[ CAS No. 88511-37-9 ] {[proInfo.proName]}

Name: 88511-37-9|1-(Isoxazol-3-yl)ethanone|95%
Brand: Ambeed
SKU: A249478
Rating: 97 (30 reviews)

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2D 3D

Structure of 88511-37-9 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 88511-37-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 88511-37-9 ]

SDS Specification

Alternatived Products of [ 88511-37-9 ]

Product Details of [ 88511-37-9 ]

CAS No. :	88511-37-9	MDL No. :	MFCD16619202
Formula :	C₅H₅NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SKISYMYDQIWNBM-UHFFFAOYSA-N
M.W :	111.10	Pubchem ID :	21349800
Synonyms :

Calculated chemistry of [ 88511-37-9 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.2
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	26.7
TPSA :	43.1 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) :	-6.7 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.51
Log Po/w (XLOGP3) :	0.39
Log Po/w (WLOGP) :	0.88
Log Po/w (MLOGP) :	-0.63
Log Po/w (SILICOS-IT) :	1.12
Consensus Log Po/w :	0.65

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.17
Solubility :	7.49 mg/ml ; 0.0675 mol/l
Class :	Very soluble
Log S (Ali) :	-0.86
Solubility :	15.3 mg/ml ; 0.138 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.51
Solubility :	3.41 mg/ml ; 0.0307 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.15

Safety of [ 88511-37-9 ]

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

Application In Synthesis of [ 88511-37-9 ]

* 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.

Downstream synthetic route of [ 88511-37-9 ]

[ 88511-37-9 ] Synthesis Path-Downstream 1~88

1
[ 35210-70-9 ]
[ 88511-37-9 ]

Reference： [1]Gazzetta Chimica Italiana,1939,vol. 69,p. 508,512, 522
Gazzetta Chimica Italiana,1940,vol. 70,p. 779,783

2
[ 88511-37-9 ]
[ 917-64-6 ]
2-isoxazol-3-yl-propan-2-ol [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1939,vol. 69,p. 508,512, 522
Gazzetta Chimica Italiana,1940,vol. 70,p. 779,783

3
[ 88511-37-9 ]
[ 74-86-2 ]
[ 872788-64-2 ]

Reference： [1]Gazzetta Chimica Italiana,1947,vol. 77,p. 586,591

4
[ 88511-37-9 ]
bis-(isoxazole-3-carbonyl)-furazan-2-oxide [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1947,vol. 77,p. 586,591

5
[ 68776-57-8 ]
[ 917-64-6 ]
[ 88511-37-9 ]

Reference： [1]Gazzetta Chimica Italiana,1932,vol. 62,p. 436,442

6
[ 67-64-1 ]
[ 88511-37-9 ]

Reference： [1]Gazzetta Chimica Italiana,1947,vol. 77,p. 586,591

8
[ 7697-37-2 ]
[ 74-86-2 ]
1-nitro-1-hydroxyimino-acetone [ No CAS ]
[ 88511-37-9 ]

Reference： [1]Gazzetta Chimica Italiana,1947,vol. 77,p. 586,591

9
[ 6868-83-3 ]
[ 7697-37-2 ]
[ 74-86-2 ]
[ 88511-37-9 ]

Reference： [1]Gazzetta Chimica Italiana,1947,vol. 77,p. 586,591

10
[ 88511-37-9 ]
[ 34253-03-7 ]
[ 1354044-12-4 ]

Yield	Reaction Conditions	Operation in experiment
39%		Intermediate 8[00490] This compound was synthesized by the following procedure:To a -78 C cooled solution of l-(isoxazol-3-yl)ethanone (2.01 g, 18.09 mmol) in THF (50 mL) was added lithium hexamethyldisilazide (15.5 mL, 15.50 mmol) (1M solution in toluene) slowly. Reaction mixture became yellow-orange. Reaction mixture was stirred at this temperature for 10 min. Reaction mixture was warmed to 0 C for 30 min. Methyl pyrimidine-2-carboxylate (2.499 g, 18.09 mmol) in THF (25 rnL) was added slowly and stirring continued at this temperature for 15 min. Reaction mixture stirred at room temperature for 1.83h. EtOH (60 mL), AcOH (6 mL), and hydrazine hydrate (1.014 mL, 20.81 mmol) were added and the reaction mixture was heated at 65 C for 2.25h. Concentrated in vacuo. The reaction mixture was diluted with water and ether, and then filtered and washed with water and ether. The ether contained some of the desired product. NMR is consistent with product. Product was a faint tan solid (39%). 1H NMR (400 MHz, CD3OD) delta 8.85 (d, 2H), 8.73 (s, 1H), 7.46 (s, 1H), 7.40 (t, 1H), 6.92 (d, 1H).

Reference： [1]Patent: WO2012/3405,2012,A1 .Location in patent: Page/Page column 261-262

11
[ 88511-37-9 ]
[ 34253-03-7 ]
[ 1354042-30-0 ]

Reference： [1]Patent: WO2012/3405,2012,A1

12
[ 88511-37-9 ]
[ 34253-03-7 ]
[ 1221504-13-7 ]
[ 1446359-20-1 ]

Yield	Reaction Conditions	Operation in experiment
12%		To a -78 C solution of l-(isoxazol-3-yl)ethanone (60 mg, 0.54 mmol) in tetrahydrofuran (5.4 mL) was added lithium hexamethyldisilazide (1 M in toluene, 486 mu, 0.486 mmol) in a dropwise manner over the course of 5 minutes. The solution was immediately warmed to 0 C for 30 minutes at which point <strong>[34253-03-7]methyl pyrimidine-2-carboxylate</strong> (75 mg, 0.54 mmol) was added in a single portion. After stirring for 15 minutes at 0 C, the solution was warmed to room temperature for 18 hours. The solvent was removed in vacuo, and residue was diluted with ether (5 mL) and filtered. The resulting solid (30 mg, 0.13 mmol) was re-suspended in isopropanol (1.3 mL), and treated with triethylamine (38 mu, 0.27 mmol), trifluoroacetic acid (21 0.27 mmol), and 3-fluoro-4-(hydrazinylmethyi)pyridine trifluoroacetic acid (192 mg, 0.75 mmol). The solution was heated to 80 C until LCMS indicated consumption of intermediate dione. The solvent was removed in vacuo. Contents diluted with ethyl acetate (5 mL) and washed with saturated sodium bicarbonate solution (5 mL), water (5 mL), and brine (5 mL). The organics were dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. The crude residue was purified via silica gel chromatography (3-100% hexanes in ethyl acetate, followed by a second purification with 0-60% hexanes in acetone) to give compound A (5.1 mg, 12% yield) as an off-white solid. Compound-66: 1H-NMR (400 MHz, CDC13) delta 8.84 (d, 2H), 8.48 (d, 1H), 8.08 (d, 1H), 7.49 (s, 1H), 7.23-7.29 (m, 2H), 7.03 (t, 1H), 6.64 (d, 1H), 6.02 (s, 2H).

Reference： [1]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 154-155

13
[ 88511-37-9 ]
[ 1221504-13-7 ]
[ 95-92-1 ]
[ 1446353-48-5 ]

Yield	Reaction Conditions	Operation in experiment
51%		To a -78 C solution of l-(isoxazol-3-yl)ethanone (155 mg, 1.40 mmol) in tetrahydrofuran (14 mL) was added lithium hexamethyldisilazide (1 M in toluene, 1.33 mL, 1.33 mmol) in a dropwise manner over the course of 5 minutes. The solution was immediately warmed to 0 C for 30 minutes at which point diethyl oxalate (227 mu , 1.67 mmol) was added in a dropwise manner over the course of 5 minutes. After stirring for 10 min at 0 C, the solution was warmed to room temperature for 1 hour. Ethanol (14 mL) and 3-fluoro-4- (hydrazinylmethyl)pyridine trifluoroacetic acid (463 mg, 1.81 mmol) were added and the solution was heated to 40 C until LCMS indicated consumption of intermediate dione. The solvent was removed in vacuo. Water (20 mL) and dichloromethane (20 mL) were added to the resulting residue. The layers were separated and the aqueous layer was extracted with dichloromethane (3 x 30 mL). The organics were washed with brine (10 mL), dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. The crude residue was purified via silica gel chromatography (0-80% hexanes in ethyl acetate) to give Intermediate-5B (227 mg, 51% yield) as a white solid. Intermediate-5B: 1H-NMR (400 MHz, CDC13) delta 8.49 (d, 1H), 8.11 (d, 1H), 7.19-7.25 (m, 2H), 7.03-7.10 (m, 1H), 6.59 (d, 1H), 5.95 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H).

Reference： [1]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 102

14
[ 88511-37-9 ]
[ 1216246-45-5 ]
[ 95-92-1 ]
[ 1354044-05-5 ]

Yield	Reaction Conditions	Operation in experiment
28.4%		To a cooled (-73 C) solution of l-(isoxazol-3-yl)ethanone (44.0 g, 356 mmol) in THF (1100 ml) was added LiHMDS (1M in toluene, 346 mL, drop-wise addition over 60 min). The reaction mixture was warmed to 0 C, the vessel was placed in an ice bath, and diethyl oxalate (58 mL, 428 mmol) was added. The bath was removed and reaction was stirred for 45 min. At this juncture, the reaction vessel was placed back in the ice bath and the reaction mixture was consecutively charged with (2-fluorobenzyl)hydrazine hydrochloride (79.0 g, 447 mmol, dissolved in 800 mL absolute EtOH) and acetic acid (110 mL). The ice bath was removed and the reaction was stirred overnight at rt, then at 60 C for 3 h. The reaction was then cooled to 0 C, and then filtered through Celite. The filtrate was then concentrated and the crude material was purified via silica gel chromatography employing a hexane/ethyl acetate gradient (95:5 - 3:2) to afford the desired material (31.9 g, 28.4%).

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 465 - 469
[2]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 103

15
[ 88511-37-9 ]
[ 34253-03-7 ]
[ 1446360-17-3 ]
C₁₆H₁₁FN₆O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%		To a -78 C solution of 1 -(isoxazol-3 -yl)ethanone (54 mg, 0.43 mmol) in tetrahydrofuran (2 mL) was added lithium hexamethyldisilazide (1 M in toluene, 411 mu, 0.411 mmol) in a dropwise manner over the course of 5 min. The solution was immediately warmed to 0 C for 30 minutes at which point <strong>[34253-03-7]methyl pyrimidine-2-carboxylate</strong> (60 mg, 0.43 mmol) was added in a single portion. After stirring for 15 min at 0 C, the solution was warmed to room temperature for 2 hours. Ethanol (2 mL), 3-fluoro-4-(hydrazinylmethyl)pyridine hydrochloride (100 mg, 0.56 mmol), and acetic acid (200 mu) were added and the solution was heated to 70 C until LCMS indicated consumption of intermediate dione. The solvent was removed in vacuo. Water (50 mL) and dichloromethane (75 mL) were added to the resulting residue. The layers were separated and the aqueous layer was extracted with dichloromethane (2 x 30 mL). The organics were dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. The crude residue was purified via silica gel chromatography (30-100% hexanes in ethyl acetate) to give compound 23 (26 mg, 19% yield) as a yellow solid. Compound 23: 1H-NMR (400 MHz, CDC13) delta 8.82 (d, 2H), 8.45 (d, 1H), 8.41 (s, 1H), 8.20 (d, 1H), 7.49 (s, 1H), 7.24 (t, 1H), 6.69 (t, 1H), 6.63 (d, 1H), 6.06 (s, 2H).

Reference： [1]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 152-153

16
[ 88511-37-9 ]
[ 34253-03-7 ]
3-fluoro-2-(hydrazinylmethyl)pyridine dihydrochloride [ No CAS ]
[ 1446359-19-8 ]

Yield	Reaction Conditions	Operation in experiment
20%		To a -78 C solution of l-(isoxazol-3-yl)ethanone (46 mg, 0.41 mmol) in tetrahydrofuran (1 mL) was added lithium hexamethyldisilazide (1 M in toluene, 370 mu, 0.37 mmol) in a dropwise manner over the course of 5 minutes. The solution was immediately warmed to 0 C for 30 minutes at which point <strong>[34253-03-7]methyl pyrimidine-2-carboxylate</strong> (49 mg, 0.35 mmol) was added in a single portion. After stirring for 15 minutes at 0 C, the solution was warmed to room temperature for 18 hours. The solvent was removed in vacuo, and residue was diluted with ether (5 mL) and filtered. The resulting solid (72 mg, 0.32 mmol) was re-suspended in ethanol (0.5 mL) with 3-fluoro-2-(hydrazinylmethyl)pyridine dihydrochloride (60 mg, 0.28 mmol). The solution was heated to 40 C until LCMS indicated consumption of intermediate dione. The solvent was removed in vacuo. The crude residue was purified via silica gel chromatography (3-100% hexanes in ethyl acetate) to give compound 57 (20 mg, 20% yield) as an off-white solid. Compound-57: 1H-NMR (400 MHz, CDC13) delta 8.81 (d, 2H), 8.43 (d, 1H), 8.21 (d, 1H), 7.49 (s, 1H), 7.35 (dt, 1H), 7.21 (t, 1H), 7.12-7.16 (m, 1H), 6.68 (d, 1H), 6.19 (s, 2H).

Reference： [1]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 153-154

17
[ 88511-37-9 ]
[ 95-92-1 ]
[ 1446353-36-1 ]

Yield	Reaction Conditions	Operation in experiment
59%		To a -78 C solution of l-(isoxazol-3-yl)ethanone (2.18 g, 19.62 mmol) in tetrahydrofuran (58 mL) was added lithium hexamethyldisilazide (1 M in toluene, 18 mL, 18 mmol) dropwise over the course of 20 minutes. The solution was warmed to 0 C and stirred for 30 minutes, at which point diethyl oxalate (2.9 mL, 21.6 mmol) was added over the course of 5 minutes. The solution was warmed to room temperature and stirred for 45 minutes. Ethanol (58 mL), hydrazine hydrate (0.88 mL, 18 mmol), and acetic acid (5.8 mL) were sequentially added. The heterogeneous solution was heated to 70 C. After stirring for 2.25 hours at this temperature, the solvent was removed under vacuum. Water (300 mL) and dichloromethane (300 mL) were added, the layers were separated, and the aqueous layer was extracted with dichloromethane (5 x 150 mL). The organics were combined, dried over magnesium sulfate, filtered, and the solvent was removed under vacuum. Purification by silica gel chromatography (0-15% methanol in dichloromethane) and re-purification (ethyl acetate in dichloromethane) gave impure product. The resulting solid was triturated with diethyl ether to give Interraediate-3 (2.21 g, 59%) as a white solid.

Reference： [1]Patent: WO2013/101830,2013,A1 .Location in patent: Page/Page column 101

18
[ 88511-37-9 ]
[ 95-92-1 ]
[ 1579999-84-0 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of ketone A in THF cooled to -78 C, LiHMDS (e.g., 0.9 eq, 1.0 M in toluene) is added dropwise, for example using a syringe. The reaction mixture is then allowed to warm to about 0 C, then charged with diethyl oxalate (1.2 eq). At this time, the reaction mixture is warmed to room temperature and stirred at that temperature until judged complete (e.g., using either TLC or LC/MS analysis). Once the reaction is complete (reaction time typically about 45 minutes), the product dione enolate B is used as-is in Step 2, i.e., the cyclization step, without any further purification
	In tetrahydrofuran; toluene; at -78 - 20℃; for 0.75h;	General procedure: Dione enolate formation: To a solution of ketone A in THF cooled to -78 C, LiHMDS (e.g., 0.9 equiv, 1.0 M in toluene) was added dropwise via syringe. The reaction was allowed to warm to 0 C, then charged with diethyl oxalate (1.2 equiv). At this time, the reaction was warmed to room temperature and stirred at that temperature until judged complete (e.g., using either TLC or LC/MS analysis). Once the reaction was complete (reaction time was typically 45 minutes), the product dione enolate B was used ?as-is? in Step 2, i.e., the cyclization step, without any further purification. The above compound was prepared following general procedure A, using <strong>[88511-37-9]1-(isoxazol-3-yl)ethanone</strong> in step 1 and 2,3-difluorobenzylhydrazine in step 2.
		General procedure: To a solution of ketone A in THF cooled to -78 C, LiHMDS (e.g., 0.9 equiv, 1.0 M in toluene) was added dropwise via syringe. The reaction was allowed to warm to 0 C, then charged with diethyl oxalate (1.2 equiv). At this time, the reaction was warmed to room temperature and stirred at that temperature until judged complete (e.g., using either TLC or LC/MS analysis). Once the reaction was complete (reaction time was typically 45 minutes), the product dione enolate B was used "as-is" in Step 2, i.e., the cyclization step, without any further purification.

Reference： [1]Patent: WO2014/47111,2014,A1 .Location in patent: Paragraph 00209; 00210; 00211
[2]Patent: WO2014/144100,2014,A2 .Location in patent: Paragraph 00273
[3]Patent: WO2016/44447,2016,A1 .Location in patent: Paragraph 00178

19
[ 88511-37-9 ]
[ 1579999-85-1 ]

Reference： [1]Patent: WO2014/47111,2014,A1

20
[ 88511-37-9 ]
[ 1579999-81-7 ]

Reference： [1]Patent: WO2014/47111,2014,A1

21
[ 88511-37-9 ]
[ 1579999-83-9 ]

Reference： [1]Patent: WO2014/47111,2014,A1

22
[ 88511-37-9 ]
[ 1579999-86-2 ]

Reference： [1]Patent: WO2014/47111,2014,A1

23
[ 88511-37-9 ]
2-fluorobenzylhydrazine hydrate [ No CAS ]
[ 95-92-1 ]
[ 1354044-05-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2:Pyrazole formation: Dione enolate B was diluted with ethanol and consecutively charged with HCI (e.g., 3 equiv, 1.25 M solution in ethanol) and arylhydrazine hydrate (e.g., 1.15 equiv). The reaction mixture was heated to 70 C and stirred at this temperature until cyclization was deemed complete (e.g., by LC/MS analysis, typically 30 minutes). Once complete, the reaction mixture was treated carefully with solid sodium bicarbonate (e.g., 4 equiv) and diluted with dichloromethane and water. Layers were separated, and aqueous layer was futher diluted with water before extraction with dichloromethane (3x). The combined organics were washed with brine, dried over MgS04, filtered, and concentrated in vacuo. The resulting pyrazole C was then purified by S1O2 chromatography using an appropriate gradient of EtOAc in hexanes.

Reference： [1]Patent: WO2016/44445,2016,A2 .Location in patent: Paragraph 00313

24
[ 88511-37-9 ]
[ 1354041-91-0 ]