[ CAS No. 4570-45-0 ] {[proInfo.proName]}

Name: 4570-45-0|Oxazol-2-amine|97%
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Quality Control of [ 4570-45-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 4570-45-0 ]

Product Details of [ 4570-45-0 ]

CAS No. :	4570-45-0	MDL No. :	MFCD07364485
Formula :	C₃H₄N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ACTKAGSPIFDCMF-UHFFFAOYSA-N
M.W :	84.08	Pubchem ID :	558521
Synonyms :

Calculated chemistry of [ 4570-45-0 ]

Physicochemical Properties

Num. heavy atoms :	6
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	20.91
TPSA :	52.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.09
Log Po/w (XLOGP3) :	-0.18
Log Po/w (WLOGP) :	0.26
Log Po/w (MLOGP) :	-1.13
Log Po/w (SILICOS-IT) :	0.42
Consensus Log Po/w :	0.09

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.86
Solubility :	11.5 mg/ml ; 0.137 mol/l
Class :	Very soluble
Log S (Ali) :	-0.46
Solubility :	29.3 mg/ml ; 0.349 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.77
Solubility :	14.3 mg/ml ; 0.17 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.86

Safety of [ 4570-45-0 ]

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

Application In Synthesis of [ 4570-45-0 ]

* 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 [ 4570-45-0 ]
Downstream synthetic route of [ 4570-45-0 ]

[ 4570-45-0 ] Synthesis Path-Upstream 1~6

1
[ 420-04-2 ]
[ 141-46-8 ]
[ 4570-45-0 ]

Yield	Reaction Conditions	Operation in experiment
71.3%	With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 24 h;	Example 2: Preparation of 2-amino-oxazole. To a solution of cyanamide (19.8 ml of 50percent w/w in water, 0.25 mol) in THF (60 ml) was added the hydroxyacetaldehyde (15 g, 0.25 mol) in 24 ml of water. The reaction mixture was treated at 0⁰C with a solution of sodium hydroxide 2 M (25.2 ml, 0.05 mol). The mixture was allowed to warm to room temperature and stirred for 24 hrs. The volatiles were removed in vacuo (THF) and the remaining aqueous solution was extracted with four portions of 200 ml of ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated in vacuo, yielding 14.968 g (71.3percent) of a white solid. 400 MHz ¹H NMR (CDCl₃) δ: 7.13 (s, IH), 6.74 (s, IH), 5.26 (br. s, 2H). CaIc. for C₃H₄N₂O: C 42.86, H 4.80, N 33.32; found C 43.01, H 4.87, N 33.11.
66%	With sodium hydroxide In tetrahydrofuran; water at 0℃; for 24 h;	To a solution of cyanamide (33ml, 50percentwt in water, 0.416mol) in THF (100ml), wasadded an aqueous solution of 2-hydroxyacetaldehyde (25g, 0.41 6mol) in water (40ml),followed by the dropwise addition of 2M sodium hydroxide (42ml, 0.083mol) at 0°C. Stirringwas continued for a total of 24 hours. Then, the reaction mixture was concentrated in vacua toremove most of the THF. The remaining water layer was extracted with ethyl acetate (4 x200ml). The extract was dried over sodium sulfate and the solvent was evaporated in vacua.This gave the white solid product A (23 g, 66percent).
66%	With sodium hydroxide In tetrahydrofuran; water at 0℃; for 24 h;	Example 35: Preparation of 2-amino-oxazole.; To a solution of cyanamide (33 ml, 50percent wt in water, 0.416 mol) in THF (100 ml), is added an aqueous solution of 2-hydroxyacetaldehyde (25g, 0.416 mol) in water (40ml),followed by the dropwise addition of 2M sodium hydroxide (42 ml, 0.083 mol) at O°C.Stirring is continued for a total of 24 hours. Then, the reaction mixture is concentrated in vacuo to remove most of the THF. The remaining water layer is extracted four times with 200 ml each of ethyl acetate. The extract is dried over sodium sulfate and the solvent is evaporated in vacuo. This produces a white solid product (23g, 66percent).

Reference： [1] Patent: WO2007/123892, 2007, A2, . Location in patent: Page/Page column 50
[2] Patent: WO2004/110990, 2004, A2, . Location in patent: Page 37
[3] Patent: WO2006/44869, 2006, A1, . Location in patent: Page/Page column 132
[4] Chemistry - A European Journal, 2013, vol. 19, # 14, p. 4586 - 4595
[5] Synthesis, 1976, p. 591 - 593
[6] Journal of the American Chemical Society, 2017, vol. 139, # 26, p. 8780 - 8783

2
[ 7166-44-1 ]
[ 57-13-6 ]
[ 4570-45-0 ]

Reference： [1] Journal of the American Chemical Society, 1942, vol. 64, p. 2902

3
[ 420-04-2 ]
[ 141-46-8 ]
[ 4570-45-0 ]
[ 7720-39-0 ]

Reference： [1] Journal of the American Chemical Society, 2017, vol. 139, # 26, p. 8780 - 8783

4
[ 57-13-6 ]
[ 17157-48-1 ]
[ 4570-45-0 ]

Reference： [1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1987, vol. 27, # 7, p. 258 - 259
[2] Bulletin de la Societe Chimique de France, 1960, p. 2052 - 2061

5
[ 420-04-2 ]
[ 4124-63-4 ]
[ 141-46-8 ]
[ 4570-45-0 ]
[ 96-50-4 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 33, p. 13889 - 13895

6
[ 420-04-2 ]
[ 141-46-8 ]
[ 4570-45-0 ]
[ 7720-39-0 ]

Reference： [1] Journal of the American Chemical Society, 2017, vol. 139, # 26, p. 8780 - 8783

[ 4570-45-0 ] Synthesis Path-Downstream 1~88

1
[ 4570-45-0 ]
[ 98-74-8 ]
4-nitro-benzenesulfonic acid oxazol-2-ylamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1942,vol. 64,p. 2902

2
[ 420-04-2 ]
[ 141-46-8 ]
[ 4570-45-0 ]

Yield	Reaction Conditions	Operation in experiment
71.3%	With sodium hydroxide; In tetrahydrofuran; water; at 0 - 20℃; for 24h;	Example 2: Preparation of 2-amino-oxazole. To a solution of cyanamide (19.8 ml of 50% w/w in water, 0.25 mol) in THF (60 ml) was added the hydroxyacetaldehyde (15 g, 0.25 mol) in 24 ml of water. The reaction mixture was treated at 00C with a solution of sodium hydroxide 2 M (25.2 ml, 0.05 mol). The mixture was allowed to warm to room temperature and stirred for 24 hrs. The volatiles were removed in vacuo (THF) and the remaining aqueous solution was extracted with four portions of 200 ml of ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated in vacuo, yielding 14.968 g (71.3%) of a white solid. 400 MHz 1H NMR (CDCl3) delta: 7.13 (s, IH), 6.74 (s, IH), 5.26 (br. s, 2H). CaIc. for C3H4N2O: C 42.86, H 4.80, N 33.32; found C 43.01, H 4.87, N 33.11.
66%	With sodium hydroxide; In tetrahydrofuran; water; at 0℃; for 24h;	To a solution of cyanamide (33ml, 50%wt in water, 0.416mol) in THF (100ml), wasadded an aqueous solution of 2-hydroxyacetaldehyde (25g, 0.41 6mol) in water (40ml),followed by the dropwise addition of 2M sodium hydroxide (42ml, 0.083mol) at 0C. Stirringwas continued for a total of 24 hours. Then, the reaction mixture was concentrated in vacua toremove most of the THF. The remaining water layer was extracted with ethyl acetate (4 x200ml). The extract was dried over sodium sulfate and the solvent was evaporated in vacua.This gave the white solid product A (23 g, 66%).
66%	With sodium hydroxide; In tetrahydrofuran; water; at 0℃; for 24h;	Example 35: Preparation of 2-amino-oxazole.; To a solution of cyanamide (33 ml, 50% wt in water, 0.416 mol) in THF (100 ml), is added an aqueous solution of 2-hydroxyacetaldehyde (25g, 0.416 mol) in water (40ml),followed by the dropwise addition of 2M sodium hydroxide (42 ml, 0.083 mol) at OC.Stirring is continued for a total of 24 hours. Then, the reaction mixture is concentrated in vacuo to remove most of the THF. The remaining water layer is extracted four times with 200 ml each of ethyl acetate. The extract is dried over sodium sulfate and the solvent is evaporated in vacuo. This produces a white solid product (23g, 66%).

Reference： [1]Patent: WO2007/123892,2007,A2 .Location in patent: Page/Page column 50
[2]Patent: WO2004/110990,2004,A2 .Location in patent: Page 37
[3]Patent: WO2006/44869,2006,A1 .Location in patent: Page/Page column 132
[4]Chemistry - A European Journal,2013,vol. 19,p. 4586 - 4595
[5]Synthesis,1976,p. 591 - 593
[6]Journal of the American Chemical Society,2017,vol. 139,p. 8780 - 8783

3
[ 57-13-6 ]
[ 17157-48-1 ]
[ 4570-45-0 ]

Reference： [1]Zeitschrift fur Chemie,1987,vol. 27,p. 258 - 259
[2]Bulletin de la Societe Chimique de France,1960,p. 2052 - 2061

4
[ 4570-45-0 ]
[ 108-24-7 ]
[ 41215-13-8 ]

Reference： [1]Zeitschrift fur Chemie,1987,vol. 27,p. 258 - 259

5
[ 4570-45-0 ]
[ 64321-70-6 ]
[ 114350-78-6 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1453 - 1462

6
[ 4570-45-0 ]
[ 98-88-4 ]
[ 115367-51-6 ]

Reference： [1]Zeitschrift fur Chemie,1987,vol. 27,p. 258 - 259

7
[ 4570-45-0 ]
[ 59197-85-2 ]
[ 59197-93-2 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1453 - 1462

8
[ 4570-45-0 ]
[ 762-42-5 ]
[ 104746-84-1 ]
[ 104746-75-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 1281 - 1284

9
[ 4570-45-0 ]
[ 75999-37-0 ]
[ 75999-38-1 ]

Yield	Reaction Conditions	Operation in experiment
30.8%	With triethylamine; In water; ethyl acetate;	EXAMPLE 2 2,8-bis-(trifluoromethyl)-4-hydroxy-N-(oxazol-2-yl)-3-quinoline-carboxamide A solution of 15.9 g of 2,8-bis-(trifluoromethyl)-4-hydroxy-3-quinoline-carboxylic acid chloride in 210 ml of ethyl acetate was added with stirring at 5-8 C. under nitrogen to a solution of 3.57 g of <strong>[4570-45-0]2-amino-oxazole</strong> and 4.3 g of triethylamine in 50 ml of ethyl acetate and after the temperature returned to room temperature, it stood overnight at that temperature. The mixture was vacuum filtered and the filtrate was washed and evaporated to dryness under reduced pressure. The 14.23 g of residue was triturated with 100 ml of N sodium hydroxide solution for 3 hours and was then diluted with 200 ml of water. The mixture was vacuum filtered and the filtrate was treated with activated carbon. The pH was adjusted to 1 by addition of N hydrochloric acid and the mixture was vacuum filtered. The recovered product was washed with water and dissolved in ethyl acetate. The solution was evaporated to dryness and the 8.77 g of product were crystallized twice from acetic acid to obtain 5.73 g (30.8% yield) of 2,8-bis-(trifluoromethyl)-4-hydroxy-N-(oxazol-2-yl)-3-quinoline-carboxamide melting at 258 C.

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1453 - 1462
[2]Patent: US4299831,1981,A

10
[ 4570-45-0 ]
[ 141-46-8 ]
(3aS,6R,6aR)-2-Amino-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,6S,6aR)-2-Amino-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 16677 - 16688
[2]Angewandte Chemie - International Edition,2006,vol. 45,p. 6176 - 6179
[3]Chemistry - A European Journal,2013,vol. 19,p. 4586 - 4595

11
[ 4570-45-0 ]
[ 56-82-6 ]
(3aS,5S,6R,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,5R,6R,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,5S,6S,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,5R,6S,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 6176 - 6179

12
[ 865625-60-1 ]
[ 4570-45-0 ]
C₁₃H₁₁F₃N₂O₅S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3984 - 4002

13
[ 4570-45-0 ]
[ 15781-73-4 ]
C₁₂H₈N₂O₃ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 8250 - 8252

14
[ 4570-45-0 ]
[ 591-57-1 ]
D-ribose aminooxazoline-5′-phosphate [ No CAS ]
D-arabinose aminooxazoline-5′-phosphate [ No CAS ]
D-xylose aminooxazoline-5′-phosphate [ No CAS ]
C₆H₁₁N₂O₇P [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 24 - 25

15
[ 4570-45-0 ]
[ 403-29-2 ]
[ 815597-08-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	In tetrahydrofuran; acetonitrile; at 20℃; for 24.33h;	To a solution of 2-bromo-l-(4-fluorophenyl)-ethanone (CASNo. 403-29-2, 1) (60g,0.376mol) in anhydrous tetrahydrofuran (THF) solution (200ml) was added over 20 minutes asolution of <strong>[4570-45-0]2-amino-oxazole</strong> (A) (16g, 0.19mol) in anhydrous acetonitrile at room temperature.The mixture was stirred for 24 hours before cooling to 0C. The precipitate was collected byfiltration and washed with cold acetonitrile (3 x 30mL) and dried in a vacuum oven to yieldlight yellow crystals of l-(4-fluorophenyl)-2-(2-imino-l,3-oxazol-3(2F)-yl)ethanonehydrobromide (B) (42.0g, 77%). MS (ES+) 203 (M+l).'H NMR (300 MHz, DMSO) 6: 7.95 (brs, 1H), 9.7 (brs, 1H), 8.14 (m, 2H), 7.99 (d, J= 0.9,1H), 7.61 (d, J= 1.5 Hz, 1H), 7.51 (t, J= 8.7 Hz, 2H), 5.79 (s, 2H).
72%	In tetrahydrofuran; acetonitrile; at 20℃; for 24.33h;	Example 3: Preparation of N-[4-(dimethylammo')phenyl]-4-((4-f6-(4-fluorophenyl)- imidazof 2.1 -bl [ 13]oxazol-5-yl1pyrimidin-2-yl) amino*)piperidme-l -carboxamide3a: Preparation of l-(4-fluorophenyl)-2-(2-imino-l,3-oxazol-3(2H)-yl)ethanone hydrobromidbetaA solution of <strong>[4570-45-0]2-amino-oxazole</strong> (14.9 g, 0.179 mol) in acetonitrile (100 ml) was slowly added over a period of 20 minutes to a solution of 2-bromo-l-(4-fluorophenyl)ethanone (57.6 g, 0.36 mol) in THF (150 ml). The reaction mixture was stirred at room temperature for 24 hrs then cooled to O0C. A precipitate formed and was filtered off. The solid was <n="53"/>washed with three portions of 30 ml of cold acetonitrile and dried at 500C under vacuum, yielding 38.75 g (72%) of an off-white solid. M.p. = 218-221 C; 300 MHz 1H NMR (DMSOd6) delta: 9.80 (br. s, IH)5 8.16-8.11 (m, 2H), 8.00 (s, IH), 7.62 (s, IH), 7.52-7.46 (m, 2H), 5.80 (s, 2H); LCMS: 221 [M+H], CaIc. for CuH9N2O2F ' 1.05 HBr ? 0.14 ACN: C 43.58, H 3.39, N 9.64; found C 43.63, H 3.38, N 9.65.

Reference： [1]Patent: WO2004/110990,2004,A2 .Location in patent: Page 37-38
[2]Patent: WO2007/123892,2007,A2 .Location in patent: Page/Page column 50-51

16
[ 4570-45-0 ]
5-Acetyl-2-chloro-5,6-dihydro-dibenzo[b,f]azocine-8-carboxylic acid [ No CAS ]
5-Acetyl-2-chloro-5,6-dihydro-dibenzo[b,f]azocine-8-carboxylic acid oxazol-2-ylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With dmap; dicyclohexyl-carbodiimide; In DMF (N,N-dimethyl-formamide); at 20℃; for 7h;	To an oven dried 10 mL round bottom flask was added Example 254B (20 mg, 0.06 mmol), DMF (1 mL), DMAP (11 mg, 0.09 mmol) and oxazol-2-ylamine (13 mg, 0.15 mmol), followed by DCC (20 mg, 0.09 mmol). The mixture was stirred at room temperature for 7 hours then concentrated. The residue was purified by preparative reversed-phase HPLC to give Example 255 (3 mg, 13 %). HPLC Rt=2.03(b) min. m/z=394 (M+H+).

Reference： [1]Patent: US2005/250753,2005,A1 .Location in patent: Page/Page column 75

17
[ 4570-45-0 ]
[ 300355-34-4 ]
[ 56602-33-6 ]
3-cyclopentyl-2-(3,4-dichlorophenyl)-N-oxazol-2-yl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	EXAMPLE 57 3-Cyclopentyl-2-(3,4-dichlorophenyl)-N-oxazol-2-yl-propionamide A solution of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (102 mg, 0.23 mmol), 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared in Example 38, 60 mg, 0.21 mmol), N,N-diisopropylethylamine (73 muL, 0.42 mmol), and 2-aminooxazole (27 mg, 0.31 mmol) in dry N,N-dimethylformamide (1 mL) was stirred at 25 C. under nitrogen for 15 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with a 1N aqueous hydrochloric acid solution, washed with water, and washed with a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-oxazol-2-yl-propionamide (34.9 mg, 47%) as a white solid: mp 134-136 C.; EI-HRMS m/e calcd for C17H18Cl2N2O2(M+) 352.0745, found 352.0750.
47%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	EXAMPLE 57 3-Cyclopentyl-2-(3,4-dichlorophenyl)-N-oxazol-2-yl-propionamide A solution of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (102 mg, 0.23 mmol), 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 60 mg, 0.21 mmol), N,N-diisopropylethylamine (73 muL, 0.42 mmol), and 2-aminooxazole (27 mg, 0.31 mmol) in dry N,N-dimethylformamide (1 mL) was stirred at 25 C. under nitrogen for 15 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed sequentially with a 1N aqueous hydrochloric acid solution, water, and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-oxazol-2-yl-propionamide (34.9 mg, 47%) as a white solid: mp 134-136 C.; EI-HRMS m/e calcd for C17H18Cl2N2O2 (M+) 352.0745, found 352.0750.

Reference： [1]Patent: US2001/39344,2001,A1
[2]Patent: US6610846,2003,B1

18
[ 4570-45-0 ]
[ 17042-08-9 ]
9H-Thioxanthene-9-carboxylic acid oxazol-2-ylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With dmap; sodium hydrogencarbonate; In pyridine; dichloromethane; water;	EXAMPLE 31 9H-Thioxanthene-9-carboxylic acid oxazol-2-ylamide To a stirred solution of (0.048 g, 0.575 mmol) <strong>[4570-45-0]2-amino-oxazole</strong> [Cockerill & al., Synthesis 591(1976)], and DMAP (0.003 g, 0.03 mmol) in pyridine (2 ml) was added at 0 C. (0.100 g, 0.384 mmol) 9H-thioxanthene-9-carbonyl chloride. Stirring was continued at RT for 16 h, the reaction mixture was evaporated and water (5 ml)/sat. NaHCO3 solution (2 ml) was added. The solid was filtered off, dissolved in dichloromethane, dried (MgSO4), and concentrated in vaccuo. The crude material was purified by column chromatobraphy on silica gel (methylene chloride/methanol 40:1) to give the product (0.022 g, 18%) as a white solid, m.p. 188-191 C. and MS: m/e=309.1 (M+H+).

Reference： [1]Patent: US2002/91150,2002,A1

19
[ 4570-45-0 ]
[ 912673-53-1 ]
S-6-methyl-4-(oxazol-2-ylamino)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90 - 100℃; for 20h;	A mixture of S-4-chloro-6-methyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-l- yl}pyrimidine (165mg, 0.42mmol), <strong>[4570-45-0]2-amino-oxazole</strong> (43mg, 0.51mmol) and cesium carbonate (290mg, 0.89mmol) in 1,4-dioxane (4ml) was degassed, then tris(dibenzylideneacetone)dipalladium(0) (24mg, 0.03mmol) and 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (23mg, 0.04mmol) were added and the mixture was heated at 90C for 4 hours. Further <strong>[4570-45-0]2-amino-oxazole</strong> (43mg, 0.51mmol), tris(dibenzylideneacetone)- dipalladium(O) (24 mg, 0.03mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (23mg, 0.04mmol) were added, and the mixture heated at 100C for a further 16 hours. The mixture was allowed to cool and the insolubles were removed by filtration through diatomeous earth. The filter pad was washed through with DCM and the solvent removed from the filtrate by evaporation. The residue was purified by column chromatography on silica gel eluting with EtOAc / isohexane (50:50 increasing in polarity to 70:30) to give the title compound (llOmg, 67%); NMR (500.133 MHz, 373K) 2.04-2.09 (2H, m), 2.13-2.17 EPO <DP n="107"/>(IH, m), 2.21 (3H, s), 2.32-2.39 (IH, m), 3.67-3.76 (2H, m), 5.45-5.48 (IH, m), 6.70 (IH5 s), 6.91 (IH, s), 6.99 (IH, s), 7.42-7.45 (IH, m), 7.62 (IH, s), 7.87-7.90 (IH, m), 7.94 (IH, d), 8.64 (IH, d), 10.04 (IH, s); m/z 390 [MH]+.

Reference： [1]Patent: WO2007/31745,2007,A1 .Location in patent: Page/Page column 105-106

20
[ 4570-45-0 ]
[ 193977-34-3 ]
[ 1033041-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; acetonitrile; at 23℃; for 20h;	General Procedure O: Cyclization to form an imidazo[l,2-Zphixazole; To a flask containing a bromoketone (1-2 equiv, preferably 1.5 equiv) in an organic solvent or solvents (such as THF, ACN, DCM, dioxane, or THF/ACN, preferably THF/ACN) is added an optionally substituted <strong>[4570-45-0]oxazole-2-amine</strong> (preferably 1 equiv). The mixture is stirred at about 0-70 0C (preferably about 23 0C) for about 2-30 h (preferably about 20 h). The reaction mixture is cooled to about -78-0 0C (preferably about -10 0C) for about 5-30 min (preferably about 15 min) and the solid is collected by vacuum filtration, washed with additional organic solvent (such as THF, ACN, DCM, or 1 ,4-dioxane, preferably ACN), and dried under vacuum. To this intermediate (preferably 1 equiv) is added an organic solvent (for example, toluene). A solution of TiCU (1-5 equiv, preferably 2.5 equiv, in an organic solvent (for example, toluene) is added over about 15 min-1 h (preferably about 30 nun) at about -10-23 0C (preferably about 0 0C). The resulting mixture is stirred at about -10-23 0C (preferably about 0 0C) for about 30 min-1 h (preferably about 30 min), followed by heating to about 70-110 0C (preferably about 100 0C) for about 30 min-5 h (preferably about 3 h). The mixture is cooled and the organic solvent is optionally decanted off. Ice water is added to the reaction flask with stirring. The resulting thick suspension is stirred at ambient temperature for about 1-12 h (preferably about 1 h) followed by the addition of a base (for example, Na2CO3) and an organic solvent (such as EtOAc or DCM). The resulting mixture is stirred at ambient temperature for about 30 min-2 h (preferably about 1 h) and then optionally filtered through Celite. The layers are separated and the organic solution is dried over Na2SO4 or MgSO4, filtered, and concentrated under reduced pressure to give the target compound. Optionally, the product can be purified by crystallization or trituration from an appropriate solvent or solvents, or by chromatography to give the target compound.Illustration of General Procedure OPreparation No.O:1: 6-(2,4,5-Trifluorophenyl)imidazo[2,l-£]oxazoleA round bottom flask was charged with 2-bromo-l-(2,4,5-trifluorophenyl)ethanone (50.0 g, 198 mmol; Example No.N.l), <strong>[4570-45-0]oxazole-2-amine</strong> (11.1 g, 132 mmol; GL Synthesis), THF (200 mL), and ACN (330 mL). The resulting mixture was stirred at about 23 0C for about 20 h. The suspension was cooled to about -10 0C for about 15 min and the solid was collected by vacuum filtration, washed with additional ACN (150 mL), and dried under vacuum to give 2-(2-iminooxazol-3(2/f)-yl)-l -(2,4,5- <n="112"/>trifluorophenyl)ethanone hydrobromide (35.1 g, 79%) as a white solid. A portion of this material (20.0 g, 59.3 mmol) was suspended in toluene (140 mL) and the suspension was cooled to about 0 0C. To the flask was added a 1.0 M solution Of TiCl4 in toluene (154 mL) over about 30 min. The mixture was stirred at about 0 0C for about 30 min and was then heated to about 100 0C for about 3 h. The mixture was cooled to ambient temperature, the toluene was decanted off, and ice was added with stirring to the remaining residue. The mixture was adjusted to about pH 8 with the addition of solid Na2CO3, followed by the addition of EtOAc. The mixture was stirred for about 1 h and then passed through a pad of Celite. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure to give the title compound as a white solid (11.7 g, 83%): LC/MS (Table 1, Method d) Rt = 2.11 min; MS m/z 239.1 (M+H)+.

Reference： [1]Patent: WO2008/63287,2008,A2 .Location in patent: Page/Page column 110-111

21
[ 4570-45-0 ]
[ 188975-34-0 ]
5(S)-oxazol-2-ylaminomethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.6%		To a stirred partial solution of 2-aminooxazole(169 mg, 2.0 mmol) in dry THF (10 ml), cooled to -78 C., under argon, was added slowly n-BuLi(1.33M, 1.5 ml, 2.0 mmol), followed after 1 h by 5(R)-methylsulfonyloxymethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one (see Example 41; 371 mg, 11.0 mol) suspended in dry THF(20 ml). The reaction was allowed to come to room temperature and then refluxed for 24 h. The reaction was quenched with ammonium chloride solution(10%w/v, 30 ml), extracting the mixture with chloroform (3×50 ml). The extracts were dried (magnesium sulfate), concentrated by rotary evaporation chromatographed by MPLC (Merck 9385 silica, 3-10% gradient methanol/dichloromethane eluent) and the pure fractions combined, concentrated and triturated with diethyl ether to give the title compound (25 mg, 4.6%). [0715] NMR (300Mz, DMSO-d6), delta/ppm: 2.31 (m, 2H),3.35 (m, 2H, obscured), 3.64 (dd, 1H), 3.84 (t, 2H), 3.90 (m, 1H), 4.15 (m, 1H), 4.24 (m, 2H), 4.46 (m, 1H), 5.97 (m, 1H), 6.90 (m, 1H), 7.19 (m, 2H, partially obscured), 7.37 (dd, 1H), 7.44 (dd, 1H). [0716] MS: ES+(M+H)=360.

Reference： [1]Patent: US2003/207899,2003,A1 .Location in patent: Page/Page column 45

22
[ 4570-45-0 ]
[ 130998-84-4 ]
C₆H₁₀N₂O₇P^(1-)*Na⁽¹⁺⁾ [ No CAS ]
C₆H₁₀N₂O₇P^(1-)*Na⁽¹⁺⁾ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2008,vol. 14,p. 2375 - 2388

23
[ 4570-45-0 ]
[ 1100363-70-9 ]
[ 1100363-87-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 1855 - 1864

24
[ 4570-45-0 ]
[ 598-21-0 ]
[ 1196093-52-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform; at 20℃; for 16h;	a) 2-Bromo-N-oxazol-2-yl-acetamide A solution of bromoacetyl bromide (0.44 mL) in dry CHCl3 (5 mL) was added dropwise to a suspension of <strong>[4570-45-0]2-amino-1,3-oxazole</strong> (0.39 g) and triethylamine (0.96 mL) in dry CHCI3 (92 mL) at room temperature. The brown mixture was allowed to stir for 16 h, then quenched with H2O (2 mL) and stirred for 20 mins before concentrating under reduced pressure to a light brown solid. The crude product was purified by silica gel chromatography eluting with 1-3% MeOH/dichloromethane to give the title compound (0.56 g) as an off-white solid. 1H NMR (400 MHz, DMSO-D6): delta 11.61 (s, 1H), 7.89 (s, 1H), 7.12 (s, 1H), 4.11 (s,2H).
	With triethylamine; In chloroform; at 20℃; for 16h;	Example 48: (/?)-l-(Oxazol-2-ylcarbamoylmethyl)-3-(l-phenyl- cycloheptanecarbonyloxy)-l-azonia-bicyclo[2.2.2]octane bromidea) 2-Bromo-N-oxazol-2-yl-acetamide A solution of bromoacetyl bromide (0.44 mL) in dry CHCl3 (5 niL) was added dropwi a suspension of 2-amino-l,3-oxazole (0.39 g) and triethylamine (0.96 mL) in dry CHC (92 mL) at room temperature. The brown mixture was allowed to stir for 16h, then quenched with H2O (2 mL) and stirred for 20mins before concentrating under reduced pressure to a light brown solid. The crude product was purified by silica gel chromatography eluting with 1-3% MeOH/dichloromethane to give the title compoun< (0.56g) as an off-white solid.1H NMR (400 MHz, DMSO-D6): delta 11.61 (s, IH), 7.89 (s, IH), 7.12 (s, IH), 4.11 (s,

Reference： [1]Patent: US2011/172237,2011,A1 .Location in patent: Page/Page column 38
[2]Patent: WO2009/138707,2009,A1 .Location in patent: Page/Page column 98

25
[ 4570-45-0 ]
[ 55332-38-2 ]
[ 1208552-68-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 493 - 498

26
[ 4570-45-0 ]
[ 13036-50-5 ]
[ 1236002-90-6 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 3259 - 3262

27
[ 4570-45-0 ]
[ 75634-04-7 ]
[ 1236002-91-7 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 3259 - 3262

28
[ 4570-45-0 ]
[ 1235406-32-2 ]
[ 1235395-39-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 95 4-(biphenyl-2-yloxy)-3-cvano-N-1 ,3-oxazol-2-ylbenzenesulfonamide; METHOD G PC33795A94 Triethylamine (38 ul, 0.27 mmol) was added to oxazol-2-ylamine (14 mg,0.169 mmol) in THF (0.5 ml) and stirred for 5 minutes. 4-(biphenyl-2-yloxy)-3- cyano-benzenesulfonyl chloride (Preparation 55, 50 mg, 0.14 mmol) in THF (0.5 ml) was then added slowly and the reaction stirred at room temperature overnight. Aqueous 2N HCI was added and the reaction extracted into ethyl acetate three times, the organic layer collected, dried (MgSO4), and concentrated in vacuo to furnish a crude residue that was purified using preparative HPLC. LCMS Rt=3.17 minutes MS m/z 418 [MH]+

Reference： [1]Patent: WO2010/79443,2010,A1 .Location in patent: Page/Page column 93-94

29
[ 4570-45-0 ]
3-(6-(ethylcarbamoyl)-5-methylpyrrolo[1,2-f][1,2,4]triazin-4-ylamino)-4-methylbenzoic acid [ No CAS ]
[ 623152-46-5 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6629 - 6639

30
[ 4570-45-0 ]
[ 1258298-00-8 ]
[ 1258294-03-9 ]

Yield	Reaction Conditions	Operation in experiment
9%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 140℃; for 3h;Microwave irradiation; Inert atmosphere;	To a microwave tube was added N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (0.30 g, 0.87 mmol), 2-aminooxazole (0.11 g, 1.0 mmol), Pd2(dba)3 (0.078 g, 0.087 mmol), XantPhos (0.096 g, 0.17 mmol), Cs2CO3 (0.57 g, 1.7 mmol) and dioxane (5 mL). The mixture was degassed with N2 for 10 min. The resulting mixture was irradiated in a microwave reactor at 140 C. for 3 hours and then cooled to room temperature. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was dissolved in DMF and purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give the desired product as a yellow solid (26 mg, yield: 9%). 1H NMR (500 MHz, DMSO-d6): delta 11.2 (s, 1H), 8.28 (s, 1H), 8.17 (d, J=5.5 Hz, 1H), 7.71 (s, 1H), 7.59 (d, J=7.5 Hz, 2H), 7.52 (t, J=3.5 Hz, 1H), 7.41 (m, 1H), 7.03 (s, 1H). LC-MS (ESI) m/z: 349.0 [M+H+].

Reference： [1]Patent: US2010/317643,2010,A1 .Location in patent: Page/Page column 97; 98

31
[ 4570-45-0 ]
[ 50-00-0 ]
[ 5098-11-3 ]
[ 1257145-43-9 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 16677 - 16688

32
[ 4570-45-0 ]
[ 141-46-8 ]
[ 5098-11-3 ]
C₉H₁₀N₆O₂ [ No CAS ]
C₉H₁₀N₆O₂ [ No CAS ]
rac-(1'S,2'S,3'S)-3'-(hydroxymethyl)-1',2',3',N-tetrahydroimidazo[1',3']-2''-aminooxazolo[1',2']-pyrimidine-4-carbonitrile [ No CAS ]
rac-(1'S,2'S,3'R)-3'-(hydroxymethyl)-1',2',3',N-tetrahydroimidazo[1',3']-2''-aminooxazolo[1',2']-pyrimidine-4-carbonitrile [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 16677 - 16688

33
[ 4570-45-0 ]
[ 56-82-6 ]
(3aS,6S,7R,7aR)-2-Amino-5,6,7,7a-tetrahydro-3aH-pyrano[2,3-d]oxazole-6,7-diol [ No CAS ]
(3aS,5R,6R,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,5S,6S,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]
(3aS,5R,6S,6aR)-2-Amino-5-hydroxymethyl-3a,5,6,6a-tetrahydro-furo[2,3-d]oxazol-6-ol [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 16677 - 16688

34
[ 4570-45-0 ]
[ 56-82-6 ]
[ 5098-11-3 ]
C₁₀H₁₂N₆O₃ [ No CAS ]
C₁₀H₁₂N₆O₃ [ No CAS ]
C₁₀H₁₂N₆O₃ [ No CAS ]
rac-3'-(1H-5-aminoimidazolo)aminooxazoline [ No CAS ]
C₁₀H₁₂N₆O₃ [ No CAS ]
rac-3'-(4',5'-dihydroxyethyl)-1',2',3',N-tetrahydroimidazo[1',3']-2''-aminooxazolo[1',2']-pyrimidine-4-carbonitrile [ No CAS ]
C₁₀H₁₂N₆O₃ [ No CAS ]
C₁₀H₁₂N₆O₃ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 16677 - 16688

35
[ 4570-45-0 ]
[ 62176-31-2 ]
[ 1285513-89-4 ]

Yield	Reaction Conditions	Operation in experiment
6.1%		General procedure: To a suspension of CDI (106 mg, 0.651 mmol) in THF (10 mL) under nitrogen at roomtemperature was added 11g (200 mg, 0.651mmol). The reaction was stirred at room temperaturefor 10 min and 4-pyridazinamine (61.9 mg, 0.651 mmol) was added dropwise. After refluxed for14 hrs, the mixture was concentrated and water was added. The mixture was then extracted withEtOAc (50 mL*3). The combined organic phases were washed with brine, dried over Na2SO4 andconcentrated. The crude product was then washed with MeOH to give the title compound 7a (95mg, 38%) as a white solid.
		Solid 5-bromo-2-[(phenylmethyl)oxy]benzoic acid (may be prepared as described in Description 5; 200 mg, 0.65 mmol) was added to a stirred suspension of CDI (106 mg, 0.65 mmol) in tetrahydrofuran ( 0 ml) under nitrogen at 20C. The reaction mixture was stirred at room temperature for 10 min. 1 ,3-Oxazol-2-amine (54.7 mg, 0.65 mmol) was then added and the reaction mixture was refluxed overnight. The reaction mixture was concentrated. Water (100 ml) was added to the residue followed by extraction with ethyl acetate (3 x 50 ml). The combined organic phase was washed with saturated brine (25 ml), dried over Na2S04, and concentrated under reduced pressure. The crude product was purified by thin layer chromatography (petroleum ether: ethyl acetate = 2:1 ) followed by Prep-HPLC (Gilson GX-281 ; Shimazu 15muiotatauiota; 250 9 mm; A: 10 mmolNH4HC03/water, B: CH3CN; 0-9 m.n. 70-80%; 9-9.3 min, 80-95%; 9.3-13 min, 95% CH3CN; RT:8.0min) to yield the title compound as a white solid. 15 mg.HNMR {400 MHz, CDCI3): 5.31 (s, 2H), 6.90 (d, J = 8.8 Hz, 1 H), 7.02 (s, H), 7.42-7.46 (m, 6H), 8.42 (d, J = 2.8 Hz, 1 H), 10.51 (s, 1 H)MS (electrospray): m/z [M+H]+ = 373

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4034 - 4038
[2]Patent: WO2011/38572,2011,A1 .Location in patent: Page/Page column 106; 107

36
[ 4570-45-0 ]
[ 56-82-6 ]
C₆H₁₀N₂O₄ [ No CAS ]
[ 27963-97-9 ]

Reference： [1]Nature Chemistry,2011,vol. 3,p. 704 - 706

37
[ 4570-45-0 ]
[ 14508-49-7 ]
[ 1380420-65-4 ]

Yield	Reaction Conditions	Operation in experiment
	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 160℃; for 1h;Inert atmosphere; Microwave irradiation;	General procedure: To an oven-dried microwave vial was added ethyl <strong>[4570-45-0]2-amino-1,3-oxazole</strong>-5-carboxylate (546 mg, 3.50 mmol), Cs2CO3 (2279 mg, 6.99 mmol), Pd2(dba)3 (80 mg, 0.09 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152 mg, 0.26 mmol) and the vial was capped and purged with nitrogen. 2,4-Dichloropyridine (0.378 mL, 3.50 mmol) was added via syringe, followed by 1,4-dioxane (18 mL) (degassed) and the reaction mixture was heated to 160 C for 1 h under microwave irradiation. CH2Cl2 (40 mL) was added to the crude reaction mixture together with silica (5 g). The solvents were removed under reduced pressure and the crude product was purified by flash silica chromatography with CH2Cl2 (containing 1% methanolic ammonia) as eluent.The resulting brown solid was triturated with Et2O to give ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (626 mg, 67%) as a pale yellow solid, which was collected by filtration and dried under vacuum.

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3038 - 3043

38
[ 4570-45-0 ]
C₂₁H₂₇ClN₂OS [ No CAS ]
C₂₄H₃₀N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	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 160℃; for 1h;Inert atmosphere; Microwave irradiation;	General procedure: To an oven-dried microwave vial was added ethyl <strong>[4570-45-0]2-amino-1,3-oxazole</strong>-5-carboxylate (546 mg, 3.50 mmol), Cs2CO3 (2279 mg, 6.99 mmol), Pd2(dba)3 (80 mg, 0.09 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152 mg, 0.26 mmol) and the vial was capped and purged with nitrogen. 2,4-Dichloropyridine (0.378 mL, 3.50 mmol) was added via syringe, followed by 1,4-dioxane (18 mL) (degassed) and the reaction mixture was heated to 160 C for 1 h under microwave irradiation. CH2Cl2 (40 mL) was added to the crude reaction mixture together with silica (5 g). The solvents were removed under reduced pressure and the crude product was purified by flash silica chromatography with CH2Cl2 (containing 1% methanolic ammonia) as eluent.The resulting brown solid was triturated with Et2O to give ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (626 mg, 67%) as a pale yellow solid, which was collected by filtration and dried under vacuum.

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3038 - 3043

39
[ 4570-45-0 ]
[ 85989-66-8 ]
[ 1394242-85-3 ]

Yield	Reaction Conditions	Operation in experiment
60.6%	In toluene; at 100℃; for 0.25h;Microwave irradiation;	A solution of phenyl benzoylcarbamate (0.121 g, 0.5 mmol) and oxazol-2-amine (0.042 g, 0.50 mmol) in toluene (5 ml) was heated to 100 C for 15 min. On cooling white crystals formed which were filtered and dried to give N-(oxazol-2-ylcarbamoyl)benzamide (0.070 g, 60.6 %)HRMS (ES) m/z calcd for (C11H10N3O3)+ 232.0717, found 232.0717.NMR: 1H NMR (400 MHz, DMSO, 30C) delta 6.41 (1H, d), 7.47 - 7.71 (4H, m), 7.94 - 8.07 (2H, m), 10.94 (1H, s), 11.04 (1H, s)

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 4802 - 4804

40
[ 420-04-2 ]
[ 4124-63-4 ]
[ 141-46-8 ]
[ 4570-45-0 ]
[ 96-50-4 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 13889 - 13895

41
[ 4570-45-0 ]
[ 4571-25-9 ]
2-bromo-1-(2,5-dichlorophenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; acetonitrile; at 20℃;	Step A: A solution of 2-bromo-1-(2,5-dichlorophenyl)ethanone (2.7 g, 10 mmol) and <strong>[4570-45-0]oxazole-2-amine</strong> (0.84 g, 10 mmol) in THF (20 mL) and acetonitrile (30 mL) was stirred at room temperature overnight. The suspension was cooled to -10 C. and the solid was collected by vacuum filtration, washed with acetonitrile and dried under vacuum. The solid was suspended in toluene (50 mL) and the suspension was cooled to 0 C. Titanium (IV) chloride (4.7 g, 25 mmol) was added at 0 C. and was then heated to 100 C. for 3 hours. The mixture was cooled to room temperature, toluene was decanted off, and ice was added with stirring to the residue. The mixture was adjusted to pH 9 with the addition of solid Na2CO3, followed by addition of EtOAc. The mixture was stirred for about 1 hour and then filtered through a pad of Celite. The organic layer was dried over Na2SO4, filtered and concentrated to give 6-(2,5-dichlorophenyl)imidazo[2,1-b]oxazole (28).

Reference： [1]Patent: US2013/59845,2013,A1 .Location in patent: Paragraph 0378; 0379

42
[ 4570-45-0 ]
[ 4411-25-0 ]
[ 1431288-13-9 ]

Yield	Reaction Conditions	Operation in experiment
42.9%		General procedure: Heteroarylamine (1.0 mmol) was added to THF (20 mL) and cooled on a dry ice in acetone bath. To that, butyllithium (400 muL, 1.0 mmol, 2.5 M in hexane) was added dropwise over 20 min. The reaction mixture was removed from the dry ice in acetone bath and 1-adamantyl isocyanate (177 mg, 1.0 mmol) was added and stirred for 1 h. Methanol (4 mL) was then added to quench any unreacted butyllithium. The solvents were then removed under reduced pressure and the residue was purified by normal phase flash column chromatography using a hexane to ethyl acetate gradient.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2587 - 2599

43
[ 4570-45-0 ]
[ 32315-10-9 ]
[ 1181105-87-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; for 0.333333h;Cooling with acetone-dry ice;	General procedure: Triphosgene (119 mg, 0.4 mmol) was dissolved in DCM (10 mL) and cooled on an acetone and dry ice bath. A solution of heteroarylamine (1 mmol) and DIPEA (393 muL, 2.2 mmol) in THF (5 mL) was then added dropwise over 15 min. After the reaction mixture stirred for an additional 5 min, a suspension of 2-adamantylamine hydrogen chloride (188 mg, 1.0 mmol) and DIPEA (393 muL, 2.2 mmol) in DCM (5 mL) was added. The reaction mixture was removed from the acetone and dry ice bath and stirred for 1 h. The solvents were removed under reduced pressure and the crude residue was purified by normal phase flash column chromatography using a hexane to ethyl acetate gradient.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2587 - 2599

44
[ 4570-45-0 ]
[ 1450923-35-9 ]
[ 1450920-97-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hexamethyldisilazane; In tetrahydrofuran; for 1.75h;Cooling with acetone-dry ice;	A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (INTERMEDIATE AB, 40.69 mg, 0.074 mmol), <strong>[4570-45-0]oxazole-2-amine</strong> (9.32 mg, 0.11 mmol, Ryan Scientific, Mt. Pleasant, SC) and THF (1 mL) to give a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (155 mu, 0.155 mmol) was added dropwise over 30 s to give a light-yellow solution. After 5 min, the flask was lowered into an ice bath for 1h. Additional portions of <strong>[4570-45-0]oxazole-2-amine</strong> (ca. 5 mg) and LHMDS solution (0.05 mL) were added in sequence. After an additional 45 min, glacial acetic acid (1 drop) was added. The mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4- (trifluoromethyl)phenyl)-N-(oxazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a light-yellow solid. 1H NMR (400MHz ,DMSO-d6) delta ppm 11.86 (br. s., 1 H), 8.38 (d, J= 2.1 Hz, 1 H), 8.05 (dd, J= 1.8, 8.8 Hz, 1 H), 7.71 (d, J= 8.6 Hz, 1 H), 7.59 (d, J= 1.7 Hz, 1 H), 7.31 (d, J= 2.1 Hz, 1 H), 7.26 - 7.17 (m, 2 H), 6.80 (d, J= 8.5 Hz, 1 H), 4.36 - 4.27 (m, 2 H), 3.87 - 3.82 (m, 2 H), m/z (ESI) 451.4 (M+H)+
	With lithium hexamethyldisilazane; In tetrahydrofuran;Cooling with acetone-dry ice;	A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (41 mg, 0.074 mmol), <strong>[4570-45-0]oxazole-2-amine</strong> (9.3 mg, 0.11 mmol, Ryan Scientific, Mt. Pleasant, SC) and THF (1 mL) to give a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (160 mul, 0.16 mmol) was added dropwise over 30 s to give a light-yellow solution. After 5 min, the flask was lowered into an ice bath for 1 h. Additional portions of <strong>[4570-45-0]oxazole-2-amine</strong> (ca. 5 mg) and LHMDS solution (0.05 mL) were added in sequence. After an additional 45 min, glacial acetic acid (1 drop) was added. The mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(oxazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (6) as a light-yellow solid. 1H NMR (400MHz ,DMSO-d6) delta ppm 11.86 (br. s., 1 H), 8.38 (d, J = 2.1 Hz, 1 H), 8.05 (dd, J = 1.8, 8.8 Hz, 1 H), 7.71 (d, J = 8.6 Hz, 1 H), 7.59 (d, J = 1.7 Hz, 1 H), 7.31 (d, J = 2.1 Hz, 1 H), 7.26 - 7.17 (m, 2 H), 6.80 (d, J = 8.5 Hz, 1 H), 4.36 - 4.27 (m, 2 H), 3.87 - 3.82 (m, 2 H). m/z (ESI) 451.4 (M+H)+. HRMS m/z Calculated for C19H14F3N4O4S [M+1]+ = 451.0688. Found [M+1]+ = 451.0688.

Reference： [1]Patent: WO2013/122897,2013,A1 .Location in patent: Page/Page column 169; 170
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3477 - 3485

45
[ 4570-45-0 ]
[ 1566543-84-7 ]
[ 1566542-86-6 ]

Yield	Reaction Conditions	Operation in experiment
6%		Example 11: Synthesis of I -(2-(2-(5-chloro-2-(oxazol-2-ylamino)pyrimidin-4- yl)ethyl)phenyl)cyclopropanecarboxamide (II)H2N 0N + CI NNflJ0 N111-(2-(2-(5-Chloro-2-(oxazol-2-ylamino)pyrimidin-4-yI)ethyl)phenyl)cyclopropanecarboxamide (11) A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl) phenyl)cyclopropanecarboxam ide Al 4 (0.150 g, 0.446 mmol), 052003 (436 mg, 1.34 mmol) and 2-aminoxazole (75.0 mg, 0.892 mmol) in 1,4-dioxane (3 mL) was sonicated for 10 minutes. Xantphos (10 mg, 18 pmol) and Pd(ll) acetate (2.0mg, 8.9 pmol) were added and the reaction was irradiated in the microwave for 20 minutes at 120 00. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g Si02 cartridge, 0-100% EtOAc in cyclohexane then 0-20% MeOH in EtOAc) to give a solid. Acetone (0.5 mL) followed by cyclohexane (25 mL) was added and the mixture was sonicated for 10 minutes.The resulting precipitate was collected by filtration and the filter cake was washed with cyclohexane (25 mL) and dried under high vacuum to give the title compound 11 as a white solid (10 mg, 6%). LCMS-B: rt 4.64 mm; m/z 384.0 [M+H].H2NAl 4

Reference： [1]Patent: WO2014/26243,2014,A1 .Location in patent: Page/Page column 116

46
[ 4570-45-0 ]
C₂₀H₂₇ClN₄OS [ No CAS ]
3-N-[4-(morpholin-4-yl)cyclohexyl]-5-N-(1,3-oxazol-2-yl)-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1⁽⁹⁾,2⁽⁷⁾,3,5-tetraene-3,5-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In 1,4-dioxane; at 100℃; for 3h;Inert atmosphere;	A solution of 11.5 (122 mg, 0.30 mmol, 1.00 equiv), <strong>[4570-45-0]1,3-oxazol-2-amine</strong> (76 mg, 0.90 mmol, 3.02 equiv), t-BuONa (87 mg, 0.91 mmol, 3.02 equiv), Pd2(dba)3 (27 mg, 0.03 mmol, 0.10 equiv) and Xantphos (17 mg, 0.03 mmol, 0.10 equiv) in dioxane (20 mL) was stirred for 3 h at 100 C. under N2. After completion, the resulting mixture was concentrated under vacuum and diluted with water, extracted with DCM, dried and concentrated in vacuo. The residue was applied onto a silica gel column with dichloromethane/methanol (1:10) to get crude product which was purified by re-crystallization from DCM/MeOH (V/V:1/1). Isolated 66.6 mg of an off-white solid in 49% yield. MS (ES): m/z 455 (M+H)+. 1H-NMR (300 MHz, CDCl3): delta 7.51 (s, 1H), 7.41 (s, 1H), 6.99 (s, 1H), 5.09 (d, 1H), 4.15-3.92 (m, 1H), 3.81 (br s, 5H), 2.90-2.50 (m, 9H), 2.32 (d, 2H), 2.15-1.98 (m, 2H), 1.88 (br s, 4H), 1.55-1.40 (m, 2H), 1.30-1.10 (m, 2H).

Reference： [1]Patent: US2014/194417,2014,A1 .Location in patent: Paragraph 0358-0359

47
[ 4570-45-0 ]
[ 933-88-0 ]
2-methyl-N-(oxazol-2-yl)benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6393 - 6402

48
[ 4570-45-0 ]
[ 933-88-0 ]
2-methyl-N-(4H-1,2,4-triazol-3-yl)benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6393 - 6402

49
[ 4570-45-0 ]
[ 13091-23-1 ]
2-(1H-[1,2,3]triazolo[4,5-c]pyridin-1-yl)oxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate; In pentan-1-ol; at 20℃; for 0.5h;Sealed tube;	The title compound was prepared in a manner analogous to Intermediate 17, Step 1 through Intermediate 19, Step 3. In the synthesis of Intermediate 17, Step 1 Pd(OAc)2 and BINAP were eliminated and these substitutions were made: 2-aminooxazole for 2-aminopyridine, NaOtBu for K2CO3, and tent-amyl alcohol for toluene, reaction carried out for 0.5 h at room temperature. MS (ESI) mass calcd. C8H5N5O, 187.0. m/z found, 188.1 [M+H]+.

Reference： [1]Patent: US2014/275015,2014,A1 .Location in patent: Paragraph 1035; 1036

50
[ 4570-45-0 ]
[ 368869-97-0 ]
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(1,3-oxazol-2-yl)-1,3-thiazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24h;	2-(2,3-Dihydro-l-benzofuran-5-yI)-iV-(l,3-oxazol-2-yl)-l,3-thiazoIe-4-carboxamide (79) To a stirred suspension of 2-(2,3-dihydro-l-benzofuran-5-yl)-l,3-thiazole-4-carboxylic acid (100 mg, 0.41 mmol), l,3-oxazol-2-amine (34 mg, 0.41 mmol) and HBTU (230 mg, 0.61 mmol) in 4.1 ml dry CH2C12, DIPEA (131 mg, 1.01 mmol) was added. The suspension was stirred at room temperature for 24 h and filtered, washed with hot CH2C12. The filtrate was evaporated to dryness. The residue was treated subsequently with water, an aqueous Na2C03 solution, water, diluted HCl and water again. The crude product was crystallized from EtOH to give the product as a white powder (67 mg, 0.21 mmol, 52 % yield). NMR (400 MHz, DMSO-c 6) 5 ppm 11.18 (s, 1 H), 8.39 (s, 1 H), 8.02 (s, 1 H), 7.92 (s, 1 H), 7.85 (d, J= 8.3 Hz, 1 H), 7.15 (s, 1 H), 6.85 (d, J- 8.3 Hz, 1 H), 4.63 (t, J H). M.p.: 192-194 C. LC/MS [M+Hf : 313.9.

Reference： [1]Patent: WO2014/202638,2014,A1 .Location in patent: Page/Page column 115-116

51
[ 4570-45-0 ]
(R,E)-4-(4-amino-1-(1-(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)benzoic acid [ No CAS ]
(R,E)-4-(4-amino-1-(1-(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-(oxazol-2-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane;	Example 14: Synthesis of (R,E)-4-(4-amino- 1-(1-(4-(cyclopropyl(methyl)amino)but-2- enoyl)pyrrolidin-3-yl)- 1H-pyrazolo [3,4-dj pyrimidin-3-yl)-N-(oxazol-2-yl)benzamide (34) [00489j (R,E)-4-(4-amino- 1 -(1 -(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3 -yl)1 H-pyrazolo [3 ,4-d]pyrimidin-3 -yl)-N-(oxazol-2-yl)benzamide (34) was obtained from (R,E)-4- (4-amino-i -(1 -(4-(cyclopropyl(methyl)amino)but-2-enoyl)pyrrolidin-3 -yl)- 1H-pyrazolo [3,4- d]pyrimidin-3-yl)benzoic acid (26) in a similar manner as described above.

Reference： [1]Patent: WO2015/48689,2015,A1 .Location in patent: Paragraph 00489

52
[ 4570-45-0 ]
4-(2-chloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine [ No CAS ]
N-(1,3-oxazol-2-yl)-4-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13.3%	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 130℃; for 1.5h;Microwave irradiation; Inert atmosphere;	j00144j A mixture of <strong>[4570-45-0]oxazole-2-amine</strong> (82 mg, 0.97 mmol), 4-(2-chloropyridin-4-yl)-1- (phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (100 mg, 0.270 mmol) and cesium carbonate (220 mg, 0.676 mmol) in 1,4-dioxane (2.3 mL, 30.0 mmol) was purged with nitrogen followed by the addition of tris(dibenzylideneacetone)dipalladium(0) (24.8 mg, 0.027 mmol) and bis(diphenylphosphino)-9,9- dimethylxanthene (15.6 mg, 0.027 mmol). The reaction mixture was heated in the microwave at 130 C for 90 mm and then diluted with ethyl acetate. Insoluble material was removed by filtration and the filtrate was concentrated by rotary evaporation. The crude material was purified by column chromatography followed by further purification by prep HPLC to yield N-(1,3-oxazol-2-yl)-4-[1- (phenylsulfonyl)- 1H-pyrrolo [2,3-c]pyridin-4-yl]pyridin-2-amine (15 mg, 13.3%). LCMS (FA): m/z = 418.8 (M+H).
13.3%	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 130℃; for 1.5h;Inert atmosphere; Microwave irradiation;	Step 2: N-(1,3-oxazol-2-yl)-4-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-amine A mixture of <strong>[4570-45-0]oxazole-2-amine</strong> (82 mg, 0.97 mmol), 4-(2-chloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (100 mg, 0.270 mmol) and cesium carbonate (220 mg, 0.676 mmol) in 1,4-dioxane (2.3 mL, 30.0 mmol) was purged with nitrogen followed by the addition of tris(dibenzylideneacetone)dipalladium(0) (24.8 mg, 0.027 mmol) and bis(diphenylphosphino)-9,9-dimethylxanthene (15.6 mg, 0.027 mmol). The reaction mixture was heated in the microwave at 130 C. for 90 min and then diluted with ethyl acetate. Insoluble material was removed by filtration and the filtrate was concentrated by rotary evaporation.

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00144
[2]Patent: US2016/333007,2016,A1 .Location in patent: Paragraph 0268

53
[ 4570-45-0 ]
N-(5-bromo-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]
N-[5-(1,3-oxazol-2-ylamino)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.5%	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 160℃; for 2h;	[00400] A mixture of i,3-oxazol-2-amine (80.6 mg, 0.959 mmol), N-(5-bromo-3,4?-bipyridin-2?- yl)acetamide (77.8 mg, 0.266 mmol), Pd2(dba)3 (24.4 mg, 0.0266 mmol), Cs2CO3 (217 mg, 0.666 mmol) and Xantphos (30.8 mg, 0.0532 mmol) in i,4-dioxane (2.3 mL) was allowed to stir for 2 h at 160 C. The reaction mixture was allowed to cool to ii and diluted with DCM, and the organic solution was washed with brine twice. The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to provide N-[5-(i,3-oxazol-2-ylammno)-3,4?-bipyridin-2?-yl]acetamide 1-472 (18.5 mg, 23.5%). LCMS (FA): m/z 296.2 (M+H). ?H NEVIR (400MFIz, DMSO-d6) 6 10.66 (s, 1H), 10.60 (s, 1H), 8.83 (d, J= 2.4 Hz, 1H), 8.48 (m, 1H), 8.45 (m, 1H),8.42 (m, 2H), 7.73 (d,J= 1.0Hz, iH), 7.41 (dd, J= 5.2, i.6 Hz, iH), 7.07 (d,J= 1.0Hz, iH), 2.i3 (s,3H).
23.5%	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 160℃; for 2h;	Step 2: N-[5-(1,3-oxazol-2-ylamino)-3,4'-bipyridin-2'-yl]acetamide A mixture of <strong>[4570-45-0]1,3-oxazol-2-amine</strong> (80.6 mg, 0.959 mmol), N-(5-bromo-3,4'-bipyridin-2'-yl)acetamide (77.8 mg, 0.266 mmol), Pd2(dba)3 (24.4 mg, 0.0266 mmol), Cs2CO3 (217 mg, 0.666 mmol) and Xantphos (30.8 mg, 0.0532 mmol) in 1,4-dioxane (2.3 mL) was allowed to stir for 2 h at 160 C. The reaction mixture was allowed to cool to rt and diluted with DCM, and the organic solution was washed with brine twice. The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to provide N-[5-(1,3-oxazol-2-ylamino)-3,4'-bipyridin-2'-yl]acetamide I-472 (18.5 mg, 23.5%). LCMS (FA): m/z=296.2 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.66 (s, 1H), 10.60 (s, 1H), 8.83 (d, J=2.4 Hz, 1H), 8.48 (m, 1H), 8.45 (m, 1H), 8.42 (m, 2H), 7.73 (d, J=1.0 Hz, 1H), 7.41 (dd, J=5.2, 1.6 Hz, 1H), 7.07 (d, J=1.0 Hz, 1H), 2.13 (s, 3H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00400
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0552; 0554

54
[ 4570-45-0 ]
[ 7693-46-1 ]
4-nitrophenyl oxazol-2-ylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With pyridine; In dichloromethane; at 0 - 20℃; for 20h;Inert atmosphere;	Step One. 4-Nitrophenyl oxazol-2-ylcarbamate (H3): To a stirred solution of compound H2 (10.1 g, 50.0 mmol) in anhydrous methylene chloride (50 mL) was added a solution of compound HI (4.20 g, 50.0 mmol) and pyridine (4.16 g, 52.5 mmol) in anhydrous methylene chloride (70 mL) dropwise over 15 min at 0 C under nitrogen. After the addition, the reaction mixture was warmed to room temperature and stirred for 20 h. The resulting mixture was filtered. The filter cake was washed with anhydrous methylene chloride (2 x 10 mL), dried under high vacuum to give compound H3 (4.88 g, 39%) as an off-white solid: MS (M+H) 250.

Reference： [1]Patent: WO2015/123003,2015,A1 .Location in patent: Paragraph 00127

55
[ 4570-45-0 ]
[ 1416235-10-3 ]
4b-hydroxy-7-isopropyl-9b-(oxazol-2-ylamino)-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With triethylamine; In tetrahydrofuran; at -30 - 20℃; for 8h;	<Example 74> Preparation of 4b-hydroxy-7-isopropyl-9b-(oxazol-2-yl amino)-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 9b-chloro-4b-hydroxy-7-isopropyl-4b, 9b-dihydro-10H-indeno[1, 2-b] benzofuran-10-one (316 mg, 1.00 mmol) is dissolved in THF (10 ml, 0.1 M). After adding 3-amino isooxazole (89 mg, 1.05 mmol) and TEA (0.15 ml, 1.1 mmol) at -30C, stirring is carried out at room temperature for 8 hours. After concentrating THF and dissolving in DCM, washing is carried out with water and brine. After extracting organic layers, water is removed with Na2SO4 and then concentration under reduced pressure is carried out. Purification is carried out in a silica gel column chromatography to obtain the target compound (50 mg, 14%). 1H-NMR (300 MHz, CDC13) delta 1.13-1.16 (m, 6H), 2.75-2.85 (m, 1H), 5.37 (br, 1H), 5.92 (br, 1H), 6.10 (s, 1H), 6.71 (s, 1H), 6.77 (d, J=7.8 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 7.55 (t, J=7.2 Hz, 1H), 7.79-7.84 (m, 2H); 7.98 (s, 1H), 8.04 (d, J=7.8 Hz, 1H); 363.1 [M+H] + for LCMS.

Reference： [1]Patent: EP2933254,2015,A1 .Location in patent: Paragraph 0198; 0199

56
[ 4570-45-0 ]
[ 280566-45-2 ]
2-chloro-N-(1,3-oxazol-2-yl)-6-(trifluoromethyl)nicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With dmap; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In tetrahydrofuran; dichloromethane; at 20℃; for 20h;	537 mg (2.38 mmol) of 2-Chloro-6-(trifluoromethyl)nicotinic acid and 200 mg (2.38 mmol) of <strong>[4570-45-0]1,3-oxazol-2-amine</strong> are dissolved at RT in 7 ml of dichloromethane, and 0.33 ml (2.38 mmol) of triethylamine, 58 mg (0.47 mmol) of DMAP and 2.27 g (3.57 mmol) of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% solution in THF) are added. The reaction mixture is stirred at RT for 20 h and then washed twice with in each case 5 ml of water. The organic phase is dried over Na2SO4 and concentrated. The residue is purified by column chromatography (HPLC, acetonitrile/water). Yield 40 mg (5%).Synthesis of 2-chloro-N-(1,3-oxazol-2-yl)-6-(trifluoromethyl)nicotinamide (Table example No. 10-1)

Reference： [1]Patent: US2015/315161,2015,A1 .Location in patent: Paragraph 0084

57
[ 4570-45-0 ]
[ 120100-77-8 ]
2-chloro-4-(methylsulfonyl)-N-(1,3-oxazol-2-yl)-3-[(2,2,2-trifluoroethoxy)methyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With dmap; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In tetrahydrofuran; dichloromethane; at 20℃; for 20h;	A. CHEMICAL EXAMPLES Synthesis of 2-chloro-4-(methylsulfonyl)-N-(1,3-oxazol-2-yl)-3-[(2,2,2-trifluoroethoxy)methyl]benzamide, (Table example No. 1-334) 347 mg (1.0 mmol) of 2-chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoic acid and 84 mg (1.0 mmol) of 1,3-<strong>[4570-45-0]oxazole-2-amine</strong> are dissolved at room temperature (RT) in 7 ml of dichloromethane, and 0.14 ml (1.0 mmol) of triethylamine, 24 mg (0.20 mmol) of DMAP and 955 mg (1.5 mmol) of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% solution in THF) are added. The reaction mixture is stirred at RT for 20 h and then washed twice with in each case 5 ml of water. The organic phase is dried over Na2SO4 and concentrated. The residue is purified by column chromatography (HPLC, acetonitrile/water). Yield 93 mg (20%).

Reference： [1]Patent: US2015/315161,2015,A1 .Location in patent: Paragraph 0081

58
[ 4570-45-0 ]
(P)-perfluorophenyl 1-(2-fluoro-5-methoxy-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate [ No CAS ]
(P)-1-(2-fluoro-5-methoxy-4′-(trifluoromethyl)-4-biphenylyl)-N-1,3-oxazol-2-yl-2-oxo-1,2-dihydro-6-quinolinesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.5%	With dimethyl sulfoxide; lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; for 0.25h;Inert atmosphere;	A 10-mL RBF was charged with (P)-perfluorophenyl 1-(2-fluoro-5-methoxy-4?-(trifluoromethyl)-[1,1?-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (200 mg, 0.303 mmol) and <strong>[4570-45-0]1,3-oxazol-2-amine</strong> (38.2mg, 0.455 mmol) then purged with nitrogen. Tetrahydrofuran (3.17 mL) and dimethyl sulfoxide (1.056 mL) were introduced, and the resultant brown solution cooled to 0 C. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran(1.0 M, 0.667 mL, 0.667 mmol) was added dropwise via syringe to the stirredreaction mixture over 3 min. After 15 min, 1.0 N HCl (5 mL) was introduced and the resultant reactionmixture was allowed to warm to ambient temperature. The mixture was diluted with and EtOAc (10 mL) andthe layers were separated, and the aqueous layer was further extracted with EtOAc (3×10 mL). The combinedorganic layers were then washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, andconcentrated under reduced pressure to furnish a yellow oil, which was dissolved in DMSO (2 mL) filteredthrough a 0.2 micron filter and purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 mumOBD 19×100 mm) gradient, 35 to 95% MeCN in water (containing 0.1% formic acid as an additive). Thefractions containing product were combined and concentrated via lyophilization to yield (P)-1-(2-fluoro-5-methoxy-4?-(trifluoromethyl)-[1,1?-biphenyl]-4-yl)-N-(oxazol-2-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (50.1 mg, 0.090 mmol, 29.5% yield) as a white amorphous solid. 1H NMR (400MHz, ACETONITRILE-d3) delta=8.23 (d, J=2.07 Hz, 1 H) 8.00 (d, J=9.64 Hz, 1 H) 7.80-7.92 (m, 5 H) 7.34 (d,J=6.84 Hz, 1 H) 7.24 (d, J=10.16 Hz, 1 H) 7.19 (d, J=1.76 Hz, 1 H) 6.94 (d, J=1.76 Hz, 1 H) 6.83 (d, J=8.91Hz, 1H) 6.75 (d, J=9.64 Hz, 1 H) 3.74 (s, 3 H). m/z (ESI) 559.8 (M+H)+.

Reference： [1]Patent: US9212182,2015,B2 .Location in patent: Page/Page column 339; 340

59
[ 4570-45-0 ]
(P)-perfluorophenyl 1-(4'-chloro-3-methoxy-3′-methyl-[1,1'-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate [ No CAS ]
(P)-1-(4'-chloro-3-methoxy-3'-methyl-4-biphenylyl)-N-1,3-oxazol-2-yl-2-oxo-1,2-dihydro-6-quinolinesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24.41%		A flask was charged with oxazol-2-amine (0.036 g, 0.428 mmol, Astatech) and (P)-perfluorophenyl 1-(4'-chloro-3-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (0.205 g, 0.330 mmol). The flask was sealed with a septum, flushed with N2 and THF (2.83 ml) was added, followed by DMSO (0.471 ml) to generate a homogeneous solution. The flask was cooled in an ice-bath for 5 min, then a THF solution of lithium bis(trimethylsilyl)amide (0.758 ml, 0.758 mmol. 1M) was added dropwise. After 10 min, the mixture was diluted with 1N aq. HCl (10 mL) and EtOAc (20 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2*20 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep column with 10-70% of a 3:1 EtOAc/EtOH solution in heptane) to give (P)-1-(4'-chloro-3-methoxy-3'-methyl-4-biphenylyl)-N-1,3-oxazol-2-yl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (0.042 g, 0.080 mmol, 24.41% yield) as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6) delta 12.15 (br. s., 1H), 8.32 (d, J=2.18 Hz, 1H), 8.14-8.23 (m, 1H), 7.81-7.88 (m, 2H), 7.63-7.71 (m, 1H), 7.57-7.62 (m, 1H), 7.50-7.57 (m, 2H), 7.41-7.47 (m, 1H), 7.34-7.40 (m, 1H), 7.25 (d, J=1.66 Hz, 1H), 6.75-6.81 (m, 1H), 6.72 (d, J=8.91 Hz, 1H), 3.74-3.81 (m, 3H), 2.44 (s, 3H); LCMS m/z (ESI) 522.0 (M+H)+.

Reference： [1]Patent: US9212182,2015,B2 .Location in patent: Page/Page column 372; 373

60
[ 4570-45-0 ]
perfluorophenyl 1-(3'-chloro-2,5'-difluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate [ No CAS ]
(P)-1-(3'-chloro-2,5'-difluoro-5-methoxy-4-biphenylyl)-N-1,3-oxazol-2-yl-2-oxo-1,2-dihydro-6-quinolinesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.9%	With lithium hexamethyldisilazane; In tetrahydrofuran; dimethyl sulfoxide; at 0℃; for 0.333333h;	A RBF was charged with perfluorophenyl 1-(3'-chloro-2,5'-difluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (106.08 mg, 0.165 mmol), oxazol-2-amine (16.62 mg, 0.198 mmol), and DMSO (412 mul) to give a clear solution. THF (1236 up was added, and the solution was cooled in an ice-water bath for 5 min. Lithium bis(trimethylsilyl)amide (1M in THF) (362 mul, 0.362 mmol) dropwise. After 15 min total, the mixture was diluted with 1N aq. HCl and EtOAc. The layers were separated, and the aq. layer was extracted with EtOAc (1*). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 10-60% of a 3:1 EtOAc/EtOH solution in heptane with 10% DCM as additive) to give (P)-1-(3'-chloro-2,5'-difluoro-5-methoxy-4-biphenylyl)-n-1,3-oxazol-2-yl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (25 mg, 0.046 mmol, 27.9% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) delta=12.17 (br. s., 1 H), 8.34 (d, J=2.1 Hz, 1 H), 8.20 (d, J=9.6 Hz, 1 H), 7.87 (dd, J=2.2, 8.9 Hz, 1 H), 7.73-7.52 (m, 5 H), 7.48 (d, J=6.9 Hz, 1 H), 7.27 (d, J=1.7 Hz, 1 H), 6.78 (dd, J=3.8, 9.2 Hz, 2 H), 3.76 (s, 3 H). m/z (ESI) 544.1 (M+H)+.

Reference： [1]Patent: US9212182,2015,B2 .Location in patent: Page/Page column 96; 97

61
[ 4570-45-0 ]
[ 3934-20-1 ]
N-(2-chloropyrimidin-4-yl)oxazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15.16%	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 100℃; for 3h;	A mixture of Xantphos (0.194 g, 0.336 mmol), Cs2CO3 (1.094 g, 3.36 mmol), Pd2(dba)3 (0.154 g, 0.168 mmol), 2,4-dichloropyrimidine (0.5 g, 3.36 mmol) and oxazol-2-amine (0.282 g, 3.36 mmol) in 1,4-dioxane (11.19 mL) was heated to 100 C. for 3 hours. The reaction was filtered to remove the solid, and the solid was rinsed with DCM (3*5 mL). The volatiles were removed under reduced pressure and the crude material was purified by SiO2 column chromatography (50 g SNAP column, 0% EtOAc in hexanes for 5 minutes, then 0-100% EtOAc in hexanes for 30 minutes) to afford N-(2-Chloropyrimidin-4-yl)oxazol-2-amine (0.1 g, 0.509 mmol, 15.16% yield).

Reference： [1]Patent: US2016/83365,2016,A1 .Location in patent: Paragraph 0886; 0887; 0888

62
[ 4570-45-0 ]
3-(5-azido-2-hydroxybenzoylamino)benzoic acid methyl ester [ No CAS ]
[ 106-96-7 ]
methyl 3-(2-hydroxy-5-(4-((oxazol-2-yl)amino)methyl-1H-1,2,3-triazol-1-yl)benzamido)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%		To a screw cap vial were added 2-aminooxazole (78.9 mg, 901 mumol), anhydrous DMF (0.9 mL), and propargyl bromide (120 mg, 991 mumol) was added. The reaction mixture was heated to 80 C and stirred for 24 h. Upon completion of the reaction, the reaction mixture was cooled to rt. Azide 15 (62.5 mg, 200 mumol), CuI (19.5 mg, 100 mumol), and DIPEA (106 mg, 901 mumol) were added and the reaction mixture was stirred at rt for 2 h. After completion of the reaction, purification by column chromatography (20:1 CH2Cl2/MeOH) yielded 8j (30.7 mg, 35%) as a beige solid. TLC: Rf 0.24 (5:1 CH2Cl2/MeOH (*2)). Mp: 189.1-191.1 C. 1H NMR (400 MHz, CD3OD): delta 8.48 (s, 1H), 8.43 (t, J = 1.6 Hz, 1H), 8.30 (s, 1H), 7.94 (dm, J = 8.0 Hz, 1H), 7.78 (dt, J = 8.0, 1.6 Hz, 1H), 7.71 (dm, J = 8.8 Hz, 1H), 7.63 (s, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.42 (s, 1H), 6.99 (d, J = 8.8 Hz, 1H), 5.25 (s, 2H), 3.93 (s, 3H). 13C NMR (100 MHz, DMSO-d6): delta 166.5, 166.2, 165.7, 157.2, 140.8, 140.0, 138.9, 132.6, 130.2, 129.3, 125.1, 124.2, 123.4, 122.0, 121.7, 121.0, 120.2, 118.9, 118.4, 52.2, 40.1. HRMS (ESI) m/z calcd for C21H19N6O5+ ([M+H]+) 435.1411, found 435.1411.
35%		In a screw cap vial at room temperature, <strong>[4570-45-0]2-amino-oxazole</strong> (78.9 mg, 901 mumol), anhydrous DMF (0.9mL), and propargyl bromide (120 m, 991 mumol) were added.The reaction mixture was heated to 80 and stirred for 24 hours The reaction was terminated and the reaction mixture was cooled to room temperature. wherein in step 2 of Example 1, a manufactured methyl 3- (5-azido-2-hydroxybenzamido) benzoate(62.5 mg, 200 mumol), CuI (19.5 mg, 100 mumol) and DIPEA (106 mg, 901 mumol) were added to the reaction mixture and stirred for 2 hours. After completion of the reaction, the residue was purified by column chromatography (20: 1 CH 2 Cl 2 / MeOH) to obtain the target compound as a beige solid (30.7 mg, 35%).

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 2114 - 2124
[2]Patent: KR101723881,2017,B1 .Location in patent: Paragraph 0248-0250

63
[ 4570-45-0 ]
[ 15761-38-3 ]
tert-butyl (1-(oxazol-2-ylamino)-1-oxopropan-2-yl)carbamate [ No CAS ]

Reference： [1]ChemMedChem,2016,p. 1695 - 1699

64
[ 4570-45-0 ]
[ 47375-34-8 ]
tert-butyl (3-(4-(tert-butoxy)phenyl)-1-(oxazol-2-ylamino)-1-oxopropan-2-yl)carbamate [ No CAS ]

Reference： [1]ChemMedChem,2016,p. 1695 - 1699

65
[ 4570-45-0 ]
[ 13726-84-6 ]
tert-butyl 4-((tert-butoxycarbonyl)amino)-5-(oxazol-2-ylamino)-5-oxopentanoate [ No CAS ]

Reference： [1]ChemMedChem,2016,p. 1695 - 1699

66
[ 4570-45-0 ]
[ 102429-07-2 ]
1-(2,4-difluorophenyl)-2-(2-iminooxazol-3(2H)-yl)ethan-1-one hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In tetrahydrofuran; acetonitrile; at 20℃; for 20h;	Step 2: A mixture of 2-bromo-l-(2,4-difluorophenyl)ethan-l-one (8.4 g, 35.7 mmol) and <strong>[4570-45-0]oxazole-2-amine</strong> (2.0 g, 23.8 mmol) in THF (36 mL) and acetonitrile (60 mL) was stirred at room temperature for 20 h. The resulting precipitate was collected by filtration, washed with acetonitrile, and dried under vacuum to l-(2,4-difluorophenyl)-2-(2-iminooxazol-3(2H)- yl)ethan-l-one hydrobromide as a white solid (5.4 g, 71%).

Reference： [1]Patent: WO2016/81364,2016,A1 .Location in patent: Paragraph 0436

67
[ 4570-45-0 ]
(R)-3-(3-((2-ethoxypyrimidin-5-yl)amino)-4-(ethyl(tetrahydro-2H-pyran-4-yl)amino)phenyl)pentanoic acid [ No CAS ]
(R)-3-(3-((2-ethoxypyrimidin-5-yl)amino)-4-(ethyl(tetrahydro-2H-pyran-4-yl)amino)phenyl)-N-(oxazol-2-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16.7%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 80℃; for 20h;	To a stirred solution of Example 498 (0.070 g, 0.158 mmol) in dry DMF (1.0 mL), was added the oxazol-2-amine (0.020 g, 0.237 mmol), HATU (0.090 g, 0.237 mmol) followed by TEA (0.066 mL, 0.475 mmol) at room temperature. Reaction mixture was heated to 80 C. and stirred for 20 h. Then the reaction mixture diluted with ethyl acetate (10 mL) and washed with water (5 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2*10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to give the crude residue. The crude material was purified via preparative LCMS to afford Example 1346 (off-white solid, 14.3 mg 0.026 mmol, 16.7%). LC-MS Anal. Calc'd. for C27H36N6O4, 508.3. found [M+H] 509.3, Tr=2.05 min (Method O). 1H NMR (400 MHz, DMSO-d6) delta10.98 (s, 1H), 8.43 (s, 2H), 7.77 (d, J=8.0 Hz, 1H), 7.31 (s, 1H), 7.11 (d, J=8.0 Hz, 1H), 7.02 (m, 1H), 6.81 (s, 1H), 6.67-6.65 (m, 1H), 4.32-4.26 (m, 2H), 3.85-3.70 (m, 2H), 3.21-3.15 (m, 2H), 3.10-2.90 (m, 4H), 2.55-2.40 (m, 2H), 1.60-1.50 (m, 3H), 1.45-1.30 (m, 3H), 1.29-1.20 (m, 3H), 0.82 (t, J=7.20 Hz, 3H), 0.67 (t, J=7.20 Hz, 3H).

Reference： [1]Patent: US2016/289171,2016,A1 .Location in patent: Paragraph 2809; 2810

68
[ 4570-45-0 ]
[ 157373-27-8 ]
ethyl 7-chloro-1-(oxazol-2-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In toluene; at 50℃;	General procedure: To a suspension of 60% sodium hydride (87 mg, 6 mmol) and RH2 (0.97 mmol) in dry toluene (50 mL) was added 5 ( 3.08 g, 0.97 mmol) in dry toluene (10 mL), the reaction mixture was stirred for 4 h at 50 C and filtered. The filtrate was adjusted to pH 7 with 20% acetic acid solution in ice bath. The toluene layer was washed with water (30 mL×2) and saturated brine (30 mL), dried over anhydrous Na2SO4, concentrated under reduced pressure and purified by silica gel column chromatography (CH2Cl2 : CH3OH = 50:1) to give the title compounds 6e-i.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 235 - 239

69
[ 4570-45-0 ]
2-((13-(2-(methylamino)-2-oxoacetamido)tridec-8(Z)-en-1-yl)oxy)acetic acid [ No CAS ]
N-methyl-N'-[(5Z)-13-[(1,3-oxazol-2-yl)carbamoyl] methoxy}tridec-5-en-1-yl]ethanediamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With dmap; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	2-[(8Z)-13-[(methylcarbamoyl)formamido]tridec-8-en-l-yl]oxy}acetic acid (BB-4, 50.0 mg, 140.3 muiotaetaomicronIota), l,3-Oxazol-2-amine (24 mg, 280.5 muiotaetaomicronIota), HBTU (53.4 mg, 140.3 muiotaetaomicronIota) and DMAP (1.7 mg, 14.0 muiotaetaomicronIota) were placed in a G16 vial. DMF (2.00 ml) and NEt 3 (78.0 muIota, 561.1 muiotaetaomicronIota) were added and the resulting mixture was stirred at r.t. for 16h. Control by LC/MS showed product. The reaction mixture was diluted with water (20 ml) and was extracted with Et 20 (3 x 20 ml). The combined organic layers were washed with sat. NaHC03 (20 ml) and brine (10 ml), dried over Na2S04 and concentrated in vacuo. The residue was purified by preparative TLC (DCM/MeOH =95:5). Yield: 11 mg (19%), white solid.

Reference： [1]Patent: WO2017/13265,2017,A1 .Location in patent: Page/Page column 74-75

70
[ 4570-45-0 ]
[ 1414882-25-9 ]
8,8’-disulfanediylbis(N-(oxazol-2-yI)quinoline-3-carboxamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		to a solution of 16b (0.2 g, 0.98 mmol) in DMF (10 mL) was added HATU (0.56 g, 1.46 mmol) and Et3N (0.204 pL, 1.46 mmol) and the mixture was stirred at 60 C for -15 mm under nitrogen atmosphere. To this was added the corresponding amine (0.146 mmol) and the solution was stirred for an additional 12 h. The resulting solution wasconcentrated under reduced pressure, then purified via reverse-phase chromatography eluting using a gradient of 0 to 100% acetonitrile in H20.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 1343 - 1361
[2]Patent: WO2017/31255,2017,A1 .Location in patent: Paragraph 00122; 00123

71
[ 4570-45-0 ]
8-[(2-methylpyridin-3-yl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzisothiazole-6-carboxylic acid [ No CAS ]
8-((2-methylpyridin-3-yl)oxy)-N-(1,3-oxazol-2-yl)-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.2 mg	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 70℃; for 1.5h;	Example 37 8-((2-Methylpyridin-3-yl)oxy)-N-(1,3-oxazol-2-yl)-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide A suspension of 8-((2-methylpyridin-3-yl)oxy)-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxylic acid (17.0 mg), oxazol-2-amine (10.1 mg), HATU (29.0 mg), and diisopropylethylamine (0.013 mL) in DMF (1.0 mL) was stirred at 70 C for 1.5 hours. Ethyl acetate and water were added to the reaction mixture, the resulting mixture was stirred, and then the organic layer was extracted and evaporated by blowing dry with a stream of air. The residue was purified by HPLC (C18, mobile phase: acetonitrile/10 mM aqueous ammonium bicarbonate solution), and the solvent was evaporated by blowing dry with a stream of air. The residue was purified again by HPLC (C18, mobile phase: water/acetonitrile (containing 0.1 % TFA)), the solution was filtered by using StratoSpheres SPE (PL-HCO3 MP-Resin), salt was removed, and then the solvent was evaporated by blowing dry with a stream of air to obtain the title compound (3.2 mg).

Reference： [1]Patent: EP3133075,2017,A1 .Location in patent: Paragraph 0357

72
[ 4570-45-0 ]
[ 124-63-0 ]
N-(oxazol-2-yl)methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.9%	With triethylamine; In dichloromethane; at 20℃; for 3h;	A solution of oxazol-2-amine (0.300 g, 3.568 mmol), methanesulfonyl chloride (0.304 mL, 3.925 mmol) and triethylamine (0.746 mL, 5.352 mmol) in dichloromethane (3 mL) was stirred at the room temperature for 3 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 4 g cartridge; ethyl acetate / hexane = 0 % to 50 %) to give N(oxazol-2-yl)methanesulfonamide as yellow oil (0.150 g, 25.9 %).

Reference： [1]Patent: WO2017/18803,2017,A1 .Location in patent: Paragraph 3099; 3100; 3101

73
[ 4570-45-0 ]
[ 87-13-8 ]
[ 32234-77-8 ]

Yield	Reaction Conditions	Operation in experiment
	at 160℃; for 16h;	A mixture of amine (1 equiv.) and diethyl ethoxymethylenemalonate (1.35 equiv.) in 1,2,4-trichlorobenzene is heated at 160 C with a distill collector for 16 hr. Ethanol that forms during the reaction is collected at the top of a short fractionating column. Next, the reaction mixture is allowed to cool and then the solid is filtered off, washed with hexane, dried to give the ethyl ester product.

Reference： [1]Patent: WO2017/40877,2017,A1 .Location in patent: Paragraph 00143; 00144

74
[ 4570-45-0 ]
5-isopropylisoxazole-3-carboxylic acid [ No CAS ]
5-isopropyl-N-(oxazol-2-yl)isoxazole-3-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 4594 - 4610

75
[ 420-04-2 ]
[ 141-46-8 ]
[ 4570-45-0 ]
[ 7720-39-0 ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 8780 - 8783

76
[ 4570-45-0 ]
[ 56-82-6 ]
C₆H₁₀N₂O₄ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 8780 - 8783

77
[ 765-34-4 ]
[ 4570-45-0 ]
C₆H₁₀N₂O₄ [ No CAS ]
[ 56-82-6 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 4919 - 4921
[2]Chemical Communications,2017,vol. 53,p. 4919 - 4921

78
[ 765-34-4 ]
[ 4570-45-0 ]
C₆H₁₀N₂O₄ [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 4919 - 4921

79
[ 765-34-4 ]
[ 4570-45-0 ]
C₆H₁₀N₂O₄ [ No CAS ]
C₆H₁₀N₂O₄ [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 4919 - 4921
[2]Chemical Communications,2017,vol. 53,p. 4919 - 4921

80
[ 4570-45-0 ]
perfluorophenyl 1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)isoquinoline-6-sulfonate [ No CAS ]
1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(oxazol-2-yl)isoquinoline-6-sulfonamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5969 - 5989

81
[ 4570-45-0 ]
[ 89-55-4 ]
C₁₀H₇BrN₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	General procedure: To a solution of 5-bromo-2-hydroxybenzoic acid (2 g, 9.22 mmol) in DMF (15 mL) was addedDIPEA (3.22 mL, 18.43 mmol), 3-aminopyridine (1.128 g, 11.98 mmol), HOBT (1.694 g, 11.06mmol) and EDC (3.53 g, 18.43mmol). The reaction was stirred overnight, water was added andthe solid was filtered to give the title compound 12 (346 mg, 12% yield).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4034 - 4038

82
[ 4570-45-0 ]
[ 626-60-8 ]
N-(pyridin-3-yl)oxazol-2-amine [ No CAS ]