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[ CAS No. 84163-13-3 ] {[proInfo.proName]}

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Chemical Structure| 84163-13-3
Chemical Structure| 84163-13-3
Structure of 84163-13-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 84163-13-3 ]

CAS No. :84163-13-3 MDL No. :MFCD06658529
Formula : C12H14ClFN2O Boiling Point : -
Linear Structure Formula :- InChI Key :CWPSRUREOSBKBQ-UHFFFAOYSA-N
M.W : 256.70 Pubchem ID :11334359
Synonyms :

Calculated chemistry of [ 84163-13-3 ]

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.42
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 69.73
TPSA : 38.06 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.91 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 2.75
Log Po/w (WLOGP) : 3.28
Log Po/w (MLOGP) : 2.44
Log Po/w (SILICOS-IT) : 3.01
Consensus Log Po/w : 2.3

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.49
Solubility : 0.0831 mg/ml ; 0.000324 mol/l
Class : Soluble
Log S (Ali) : -3.2
Solubility : 0.16 mg/ml ; 0.000625 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.41
Solubility : 0.00999 mg/ml ; 0.0000389 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.66

Safety of [ 84163-13-3 ]

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 [ 84163-13-3 ]

* 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 [ 84163-13-3 ]
  • Downstream synthetic route of [ 84163-13-3 ]

[ 84163-13-3 ] Synthesis Path-Upstream   1~17

  • 1
  • [ 885706-66-1 ]
  • [ 84163-13-3 ]
  • [ 106266-06-2 ]
YieldReaction ConditionsOperation in experiment
87.4% With potassium carbonate In acetone for 6 h; Heating / reflux Example 2; Production of risperidone of formula (I) from 3-(2-iodoethyl)-2-methyl-6,7,8,9-tetrahydro-4H- pyrido [ 1 ,2-a]pyrimidine-4-one; 2.56 g (10 mmol) of 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole HCl, 2.56 g (10 mmol) 3-(2-iodoemyl)-2-memyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidme-4- one, 2.76 g (20 mmol) of potassium carbonate and 50 ml of acetone are added into a distilling flask equipped with reflux condenser. The suspension is boiled for 6 hours during stirring and then 100 ml of water is added to the suspension and the acetone is distilled off under reduced pressure. The suspension is cooled down to 20 °C and stirred for 1 hour, filtered, washed with 50 ml of water, dried at 60 0C. 3.77 g (92 percent) product is obtained which is recrystallized from 2-propanol.Dry weight: 3.58 g (87.4percent). Melting point: 171-172 0C. Purity: 99.86 percent (determined by HPLC).
Reference: [1] Patent: WO2006/46082, 2006, A1, . Location in patent: Page/Page column 10
  • 2
  • [ 84163-13-3 ]
  • [ 106266-06-2 ]
YieldReaction ConditionsOperation in experiment
93.6% With sodium carbonate In methanol at 73 - 75℃; for 4 - 4.5 h; Example 1; Preparation of the risperidone of the formula (I) from the hydrochlorid salt of 3-(2-cUoroemyl)-2-methyl-6,7,8,9-te1xahydro-4H-pyrido[l,2-a]pyrimidme-4-one of the formula (II) and the hydrochloride salt of 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole of the formula (III). In a pressure vessel into a mixture of 13.3 g (0.052 mol) of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride, 15.0 g (0.057 mol) of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidine-4-one hydrochloride, 20.67 g of dry sodium carbonate and 200 ml of dry methanol nitrogen is introduced and the mixture is stirred for 4-4.5 hours at 73-75 °C. Then the pressure is brought to atmospheric level, the mixture is concentrated to about 150 g, 100 ml of ion exchanged water is added, then the mixture is cooled to a temperature between 0 °C and 5 °C and filtered. To the filter cake 100 ml of ion exchanged water is added, stirred for an hour at 23-25 °C and filtered. The crystals arewashed with ion exchanged water (3 x 20 ml), filtered and dried at a temperature below 60 °C to yield 20.0 g of risperidone (93.6 percent based on the starting benzisoxazole derivative).Mp: 171-172 °C; purity is at least 99 percent, determined by HPLC
Reference: [1] Patent: WO2006/5974, 2006, A1, . Location in patent: Page/Page column 6-7
[2] Patent: WO2005/30772, 2005, A1, . Location in patent: Page/Page column 10-11
[3] Patent: WO2005/30772, 2005, A1, . Location in patent: Page/Page column 11
  • 3
  • [ 63234-80-0 ]
  • [ 84163-13-3 ]
  • [ 106266-06-2 ]
YieldReaction ConditionsOperation in experiment
93.2% With sodium carbonate In water at 110 - 120℃; for 0.666667 h; Example 9; Preparation of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (risperidone)In a 50-ml reaction flask, 2.56 g of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride and 2.95 g of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one are placed, then a sodium carbonate solution or suspension (dissolved or suspended 8.5 g of sodium carbonate in 25 ml water) is added. The mixture is put into heating bath at 110-120° C. with stirring for 40 min, then cooled with continuous stirring to the room temperature and the precipitate solid is filtered, washed with pure water, and dried to give 3.82 g of the product in 93.2percent yield. The product is purified to obtain a purity of 99.5percent (determined by HPLC) with DMF and isopropanol.
Reference: [1] Patent: US2010/130740, 2010, A1, . Location in patent: Page/Page column 4
  • 4
  • [ 84163-13-3 ]
  • [ 84163-77-9 ]
YieldReaction ConditionsOperation in experiment
40% With sodium hydroxide In water at 20℃; for 1 h; Inert atmosphere To a solution of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (1.04 g, 4.05 mmol) in 50 mL H2O, 1 N NaOH (70 mL) was added at room temperature slowly. After the reaction mixture was stirred for 1 h at room temperature, DCM (100 mL) was added and then stirred for 30 min in additionally. The resulting solution was extracted with DCM thrice and dried over with anhydrous MgSO4. After the solvent was removed under vacuum, the desired product (1) was obtained as a white solid product without further purification (880 mg, 40percent yield). 1H NMR (400 MHz, CDCl3) δ 1.66 (m, 2H), 1.90 (m, 2H), 2.71 (m, 5H), 7.24 (dd, J = 6.4, 2.0 Hz, 1H), 7.31 (dd, J = 6.4, 4.2 Hz, 1H), 7.77 (dd, J = 4.2, 2.0 Hz, 1H). 13C NMR (400 MHz, CDCl3) δ 23.1 (2C), 27.4 (2C), 36.6, 118.0 (2C), 124.3, 148.8 (2C), 157.6, 161.8.
21 g With sodium hydroxide In water for 0.333333 h; Example-14
Preparation of Crystalline 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (formula-10)
To the suspension of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (formula-6) (25 grams) dissolved in water (100 ml), added aqueous sodium hydroxide (4.8 g in 20 ml water).
Stirred for 20 min and extracted with dichloromethane.
Washed the organic layer with water, distilled off the solvent under reduced pressure to obtain the title compound.
Yield: 21 grams.
Reference: [1] Bulletin of the Korean Chemical Society, 2016, vol. 37, # 9, p. 1464 - 1471
[2] Patent: WO2007/93870, 2007, A2, . Location in patent: Page/Page column 7-9
[3] Patent: US2011/293889, 2011, A1,
[4] Patent: US2011/293889, 2011, A1,
[5] Patent: US8481729, 2013, B2, . Location in patent: Paragraph 22
[6] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
[7] Journal of Chemical Sciences, 2015, vol. 127, # 10, p. 1739 - 1746
  • 5
  • [ 416852-17-0 ]
  • [ 84163-13-3 ]
Reference: [1] Patent: WO2008/108957, 2008, A2, . Location in patent: Page/Page column 36
  • 6
  • [ 135634-18-3 ]
  • [ 84163-13-3 ]
YieldReaction ConditionsOperation in experiment
35 g
Stage #1: With potassium hydroxide In methanol for 2.5 h; Heating
Stage #2: With hydrogenchloride In water; acetone at 20℃; for 0 h;
Potassium hydroxide (27 g) was added to 600 mL of methanol and added(2,4-difluorophenyl) - (4-piperidinyl) methanone oxime hydrochloride (55 g)Heating reaction for about 2.5 hours. Cold to room temperature, add appropriate amount of anhydrous MgSO4, stirring about 1h. The filtrate was concentrated under reduced pressure. Join500 mL of acetone, stirred at room temperature for about 0.5 h, filtered, the filtrate stirred into the hydrochloric acid to pH = 2 ~ 3, filter, dry, white solidBody 35g. The methanol content is 0.4percent.
Reference: [1] Patent: CN106831742, 2017, A, . Location in patent: Paragraph 0041; 0042
  • 7
  • [ 84163-41-7 ]
  • [ 84163-13-3 ]
YieldReaction ConditionsOperation in experiment
31.8% With hydrogenchloride In methanol; ethanol; benzene EXAMPLE 35
3-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole hydrochloride
A solution of 3.8 g of 3-(1-formyl-4-piperidyl)-6-fluoro-1,2-benzisoxazole was dissolved in 45 ml of ethanol (96percent) and 45 ml of 3 N hydrochloric acid was heated under reflux for 3 hrs.
The mixture was diluted with water to 500 ml, made alkaline with potassium carbonate solution and extracted with dichloromethane (5*200 ml).
The combined extracts were washed with water, dried over anhydrous magnesium sulfate and the dichloromethane was removed in vacuo to give 3.7 g of an oil.
The oil was dissolved in 30 ml of methanol and 1 ml of concentrated hydrochloric acid was added.
The methanol was distilled, 15 ml benzene was added and also distilled.
The residue was treated with 100 ml of ether to give a solid.
Two recrystallizations from isopropanol-methanol-ether yielded 1.25 g (31.8percent) of product, mp, 293°-295°.
ANALYSIS:
Calculated for C12 H13 FN2 OHCl: 56.15percentC; 5.49percentH; 10.91percentN; Found: 56.99percentC; 5.66percentH; 10.51percentN.
Reference: [1] Journal of Medicinal Chemistry, 1985, vol. 28, # 6, p. 761 - 769
[2] Patent: US4355037, 1982, A,
[3] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 8
  • [ 84162-94-7 ]
  • [ 84163-13-3 ]
Reference: [1] Journal of Medicinal Chemistry, 1985, vol. 28, # 6, p. 761 - 769
[2] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 9
  • [ 84163-43-9 ]
  • [ 84163-13-3 ]
Reference: [1] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 10
  • [ 498-94-2 ]
  • [ 84163-13-3 ]
Reference: [1] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 11
  • [ 84163-42-8 ]
  • [ 84163-13-3 ]
Reference: [1] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 12
  • [ 84162-80-1 ]
  • [ 84163-13-3 ]
Reference: [1] Organic Process Research and Development, 2003, vol. 7, # 4, p. 521 - 532
  • 13
  • [ 416852-15-8 ]
  • [ 84163-13-3 ]
Reference: [1] Patent: WO2008/108957, 2008, A2,
  • 14
  • [ 416852-16-9 ]
  • [ 84163-13-3 ]
Reference: [1] Patent: WO2008/108957, 2008, A2,
  • 15
  • [ 1550-35-2 ]
  • [ 84163-13-3 ]
Reference: [1] Patent: WO2008/108957, 2008, A2,
  • 16
  • [ 63463-36-5 ]
  • [ 84163-13-3 ]
Reference: [1] Patent: WO2008/108957, 2008, A2,
  • 17
  • [ 84163-13-3 ]
  • [ 108-10-1 ]
  • [ 129029-23-8 ]
Reference: [1] Patent: US5482943, 1996, A,
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