[ CAS No. 153559-48-9 ] {[proInfo.proName]}

Name: 153559-48-9|Methyl 4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoate|98%
Brand: Ambeed
SKU: A187165
Rating: 98 (30 reviews)

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Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 153559-48-9 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 153559-48-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 153559-48-9 ]

SDS Specification

Alternatived Products of [ 153559-48-9 ]

Product Details of [ 153559-48-9 ]

CAS No. :	153559-48-9	MDL No. :	MFCD16620614
Formula :	C₂₅H₃₀O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VSMOGQLTPWIBNI-UHFFFAOYSA-N
M.W :	362.50	Pubchem ID :	10384066
Synonyms :

Calculated chemistry of [ 153559-48-9 ]

Physicochemical Properties

Num. heavy atoms :	27
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.4
Num. rotatable bonds :	4
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	113.69
TPSA :	26.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-2.88 cm/s

Lipophilicity

Log Po/w (iLOGP) :	4.45
Log Po/w (XLOGP3) :	7.93
Log Po/w (WLOGP) :	6.19
Log Po/w (MLOGP) :	5.47
Log Po/w (SILICOS-IT) :	7.17
Consensus Log Po/w :	6.24

Druglikeness

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

Water Solubility

Log S (ESOL) :	-7.15
Solubility :	0.0000258 mg/ml ; 0.0000000711 mol/l
Class :	Poorly soluble
Log S (Ali) :	-8.33
Solubility :	0.00000169 mg/ml ; 0.0000000046 mol/l
Class :	Poorly soluble
Log S (SILICOS-IT) :	-8.41
Solubility :	0.00000141 mg/ml ; 0.0000000039 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.26

Safety of [ 153559-48-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 153559-48-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 153559-48-9 ]
Downstream synthetic route of [ 153559-48-9 ]

[ 153559-48-9 ] Synthesis Path-Upstream 1~18

1
[ 153559-48-9 ]
[ 153559-49-0 ]

Reference： [1] Journal of Medicinal Chemistry, 1994, vol. 37, # 18, p. 2930 - 2941
[2] Journal of Medicinal Chemistry, 1995, vol. 38, # 17, p. 3368 - 3383
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 19, p. 5950 - 5966
[5] Patent: WO2011/103321, 2011, A1, . Location in patent: Page/Page column 19
[6] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782
[7] Patent: WO2011/141928, 2011, A1, . Location in patent: Page/Page column 19

2
[ 1779-49-3 ]
[ 153559-45-6 ]
[ 153559-48-9 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium amide In tetrahydrofuran	Rectangular plates of compound 35 were found suitable for X-ray diffraction, and a study was conducted. To complete the synthesis of bexarotene, the Friedel-Crafts acylation of 35, by crude mono-methyl-terephthaloyl chloride (36), gave ketone (37) which was converted to alkene ester(38) by a Wittig reaction, and ester 38 was saponified by potassium hydroxide followed by acidification with aqueous hydrochloric acid to give bexarotene (39) (Scheme 2).

Reference： [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 19, p. 5950 - 5966
[2] Patent: WO2011/103321, 2011, A1, . Location in patent: Page/Page column 19
[3] Journal of Medicinal Chemistry, 1994, vol. 37, # 18, p. 2930 - 2941
[4] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712
[5] Journal of Medicinal Chemistry, 1995, vol. 38, # 17, p. 3368 - 3383

3
[ 67-56-1 ]
[ 153559-49-0 ]
[ 153559-48-9 ]

Reference： [1] Journal of Controlled Release, 2018, vol. 286, p. 10 - 19

4
[ 169126-64-1 ]
[ 199188-36-8 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782

5
[ 1779-49-3 ]
[ 153559-45-6 ]
[ 1349659-53-5 ]
[ 1349659-55-7 ]
[ 1349659-56-8 ]
[ 1349659-57-9 ]
[ 153559-48-9 ]

Reference： [1] Patent: WO2011/141928, 2011, A1, . Location in patent: Page/Page column 19

6
[ 6683-48-3 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782
[2] Journal of Medicinal Chemistry, 1995, vol. 38, # 17, p. 3368 - 3383
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712
[4] Journal of Medicinal Chemistry, 1994, vol. 37, # 18, p. 2930 - 2941
[5] Patent: WO2011/103321, 2011, A1,

7
[ 153559-49-0 ]
[ 74-88-4 ]
[ 153559-48-9 ]

Reference： [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 31, p. 9785 - 9789[2] Angew. Chem., 2018, vol. 130, # 31, p. 9933 - 9937,5

8
[ 110-03-2 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782
[2] Journal of Medicinal Chemistry, 1994, vol. 37, # 18, p. 2930 - 2941
[3] Patent: WO2011/103321, 2011, A1,

9
[ 6223-78-5 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782
[2] Patent: WO2011/103321, 2011, A1,

10
[ 7377-26-6 ]
[ 153559-48-9 ]

Reference： [1] Journal of Medicinal Chemistry, 1995, vol. 38, # 17, p. 3368 - 3383

11
[ 29020-85-7 ]
[ 153559-48-9 ]

Reference： [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712

12
[ 5455-94-7 ]
[ 153559-48-9 ]

Reference： [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712

13
[ 167958-79-4 ]
[ 153559-48-9 ]

Reference： [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712

14
[ 167958-78-3 ]
[ 153559-48-9 ]

Reference： [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36, # 7, p. 701 - 712

15
[ 3609-53-8 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782

16
[ 119999-22-3 ]
[ 153559-48-9 ]

Reference： [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5772 - 5782

17
[ 1679-64-7 ]
[ 1349659-56-8 ]
[ 153559-48-9 ]

Reference： [1] Patent: WO2011/141928, 2011, A1,

18
[ 6683-48-3 ]
[ 1349659-56-8 ]
[ 1349659-57-9 ]
[ 153559-48-9 ]

Reference： [1] Patent: WO2011/141928, 2011, A1,

[ 153559-48-9 ] Synthesis Path-Downstream 1~30

1
[ 1779-49-3 ]
[ 153559-45-6 ]
[ 153559-48-9 ]

Yield	Reaction Conditions	Operation in experiment
69%		Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed PPh3MeBr (1715 mg, 4.80 mmol, 2.50 eq.), THF (10 ml_). This was followed by the addition of KHDMS (1 M) (5.1 ml_, 5.1 1 mmol, 2.66 eq.) dropwise with stirring at -30C. The resulting solution was stirred for 30 min at 0C. To this was added a solution of methyl 4-[(3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydronaphthalen-2-yl) carbonyl] benzoate (700 mg, 1.92 mmol, 1.00 eq.) in THF (7 ml_) dropwise with stirring at -30C. The resulting solution was stirred for 1 h at 0C. The reaction was then quenched by the addition of 20 ml_ of water at 0C. The resulting solution was extracted with 2x20 ml_ of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 c20 ml_ of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). This resulted in 480 mg (69%) of methyl 4-[1-(3, 5,5,8, 8-pentamethyl-5, 6,7,8- tetrahydronaphthalen-2-yl)ethenyl]benzoate as a light yellow solid.
66%	With sodium amide; In tetrahydrofuran;	Rectangular plates of compound 35 were found suitable for X-ray diffraction, and a study was conducted. To complete the synthesis of bexarotene, the Friedel-Crafts acylation of 35, by crude mono-methyl-terephthaloyl chloride (36), gave ketone (37) which was converted to alkene ester(38) by a Wittig reaction, and ester 38 was saponified by potassium hydroxide followed by acidification with aqueous hydrochloric acid to give bexarotene (39) (Scheme 2).

Reference： [1]Patent: WO2019/169270,2019,A1 .Location in patent: Paragraph 0141; 0143
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 5950 - 5966
[3]Patent: WO2011/103321,2011,A1 .Location in patent: Page/Page column 19
[4]Journal of Medicinal Chemistry,1994,vol. 37,p. 2930 - 2941
[5]Journal of labelled compounds and radiopharmaceuticals,1995,vol. 36,p. 701 - 712
[6]Journal of Medicinal Chemistry,1995,vol. 38,p. 3368 - 3383

2
[ 153559-48-9 ]
[ 153559-49-0 ]

Yield	Reaction Conditions	Operation in experiment
78%		Rectangular plates of compound 35 were found suitable for X-ray diffraction, and a study was conducted. To complete the synthesis of bexarotene, the Friedel-Crafts acylation of 35, by crude mono-methyl-terephthaloyl chloride (36), gave ketone (37) which was converted to alkene ester(38) by a Wittig reaction, and ester 38 was saponified by potassium hydroxide followed by acidification with aqueous hydrochloric acid to give bexarotene (39) (Scheme 2).
		Example 3: Preparation of bexaroteneTo suspension of methyl 4-[l-(5,6,7,8-tetrahydro-3, 5,5,8, 8-pentamethyl-2-naphthalenyl)-l- ethenyljbenzoate (100 g) in methanol (1000 ml), 5N aqueous potassium hydroxide (170 ml) was added at 25-30C and the reaction mixture was refluxed for 8 hours. After completion of reaction (monitored by HPLC), reaction mass was cooled to 35-40 C and washed with 50% ethyl acetate: n-heptane mixture (2 x 500 ml). The organic layer was discarded and the aqueous layer was cooled to 10-15 C. Thereafter pH of aqueous layer was adjusted to 1-2 by addition of concentrated hydrochloric acid (100 ml). The resulting mixture was then stirred at 20-25C, stirred for 1 hour and precipitated solid was filtered. The resulting solid was slurry washed with demineralized water (100 ml), centrifuged and dried to give 84.6 g of title compound having purity 98.89 %, none of the impurities C, D, E, F were detected by HPLC

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 2930 - 2941
[2]Journal of Medicinal Chemistry,1995,vol. 38,p. 3368 - 3383
[3]Journal of labelled compounds and radiopharmaceuticals,1995,vol. 36,p. 701 - 712
[4]Journal of Medicinal Chemistry,2009,vol. 52,p. 5950 - 5966
[5]Patent: WO2011/103321,2011,A1 .Location in patent: Page/Page column 19
[6]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782
[7]Patent: WO2011/141928,2011,A1 .Location in patent: Page/Page column 19

3
[ 75-11-6 ]
[ 153559-48-9 ]
methyl 4-<1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl>benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%		Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed Et2Zn (1M) (1.4 ml_, 1.4 mmol, 10.00 eq.), DCM (2 ml_). This was followed by the addition of TFA (157 mg, 1.39 mmol, 10.00 eq.) dropwise with stirring at 0C. The resulting solution was stirred for 30 min at 0C. To this was added CH2I2 (370 mg, 1.4 mmol, 10.00 equiv) dropwise with stirring at 0C. The resulting solution was stirred for 30 min at 0C. To the mixture was added a solution of methyl 4-[1-(3,5,5,8,8-pentamethyl- 5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl]benzoate (50 mg, 0.14 mmol, 1.00 equiv) in DCM (1 ml_) dropwise with stirring at 0C. The resulting solution was stirred for 2 h at room temperature. The reaction was then quenched by the addition of 20 mL of water at 0C. The solid was filtered out. The resulting solution was extracted with 2x20 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1 c20 ml of brine and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). This resulted in 10 mg (19%) of methyl 4-[1-(3, 5,5,8, 8-pentamethyl-5, 6,7, 8-tetrahydronaphthalen-2- yl)cyclopropyl]benzoate as a white solid.

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3146 - 3155
[2]Patent: WO2019/169270,2019,A1 .Location in patent: Paragraph 0141; 0144

4
[ 153559-48-9 ]
methyl 4-<2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)oxiranyl>benzoate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3146 - 3155

5
[ 169126-64-1 ]
[ 199188-36-8 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782

6
[ 110-03-2 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782
[2]Journal of Medicinal Chemistry,1994,vol. 37,p. 2930 - 2941
[3]Patent: WO2011/103321,2011,A1

7
[ 6223-78-5 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782
[2]Patent: WO2011/103321,2011,A1
[3]Patent: WO2019/169270,2019,A1

8
[ 3609-53-8 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782

9
[ 6683-48-3 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782
[2]Journal of Medicinal Chemistry,1995,vol. 38,p. 3368 - 3383
[3]Journal of labelled compounds and radiopharmaceuticals,1995,vol. 36,p. 701 - 712
[4]Journal of Medicinal Chemistry,1994,vol. 37,p. 2930 - 2941
[5]Patent: WO2011/103321,2011,A1
[6]Patent: WO2019/169270,2019,A1

10
[ 119999-22-3 ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782

11
C₁₀H₁₁C₅H₁₀B(C₃H₇O)2 [ No CAS ]
[ 153559-48-9 ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 5772 - 5782

12
[ 7377-26-6 ]
[ 153559-48-9 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3368 - 3383

13
[ 153559-48-9 ]
LGD₁₂₆₈ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3146 - 3155
[2]Patent: WO2019/169270,2019,A1

14
[ 153559-48-9 ]
4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)epoxy]benzoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3146 - 3155

15
[ 29020-85-7 ]
[ 153559-48-9 ]