[ CAS No. 84163-22-4 ] {[proInfo.proName]}

Name: 84163-22-4|3-(Piperidin-4-yl)benzo[d]isoxazole hydrochloride|98%
Brand: Ambeed
SKU: A812649
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2D 3D

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Quality Control of [ 84163-22-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 84163-22-4 ]

Product Details of [ 84163-22-4 ]

CAS No. :	84163-22-4	MDL No. :	MFCD27978162
Formula :	C₁₂H₁₅ClN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JVRIOVDBNNWSHA-UHFFFAOYSA-N
M.W :	238.71	Pubchem ID :	13076437
Synonyms :

Calculated chemistry of [ 84163-22-4 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.42
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	69.77
TPSA :	38.06 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.87 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.65
Log Po/w (WLOGP) :	2.72
Log Po/w (MLOGP) :	2.04
Log Po/w (SILICOS-IT) :	2.63
Consensus Log Po/w :	2.01

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.34
Solubility :	0.109 mg/ml ; 0.000457 mol/l
Class :	Soluble
Log S (Ali) :	-3.1
Solubility :	0.189 mg/ml ; 0.000794 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.13
Solubility :	0.0177 mg/ml ; 0.0000743 mol/l
Class :	Moderately soluble

Medicinal Chemistry

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

Safety of [ 84163-22-4 ]

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

Application In Synthesis of [ 84163-22-4 ]

* 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 [ 84163-22-4 ]

[ 84163-22-4 ] Synthesis Path-Downstream 1~26

1
[ 92933-14-7 ]
[ 84163-22-4 ]
[ 84231-40-3 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 761 - 769

2
[ 84163-22-4 ]
[ 84243-02-7 ]
[ 84243-03-8 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 761 - 769

3
[ 84163-22-4 ]
[ 3312-04-7 ]
[ 84231-24-3 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 761 - 769

4
[ 84163-22-4 ]
[ 62780-89-6 ]
[ 84231-49-2 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 761 - 769

5
[ 58113-30-7 ]
[ 84163-22-4 ]
1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 1119 - 1131
[2]Organic Process Research and Development,2014,vol. 18,p. 342 - 348

6
[ 3430-03-3 ]
[ 84163-22-4 ]
1-[4-[2-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 1119 - 1131

7
[ 117022-40-9 ]
[ 84163-22-4 ]
1-[4-[4-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 1119 - 1131

8
[ 3430-04-4 ]
[ 584-08-7 ]
[ 84163-22-4 ]
1-[4-[4-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanol [ No CAS ]
1-[4-[4-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.3 g (43%)	In N-methyl-acetamide;	EXAMPLE 4 1-[4-[4-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanol A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.3 g, 0.018 mol), K2 CO3 (5.5 g, 0.04 mol), and 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (5.5 g, 0.018 mol), and dimethylformamide (60 ml) was stirred and heated at 75 C. for 16 hours. The reaction was poured into water and was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent concentrated to afford 7.2 g of a beige solid. Recrystallization (twice) from ethyl alcohol yielded 3.3 g (43%) of 1-[4-[4-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone, m.p.=99-101 C.

Reference： [1]Patent: US5364866,1994,A

9
[ 3430-03-3 ]
[ 584-08-7 ]
[ 84163-22-4 ]
[ 110-17-8 ]
1-<4-<2-<4-(1,2-benzisoxazol-3-yl)-1-piperidinyl>ethoxy>-3-methoxyphenyl>ethanone fumarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 g (17%)	In N-methyl-acetamide; ethyl acetate;	EXAMPLE 6 1-[4-[2-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone fumarate A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 0.02 mol), K2 CO3 (5.2 g, 0.04 mol), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone (5.0 g, 0.022 mol), and dimethylformamide (90 ml) was heated at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent was concentrated to afford an oil. Upon standing, the oil solidified to afford a beige solid. The crude solid was recrystallized twice from ethyl alcohol to afford 5.9 g of an off-white solid. The solid was dissolved in ethyl acetate, and fumaric acid (1.2 g, 1.1 equiv.) was added. The mixture was heated briefly on a steam bath, and then stirred at ambient temperature for 2 hours. An initial green oil settled out and the supernatant solution was decanted. Ether was added to the decantate and 4.0 g of a white fumarate salt was collected. The salt was recrystallized twice from ethanol-ether to yield 1.7 g (17%) of 1-[4-[2-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone fumarate, m.p.=127-129 C.
1.7 g (17%)	In N-methyl-acetamide; ethyl acetate;	EXAMPLE 6 1-[4-[2-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone fumarate A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 20 mmol), K2 CO3 (5.2 g, 40 mmol), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone (5.0 g, 22 mmol), and dimethylformamide (90 ml) was heated at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent was concentrated to afford an oil. Upon standing, the oil solidified to afford a beige solid. The crude solid was recrystallized twice from ethyl alcohol to afford 5.9 g of an off-white solid. The solid was dissolved in ethyl acetate, and fumaric acid (1.2 g, 1.1 equiv.) was added. The mixture was heated briefly on a steam bath, and then stirred at ambient temperature for 2 hours. An initial green oil settled out and the supernatant solution was decanted. Ether was added to the decantate and 4.0 g of a white fumarate salt was collected. The salt was recrystallized twice from ethanol-ether to yield 1.7 g (17%) of 1-[4-[2-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone fumarate, m.p.=127-129 C. ANALYSIS: Calculated for C23 H26 N2 O4.C4 H4 O4: 63.52%C, 5.92%H, 5.49%N; Found: 63.00%C, 5.87%H, 5.42%N.
1.7 g (17%)	In N-methyl-acetamide; ethyl acetate;	EXAMPLE 6 1-[4-[2-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxy-phenyl]ethanone fumarate A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 20 mmol), K2 CO3 (5.2 g, 40 mmol), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone (5.0 g, 22 mmol), and dimethylformamide (90 ml) was heated at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent was concentrated to afford an oil. Upon standing, the oil solidified to afford a beige solid. The crude solid was recrystallized twice from ethyl alcohol to afford 5.9 g of an off-white solid. The solid was dissolved in ethyl acetate, and fumaric acid (1.2 g, 1.1 equiv.) was added. The mixture was heated briefly on a steam bath, and then stirred at ambient temperature for 2 hours. An initial green oil settled out and the supernatant solution was decanted. Ether was added to the decantate and 4.0 g of a white fumarate salt was collected. The salt was recrystallized twice from ethanol-ether to yield 1.7 g (17%) of 1-[4-[2-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone fumarate, m.p.=127-129 C. ANALYSIS: Calculated for C23 H26 N2 O4: 63.52%C 5.92%H 5.49%N; Found: 63.00%C 5.87%H 5.42%N.

Reference： [1]Patent: US5364866,1994,A
[2]Patent: US5605913,1997,A
[3]Patent: US5776963,1998,A

10
[ 58113-30-7 ]
[ 584-08-7 ]
[ 84163-22-4 ]
1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6 g (33%)	With Ki; In N-methyl-acetamide;	EXAMPLE 2 1-[4-[3-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 0.02 mol), K2 CO3 (5.2 g, 0.04 mol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (5.3 g, 0.022 mol), a few crystals of KI and dimethylformamide (60 ml) was stirred at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed (water), dried (MgSO4) and concentrated to afford a brown oil. The oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetatediethylamine (2%), as eluent. Concentration of the appropriate fractions afforded 3.9 g of product as an off-white solid. Recrystallization from absolute ethyl alcohol afforded 2.6 g (33%) of 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-phenyl]ethanone, m.p.=102-104 C., as colorless needles.
2.6 g (33%)	With Ki; In N-methyl-acetamide;	EXAMPLE 2 1-[4-[3-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-ethanone A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 20 mmol), K2 CO3 (5.2 g, 40 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (5.3 g, 22 mmol), a few crystals of KI and dimethylformamide (60 ml) was stirred at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed (water), dried (MgSO4) and concentrated to afford a brown oil. The oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetate-diethylamine (2%), as eluent. Concentration of the appropriate fractions afforded 3.9 g of product as an off-white solid. Recrystallization from absolute ethyl alcohol afforded 2.6 g (33%) of 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperdinyl]propoxy]-3-methoxyphenyl]ethanone, m.p.=102-104 C., as colorless needles. ANALYSIS: Calculated for C24 H28 N2 O4: 70.56%C, 6.91%H, 6.86%N; Found: 70.73%C, 6.93%H, 6.85%N.

Reference： [1]Patent: US5364866,1994,A
[2]Patent: US5605913,1997,A

11
[ 3430-04-4 ]
[ 584-08-7 ]
[ 84163-22-4 ]
1-[4-[4-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.3 g (43%)	In N-methyl-acetamide;	EXAMPLE 4 1-[4-[4-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.3 g, 18 mmol), K2 CO3 (5.5 g, 40 mmol), and 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (5.5 g, 18 mmol), and dimethylformamide (60 ml) was stirred and heated at 75 C. for 16 hours. The reaction was poured into water and was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent concentrated to afford 7.2 g of a beige solid. Recrystallization (twice) from ethyl alcohol yielded 3.3 g (43%) of 1-[4-[4-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone, m.p.: 99-101 C. ANALYSIS: Calculated for C25 H30 N2 O4: 71.11%C, 7.16%H, 6.63%N; Found: 70.76%C, 7.24%H, 6.58%N.

Reference： [1]Patent: US5605913,1997,A

12
1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethamone [ No CAS ]
[ 584-08-7 ]
[ 84163-22-4 ]
1-[4-[3-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoyphenyl]-ethanane [ No CAS ]
1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6 g (33%)		EXAMPLE 2 1-[4-[3-[4-(1,2-Benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoyphenyl]-ethanane A mixture of <strong>[84163-22-4]3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride</strong> (4.8 g, 20 imnol), K2 CO3 (5.2 g, 40 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethamone (5.3 g, 22 mol), a few crystals of KI and dimnethylformamide (60 ml) was stirred at 90 C for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed (water), dried (MgSO4) and concentrated to afford a brown oil. The oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetate-diethylamine (2%), as eluent. Concentration of the appropriate fractions afforded 3.9 g of product as an off-white solid. Recrystallization from absolute ethyl alcohol afforded 2.6 g (33%) of 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone, m.p.=102-104 C., as colorless needles. ANALYSIS: Calculated for C24 H28 N2 O4: 70.56%C 6.91%H 6.86%N; Found: 70.73%C 6.93%H 6.85%N

Reference： [1]Patent: US5776963,1998,A

Yield	Reaction Conditions	Operation in experiment
2.0 g (57%)		EXAMPLE 44 3-(4-Piperidyl)-1,2-benzisoxazole hydrochloride A mixture of 5.0 g of 4-(1,2-benzisoxazole-3-yl)-1-piperidine carboxylic acid phenyl ester, 100 ml of ethanol, 50 g of (85%) potassium hydroxide and 50 ml of water was heated under reflux, with stirring, under nitrogen for 16 hrs. Most of the ethanol was removed in vacuo and the resultant aqueous suspension was extracted with ether (3*50 ml). The ether extracts were combined, washed with water, dried over anhydrous magnesium sulfate and the ether removed under reduced pressure to give an oil. The oil was dissolved in anhydrous ether and hydrogen chloride was introduced to precipitate a 3.0 g of a hydrochloride salt. Recrystallization from methanol-ether gave 2.0 g (57%) of product as the hydrochloride, mp, 313-315 (dec.). ANALYSIS: Calculated for C12 H14 N2 OHCl: 60.37%C; 6.33%H; 11.74%N; Found: 60.52%C; 6.32%H; 11.67%N.

14
bis-hydrochloride mono-hydrate [ No CAS ]
[ 84163-22-4 ]
[ 3312-04-7 ]
[ 84231-25-4 ]

Yield	Reaction Conditions	Operation in experiment
2.35 g (29.5%)	With potassium iodide; potassium carbonate; In N-methyl-acetamide; diethyl ether;	EXAMPLE 4 3-{1-[4,4-bis(4-Fluorophenyl)-1-butyl]-4-piperidyl}-1,2-benzisoxazole hydrochloride A mixture of 3.94 g of 3-(4-piperidyl)-1,2-benzisoxazole hydrochloride, 4.60 g of 4-chloro-1,1-bis(4-fluorophenyl)butane, 4.95 g of anhydrous potassium carbonate, a few crystals of potassium iodide and 85 ml of dimethylformamide were stirred and heated at 90 for 8 hrs and then stirred at ambient temperature over the weekend. The mixture was poured into water and extracted with ethyl acetate and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield an oil. The oil was dissolved in anhydrous diethyl ether and a sautrated hydrogen chloride-ether solution was added dropwise to precipitate a gum. The gum was recrystallized from ethyl acetate-ether to yield a solid. The mother liquor was concentrated to yield an additional solid. The solids were combined and recrystallized twice from ethyl acetate-ether to yield 2.35 g (29.5%) of product, mp, 156-157. ANALYSIS: Calculated for C28 H28 F2 N2 O HCl: 69.63%C, 6.05%H, 5.80%N; Found: 69.65%C, 6.10%H, 5.94%N.

Reference： [1]Patent: US4352811,1982,A

15
2-methyl-3-(phenylsulfonylpropyl)indole [ No CAS ]
[ 84163-22-4 ]
[ 84231-40-3 ]

Yield	Reaction Conditions	Operation in experiment
1.60 g (15.4%)	With potassium carbonate; In N-methyl-acetamide; ethyl acetate;	EXAMPLE 11 3-{3-[4-(1,2-benzisoxazol-3-yl)piperidyl]propyl}-2-methylindole A mixture of 1.67 g of 3-(4-piperidyl)-1,2-benzisoxazole hydrochloride, 2.47 g of 2-methyl-3-(phenylsulfonylpropyl)indole, 40 ml of dimethylformamide and 5.0 g of potassium carbonate was stirred under nitrogen at 90 for 4 hrs. The reaction mixture was poured into water. The precipitate was extracted with ethyl acetate and the ethyl acetate was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield an oil. The oil was combined with 1.39 g of previously prepared material and the sample was chromatographed in 120 g of silica gel, using 1% methanol-chloroform as eluent. The eluent was evaporated and the residue was recrystallized two times from ethanol-water to yield 1.60 g (15.4%) of the product, mp 110-112. ANALYSIS: Calculated for C24 H27 N3 O: 77.18%C, 7.23%H, 11.25%N; Found: 76.86%C, 7.29%H, 11.09%N.

Reference： [1]Patent: US4352811,1982,A

16
[ 1443257-42-8 ]
[ 84163-22-4 ]
[ 1443253-94-8 ]

Yield	Reaction Conditions	Operation in experiment
		7.02.01. 1-(4-Benzo[d]isoxazol-3-yl-piperidin-1-yl)-2-(3,5-bis-(4-fluoro-phenyl)-(1,2,4)triazol-1-yl)-ethanone 32 mg (3,5-bis-(4-fluoro-phenyl)-(1,2,4)triazol-1-yl)-acetic acid was dissolved in 2 mL DMF. 32 mg TBTU and 26 μL DIPEA were added to this solution and the mixture was stirred for 5 minutes at RT. Then, 24 mg 3-piperidin-4-yl-benzo[d]isoxazolehydrochloride was added. The mixture was stirred for 2 h at RT. The reaction solution was purified by HPLC to yield 19.8 mg of the desired compound. Rt: 2.24 (method D), (M+H)+: 500
19.8 mg		1-(4-benzo[d]isoxazol-3-ylpiperidin-1-yl)-2-(3,5-bis-(4-fluorophenyl)-(1,2,4)triazol-1-yl)ethanone 32 mg (3, 5-bis-(4-fluoro-phenyl)-(l, 2, 4) triazol-l-yl)-acetic acid was dissolved in 2 mL DMF. 32 mg TBTU and 26 DIPEA were added to this solution and the mixture was stirred for 5 minutes at RT. Then, 24 mg 3-piperidin-4-yl-benzo[d]isoxazolehydrochloride was added. The mixture was stirred for 2 h at RT. The reaction solution was purified by HPLC to yield 19.8 mg of the desired compound. Rt: 2.24 (method D), (M+H)+: 500

Reference： [1]Patent: US2013/150341,2013,A1 .Location in patent: Paragraph 0500; 0501
[2]Patent: WO2013/83741,2013,A1 .Location in patent: Page/Page column 124

17
[ 84163-22-4 ]
[ 107-04-0 ]
3-[1-(2-chloroethyl)piperidin-4-yl]-1,2-benzoisoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.1 g		Reference Example 3 3-[1-(2-Chloroethyl)piperidin-4-yl]-1,2-benzoisoxazole To a mixture of <strong>[84163-22-4]3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride</strong> (2.01 g), tetrahydrofuran (4.0 mL), water (2.4 mL) was added potassium hydroxide (1.42 g), and the mixture was stirred at room temperature for 30 minutes. Then, 1-bromo-2-chloroethane (2.79 mL) was added thereto, and the mixture was stirred at room temperature for 24 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the titled compound (1.10 g). 1H-NMR (400 MHz, CDCl3) δ: 2.04-2.20 (4H, m), 2.27-2.36 (2H, m), 2.80 (2H, t, J=7.1 Hz), 3.04-3.15 (3H, m), 3.64 (2H, t, J=7.1 Hz), 7.27-7.32 (1H, m), 7.51-7.59 (2H, m), 7.74-7.78 (1H, m).

Reference： [1]Patent: US2020/172543,2020,A1 .Location in patent: Paragraph 0365; 0366; 0367

18
[ 84163-22-4 ]
6-{2-[4-(1,2-benzoisoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [ No CAS ]