

5
[ 86108-58-9 ]
[ 34259-99-9 ]
[ 82326-33-8 ]

Reference： [1]Synthesis,1987,p. 185 - 186

6
[ 108306-58-7 ]
[ 34259-99-9 ]
[ 89324-31-2 ]

Reference： [1]Synthesis,1987,p. 185 - 186

7
[ 108306-59-8 ]
[ 34259-99-9 ]
[ 111185-06-9 ]

Reference： [1]Synthesis,1987,p. 185 - 186

8
[ 34259-99-9 ]
[ 107-13-1 ]
[ 111601-01-5 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 823 - 828

9
[ 34259-99-9 ]
[ 536-74-3 ]
[ 111600-88-5 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 204 - 206
[2]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 823 - 828

10
[ 34259-99-9 ]
[ 7605-28-9 ]
[ 143031-99-6 ]

Reference： [1]Synthesis,1992,p. 552 - 554

11
[ 34259-99-9 ]
[ 140-88-5 ]
[ 111601-00-4 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 823 - 828

12
[ 34259-99-9 ]
[ 1066-54-2 ]
[ 111600-89-6 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 823 - 828

13
[ 57314-13-3 ]
[ 34259-99-9 ]
[ 4175-77-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1992,p. 215 - 219
[2]Journal of the Chemical Society. Perkin transactions I,1992,p. 215 - 219

14
[ 34259-99-9 ]
[ 14347-78-5 ]
[ 143234-80-4 ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 5158 - 5162

15
[ 4175-77-3 ]
[ 34259-99-9 ]

Yield	Reaction Conditions	Operation in experiment
99%		a) Synthesis of 4-bromothiazol A solution of 10.0 g (41.2 mmol) 2,4-dibromothiazol in ether (210 ml) was cooled to -78° C. and 28.3 ml (45.3 mmol, 15percent in hexane) n-butyllithium was added in drops at this temperature. After 30 min of stirring, 3.3 ml (82.3 mmol) methanol was added at -78° C. to the reaction mixture. Heating was subsequently performed to RT over a period of 16 h. The reaction mixture was filtered over silica gel and washed with a n-hexane/AE mixture (2:1). The filtrate was concentrated in a vacuum, whereby 6.7 g (40.9 mmol, 99percent) 4-bromothiazol was obtained.
	With sodium hydroxide; In dichloromethane; acetic acid;	Reference Example 2 4-Bromothiazole Following the procedure of M. Robba and R. C. Moreau, Annales pharm. franc. 22, #3, 201-210 (1965); 10 g of 2,4-dibromothiazole and 5 g of powdered zinc in 40 ml of glacial acetic acid is stirred at 60°-65° C. for 45 minutes. The mixture is cooled in an ice bath, as 40 ml of 10 N sodium hydroxide is added in portions. Stirring is continued for 30 minutes. Ten milliliters of 10 N sodium hydroxide is added and the reaction is extracted with diethyl ether followed by methylene chloride. The combined organic layers are dried over sodium sulfate, filtered and concentrated in vacuo to give 5.4 g of the product as a yellow oil.
		2,4-Dibromothiazole (5.00 g, 20.7 mmol) is placed in a flask which has been back filled with Argon three times. Anhydrous ether (82 mL) is added and the solution is cooled to -78°C. n-Butyllithium (2.5 M in cyclohexane, 10.0 mL) is added and the reaction mixture is stirred for 90 minutes at -78°C before quenching with HCl/ether solution (2.0 m x 15 mL). The reaction mixture is warmed to room temperature. The mixture is washed with NaHCpsi3 (saturated aqueous solution, 60 mL) and the organic phase is dried with Na2SO4. After evaporation, 4-bromothiazole is obtained as a crude product.

Reference： [1]Patent: US2008/261996,2008,A1 .Location in patent: Page/Page column 44
[2]Journal of Materials Chemistry C,2017,vol. 5,p. 11927 - 11936
[3]Journal of Organic Chemistry,2006,vol. 71,p. 3754 - 3761
[4]Tetrahedron Letters,1995,vol. 36,p. 9293 - 9296
[5]Patent: US4990520,1991,A
[6]Patent: WO2008/94737,2008,A2 .Location in patent: Page/Page column 41-42
[7]Journal of Organic Chemistry,2017,vol. 82,p. 5947 - 5951

16
4-bromo-2-(tributylstannyl)thiazole [ No CAS ]
[ 34259-99-9 ]

Reference： [1]Tetrahedron Letters,1995,vol. 36,p. 9293 - 9296

17
[ 34259-99-9 ]
[ 288-47-1 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 4081 - 4086

18
[ 3034-52-4 ]
[ 34259-99-9 ]
2'-chloro-2,5'-bithiazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 3754 - 3761

19
[ 889672-72-4 ]
[ 34259-99-9 ]
2'-chloro-2,5'-bithiazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 3754 - 3761

20
[ 34259-99-9 ]
[ 1066-54-2 ]
[ 630094-87-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; at 75℃; for 5h;Inert atmosphere;	[544] Example 129 - 3-ri-Methyl-5-(4-methyl-cvclohexyl)-l,2,3,6-tetrahydro-pyridin-4-yl1-5-(4-HCl; [545] Bromothiazole (1 g, 6.10 mmol), copper (1) iodide (50 mg, 0.26 mmol), Pd(PPh3)2Cl2 (66 mg, 0.94 mmol), and trimethylsilylacetylene (1.04 mL, 7.36 mmol) in TEA (4 mL) were degassed, placed under N2, and stirred at 75 °C for 5 hr. The reaction mixture was cooled to RT and partitioned between DCM and water. The organic phase was dried over MgS04, concentrated, and column chromatography using 0-25percent EtOAc/hexane afforded 129A as a brown residue (1.05 g, 95 percent). MS calcd: (M+H)+ = 182. MS found: (M+H)+ = 182.
79%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 80℃; for 3h;Inert atmosphere;	The mixture of 5a (5 g, 30.5 mmol), Trimethylsilylacetylene (3.6 g, 36.6 mmol), Pd(PPh3)2C12 (210 mg, 0.3 mmol) and Cul (85 mg, 0.45 mmol) in TEA (150 mE) was heated at 80° C. for 3 h under N2, then cooled, diluted with Et20 (100 mE) and washed with brine (100 mE). The organic phase was separated, dried over anhydrous Na2504 and concentrated under reduced pressure. The residue was purified by colunm chromatography (silica, EtOAc/petroleum ether 1:15) to provide Sb (4.3 g, 79percent yield) as a yellow oil. ?H-NMR (CDC13, 400 MHz): oe=8.74 (d, 1H), 7.53 (d, 1H), 0.26 (s, 9H)
72%		Compound 11A was prepared following step 4A starting with 0.59 g of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> and substituting 3-phenyl-1-propyne with trimethylsilyl acetylene. Yield: 0.475 g (72percent).

72.4%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 75℃; for 5h;Inert atmosphere;	4- Bromothiazole (1 g, 6.1 mmol), Cul (58.1 mg, 0.3 mmol), Pd(PPh3)2Cl2 (128.4 mg, 0.18 mmol), and ethynyl(trimethyl)silane (898.2 mg, 9.15 mmol) in TEA (4 mL) were degassed, placed under N2, and stirred at 75 °C for 5 hr. The reaction mixture was cooled to RT and partitioned between DCM and water. The organic phase was dried over MgSC , concentrated, and column chromatography using 0-25percent EtOAc/hexane afforded the title product 800 mg (72.4percent) as a brown oil. ESI-MS m/z calcd for [C8Hi2NSSi]+ (M+H)+: 182.0; found: 182.1.
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 75℃; for 5h;	Intermediate 4; 4-[(Trimethylsilyl)ethynyl]-1 ,3-thiazole; 4-Bromo-1 ,3-thiazole (1 g), copper (I) iodide (50 mg), Pd(PPh3)2CI2 (66 mg), trimethylsilyl acetylene (1.04 ml_), and triethylamine (4 ml.) were degassed and placed under a nitrogen atmosphere in a Reactivial.(TM). , then heated at 75°C for 5 h. The reaction mixture was allowed to cool, then partitioned between DCM and water. The organic phase was dried by using a hydrophobic frit, and the solvent removed under vacuum to give an oil. This was then purified by ISCO companion silica chromatography eluting with a gradient of EtOAc /cyclohexane (0percent to 25percent) to give the title compound MS calcd for (C8H11 NSiS+ H)+: 182MS found (electrospray): (M+H)+ = 182

Reference： [1]Patent: WO2012/83105,2012,A1 .Location in patent: Page/Page column 122-123
[2]Patent: US2015/252021,2015,A1 .Location in patent: Paragraph 0253; 0254
[3]Patent: WO2003/99206,2003,A2 .Location in patent: Page 42
[4]Patent: WO2018/11093,2018,A1 .Location in patent: Page/Page column 75
[5]Patent: WO2008/125599,2008,A1 .Location in patent: Page/Page column 26

21
C₁₈H₁₇N₇O₂S [ No CAS ]
[ 34259-99-9 ]
N<SUP>6</SUP>-(4-methanesulfonyl-phenyl)-N<SUP>2</SUP>-pyridin-2-ylmethyl-9-thiazol-4-yl-9H-purine-2,6-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 88℃;	After the mixture is cooled to room temperature, acetic acid (1.0 mL) is added and the mixture is filtered through a syringe filter (washed with DMF). The filtrate purified by reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90 percent CH3CN in 7.5 minutes, Ultro 120 5muM C18Q, 75x30mmID). The collected water/MeCN solution of the product is evaporated to remove the acetonitrile. NaHCO3 (saturated aqueous solution) is added to raise the pH to 9. DCM is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yielded the product as free base, N -(4- Methanesulfonyl-phenyl)-N2-pyridin-2-ylmethyl-9-thiazol-4-yl-9H-purine-2,6-diamine as a white powder; 1H NMR 400 MHz ( d-DMSO ) delta 10.21 (s, IH), 9.26 (s, IH), 8.53-7.70 ( m, 9H), 7.42 (d, IH, J = 8.0 Hz,), 7.24 (t, IH, J = 6.0 Hz), 4.67 (d, 2H, J = 5.6 Hz), 3.17 (s, 3H); MS m/z 479.3 (M+l).
	With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In DMF (N,N-dimethyl-formamide); at 88℃;	A mixture of 2-fluoro-6-chloropurine (17.26 g, 100 mmol), 3,4-dihydro-2H-pyran (12.62 g, 150 mmol) and p-toluenesulfonic acid monohydrate (1.90 g, 10 mmol) are dissolved in anhydrous dichloromethane (200 mL) and stirred at room temperature for 4 hours. The reaction mixture is filtered, washed with Na2CO3 (10percent aqueous solution, 100 mL) and water (100 mL) and the organic layer dried with Na2SO4. Evaporation of the solvent results in an oil which is triturated with ethyl acetate (10 mL) and hexanes (60 mL) which induces precipitate formation. The product, 2-fluoro-6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine, is collected by filtration. A mixture of 2-fluoro-6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine (2.56 g, 10 mmol), 4-(methylthio)aniline (1.39 g, 10 mmol) and DIEA (1.93 g, 15 mmol) in ethanol (20 ml) is stirred overnight at 78° C. The mixture is cooled down to room temperature. Evaporation of the solvent followed by column chromatography (EtOAc/DCM from 10percent to 30percent) yields [2-Fluoro-9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-(4-methylsulfanyl-phenyl)-amine as a white solid. To a solution of the compound obtained above (3.33 g, 9.25 mmol) in DCM (10 ml) is added 3-chloroperoxybenzoic acid (6.22 g, 77percent maximum, 27.8 mmol) portion wise slowly (in an ice bath). After addition, the mixture is stirred at room temperature for another 2 hours. The mixture is diluted with DCM (50 ml) and the suspension is washed with saturated Na2S2O3 (50 ml) and saturated NaHCO3 (50 ml.x.2) until the organic phase is clear. The organic layer is further washed with water (50 ml) and brine (50 ml) and dried with MgSO4. Evaporation of the solvent followed by column chromatography (EtOAc/DCM from 30percent to 70percent) gives [2-fluoro-9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-(4-methylsulfonyl-phenyl)-amine as a pale yellow solid. The mixture of the 2-fluoropurine substrate (4.6 g, 11.8 mmol) and 2-(aminomethyl) pyridine (15.0 g) is heated in an 84° C. oil bath, overnight. The mixture is distributed between ethyl acetate (200 mL) and water (200 mL). The organic phase is washed with NH4Cl (2.x.150 mL, saturated aqueous solution) and water (200 mL) and dried over Na2SO4. Evaporation of the solvent gives the crude product which is used in the next reaction without further purification. The compound obtained above (1.93 g, 4.02 mmol) is stirred with p-toluenesulfonic acid monohydrate (950 mg, 5.0 mmol) in methanol (20 mL) at 60° C. until the starting material is no longer be detected (monitored by TLC or LC-MS). Triethylamine (1.0 mL) is added. As the reaction mixture is cooled to room temperature precipitate forms which is collected by filtration to give the deprotected product. The deprotected 2,6-disubstituted purine (1.98 g, 5.0 mmol), Cul (475 mg, 2.50 mmol) and K3PO4 (3.18 g, 15 mmol) are combined in a flask (backfilled with argon). Trans-N,N'-dimethylcyclohexane-1,2-diamine (355 mg, 2.50 mmol) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (932 mg, 88percent pure, 5.0 mmol) in DMF (9.0 mL) is added and the mixture is stirred at 88° C. overnight. After the mixture is cooled to room temperature, acetic acid (1.0 mL) is added and the mixture is filtered through a syringe filter (washed with DMF). The filtrate purified by reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90percent CH3CN in 7.5 minutes, Ultro 120 5 muM C18Q, 75.x.30 mmID). The collected water/MeCN solution of the product is evaporated to remove the acetonitrile. NaHCO3 (saturated aqueous solution) is added to raise the pH to 9. DCM is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yielded the product as free base, N6-(4-Methanesulfonyl-phenyl)-N2-pyridin-2-ylmethyl-9-thiazol-4-yl-9H-purine-2,6-diamine as a white powder; 1H NMR 400 MHz (d-DMSO) delta 10.21 (s, 1H), 9.26 (s, 1H), 8.53-7.70 ( m, 9H), 7.42 (d, 1H, J=8.0 Hz,), 7.24 (t, 1H, J=6.0 Hz), 4.67 (d, 2H, J=5.6 Hz), 3.17 (s, 3H); MS m/z 479.3 (M+1).

Reference： [1]Patent: WO2008/94737,2008,A2 .Location in patent: Page/Page column 38-39
[2]Patent: US2005/124637,2005,A1 .Location in patent: Page/Page column 13-15

22
C₁₇H₂₀N₆O₃S [ No CAS ]
[ 34259-99-9 ]
(R)-(4-methanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-thiazol-4-yl-9H-purin-6-yl]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 88℃;	The deprotected 2,6-disubstituted purine (1.44 g, 3.71 mmol), CuI (352 mg, 1.86 mmol) and CS2CO3 (3.62 g, 3.0 eq) are combined in a flask (previously backfilled with argon). Trans-N,N'-dimethylcyclohexane-l,2-diamine (264 mg, 1.86 mmol) and 4- bromothiazole (691 mg, 88percent pure, 3.71 mmol) in DMF (8.0 mL) is added and the mixture is stirred at 880C, overnight. After the mixture is cooled to room temperature, acetic acid (1.0 mL) is added and the mixture is filtered through a syringe filter (washed with DMF). The filtrate purified by reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90 percent CH3CN in 7.5 minutes, Ultra 120 5uM C18Q, 75x30mmID). The collected water/MeCN solution of the product is evaporated to remove the acetonitrile. NaHCpsi3 (saturated aqueous solution) is added to raise the pH to 9. DCM is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yields R-(4- Metfaanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-tfaiazol-4-yl-9H-purin-6-vH- amine as free base/white powder; 1H NMR 400 MHz ( CDCl3 ) delta 9.69 (s, IH), 8.87 (d, IH, J = 2.4 Hz), 8.83 (s, IH), 8.26 (d, IH, J = 2.4 Hz), 8.07 (d, 2H, J = 8.8 Hz), 7.95 (d, 2H, J = <n="45"/>8.8 Hz), 4.53 (t, 2H, J = 10.8 Hz), 4.10-4.07 (m, IH), 3.74-3.65 (m, 2H), 3.25-3.10 ( m, IH), 3.08 (s, 3H), 2.90-2.84 (m, IH), 1.33 (d, 3H, J = 6.4 Hz); MS m/z 472.3 (M+l).
	With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; caesium carbonate; In DMF (N,N-dimethyl-formamide); at 88℃;	N-Benzylethanolamine (9.06 g, 60 mmol) is stirred with (R)-(+)-propylene oxide (6.96 g, 99percent, 120 mmol) in a sealed tube at 45° C. overnight. Evaporation of the excess of propylene oxide in vacuo gives the diol residue which is used directly for the next step. The diol is dissolved in dioxane (60 mL, anhydrous). KOH (10.08 g, 180 mmol) and tris(3,6-dioxaheptyl)amine (200 mg, 0.62 mmol) are added and the mixture is cooled to 0° C. after which tosyl chloride (12.58 g, 66 mmol, in 60 mL anhydrous dioxane) is added dropwise. The reaction mixture is allowed to stir at 0° C. for 45 minutes after which it is warmed to room temperature and stirred for an additional 4 hours . The reaction mixture is filtered and the filtrate is evaporated in vacuo. HCl (2 N, 200 mL) is added to the product and the resulting acidic aqueous solution is washed with ethyl acetate (150 mL.x.2), the solution cooled to 0° C. and neutralized by adding NaOH. The product is then extracted with ethyl acetate. The organic phase is dried with Na2SO4 and then subjected to evaporation. The residue is chromatographed (520percent ethyl acetate in DCM) to give the cyclized product (6.66 g). The free base is converted to the HCl salt and recrystallized as follows: The free base obtained above is treated with HCl (2 M in ether, 50 mL) and subject to evaporation to yield the HCl salt. The salt (6.0 gram) is mixed with ethyl acetate (120 mL) and heated to reflux. EtOH is added dropwise cautiously until the entire solid has dissolved. Then it is cooled to room temperature and kept in the refrigerator overnight. The precipitate obtained is filtered to give pure product (2.8 g). A solution of the recrystallized salt (1.35 g, 5.94 mmol) in ethanol (30 mL) is hydrogenated over 10percent Pd/C (0.20 g) under pressure (55 psi) at room temperature overnight. The mixture is filtered through celite (washed with EtOH) and the filtrate is evaporated to give oil. Addition of ether and subsequent evaporation gives R-2-methylmorpholine hydrochloride as solid. The mixture of the 2-fluoropurine substrate (4.6 g, 11.8 mmol), R-2-methylmorpholine hydrochloride (1.78 g, 12.9 mmol) and DIEA (3.78 g, 29.4 mmol) in ethanol (20 ml) is refluxed overnight. Ethanol is evaporated and the residue is redissolved in DCM (100 ml). It is washed with saturated NaHCO3 (50 ml), water (50 ml), brine (50 ml) and dried over MgSO4. Evaporation of the solvent followed by column chromatography (EtOAc/DCM from 30percent to 50percent) yields R-4-methanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-amine as pale brown solid. The compound obtained above (1.90 g, 4.02 mmol) is stirred with p-toluenesulfonic acid monohydrate (380 mg, 2.0 mmol) in methanol (20 mL) at 60° C. until the starting material is no longer detected (monitored by TLC or LC-MS). Triethylamine (0.5 mL) is added and ethanol is evaporated. Column chromatography (MeOH/DCM from 0 to 5percent) yields the deprotection product. 2,4-Dibromothiazole (5.00 g, 20.7 mmol) is placed in a flask which has been back filled with Argon three times. Anhydrous ether (82 mL) is added and the solution is cooled to -78° C. n-Butyllithium (2.5 M in cyclohexane, 10.0 mL) is added and the reaction mixture is stirred for 90 minutes at -78° C. before quenching with HCl/ether solution (2.0 m.x.15 mL). The reaction mixture is warmed to room temperature. The mixture is washed with NaHCO3 (saturated aqueous solution, 60 mL) and the organic phase is dried with Na2SO4. After evaporation, <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> is obtained as a crude product. The deprotected 2,6-disubstituted purine (1.44 g, 3.71 mmol), Cul (352 mg, 1.86 mmol) and Cs2CO3 (3.62 g, 3.0 eq) are combined in a flask (previously backfilled with argon). Trans-N,N'-dimethylcyclohexane-1,2-diamine (264 mg, 1.86 mmol) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (691 mg, 88percent pure, 3.71 mmol) in DMF (8.0 mL) is added and the mixture is stirred at 88° C., overnight. After the mixture is cooled to room temperature, acetic acid (1.0 mL) is added and the mixture is filtered through a syringe filter (washed with DMF). The filtrate purified by reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90percent CH3CN in 7.5 minutes, Ultro 120 5 uM C18Q, 75.x.30 mmID). The collected water/MeCN solution of the product is evaporated to remove the acetonitrile. NaHCO3 (saturated aqueous solution) is added to raise the pH to 9. DCM is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yields R-(4-Methanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-thiazol-4-yl-9H-purin-6-yl]-amine as free base/white powder; 1H NMR 400 MHz (CDCl3 ) delta 9.69 (s, 1H), 8.87 (d, 1H, J=2.4 Hz), 8.83 (s, 1H), 8.26 (d, 1H, J=2.4 Hz), 8.07 (d, 2H, J=8.8 Hz), 7.95 (d, 2H, J=8.8 Hz), 4.53 (t, 2H, J=10.8 Hz), 4.10-4.07 (m, 1H), 3.74-3.65 (m, 2H), 3.25-3.10 (m, 1H), 3.08 (s, 3H), 2.90-2.84 (m, 1H), 1.33 (d, 3H, J=6.4 Hz); MS m/z 472.3 (M+1).

Reference： [1]Patent: WO2008/94737,2008,A2 .Location in patent: Page/Page column 42-43
[2]Patent: US2005/124637,2005,A1 .Location in patent: Page/Page column 16-18

23
[ 173978-99-9 ]
[ 34259-99-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In diethyl ether; cyclohexane; at -78 - 20℃;	N-Benzylethanolamine (9.06 g, 60 mmol) is stirred with (R)-(+)-propylene oxide (6.96 g, 99percent, 120 mmol) in a sealed tube at 45° C. overnight. Evaporation of the excess of propylene oxide in vacuo gives the diol residue which is used directly for the next step. The diol is dissolved in dioxane (60 mL, anhydrous). KOH (10.08 g, 180 mmol) and tris(3,6-dioxaheptyl)amine (200 mg, 0.62 mmol) are added and the mixture is cooled to 0° C. after which tosyl chloride (12.58 g, 66 mmol, in 60 mL anhydrous dioxane) is added dropwise. The reaction mixture is allowed to stir at 0° C. for 45 minutes after which it is warmed to room temperature and stirred for an additional 4 hours . The reaction mixture is filtered and the filtrate is evaporated in vacuo. HCl (2 N, 200 mL) is added to the product and the resulting acidic aqueous solution is washed with ethyl acetate (150 mL.x.2), the solution cooled to 0° C. and neutralized by adding NaOH. The product is then extracted with ethyl acetate. The organic phase is dried with Na2SO4 and then subjected to evaporation. The residue is chromatographed (520percent ethyl acetate in DCM) to give the cyclized product (6.66 g). The free base is converted to the HCl salt and recrystallized as follows: The free base obtained above is treated with HCl (2 M in ether, 50 mL) and subject to evaporation to yield the HCl salt. The salt (6.0 gram) is mixed with ethyl acetate (120 mL) and heated to reflux. EtOH is added dropwise cautiously until the entire solid has dissolved. Then it is cooled to room temperature and kept in the refrigerator overnight. The precipitate obtained is filtered to give pure product (2.8 g). A solution of the recrystallized salt (1.35 g, 5.94 mmol) in ethanol (30 mL) is hydrogenated over 10percent Pd/C (0.20 g) under pressure (55 psi) at room temperature overnight. The mixture is filtered through celite (washed with EtOH) and the filtrate is evaporated to give oil. Addition of ether and subsequent evaporation gives R-2-methylmorpholine hydrochloride as solid. The mixture of the 2-fluoropurine substrate (4.6 g, 11.8 mmol), R-2-methylmorpholine hydrochloride (1.78 g, 12.9 mmol) and DIEA (3.78 g, 29.4 mmol) in ethanol (20 ml) is refluxed overnight. Ethanol is evaporated and the residue is redissolved in DCM (100 ml). It is washed with saturated NaHCO3 (50 ml), water (50 ml), brine (50 ml) and dried over MgSO4. Evaporation of the solvent followed by column chromatography (EtOAc/DCM from 30percent to 50percent) yields R-4-methanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-amine as pale brown solid. The compound obtained above (1.90 g, 4.02 mmol) is stirred with p-toluenesulfonic acid monohydrate (380 mg, 2.0 mmol) in methanol (20 mL) at 60° C. until the starting material is no longer detected (monitored by TLC or LC-MS). Triethylamine (0.5 mL) is added and ethanol is evaporated. Column chromatography (MeOH/DCM from 0 to 5percent) yields the deprotection product. 2,4-Dibromothiazole (5.00 g, 20.7 mmol) is placed in a flask which has been back filled with Argon three times. Anhydrous ether (82 mL) is added and the solution is cooled to -78° C. n-Butyllithium (2.5 M in cyclohexane, 10.0 mL) is added and the reaction mixture is stirred for 90 minutes at -78° C. before quenching with HCl/ether solution (2.0 m.x.15 mL). The reaction mixture is warmed to room temperature. The mixture is washed with NaHCO3 (saturated aqueous solution, 60 mL) and the organic phase is dried with Na2SO4. After evaporation, 4-bromothiazole is obtained as a crude product. The deprotected 2,6-disubstituted purine (1.44 g, 3.71 mmol), Cul (352 mg, 1.86 mmol) and Cs2CO3 (3.62 g, 3.0 eq) are combined in a flask (previously backfilled with argon). Trans-N,N'-dimethylcyclohexane-1,2-diamine (264 mg, 1.86 mmol) and 4-bromothiazole (691 mg, 88percent pure, 3.71 mmol) in DMF (8.0 mL) is added and the mixture is stirred at 88° C., overnight. After the mixture is cooled to room temperature, acetic acid (1.0 mL) is added and the mixture is filtered through a syringe filter (washed with DMF). The filtrate purified by reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90percent CH3CN in 7.5 minutes, Ultro 120 5 uM C18Q, 75.x.30 mmID). The collected water/MeCN solution of the product is evaporated to remove the acetonitrile. NaHCO3 (saturated aqueous solution) is added to raise the pH to 9. DCM is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yields R-(4-Methanesulfonyl-phenyl)-[2-(2-methyl-morpholin-4-yl)-9-thiazol-4-yl-9H-purin-6-yl]-amine as free base/white powder; 1H NMR 400 MHz (CDCl3 ) delta 9.69 (s, 1H), 8.87 (d, 1H, J=2.4 Hz), 8.83 (s, 1H), 8.26 (d, 1H, J=2.4 Hz), 8.07 (d, 2H, J=8.8 Hz), 7.95 (d, 2H, J=8.8 Hz), 4.53 (t, 2H, J=10.8 Hz), 4.10-4.07 (m, 1H), 3.74-3.65 (m, 2H), 3.25-3.10 (m, 1H), 3.08 (s, 3H), 2.90-2.84 (m, 1H), 1.33 (d, 3H, J=6.4 Hz); MS m/z 472.3 (M+1).

Reference： [1]Patent: US2005/124637,2005,A1 .Location in patent: Page/Page column 16-18

24
[ 34259-99-9 ]
3-formyl-4-methoxyphenylboronic acid [ No CAS ]
2-Methoxy-5-(thiazol-4-yl)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane; hexane; water;	Step A 2-Methoxy-5-(thiazol-4-yl)benzaldehyde (3-Formyl-4-methoxyphenyl)boronic acid (309 mg, 1.71 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (250 mg, 1.52 mmol, prepared as described by J. Trybulski and H. J. Brabander, U.S. Pat. No. 4,990,520, 1991), and tetrakis(triphenylphosphine)palladium(0) (88 mg, 0.076 mmol) were added to a mixture of water (3.5 mL), ethylene glycol dimethyl ether (3.5 mL), and sodium carbonate (805 mg, 7.6 mmol). The mixture was heated in an oil bath at 80° C. for 3 h, allowed to cool to 25° C., and partioned between ethyl acetate (40 mL) and water (20 mL). The aqueous layer was extracted with 2*40 mL of dichioromethane and the combined organic layers dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on silica gel, eluding with 10percent ethyl acetate in hexane to give 182 mg (55percent yield) of the title compound as a white solid. NMR (400 MHz, CDCl3): delta 10.51 (s, 1H), 8.88 (d, 1H, J=2 Hz), 8.32 (d, 1H, J=2 Hz), 8.24 (dd, 1H, J=9,2 Hz), 7.54 (d, 1H, J=2 Hz), 7.09 (d, 1H, J=9 Hz), 3.99 (s, 3H). Mass spectrum (NH3 /CI): 220 (M+1).

Reference： [1]Patent: US5750549,1998,A

25
[ 34259-99-9 ]
[ 99768-12-4 ]
[ 877674-94-7 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; for 18h;Heating / reflux;	Procedure M: A suspension of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (1.13 g, 6.89 mmol), 4-methoxycarbonylphenylboronic acid (1.85 g, 10.3 mmol) and Tetrakis (triphenylphosphine) palladium (0) (0.35 g, 0.30 mmol) in dioxane (45 mL) and 2M Na2CC>3 (17.2 mL) is heated to reflux for 18h. The reaction is allowed to cool and filtered. The filtrate is evaporated in vacuo, and the residue is dissolved in ethyl acetate and washed with water (2X) and brine (2X). The combined organic layers are dried over Na2S04, and concentrated in vacuo. The crude material is purified by flash chromatography (100percent hexanes - 40percent ethyl acetate/hexanes) to give 4-thiazol-4-yl-benzoic acid methyl ester as a white solid (0.68g, 45percent) MS (ES+) 220.2

Reference： [1]Patent: WO2006/23462,2006,A1 .Location in patent: Page/Page column 55

26
[ 34259-99-9 ]
3-(3-chloro-5-thiazol-4-yl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%		Example 112.; Preparation of 3-(3-chloro-5-thiazol-4-yl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl- imidazo[1,2-b]pyridazine.; To a 0 °C solution of 3-(5-bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6- dimethyl-imidazo[1,2-b]pyridazine (0.60 g, 1.45 mmol) and THF (2 mL) is added 0.05 g/ mL of Reike Zn (3.80 mL, 2.91 mmol). The solution is heated at a reflux for 1 hour, and the excess Zn allowed to settle for 1 hour at ambient temperature. The solution is transferred to a flask of <strong>[34259-99-9]4-bromo-thiazole</strong> (Kelly, T. et al. Tetrahedron Lett. 1995, 51, 9293) (0.29 g, 1.74 mmol). PdCl2(dppf) (0.027 g, 0.036 mmol) is added and the solution heated at 65 °C overnight, diluted with EtOAc (40 mL), washed with sat. NH4Cl (30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15percent-20percent EtOAc/hexane gradient) followed by ISCO column chromatography (100percent Et2O) to furnish the title compound (0.098 g, 0.24 mmol, 16percent). 1H NMR (CDCl3) delta 0.88 (d, J = 7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.52 (s, 3H), 2.53 (s, 3H), 3.28-3.38 (m, 1H), 6.70 (s, 1H), 7.45 (s, 1H), 7.49 (d, J = 2.0 Hz, 1H), 8.85 (d, J = 2.0 Hz, 1H). LC/MS (m/z): calcd. for C20H2iClN4S2 (M+H)+: 417.1; found: 417.3.

Reference： [1]Patent: WO2006/102194,2006,A1 .Location in patent: Page/Page column 104

27
[ 20731-74-2 ]
[ 34259-99-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In water; acetic acid;	EXAMPLE 25 4-Bromothiazole A solution of 15 g of 3-(methylthio)thiophene in 60 ml of acetic acid is stirred and cooled 15° C. Twenty and four tenths grams of N-bromosuccinimide is added in portions at a rate so as to maintain the reaction temperature between 15°-17° C. and the reaction is stirred at room temperature for 2.5 hours. The reaction mixture is treated with 75 ml of water, extracted with 600 ml of diethyl ether, the diethyl ether portion is washed with water and then carefully shaken three times with saturated sodium bicarbonate. The diethyl ether layer is washed again with water, dried over sodium sulfate and concentrated in vacuo. The dark green oil was purified by Kugelrohr distillation to give 19.5 g of a pale yellow-green oil, by 74°-78° C. (0.15 mm Hg).

Reference： [1]Patent: US5025099,1991,A

28
[ 34259-99-9 ]
[ 262422-94-6 ]
[ 935460-44-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	tris(dibenzylideneacetone)dipalladium(0) chloroform complex; johnphos; In tetrahydrofuran; at 70℃; for 24h;	Step 1. 4-Neopentylthiazole. <strong>[34259-99-9]4-Bromothiazole</strong> (1.98 g, 12.1 mmol) was covered with a 0.5 M solution of neopentylzinc iodide in THF (96 mL, 48.2 mmol). Pd2dba3.CHCI3 (624 mg, 0.603 mmol) and 2(-di-te/t-butylphosphine)biphenyl (720 mg, 2.41 mmol) were added and the reaction mixture was placed in an oil bath pre-heated to 70 °C. The resulting solution was allowed to stir for 24 h at 70 °C. The resulting mixture was cooled to room temperature and concentrated under vacuum and the residue was dissolved in ethyl acetate (100 mL) and subsequently washed with aqueous NaOH (2 x 40 mL, 3N). The organic phase was then dried (Na2SO4), filtered, concentrated under vacuum and the residue was purified on a silica gel column (eluant hexane to hexane/ethyl acetate 8/2) to give 4-neopentylthiazole (1.42 g, 75percent), retention time (min) = 1.198, method [1], MS(ESI) 156.1 (M+H).

Reference： [1]Patent: WO2007/47306,2007,A1 .Location in patent: Page/Page column 119

29
[ 75336-86-6 ]
[ 34259-99-9 ]
[ 943326-07-6 ]

Yield	Reaction Conditions	Operation in experiment
9%	at 100℃; for 20h;	b) Synthesis of (R)-4-(3-methylpiperazine-1-yl)thiazol 10.0 g (100 mmol) (R)-2-methylpiperazine were fused at 100 C. 2.7 g (16.8 mmol) <strong>[34259-99-9]4-bromothiazol</strong> was added in portions to this fusion over a period of 2 h. Stirring was subsequently performed for 18 h at 100 C. After cooling to RT, the residue was received in 10% aq. hydrochloric acid and washed with AE. Alkalic adjustment was subsequently performed with a 10% aq. NaOH sol. (pH>12) and extracted with DCM. The organic phase was dried over MgSO4, filtered and concentrated in a vacuum. CC (SiO2, DCM/MeOH 9:1) was performed with the residue, whereby 277 mg (1.5 mmol, 9%) (R)-4-(3-methylpiperazine-1-yl)thiazol was obtained.

Reference： [1]Patent: US2008/261996,2008,A1 .Location in patent: Page/Page column 44

30
[ 675108-96-0 ]
[ 34259-99-9 ]
[ 73183-34-3 ]
[ 675109-07-6 ]

Yield	Reaction Conditions	Operation in experiment
		Prepared in a similar manner to Example 7 using <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (Synthesis, 1986, 9, 757-60) to give the title compound (50 mg, 42percent). 1H NMR (400 MHz, CDCl3) ? 8.92 (1H, s), 8.52 (1H, d, J=1.1 Hz), 8.08 (1H, dd, J=8.0, 1.6 Hz), 7.67 (1H, d, J=1.9 Hz), 7.57-7.54 (2H, m), 7.47-7.40 (3H, m), 7.35 (1H, dd, J=8.2, 0.6 Hz), 4.05 (2H, s), 2.72 (3H, s), m/z (ES+) 398 (M+H)+.

Reference： [1]Patent: US2004/58970,2004,A1 .Location in patent: Page 10

31
8-((3,5-dichloropyridin-4-yl)methoxy)-2-methylquinolin-4-ylboronic acid bis-trifluoroacetate [ No CAS ]
[ 34259-99-9 ]
[ 76-05-1 ]
8-(3,5-dichloro-pyridin-4-ylmethoxy)-2-methyl-4-thiazol-4-yl-quinoline trifluoroacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 4370 - 4379

32
[ 1200605-90-8 ]
[ 34259-99-9 ]
[ 1200605-44-2 ]

Yield	Reaction Conditions	Operation in experiment
8.13%	With caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	A screw-cap vial was charged with lambdaf-[(lS)-l-(5-Fluoropyrimidin-2-yl)ethyl]-6- morpholin-4-yl-l,3,5-triazine-2,4-diamine (Intermediate 18, 234 mg, 0.73 mmol), A- bromothiazole (100 mg, 0.61 mmol), CS2CO3 (497 mg, 1.52 mmol), Xantphos.(R). (35.3 mg, 0.06 mmol) and Pd2(dba)3 (27.9 mg, 0.03 mmol). The vial was flushed with nitrogen and dioxane (3048 mul) was added. The resulting mixture was heated to 100 0C for 12 hours. Evaporation of the volatiles under reduced pressure gave a residue that was purified by column chromatography (10percent-20percent-50percent-100percent EtOAc/hexanes) to give the title product (20.00 mg, 8.13 percent).1H NMR (300 MHz, MeOD) delta ppm 1.46 (d, 3 H), 3.38 - 3.73 (m, 8 H), 5.04 - 5.36 (m, 1 H), 7.37 (br. s., 0.5 H), 7.56 (br. s., 0.5 H), 8.59 (s, 2 H), 8.64 (br. s., 1 H). LCMS: 404 [M+H]+.

Reference： [1]Patent: WO2009/150462,2009,A1 .Location in patent: Page/Page column 133-134

33
[ 75-66-1 ]
[ 34259-99-9 ]
[ 1147849-18-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 17; Preparation of 1 ,2-di(thiazol-4-yl)disulfane; Step 1 : Na (0.69 g, 30 mmol) was added to a solution of ^-butylthiol(3.38 mL, 30 mmol) at it portionwise and stirred for 0.5 hrs. Then, <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> 1 (0.49 g, 3.0 mmol) was added and the mixture was heated to reflux overnight. LC-MS indicate desired product formed and the reaction was concentrated. The residue was dissolved in ethyl acetate, filtered through silica gel and the filtrate was concentrated again. The residue was used for the next step directly.
	With sodium ethanolate; In ethanol; at 85℃; for 16h;	Step 1 : Na (0.69 g, 30 mmol) was added to a solution of ^-butylthiol(3.38 mL, 30 mmol) at room temperature portionwise and stirred for 0.5 h. Then, 4- bromothiazole 1 (0.49 g, 3.0 mmol) was added and the mixture was heated to reflux overnight. LC-MS indicate desired product formed and the reaction was concentrated. The residue was dissolved in EA, filtered through silica gel and the filtrate was concentrated again. The residue was used for the next step directly.

Reference： [1]Patent: WO2010/30811,2010,A2 .Location in patent: Page/Page column 72
[2]Patent: WO2009/55696,2009,A1 .Location in patent: Page/Page column 86

34
[ 28240-69-9 ]
[ 34259-99-9 ]
[ 1242167-10-7 ]

Reference： [1]Journal of Organometallic Chemistry,2010,vol. 695,p. 1891 - 1897

35
[ 1224432-90-9 ]
[ 34259-99-9 ]
[ 1239586-78-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6044 - 6054

36
3-fluoro-4-formylphenylboronic acid [ No CAS ]
[ 34259-99-9 ]
[ 1240321-57-6 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6337 - 6354

37
[ 87199-17-5 ]
[ 34259-99-9 ]
[ 127406-12-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 16h;Reflux; Inert atmosphere;	To a solution of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (see The Journal of Organic Chemistry, 71, 3754 (2006)) (1.31 g, 7.98 mmol) in 1,2-dimethoxyethane (38.0 ml) were added 4-formylphenylboronic acid (1.45 g, 9.67 mmol), sodium hydrogencarbonate (2.00 g, 23.8 mmol) and water (19 ml), which was deaerated under reduced pressure, followed by argon substitution. Tetrakis(triphenylphosphine)palladium (270 mg, 0.234 mmol) was then added, followed by heating to reflux for 16 hours under argon atmosphere. After completion of the reaction, a saturated aqueous sodium chloride solution was added to the reaction solution, followed by extraction with chloroform. The separated organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=4:1 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (1.29 g) as a slightly yellow solid. (Yield: 85percent) Mass spectrum (CI, m/z): 190 (M++1). 1H-NMR spectrum (CDCl3, ppm): 10.05 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.14-8.10 (m, 2H), 799-7.94 (m, 2H), 7.73 (d, J=2.0Hz, 1H).
85%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 16h;Inert atmosphere; Reflux;	15-(a) 4-(Thiazol-4-yl)benzaldehyde To a solution of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (see The Journal of Organic Chemistry, 71, 3754 (2006)) (1.31 g, 7.98 mmol) in 1,2-dimethoxyethane (38.0 ml) were added 4-formylphenylboronic acid (1.45 g, 9.67 mmol), sodium hydrogencarbonate (2.00 g, 23.8 mmol) and water (19 ml), which was deaerated under reduced pressure, followed by argon substitution. Tetrakis(triphenylphosphine)palladium (270 mg, 0.234 mmol) was then added, followed by heating to reflux for 16 hours under argon atmosphere. After completion of the reaction, a saturated aqueous sodium chloride solution was added to the reaction solution, followed by extraction with chloroform. The separated organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=4:1 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (1.29 g) as a slightly yellow solid. (Yield: 85percent) Mass spectrum (CI, m/z): 190 (M++1). 1H-NMR spectrum (CDCl3, deltappm): 10.05 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.14-8.10 (m, 2H), 7.99-7.94 (m, 2H), 7.73 (d, J=2.0Hz, 1H).

Reference： [1]Patent: EP2264009,2010,A1 .Location in patent: Page/Page column 106
[2]Patent: EP2415763,2012,A1 .Location in patent: Page/Page column 108

38
[ 79-37-8 ]
[ 34259-99-9 ]
[ 1173834-21-3 ]

Yield	Reaction Conditions	Operation in experiment
74%	N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 2.5h;	Bromothiazole (10 g, 1.3 eq.) was suspended in dichloromethane and cooled down to 00C. Oxalyl chloride (8.1 mL, 2.6 eq.) was added slowly, and then DMF dropwise. The mixture was stirred at 0 0C for 30 min, and then at room temperature. After 2 hrs, the bubbling stopped. The reaction was complete as determinated by TLC analysis. The solvent was removed in vacuo to give a beige residue. This residue was suspended in dioxane and a solution of a derivatized aniline (6.62 g, 1 eq.) in dioxane was added into the acyl chloride solution. The reaction mixture was stirred at room temperature for 16 hrs. Water (100 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated under vacuo to give a beige residue. The residue was triturated in TBDME and the beige solid was recovered by filtration and dried in vacuo to give compound 207b in 74% yield. 1H NMR (CDCl3, 400 MHz) delta (ppm) 2.14 (s, 3H), 2.59 (s, 3H), 3.94 (s, 3H), 6.81 (d, J= 8.76 Hz, IH), 7.51 (s, IH), 7.78 (d, J= 8.76 Hz, IH), 11.20 (s, IH).

Reference： [1]Patent: WO2011/17389,2011,A1 .Location in patent: Page/Page column 141

39
[ 1309365-88-5 ]
[ 34259-99-9 ]
[ 1309365-89-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In ethanol; water; for 5h;Reflux;	Step 8; Bis(4-(di-teri-butylphosphino)- V, Lambda^-dimethylbenzenamine) dichloropalladium (II) (0.0064 g, 0.0090 mmol) was added to a degassed solution of 3-(2-(4- methoxybenzylamino)-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)quinolin-3-yl)-A^- (cyclohexylmethyl)propanamide (0.10 g, 0.18 mmol), potassium acetate (0.035 g, 0.36 mmol), and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.024 mL, 0.27 mmol) in EtOH (1.7 mL) and water (0.30 mL). The reaction was refluxed 5 h until determined to be complete by LC/MS. After cooling, the reaction was partitioned between DCM and a 9:1 saturated aqueous ammonium chloride/ammonium hydroxide solution. The aqueous layer was extracted with DCM and the combined organics were washed with a 9:1 saturated ammonium chloride/ammonium hydroxide solution, water, brine, dried over sodium sulfate, filtered, and concentrated to afford 3-(2-amino-6-(thiazol-4-yl)quinolin-3-yl)- V- (cyclohexylmethyl)propanamide (representative compound 13).

Reference： [1]Patent: WO2011/63233,2011,A1 .Location in patent: Page/Page column 37

40
[ 64-10-8 ]
[ 34259-99-9 ]
[ 1309439-42-6 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 3262 - 3265

41
[ 34259-99-9 ]
[ 19686-05-6 ]
[ 1332447-71-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; L-proline; In N,N-dimethyl-formamide; at 150℃; for 16h;	Example No. 19; Preparation of Compound No. 19[0316] A solution of 2,8-dimethyl-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole (0.2 g, lmmol), <strong>[34259-99-9]4-bromo-thiazole</strong> (0.246 g, 1.5 mmol), K3P04 (0.636 g, 3 mmol), Cul (19 mg, 0.1 mmol) and L-Proline (23 mg, 0.2 mmol) in dry DMF (5 mL) was stirred at 150 °C for 16h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-thiazol-4- yl-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole (59 mg). 1H NMR (TFA salt, CD3OD) d (ppm): 9.10 (s, 1H), 7.62 (s, 1H), 7.38 (d, 1H), 7.30 (s, 1H), 7.10 (d, 1H), 4.70 (d, 1H), 4.30 (d, 1H), 3.80 (m, 1H), 3.50 (m, 1H), 3.26 (m, 1H), 3.18 (s, 3H), 3.16 (m, 1H), 2.42 (s, 3H).
	With potassium phosphate; copper(l) iodide; L-proline; In N,N-dimethyl-formamide; at 150℃; for 16h;	Example No. 19: Preparation of Compound No. 19[0307] A solution of 2,8-dimethyl-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole (0.2 g, lmmol), <strong>[34259-99-9]4-bromo-thiazole</strong> (0.246 g, 1.5 mmol), K3P04 (0.636 g, 3 mmol), Cul (19 mg, 0.1 mmol) and L- Proline (23 mg, 0.2 mmol) in dry DMF (5 mL) was stirred at 150 °C for 16h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-thiazol-4-yl-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole (59 mg). 1H NMR (TFA salt, CD3OD) delta (ppm): 9.10 (s, 1H), 7.62 (s, 1H), 7.38 (d, 1H), 7.30 (s, 1H), 7.10 (d, 1H), 4.70 (d, 1H), 4.30 (d, 1H), 3.80 (m, 1H), 3.50 (m, 1H), 3.26 (m, 1H), 3.18 (s, 3H), 3.16 (m, 1H), 2.42 (s, 3H).

Reference： [1]Patent: WO2011/103430,2011,A1 .Location in patent: Page/Page column 166
[2]Patent: WO2012/112962,2012,A1 .Location in patent: Page/Page column 145

42
[ 34259-99-9 ]
[ 333-27-7 ]
[ 1341198-69-3 ]

Reference： [1]Polyhedron,2011,vol. 30,p. 2776 - 2782

43
[ 122307-41-9 ]
[ 34259-99-9 ]
[ 1355019-60-1 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 862 - 865

44
[ 1262879-84-4 ]
[ 34259-99-9 ]
[ 1262879-86-6 ]

Yield	Reaction Conditions	Operation in experiment
		Reference Example 9-16-Methoxy-2-thiazol-4-yl-1H-indoleTo a solution of N-(2-ethynyl-5-methoxyphenyl)-2,2,2-trifluoroacetamide (209 mg), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.115 mL) and triethylamine (0.298 mL) in acetonitrile (5.0 mL) were added bis(triphenylphosphine)palladium (II) dichloride (18 mg) and copper iodide (10 mg), and the mixture was stirred at 120° C. for 10 minutes under microwave irradiation. After cooling to room temperature, to the mixture was added potassium carbonate (297 mg), and the mixture was stirred at 120° C. for 10 minutes under microwave irradiation. To the reaction mixture was added saturated brine, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluting solvent: hexane-ethyl acetate) to obtain the title compound (60.0 mg).

Reference： [1]Patent: US2012/122931,2012,A1 .Location in patent: Page/Page column 23-24

45
[ 14396-90-8 ]
[ 34259-99-9 ]
[ 1262029-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; for 5h;Inert atmosphere; Reflux;	(10) In the general formula (I), R1 = 4-thiazolyl, R2 = H, and R3-R4 = thiophene (Synthesis of compound No. 61 in Table 1)Stage A: 2-(4-Thiazolyl-3-butynyl)isoindol-1,3-dione Under a nitrogen atmosphere, 78 ml of tetrahydrofuran, 5.49 g of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong>, and 20.3 ml of triethylamine were added to 1184 mg of dichlorobis(triphenylphosphine)palladium, 322 mg of copper iodide, and 6.64 g of N-(3-butynyl)phthalimide. The obtained mixture was stirred under reflux for 5 hours. After completion of the stirring, the reaction solution was cooled to a room temperature, and a solid was then filtrated. The filtrate was concentrated, and the residue was then purified by column chromatography (Wako Gel C-200; toluene : ethyl acetate = 4 : 1), so as to obtain 6.35 g of a phthalimide compound.

Reference： [1]Patent: EP2455371,2012,A1 .Location in patent: Page/Page column 24

46
[ 34259-99-9 ]
[ 621-79-4 ]
N-(thiazol-4-yl)cinnamamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 4710 - 4713

47
[ 1382996-68-0 ]
[ 34259-99-9 ]
[ 1382996-69-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃;Microwave; Inert atmosphere;	Step 2.1-[5-Chloro-2-methoxy-4-methyl-3-(1,3-thiazol-4-yl)phenyl]ethanoneInto a microwave vial was added 1-[5-chloro-2-methoxy-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanone (0.040 g, 0.12 mmol), <strong>[34259-99-9]4-bromo-1,3-thiazole</strong> (0.024 g, 0.15 mmol), 1 M sodium carbonate solution (0.30 mL, 0.31 mmol), 1,4-dioxane (1 mL) and tetrakis(triphenylphosphine)palladium(0) (8.5 mg, 0.0074 mmol).The mixture was bubbled with N2 for 5 minutes, and then heated at 95° C. overnight.The cooled reaction was purified on silica gel column (eluting with 0 to 30percent EtOAc in hexanes) to give the desired product. LCMS calculated for C13H13ClNO2S (M+H)+: m/z=282.0. found: 282.0.

Reference： [1]Patent: US2012/157430,2012,A1 .Location in patent: Page/Page column 100

48
[ 34259-99-9 ]
[ 536-74-3 ]
[ 329203-16-9 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 5381 - 5388

49
[ 1207557-48-9 ]
[ 34259-99-9 ]
[ 1383675-65-7 ]

Yield	Reaction Conditions	Operation in experiment
42%	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 4h;Inert atmosphere;	General procedure: Reactions were carried out in a Bohdan XT 24 position block using the appropriate halide indicated.2M Sodium carbonate (0.680 mL, 1.36 mmol) was added to a stirred mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (10, 151 mg, 0.62 mmol), the appropriate halide (0.74 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Pd(Amphos)Cl2) (26.3 mg, 0.04 mmol) in DME (4 mL) under nitrogen. The resulting mixture was stirred at 80 °C for 4 h, allowed to cool, diluted with water (10 mL), extracted with EtOAc (2.x.25 mL) and the organic layer was evaporated to afford crude products. Unless otherwise stated the crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5 mu silica, 19 mm diameter, 100 mm length, 5-95percent MeCN/1percent NH3 in H2O).

Reference： [1]Tetrahedron,2012,vol. 68,p. 5434 - 5444

50
[ 863886-23-1 ]
[ 34259-99-9 ]
C₁₉H₂₀N₂O₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7650 - 7666,17

51
[ 34259-99-9 ]
[ 95-15-8 ]
[ 1453841-30-9 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 615 - 619
Angew. Chem.,2013,vol. 125,p. 643 - 647,5

52
[ 1297138-71-6 ]
[ 34259-99-9 ]
[ 1297140-83-0 ]

Yield	Reaction Conditions	Operation in experiment
34%	With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 85℃; for 2h;Inert atmosphere;	Step AMethyl 3-chloro-5-cyclopropyl-7-(1,3-thiazol-4-yl)pyrazolo[ 1, 5-a]pyridine-2-carboxylate A mixture of methyl 3-chloro-5-cyclopropyl-7-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)pyrazolo[1 ,5-a]pyriciine-2-carboxylate (250 mg, 0.664 mmol), 4-bromo- 1 ,3-thiazole (435 mg, 2.66 mmol), KsP04 (564 mg, 2.66 mmol), and [1 ,1 '- bis(diphenylphosphino)ferrocene]dichloro palladium(ll) DC complex (27 mg, 0.033 mmol) in 10 mL of 1 ,4-dioxane was sparged with nitrogen and heated to 85°C with stirring.After 2 hours the mixture was cooled to room temperature, diluted with EtOAc, washed with water (2x), brine (1x), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude material was subjected to flash chromatography (silica gel, gradient from hexane to EtOAc) to afford the title compound (76 mg, 34percent) as a white foam. ES-LCMS m/z: 334 (M+1 ).

Reference： [1]Patent: WO2011/50284,2011,A1 .Location in patent: Page/Page column 205

53
[ 1227685-25-7 ]
[ 34259-99-9 ]
[ 1426254-50-3 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 2661 - 2669

54
[ 905300-76-7 ]
[ 34259-99-9 ]
[ 1431960-86-9 ]

Yield	Reaction Conditions	Operation in experiment
58.6%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.5h;Microwave irradiation; Inert atmosphere;	To a solution of compound TA-P-3 (333 mg, 1 mmol) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (163 mg, 1 mmol) in dioxane (8 mL) and H20 (2 mL) was added K2C03 (276 mg, 2 mmol) and Pd(PPh3)4 (1 15.6 mg, 0.1 mmol) under nitrogen atmosphere protection. The mixture was heated to 120 °C by microwave and stirred for 0.5 hour. Then the mixture was condensed and dissolved in H20 (100 mL) and extracted with EtOAc (50 mL x 2). The combined organic phase was dried over Na2S04 and condensed. The residue was purified by flash chromatography (petroleum ether/EtOAc = 5:1 ) to give compound TA-1 -2A (170 mg, 58.6percent) as white solid.

Reference： [1]Patent: WO2013/62945,2013,A1 .Location in patent: Page/Page column 132

55
[ 32117-52-5 ]
[ 34259-99-9 ]
[ 1438286-81-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 3664 - 3673

56
[ 1448348-26-2 ]
[ 34259-99-9 ]
[ 1448346-12-0 ]
[ 1448346-11-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 110℃; for 0.5h;Microwave irradiation;	Example 3. Preparation of (S)-N-((S)-l-(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino) - 2-oxoethyl)-N-(3-fluorophenyl)-5-oxo-l-(thiazol-4-yl)pyrrolidine-2-carboxamide Compounds 42 and 43 were prepared according to the following scheme, using the following rotocol. Compound 43 A mixture (2>S)-N-(l-(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2 -oxoethyl)-N- (3-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (200 mg, 0.417 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.045 mL, 0.626 mmol, 1.5 eq), K3P04 (124 mg, 0.585 mmol, 1.4 eq), Cul (8 mg, 0.1 eq) and trans- 1 ,2-diaminocyclohexane (0.24 eq) in dioxane (2 mL) was stirred at 1 10 °C under microwave for 30 min. The resulting mixture was filtered through a Celite pad. The filtrate was concentrated and the residue was purified by a standard method to give the desired product. (S)-N-((R)-l-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-N-(3- fluorophenyl)-5-oxo-l-(thiazol-4-yl)pyrrolidine-2-carboxamide (Compound 42) FontWeight="Bold" FontSize="10" H NMR (400 MHz, CDC13): delta 8.68 (d, J= 2.1 Hz, 1H), 7.65 (m, 5H), 7.30 - 6.90 (m, 4H), 6.47 (s, 1H), 6.23 (s, 1H), 4.88 (dd, J = 9.3, 3.0 Hz, 1H), 4.20 (s, 1H), 3.17 - 2.63 (m, 3H), 2.58 - 1.99 (m, 5H). MS: 563.1 (M+l)+. (S)-N-((S)-l-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-N-(3- fluorophenyl)-5-oxo-l-( thiazol-4-yl)pyrrolidine-2-carboxamide ( Compound 43) FontWeight="Bold" FontSize="10" H NMR (400 MHz, CDC13): delta 8.60 (s, 1H), 8.06 - 7.56 (m, 2H), 7.35 (s, 1H), 7.22 - 6.79 (m, 5H), 6.42 (s, 1H), 6.13 (s, 1H), 4.96 (d, J= 7.8 Hz, 1H), 4.25 (m, 1H), 3.14 - 2.70 (m, 4H), 2.63 - 2.21 (m, 4H). MS: 563.1 (M+l)+.
	With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 110℃; for 0.5h;Microwave irradiation;	A mixture(2S)-N-(1 -(2-chlorophenyl)-2-(3 ,3 -difluorocyclobutylamino)-2-oxoethyl)-N-(3 -fluorophenyl)-5 -oxopyrrolidine-2-carboxamide (200 mg, 0.417 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.045mL, 0.626 mmol, 1.5 eq), K3P04 (124 mg, 0.585 mmol, 1.4 eq), CuT (8mg, 0.1 eq)and trans-1,2- diaminocyclohexane (0.24 eq) in dioxane (2 mL) was stirred at 110 °C under microwave for 30 mm. The resulting mixture was filtered through a C elite pad. The filtrate was concentrated and the residue was purified by a standard method to give the desired product.(S)-N-((R)- 1-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-N-(3- fluorophenyl)-5-oxo-1 -(thiazol-4-yl)pyrrolidine-2-carboxamide(Conipound 42)?HNMR(400MHz, CDC13): 8.68 (d,J=2.1 Hz, 111), 7.65 (m, 511), 7.30?6.90(m,4H), 6.47(s, 111), 6.23 (s, 111), 4.88 (dd, J = 9.3, 3.0 Hz, 111), 4.20 (s, 111), 3.17 ? 2.63 (m, 311), 2.58 ?1.99 (m, 5H). MS: 563.1 (M+1);(S)-N-((S)-1-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-N-(3-fluorophenyl)-5-oxo-1-(thiazol-4-yI)pyrrolidiiie-2-carboxamide(Conipouiid 43)NMR (400 MHz, CDC13): 8.60 (s, 111), 8.06 ? 7.56 (m, 211), 7.35 (s, 111), 7.22 ? 6.79 (m, 511), 6.42 (s, 111), 6.13 (s, 111), 4.96 (d, J= 7.8 Hz, 111), 4.25 (m, 111), 3.14?2.70 (m, 411), 2.63?2.21 (m,4H).MS: 563.1 (M+1).
	With potassium phosphate; copper(l) iodide; (S,S)-1,2-diaminocyclohexane; In 1,4-dioxane; at 110℃; for 0.5h;Microwave irradiation;	Example 3. Preparation of (S)-N-((S)-l-(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino) - 2-oxoethyl)-N-(3-fluorophenyl)-5-oxo-l-(thiazol-4-yl)pyrrolidine-2-carboxamide Compounds 42 and 43 were prepared according to the following scheme, using the following rotocol. A mixture (2S)-N-( \ -(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2 -oxoethyl)-N- (3-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (200 mg, 0.417 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.045 mL, 0.626 mmol, 1 .5 eq), 3P04 ( 124 mg, 0.585 mmol, 1 .4 eq), Cul (8 mg, 0.1 eq) and trans- 1 ,2-diaminocyclohexane (0.24 eq) in dioxane (2 mL) was stirred at 1 10 °C under microwave for 30 min. The resulting mixture was filtered through a Celite pad. The filtrate was concentrated and the residue was purified by a standard method to give the desired product. (S)-N-((R)-l-(2-Chlorophenyl)-2-(3,3-difluorocycloburylamino)-2-oxoethyl)-N-(3- fluorophenyl)-5-oxo-l-(thiazoI-4-yl)pyrrolidine-2-carboxamide (Compound 42) NMR (400 MHz, CDC13): delta 8.68 (d, J = 2.1 Hz, 1 H), 7.65 (m, 5H), 7.30 - 6.90 (m, 4H), 6.47 (s, 1 H), 6.23 (s, 1 H), 4.88 (dd, J = 9.3, 3.0 Hz, 1 H), 4.20 (s, 1 H), 3.17 - 2.63 (m, 3H), 2.58 - 1.99 (m, 5H). MS: 563. 1 (M+ l )+. (S)-N-((S)-l-(2-Chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoe fluorophenyl)-5-oxo-l-(thiazol-4-yl)pyrrolidine-2-carboxamide ( Compound 43) 1 H NMR (400 MHz, CDCI3): delta 8.60 (s, 1 H), 8.06 - 7.56 (m, 2H), 7.35 (s, 1 H), 7.22 - 6.79 (m, 5H), 6.42 (s, 1 H), 6.13 (s, 1 H), 4.96 (d, J= 7.8 Hz, 1 H), 4.25 (m, 1 H), 3.14 - 2.70 (m, 4H), 2.63 - 2.21 (m, 4H). MS: 563. 1 (M+ l )+.

Reference： [1]Patent: WO2013/107291,2013,A1 .Location in patent: Page/Page column 89; 90
[2]Patent: WO2015/10626,2015,A1 .Location in patent: Page/Page column 89; 90
[3]Patent: WO2015/10297,2015,A1 .Location in patent: Page/Page column 89-90

57
[ 1452573-27-1 ]
[ 34259-99-9 ]
[ 1452573-73-7 ]

Yield	Reaction Conditions	Operation in experiment
19%	With copper(l) iodide; dichlorobis(triphenylphosphine)palladium(II); N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 80℃; for 2h;Inert atmosphere;	A mixture of tert-butyl-N-[l-[(l-ethynylisoquinolin-3-yl)amino]-l-oxopropan-2-yl]- carbamate D4a (50 mg, 0.15 mmol), 4-bromo-l,3-thiazole (24 mg, 0.15 mmol), copper(I) iodide (3 mg, 0.02 mmol), Dichlorobis(triphenylphosphine)palladium(II) (10 mg, 0.01 mmol) and DIPEA (75 mu, 0.44 mmol) is stirred under argon atmosphere in NMP (1 ml) for 2 h at 80°C. The mixture is concentrated in vacuo and the product purified by RP HPLC. Yield: 12 mg (19percent). HPLC-MS: M+H=423; tR=1.84 min
19%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 80℃; for 2h;Inert atmosphere;	E4b) tert-butyl-N-[1-oxo-1-[[1-[2-(1,3-thiazol-4-yl)ethynyl]isoquinolin-3-yl]amino]-propan-2-yl]carbamate A mixture of tert-butyl-N-[1-[(1-ethynylisoquinolin-3-yl)amino]-1-oxopropan-2-yl]-carbamate D4a (50 mg, 0.15 mmol), <strong>[34259-99-9]4-bromo-1,3-thiazole</strong> (24 mg, 0.15 mmol), copper(I) iodide (3 mg, 0.02 mmol), Dichlorobis(triphenylphosphine)palladium(II) (10 mg, 0.01 mmol) and DIPEA (75 mul, 0.44 mmol) is stirred under argon atmosphere in NMP (1 ml) for 2 h at 80° C. The mixture is concentrated in vacuo and the product purified by RP HPLC. Yield: 12 mg (19percent). HPLC-MS: M+H=423; tR=1.84 min (*Method-4).

Reference： [1]Patent: WO2013/127729,2013,A1 .Location in patent: Page/Page column 120
[2]Patent: US2013/225567,2013,A1 .Location in patent: Paragraph 0387; 0388

58
[ 5720-05-8 ]
[ 34259-99-9 ]
[ 1826-19-3 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 3950 - 3953

59
[ 14396-90-8 ]
[ 34259-99-9 ]
2-(4-thiazolyl-3-butynyl)isoindole-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6.35 g	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; for 5h;Inert atmosphere; Reflux;	To 1184 mg of dichlorobis(triphenylphosphine)palladium, 322 mg of copper iodide, and 6.64 g of N-(3-butynyl)phthalimide were added 78 ml of tetrahydrofuran, 5.49 g of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong>, and 20.3 ml of triethylamine in a nitrogen atmosphere, and the mixture was stirred under reflux for 5 hours. After the stirring, the reaction mixture was cooled to room temperature and the solids were filtered. After concentrating the filtrate, the residue was purified by column chromatography (Wakogel C-200; toluene:ethyl acetate=4:1) to give 6.35 g of a phthalimide compound.

Reference： [1]Patent: US2013/296271,2013,A1 .Location in patent: Paragraph 0189

60
di-tert-butyl ((((4'-(tert-butyl)-5-(4,4,5,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)-[1,1'-biphenyl]3-yl)methyl)amino)methylene)dicarbamate [ No CAS ]
[ 34259-99-9 ]
C₃₁H₄₀N₄O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	A 25-mL round bottom flask equipped with a magnetic stirrer, a condenser and anitrogen in/outlet adapter was charged with di-tert-butyl ((((4?-(tert-butyl)-5-(4,4,5,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)-[ 1,1 biphenyl] 3 -yl)methyl)amino)methylene)dicarbamate 53b (30 mg,0.05 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (11 mg, 0.07 nimol), water/dioxane (1 mL/3 ml), K2C03 (15 mg,0.11 mmol). The resulting solution was degassed for 5 minutes, then Pd(PPh3)4 ( 8 mg, 0.00 7mmol) was added. The reaction mixture was heated to 100 °C for 2 hours. After being allowedto cool to room temperature, the reaction mixture was diluted with EtOAc (30 mL) and washedwith saturated NaHCO3 (10 mL), brine (10 mL), dried over Na2SO4. The organic layer wasconcentrated under reduced pressure and purified on silica gel. Elution with 10percentEtOAc/hexanes afforded the title compound (25 mg, 68percent) as a white solid. ?H NMR (CDC13,300 MHz) 6 9.47 (broad s, 1H), 9.32 (broad s, 1H), 8.88-8.9 (s, 1H), 8.06 (s, 1H),7.84 (s, 1H),7.55 - 7.60 (m, 4H), 7.47 (d, 2H, J= 8.10 Hz), 5.28 (s, 2H), 1.49 (s, 9H), 1.36 (s, 18H).

Reference： [1]Patent: WO2013/106761,2013,A2 .Location in patent: Page/Page column 109

61
C₃₀H₄₂BN₃O₆ [ No CAS ]
[ 34259-99-9 ]
C₂₇H₃₂N₄O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	A 25-mL round bottom flask equipped with a magnetic stirrer, a condenser and anitrogen in/outlet adapter was charged with 55a (40 mg, 0.07 mmol), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (14 mg,0.09 mmol), water/dioxane (1 mL/3 ml), K2C03 (20 mg, 0.14 mmol). The resulting solutiondegassed for 5 minutes, then Pd(PPh3)4 (10 mg, 0.009 mmol) was added. The reaction mixturewas heated to 100 °C for 2 hours. After being allowed to cool to room temperature, the reactionmixture was diluted with EtOAc (30 mL) and washed with saturated NaHCO3 (10 mL), brine(10 mL), dried over Na2SO4. The organic layer was concentrated under reduced pressure andpurified on silica gel. Elution with 10percent EtOAc/hexanes afforded the title compound (2* mg,76percent) as a white solid. ?H NMR (CDC13, 300 MHz) 9.49 (broad s, 1H), 9.35 (broad s, IH),8.90 - 8.91 (m, 1H), 8.00 (d, 1H, J 7.80 Hz), 7.67 (d, 1H, J 7.50 Hz), 7.35 (s, 1H), 7.58 -7.59 (m, 1H), 7.53 (d, 1H, J 7.80 Hz), 7.39 (t, 1H, J? 7.80 Hz), 7.24 - 7.26 (m, 1H), 5.25 (s,2H), 1.50 (s, 9H), 1.36 (s, 9H).

Reference： [1]Patent: WO2013/106761,2013,A2 .Location in patent: Page/Page column 112; 113

62
[ 1135950-23-0 ]
[ 34259-99-9 ]
C₂₁H₁₂F₆N₂S₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; at 20℃;Reflux;	Pd(PPh3)4 (149 mg, 129 mumol) was added to a mixture of 6 (400 mg, 0.645 mmol) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (424 mg, 2.59 mmol) in aqueous Na2CO3 (2 M, 1.3 mL, 2.6 mmol) and anhydrous THF (12.0 mL), and the solution was stirred at room temperature for 15 min. The resulting two-phase system was refluxed under stirring overnight, and was then allowed to cool to room temperature. To this was added water (30 mL), and the mixture was extracted with CHCl3 (60 mL×3). The organic layer was washed with water (30 mL), dried over anhydrous MgSO4, and filtered. After the solvent was removed by evaporation, the residue was subjected to SEC fractionation to obtain 3 (185 mg, 54percent) as a deep blue solid. Mp: 197.8?198.9 °C. IR (KBr, cm?1): 1337, 1273, 1188, 1108, 1057, 983, 873. 1H NMR (500 MHz, CDCl3): delta 8.82 (d, J=2.6 Hz, 2H, thiazoleH), 7.45 (s, 2H, ArH), 7.40 (d, J=2.6 Hz, 2H, thiazoleH), 1.97 (s, 6H, CH3). 13C NMR (125 MHz, CDCl3): delta 153.3, 149.9, 142.1, 136.3, 125.7, 123.6, 111.9, 14.7. HRMS (ESI+): m/z calcd for C21H13F6N2S4 (M+H+)=534.9866; found, 534.9852.

Reference： [1]Tetrahedron,2013,vol. 69,p. 11064 - 11069

63
[ 34259-99-9 ]
[ 1522380-26-2 ]

Yield	Reaction Conditions	Operation in experiment
31%	With sulfuric acid; nitric acid; at 0 - 60℃; for 16h;	Step 1: In a 250 mL flask is placed compound i (5.0 g, 9.6 mmol) in 40 mL of H2SO4. This is then cooled to 0°C where 8 mL of fuming nitric acid is added dropwise. The reaction is equipped with a condenser and heated at 60°C for 1 6h. Reaction is cooled to room temperature and poured into 300 mL of ice. Once the ice is melted, the white foamwas filtered through a frit. The solids were allowed to dry and are then placed on the lyophilizer for 1 8h to provide 2g (31percent) of compound j as a pale yellow solid.

Reference： [1]Patent: WO2013/191984,2013,A1 .Location in patent: Page/Page column 41; 42

64
[ 368-39-8 ]
[ 34259-99-9 ]
[ 1429650-85-0 ]

Reference： [1]Crystal Growth and Design,2013,vol. 13,p. 4533 - 4541

65
[ 34259-99-9 ]
[ 108306-60-1 ]

Reference： [1]Patent: WO2018/205948,2018,A1 .Location in patent: Page/Page column 33
[2]Crystal Growth and Design,2013,vol. 13,p. 4533 - 4541

66
[ 616-45-5 ]
[ 34259-99-9 ]
[ 1572031-52-7 ]

Yield	Reaction Conditions	Operation in experiment
4.5 g	With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 16h;	To a solution of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (10.0 g, 60.97 mmol) in 1,4-Dioxane was added pyrrolidone (4.63 mL , 60.97 mmol) , N?,N2-dimethyl ethylene diamine (1.98 mL, 18.29 mmol), Cul (11.61 g, 60.97 mmol) and K3P04 (25.88 g, 121.95 mmol) at RT and themixture was heated to 100 °C for 1 6h. The reaction mixture was filtered and concentrated. Purification of the evaporation residue by column chromatography (15percent EtOAc in petroleum ether) afforded 4.5 g of 1-(thiazol-4-yl)pyrrolidin-2-one as brown solid. mlz [M+1]:169.1

Reference： [1]Chemical Communications,2014,vol. 50,p. 3163 - 3165
[2]Patent: WO2016/193551,2016,A1 .Location in patent: Page/Page column 49

67
[ 1616828-84-2 ]
[ 34259-99-9 ]
[ 1616830-15-9 ]

Yield	Reaction Conditions	Operation in experiment
18%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In water; N,N-dimethyl-formamide; at 80 - 100℃;	a) 6- (Thiazol-4-yl)- 8-((2- (trimethylsilyl)ethoxy)methoxy)-3- ((2- (trimethylsilyl)ethoxy)methyl)guinazolin-4(3H)-oneA suspension of <strong>[34259-99-9]4-bromo-thiazole</strong> (0.02 g, 0.1 mmol), (6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-8- ((2- (trimethylsilyl)ethoxy)methoxy)-3-((2-(trimethylsilyl)ethoxy)methyl)quinazolin-4(3H)-one (0.05 g, 0.08 mmol, example 28), bis (diphenylphosphino)feffocene-palladium(II)dichloride (0.01 g, 0.01 mmol), potassium carbonate (0.03 g, 0.25 mmol) and water (0.2 ml) in dimethylformamide (1 ml) was stirred in a sealed tube at 100 °C for 2 hours and then at 80 °C overnight. Filtration and chromatography (C18 reverse phase HPLC, methanol / water (0.1percent formic acid) = 40:60 to 100:0) yielded thetitle compound as white solid (0.01 g, 18 percent). MS: mle = 506.7 [M+Hf?.

Reference： [1]Patent: WO2014/102233,2014,A1 .Location in patent: Page/Page column 116

68
[ 34259-99-9 ]
[ 100-79-8 ]
[ 54666-48-7 ]

Yield	Reaction Conditions	Operation in experiment
		NaH (60percent dispersion in mineral oil, 12.19 g, 305.3 mmol) was added portionwise to DL- 1 ,2-isoproylideneglycerol (16.1 1 g, 1218 mmol) and the mixture was stirred until gas evolution had ceased (ca. 30 min RT, followed by 2 h at 60°C). Subsequently, 4- bromothiazole (20.00 g, 121 .9 mmol) was added and the mixture was stirred at 140°C for 45 min. Subsequently, the reaction mixture was quenched with aq. sat. NH4CI and extracted with EtOAc. The comb. org. layers were washed with brine, dried over MgS04, and cone, in vacuo. The residue was subjected to distillation and the volatiles (HV, 60°C)were removed. The residue was purified by means of CC (5-40percent EtOAc/Hept) to provide a yellow oil. LC-MS (3): tR = 0.52 min; [M+H]+: 216.20.
		A.1.10.1. 4-((2,2-Dimethyl-1 ,3-dioxolan-4-yl)methoxy)thiazole NaH (60percent dispersion in mineral oil, 12.19 g, 305.3 mmol) was added portionwise to DL- 1 ,2-isoproylideneglycerol (16.11 g, 1218 mmol) and the mixture was stirred until gas evolution had ceased (ca. 30 min RT, followed by 2 h at 60°C). Subsequently, 4- bromothiazole (20.00 g, 121.9 mmol) was added and the mixture was stirred at 140°C for 45 min. Subsequently, the reaction mixture was quenched with aq. sat. NH4CI and extracted with EtOAc. The comb. org. layers were washed with brine, dried over MgS04, and cone, in vacuo. The residue was subjected to distillation and the volatiles (HV, 60°C) were removed. The residue was purified by means of CC (5-40percent EtOAc/Hept) to provide a yellow oil. LC-MS (3): tR = 0.52 min; [M+H]+: 216.20.

Reference： [1]Patent: WO2014/115078,2014,A1 .Location in patent: Page/Page column 43-44
[2]Patent: WO2014/115072,2014,A1 .Location in patent: Page/Page column 51

69
[ 34259-99-9 ]
[ 106-95-6 ]
[ 1319212-46-8 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 7933 - 7937
Angew. Chem.,2014,vol. 126,p. 8067 - 8071,5

70
3-amino-7-bromo-5-(2-chlorophenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one [ No CAS ]
[ 34259-99-9 ]
3-amino-5-(2-chlorophenyl)-7-(1,3-thiazol-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20 mg		A mixture of 3-amino-7-bromo-5-(2-chlorophenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step B of Example 18 (200 mg), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (179 mg), (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (21.6 mg), potassium acetate (116 mg) and N,N-dimethylformamide (3.0 mL) was stirred overnight at 110°C under argon atmosphere. The reaction mixture was cooled to room temperature, <strong>[34259-99-9]4-bromo-1,3-thiazole</strong> (0.105 mL), aqueous sodium carbonate solution (2 M, 0.589 mL) and tetrakis(triphenylphosphine)palladium(0) (68.1 mg) were added thereto, and the reaction mixture was stirred overnight at 120°C under argon atmosphere. The reaction mixture was cooled to room temperature, water was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (basic silica gel, methanol/ethyl acetate) to give the title compound (20.0 mg). MS (ESI+) : [M+H]+344.0

Reference： [1]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0666; 0667

71
5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-[(1-[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]benzamide [ No CAS ]
[ 34259-99-9 ]
5-(1,3-thiazol-4-yl)-2-[(1-[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In N,N-dimethyl-formamide; at 130℃; for 0.25h;Inert atmosphere;	Library Protocol 2 To a 0.2M solution of 5-(4,4, 5,5-tetramethyl- 1, 3,2-dioxaborolan-2-yl)-2-[( 1 -[4-(trifluoromethoxy) phenyl]acetyl}piperidin-4-yl)oxy]benzamide (Preparation 14, 500 p L, 100 pmol) in DMF was added a 0.2M solution of compounds of formula (IV) (500 pL, lOOpmol) in DMF with argon purging. A 2M solution of cesium carbonate (100 pL, 200 pmol) in degassed water was added followed by tetrakis(triphenylphosphine)palladium (0) (5.7 mg, 5 pmol) and the reaction was heated to 130°C under microwave irradiation for 15 minutes. The reaction wascooled and concentrated in vacuo. the residue was dissolved in DMSO (1 mL) and purified using preparative HPLC:

Reference： [1]Patent: WO2015/92610,2015,A1 .Location in patent: Page/Page column 89; 90

72
tert-butyl 2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate [ No CAS ]
[ 34259-99-9 ]
tert-butyl 2-methyl-3-oxo-4-(thiazol-4-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With potassium phosphate; copper(l) iodide; (1R,2R)-1,2-diaminocyclohexane; In 1,4-dioxane; at 110℃;Inert atmosphere;	Intermediate 3R: tert-butyl 2-methyl-3-oxo-4-(thiazol-4-yI)-1 -oxa-4,9-diazaspiro[5.5]u ndecane-9-carboxylate A mixture of intermediate 3H (500 mg, 1.76 mmol), K3P04 (747 mg, 3.52 mmol), Cul(33 mg, 0.176 mmol), trans-i ,2-cyclohexanediamine (0.042 mL, 0.352 mmol) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.19 mL, 2.11 mmol) in dry 1,4-dioxane (5 mL) was heated under an argon atmosphere at 110 °C overnight. The reaction crude was cooled and ethyl acetate and water were added. The phases were separated and the aqueous phase was back extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and concentrated under vacuum. The residue was purified by flashchromatography, silica gel, gradient dichloromethane to methanol:dichloromethane (1:4) to give the title compound (270 mg, 41percent yield). HPLC retention time: 4.16 mm; MS: 312 (M+H-56).

Reference： [1]Patent: WO2015/185207,2015,A1 .Location in patent: Page/Page column 180; 181

73
[ 59016-93-2 ]
[ 34259-99-9 ]
[ 1187450-90-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃;	Aqueous potassium carbonate solution (3.0 M, 17 mL, 51 mmol) was added to a solution of [4-(hydroxymethyl)phenyl]boronic acid (96percent, 4.0 g, 25 mmol) and 4-bromo- 1 ,3-thiazole (96percent, 6.48 g, 37.9 mmol) in 1 ,4-dioxane (75 mL). Tetrakis(triphenylphosphine)palladium(0) (885 mg, 0.766 mmol) was added, and thereaction mixture was heated at 100 00 overnight. After cooling to room temperature, the reaction mixture was diluted with water and extracted several times with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo; silica gel chromatography (Gradient: 25percent to 50percent ethyl acetate in heptane) provided the productas a cream-colored solid. Yield: 3.60 g, 18.8 mmol, 75percent. LCMS m/z 192.0 [M+H]. 1H NMR (400 MHz, ODd3) oe 8.92 (d, J=2.0 Hz, 1 H), 7.95 (br d, J=8.2 Hz, 2H), 7.56 (d, J=2.0 Hz, 1H), 7.46 (br d, J=8.3 Hz, 2H), 4.76 (5, 2H).

Reference： [1]Patent: WO2016/9297,2016,A1 .Location in patent: Page/Page column 90; 91; 143

74
(S)-N-(7-(methylamino)-7-oxo-1-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide [ No CAS ]
[ 34259-99-9 ]
(S)-N-(7-(methylamino)-7-oxo-1-(5-(4-(thiazol-4-yl)phenyl)-1H-imidazol-2-yl)heptyl)thiazole-5-carboxamide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 454 - 459

75
[ 34259-99-9 ]
[ 65-85-0 ]
[ 128979-10-2 ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 3447 - 3456

76
[ 462-06-6 ]
[ 34259-99-9 ]
4-(2-fluorophenyl)thiazole [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 10463 - 10467
Angew. Chem.,2016,vol. 128,p. 10619 - 10623,5

77
2,2'-((2-phenylanthracene-9,10-diyl)bis(4,1-phenylene))bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) [ No CAS ]
[ 34259-99-9 ]
4,4 '-((2-phenylanthracene-9,10-diyl)bis(4,1-phenylene))dithiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.4 g	With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate; In water; for 6h;Reflux;	2,2'-((2-phenylanthracene-9,10-diyl)bis(4,1-phenylene))bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (3.3 g), <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (2.0 g), tetrabutylammonium bromide (0.2g), potassium carbonate (2.8 g), Pd(PPh3)4 (0.2 g), 1,2, 4-trimethyl benzene (20 ml) and water (2 ml) was stirred for 6 hours the flask was heated at the reflux temperature. The reaction mixture was cooled to room temperature. And it was separated by adding water and toluene. Then, silica gel chromatography and then purified by (eluent toluene / ethyl acetate = 9/1 (volume ratio)) and then recrystallized from chlorobenzene. In addition, not recrystallized from solo, compound (1-274): 4,4 '-((2-phenylanthracene-9,10-diyl)bis(4,1-phenylene))dithiazole (1.4 g)

Reference： [1]Patent: KR2015/138163,2015,A .Location in patent: Paragraph 0374; 0375

78
(2R*,3R*,4R*)-4-((benzyloxy)methyl)-2,3-bis((triisopropylsilyl)oxy)cyclopentanone [ No CAS ]
[ 34259-99-9 ]
(1R*,2R*,3R*,4R*)-4-((benzyloxy)methyl)-1-(thiazol-4-yl)-2,3-bis-((triisopropylsilyl)oxy)cyclopentanol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 3382 - 3402

79
5-phenylbenzofuran-2-MIDA boronate [ No CAS ]
[ 34259-99-9 ]
C₁₇H₁₁NOS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); triethylamine; In water; at 40℃; for 22h;Inert atmosphere;	General procedure: 2 wtpercent DL-alpha-Tocopherolmethoxypolyeneglycol succinate solution (1.5 mL) was added to a mixture of 5-methoxycarbonylbenzofuran-2-MIDA boronate (200 mg, 0.604 mmol), (dtbpf)PdCl2 (32 mg, 0.048 mmol) and bromobenzene (95 mg, 0.604 mmol) under N2. Et3N (0.25 mL, 1.81 mmol) was added to thesuspension under N2. The reaction mixture was vigorously stirred at 40 °C for 22 h under N2. Theresulting mixture was diluted with water to form a precipitate, which was filtered, washed with water anddissolved with CHCl3. The obtained organic solutions were dried over Na2SO4 and concentrated. Theresidue was purified by flash chromatography (SiO2, AcOEt : hexane = 30 : 70) to give 143.0 mg (94percent)of white powde;

Reference： [1]Heterocycles,2017,vol. 94,p. 1322 - 1336

80
5-nitrofuro[2,3-b]pyridine-2-2-MIDA boronate [ No CAS ]
[ 34259-99-9 ]
5-nitro-2-(thiazol-4-yl)furo[2,3-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.5 mg	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); triethylamine; In water; at 40℃; for 22h;Inert atmosphere;	Prepared from 2-hydroxy-3-iodo-5-nitropyridine and ethynylboronic acid MIDA ester. The resultingmixture was diluted with water and extracted with AcOEt. The organic layers were dried over Na2SO4and concentrated. The residue was purified by flash chromatography (SiO2, AcOEt) to give 212.7 mg of apale brown amorphous solid. The crude product was used in the next reaction without further purification.2 wtpercent DL-alpha-Tocopherolmethoxypolyeneglycol succinate solution (3.5 mL) was added to a mixture of thecrude furo[2,3-b]pyridine-2-MIDA boronate, (dtbpf)PdCl2 (104 mg) and <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (0.33 g) under N2. Et3N (0.61 mL) was added to the suspension under N2. The reaction mixture was vigorously stirred at40 °C for 22 h under N2. The resulting mixture was diluted with water and extracted with AcOEt. The organic layers were dried over Na2SO4 and concentrated. The residue was purified by flashchromatography (SiO2, AcOEt : hexane = 30 : 70) to give 16 (34.5 mg, 7percent, 2 steps) as a yellow solid; mp273-276 °C (Dec., AcOEt-hexane, yellow powder); IR (cm-1) 1738, 1604, 1508, 1471, 1348, 1265, 1155,1076, 1041; 1H-NMR (CDCl3) delta 7.37 (s, 1H), 8.01 (d, J = 2.0 Hz, 1H), 8.79 (d, J = 2.5 Hz, 1H), 8.95 (d, J= 2.0 Hz, 1H), 9.24 (d, J = 2.5 Hz, 1H); HRMS calcd for C10H6N3O3S [M+H] 248.0124, found 248.0122(Delta 0.23).

Reference： [1]Heterocycles,2017,vol. 94,p. 1322 - 1336

81
5-methoxy-1-Ns-1H-indole-2-MIDA boronate [ No CAS ]
[ 34259-99-9 ]
5-methoxy-N-Ns-indole [ No CAS ]
C₁₈H₁₃N₃O₅S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%; 33%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); triethylamine; In water; at 40℃; for 22h;Inert atmosphere;	General procedure: 2 wtpercent DL-alpha-Tocopherolmethoxypolyeneglycol succinate solution (1.5 mL) was added to a mixture of 5-methoxycarbonylbenzofuran-2-MIDA boronate (200 mg, 0.604 mmol), (dtbpf)PdCl2 (32 mg, 0.048 mmol) and bromobenzene (95 mg, 0.604 mmol) under N2. Et3N (0.25 mL, 1.81 mmol) was added to thesuspension under N2. The reaction mixture was vigorously stirred at 40 °C for 22 h under N2. Theresulting mixture was diluted with water to form a precipitate, which was filtered, washed with water anddissolved with CHCl3. The obtained organic solutions were dried over Na2SO4 and concentrated. Theresidue was purified by flash chromatography (SiO2, AcOEt : hexane = 30 : 70) to give 143.0 mg (94percent)of white powde;

Reference： [1]Heterocycles,2017,vol. 94,p. 1322 - 1336

82
5-methoxycarbonylbenzofuran-2-MIDA boronate [ No CAS ]
[ 34259-99-9 ]
C₁₃H₉NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); triethylamine; In water; at 40℃; for 22h;Inert atmosphere;	General procedure: 2 wtpercent DL-alpha-Tocopherolmethoxypolyeneglycol succinate solution (1.5 mL) was added to a mixture of 5-methoxycarbonylbenzofuran-2-MIDA boronate (200 mg, 0.604 mmol), (dtbpf)PdCl2 (32 mg, 0.048 mmol) and bromobenzene (95 mg, 0.604 mmol) under N2. Et3N (0.25 mL, 1.81 mmol) was added to thesuspension under N2. The reaction mixture was vigorously stirred at 40 °C for 22 h under N2. Theresulting mixture was diluted with water to form a precipitate, which was filtered, washed with water anddissolved with CHCl3. The obtained organic solutions were dried over Na2SO4 and concentrated. Theresidue was purified by flash chromatography (SiO2, AcOEt : hexane = 30 : 70) to give 143.0 mg (94percent)of white powde;

Reference： [1]Heterocycles,2017,vol. 94,p. 1322 - 1336

83
[ 71597-85-8 ]
[ 34259-99-9 ]
[ 68535-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere;	In a 100mL three-necked flask, were added 4-hydroxyphenyl boronic acid (10.0g, 61.4mmol), 4- bromothiazole (10.2g, 73.7mmol), potassium carbonate (25.4g, 184.2mmol), 1,4- dioxane (30mmol), water (10mL) and bis triphenylphosphine palladium dichloride (2.15g, 3.07mmol). Under nitrogen, the reaction system was heated to 90 , stirred for 3h. Concentrated under reduced pressure to remove the solvent by distillation, the residue was dissolved in ethyl acetate (100 mL), saturated brine was added, extracted liquid separation. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product as a pale yellow oil, purified by column chromatography to give the title product as a beige solid.

Reference： [1]Patent: CN106866737,2017,A .Location in patent: Paragraph 0093; 0095; 0096

84
[ 34259-99-9 ]
[ 94-09-7 ]
ethyl (4-thiazol-4-ylamino)benzoate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 10569 - 10572
Angew. Chem.,2017,vol. 129,p. 10705 - 10708,4

85
[ 504-29-0 ]
[ 34259-99-9 ]
N-(pyridin-2-yl)thiazol-4-amine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 10569 - 10572
Angew. Chem.,2017,vol. 129,p. 10705 - 10708,4

86
[ 5049-61-6 ]
[ 34259-99-9 ]
N-(pyrazin-2-yl)thiazol-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15 mg	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 40h;Inert atmosphere;	Under Ar(g), to a mixture of pyrazin-2-amine (1) (209mg, 2.2mmol), 4- bromothiazole (2) (328mg, 2.0mmol), Cs2C03 (1.30g, 4.0mmol) was added degassed dry 1 ,4-dioxane (13mL). The reaction mixture was then flushed with Ar(g) for 1 min before Pd2(dba)3 (92mg, 0.1 mmol) and Xantphos (127mg, 0.22mmol) were added. The reaction mixture was heated up to 90C for 40h. It was then cooled down to rt. EtOAc (15ml_), H20 (10mL) and brine (5ml_) were added to the reaction mixture. The organic phase was separated and the aqueous phase was extracted with EtOAc (15ml_). The organic layers were combined and Pd-scavenger (MP-TMT, ~400mg, 1.3mmol/g) was added. This was shaken for several hours followed by filtration. The filtrate was concentrated in vacuo, dissolved in DMSO (4ml_) and purified by basic prep LCMS to yield (3) as a solid (15mg, 4%).

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 10569 - 10572
Angew. Chem.,2017,vol. 129,p. 10705 - 10708,4
[2]Patent: WO2019/166824,2019,A1 .Location in patent: Page/Page column 21; 22

87
[ 163133-86-6 ]
[ 34259-99-9 ]
N-(pyrimidine-4-yl)thiazol-4-amine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 10569 - 10572
Angew. Chem.,2017,vol. 129,p. 10705 - 10708,4

88
[ 34259-99-9 ]
[ 62-53-3 ]
N-phenylthiazol-4-amine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 10569 - 10572
Angew. Chem.,2017,vol. 129,p. 10705 - 10708,4

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
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P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
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P411
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P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 34259-99-9 ] {[proInfo.proName]}

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[ 34259-99-9 ] Synthesis Path-Upstream 1~9

[ 34259-99-9 ] Synthesis Path-Downstream 1~88

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Bromides

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Thiazoles

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