5-(tert-Butyl)isobenzofuran-1,3-dione | Furans

CAS No. :	32703-79-0
Formula :	C₁₂H₁₂O₃
M.W :	204.22
SMILES Code :	O=C1OC(C2=C1C=CC(C(C)(C)C)=C2)=O
MDL No. :	MFCD00060127
InChI Key :	YLJYVKLZVHWUCT-UHFFFAOYSA-N
Pubchem ID :	122930

Safety of [ 32703-79-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 32703-79-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	15
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	55.46
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	43.37 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.94
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.27
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.29
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.85
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.0
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.67

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.4
Solubility	0.082 mg/ml ; 0.000402 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.86
Solubility	0.0285 mg/ml ; 0.00014 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.68
Solubility	0.0425 mg/ml ; 0.000208 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.22 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	2.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.05

Application In Synthesis of [ 32703-79-0 ]

* 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.

Downstream synthetic route of [ 32703-79-0 ]

[ 32703-79-0 ] Synthesis Path-Downstream 1~54

1
[ 110-86-1 ]
[ 32703-79-0 ]
[ 121-47-1 ]
3-(5-tert-butyl-1,3-dioxo-isoindolin-2-yl)-benzenesulfonic acid ; compound with pyridine [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

2
[ 67-56-1 ]
[ 32703-79-0 ]
[ 57091-50-6 ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

3
[ 253185-03-4 ]
[ 32703-79-0 ]
[ 106679-40-7 ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

4
[ 32703-79-0 ]
[ 119-90-4 ]
4,4'-bis-(5-tert-butyl-1,3-dioxo-isoindolin-2-yl)-3,3'-dimethoxy-biphenyl [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

5
[ 32703-79-0 ]
[ 83-32-9 ]
[ 855201-87-5 ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

6
[ 32703-79-0 ]
[ 106-48-9 ]
[ 857758-57-7 ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

7
[ 32703-79-0 ]
[ 106-48-9 ]
6-tert-butyl-1-chloro-4-hydroxy-anthraquinone [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

8
[ 32703-79-0 ]
[ 62-53-3 ]
5-(tert-butyl)-2-phenylisoindoline-1,3-dione [ No CAS ]

References: [1]Journal of Organic Chemistry,2019.
[2]Journal of the Chemical Society,1952,p. 680,683.
[3]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1648 - 1655.

9
[ 32703-79-0 ]
[ 123-31-9 ]
[ 857758-57-7 ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

10
[ 32703-79-0 ]
[ 108-88-3 ]
5-tert-butyl-2-p-toluoyl-benzoic acid [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

11
[ 32703-79-0 ]
[ 74-89-5 ]
4-(1,1-dimethylethyl)-N-methylphthalimide [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

12
[ 32703-79-0 ]
[ 108-46-3 ]
5-tert-butyl-3',6'-dihydroxy-spiro[phthalan-1,9'-xanthen]-3-one [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

13
[ 32703-79-0 ]
[ 50727-07-6 ]

References: [1]Canadian Journal of Chemistry,1985,vol. 63,p. 121 - 128.
[2]Journal of the Chemical Society,1952,p. 680,683.
[3]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4159 - 4162.

14
[ 7397-06-0 ]
[ 32703-79-0 ]
4-tert-butyl-2-methyl-benzoic acid-anhydride [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

15
[ 14236-13-6 ]
[ 32703-79-0 ]

References: [1]Chemische Berichte,1982,vol. 115,p. 2836 - 2853.
[2]Russian Journal of Organic Chemistry,1994,vol. 30,p. 818 - 821.
Zhurnal Organicheskoi Khimii,1994,vol. 30,p. 770 - 773.
[3]Journal of the American Chemical Society,1954,vol. 76,p. 1108.
[4]Journal of the Chemical Society,1943,p. 144.

16
[ 7397-06-0 ]
[ 766-39-2 ]
[ 32703-79-0 ]
[ 74186-27-9 ]
[ 95-47-6 ]
4-tert-butyl-phthalaldehyde [ No CAS ]

References: [1]Journal of applied chemistry of the USSR,1980,vol. 53,p. 353 - 355.
Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation),1980,vol. 53,p. 418 - 420.

17
[ 2876-35-9 ]
[ 108-31-6 ]
[ 85-44-9 ]
[ 32703-79-0 ]

References: [1]Journal of applied chemistry of the USSR,1980,vol. 53,p. 353 - 355.
Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation),1980,vol. 53,p. 418 - 420.

18
[ 32703-79-0 ]
methyl 3-amino-3-(3',4'-dimethoxyphenyl)propionate hydrochloride [ No CAS ]
3-(5-tert-Butyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3,4-dimethoxy-phenyl)-propionic acid methyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3238 - 3240.

19
[ 32703-79-0 ]
[ 212512-28-2 ]
9-tert-Butyl-2,4,6-trimethoxy-isoindolo[2,1-a]quinoline-5,11-dione [ No CAS ]
8-tert-Butyl-2,4,6-trimethoxy-isoindolo[2,1-a]quinoline-5,11-dione [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 735 - 742.

20
[ 110-86-1 ]
[ 32703-79-0 ]
sulfanyloic acid [ No CAS ]
4-(5-tert-butyl-1,3-dioxo-isoindolin-2-yl)-benzenesulfonic acid ; compound with pyridine [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

21
[ 32703-79-0 ]
[ 109-55-7 ]
[ 505059-17-6 ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1031 - 1040.
[2]Pharmaceutica Acta Helvetiae,2000,vol. 74,p. 149 - 155.

22
[ 32703-79-0 ]
[ 374592-80-0 ]

References: [1]Helvetica Chimica Acta,2001,vol. 84,p. 2051 - 2063.
[2]Angewandte Chemie - International Edition,2014,vol. 53,p. 11325 - 11328.
Angew. Chem.,.
[3]Angewandte Chemie - International Edition,2019,vol. 58,p. 13954 - 13960.
Angew. Chem.,2019,vol. 131,p. 14092 - 14098,7.

23
[ 32703-79-0 ]
C₃₆H₅₂N₄O₄⁽²⁺⁾*2Br^(1-) [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1031 - 1040.
[2]Pharmaceutica Acta Helvetiae,2000,vol. 74,p. 149 - 155.

24
[ 32703-79-0 ]
C₄₀H₆₀N₄O₄⁽²⁺⁾*2Br^(1-) [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1031 - 1040.

25
[ 32703-79-0 ]
[ 60070-04-4 ]

References: [1]Helvetica Chimica Acta,2001,vol. 84,p. 2051 - 2063.

26
[ 32703-79-0 ]
7-(tert-butyl)-1,2,4,5-tetrahydro-3H-benzocyclohepten-3-one [ No CAS ]

References: [1]Helvetica Chimica Acta,2001,vol. 84,p. 2051 - 2063.

27
[ 32703-79-0 ]
[ 374592-81-1 ]

References: [1]Helvetica Chimica Acta,2001,vol. 84,p. 2051 - 2063.

28
[ 32703-79-0 ]
8-tert-Butyl-2,4,6-trihydroxy-isoindolo[2,1-a]quinoline-5,11-dione [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 735 - 742.

29
[ 32703-79-0 ]
9-tert-Butyl-2,4,6-trihydroxy-isoindolo[2,1-a]quinoline-5,11-dione [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 735 - 742.

30
[ 95-47-6 ]
saturated hydriodic acid [ No CAS ]
[ 32703-79-0 ]

References: [1]Russian Journal of Organic Chemistry,1994,vol. 30,p. 818 - 821.
Zhurnal Organicheskoi Khimii,1994,vol. 30,p. 770 - 773.

31
[ 7397-06-0 ]
[ 32703-79-0 ]

References: [1]Russian Journal of Organic Chemistry,1994,vol. 30,p. 818 - 821.
Zhurnal Organicheskoi Khimii,1994,vol. 30,p. 770 - 773.
[2]Chemische Berichte,1982,vol. 115,p. 2836 - 2853.

32
[ 32703-79-0 ]
[ 18798-85-1 ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

33
[ 95-47-6 ]
[ 32703-79-0 ]

References: [1]Journal of the Chemical Society,1952,p. 680,683.

34
[ 91-20-3 ]
[ 32703-79-0 ]

References: [1]Journal of the American Chemical Society,1954,vol. 76,p. 1108.

35
[ 32703-79-0 ]
7-tert-butyl-1,2-dihydro-cyclopenta[cd]pleiadene-5,10-dione [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

36
[ 32703-79-0 ]
9-tert-butyl-7,12-dioxo-7,12-dihydro-pleiadene-3,4-dicarboxylic acid-anhydride [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

37
[ 32703-79-0 ]
1,4-diamino-6-tert-butyl-anthraquinone [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.
[2]Journal of the Chemical Society,1952,p. 1368,1372.

38
[ 32703-79-0 ]
4-tert-butyl-2-(7-oxo-7H-benzo[de]benz[4,5]imidazo[2,1-a]isoquinoline-3-carbonyl)-benzoic acid [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

39
[ 32703-79-0 ]
4-tert-butyl-2-(1,3-dioxo-1H,3H-benz[de]isochromene-6-carbonyl)-benzoic acid [ No CAS ]

References: [1]Journal of the Chemical Society,1952,p. 1368,1372.

40
[ 3905-64-4 ]
[ 32703-79-0 ]

References: [1]Journal of the American Chemical Society,1954,vol. 76,p. 1108.

41
[ 31592-22-0 ]
[ 32703-79-0 ]

References: [1]Journal of the American Chemical Society,1954,vol. 76,p. 1108.

42
[ 253185-03-4 ]
[ 32703-79-0 ]
[ 106679-32-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	aluminum (III) chloride; at 0 - 20℃;	Into a 500 ml three-necked flask, 36 g (176 mmole) of <strong>[32703-79-0]4-t-butylphthalic anhydride</strong>, 27 g (200 mmole) of t-butylbenzene and 100 ml of dichloroethane were placed under a stream of argon and cooled to 0C. To the obtained mixture, 56 g (420 mmole) of aluminum chloride was slowly added. After the addition was completed, the resultant mixture was stirred at the room temperature for one night. After the reaction was completed, ice was added slowly, and then concentrated hydrochloric acid was added. The formed precipitates were separated by filtration and washed well with water, and 32 g of the benzoic acid compound of the object compound was obtained (the yield: 54%; a white powder).

References: [1]Patent: EP1440959,2004,A1 .Location in patent: Page 21-22.

43
[ 565471-96-7 ]
[ 32703-79-0 ]
[ 565472-23-3 ]

Yield	Reaction Conditions	Operation in experiment
		(26) Ethyl 3-(5-t-butyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate Ethyl 3-(5-t-butyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]-dioxolan-2-yl)propionate was prepared (0.54 g, 35%) in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.80 g, 3.94 mmol) and <strong>[32703-79-0]4-t-butylphthalic anhydride</strong> (0.88 g, 4.33 mmol), and the obtained product was identified with the following NMR data. 1H NMR (CDCl3, 300 MHz) delta 7.78 (s, 1H. ph), 7.64 (dd, 2H. ph, J=12.8 Hz, J=1.3 Hz), 4.07-3.87 (m, 8H, acetal H, -CHCH2NPht, -OCH2CH3), 3.21 (m, 1H, -CHCH2NPht), 1.44 (s, 3H, CH3), 1.29 (s, 9H, C(CH3)3), 1.10 (t, 3H, -OCH2CH3, J=7.1 Hz) 13C NMR (CDCl3, 300 MHz) 170.8, 168.7, 158.9, 132.6, 131.3, 129.7, 123.4, 120.8, 109.0, 65.3, 65.1, 31.3, 51.9, 36.9, 36.1, 31.5, 22.1, 14.4.

References: [1]Patent: US2003/139464,2003,A1 .

44
[ 565471-95-6 ]
[ 32703-79-0 ]
[ 565472-05-1 ]

Yield	Reaction Conditions	Operation in experiment
		(8) Methyl 3-(5-t-butyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate Methyl 3-(5-t-butyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]-dioxolan-2-yl)propionate was prepared (0.14 g, 14%) in the same manner as described in the above example 5 (1) from methyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.50 g, 2.64 mmol) and <strong>[32703-79-0]4-t-butylphthalic anhydride</strong> (0.70 g, 3.43 mmol), and the obtained product was identified with the following NMR data. 1H NMR (CDCl3, 300 MHz) delta 7.86 (s, 1H, ph), 7.73 (m, 2H, ph), 3.99 (m, 6H, -CHCH2NPht, acetal H), 3.58 (s, 3H, -CO2CH3), 3.28 (dd, 1H, -CHCH2NPht, J=8.3 Hz, J'=6.5 Hz), 1.50 (s, 3H, -COCH3, 1.33 (s, 9H, -C(CH3)3) 13C NMR (CDCl3, 300 MHz) delta 173.0, 171.6, 168.3, 168.4, 158.9, 156.6, 155.1, 134.4, 130.9, 129.7, 127.9, 109.0, 65.3, 62.2, 60.3, 52.5, 36.9, 61.5, 22.1, 14.5.

References: [1]Patent: US2003/139464,2003,A1 .

45
[ 32703-79-0 ]
[ 24544-04-5 ]
5-tert-butyl-N-(o,o'-diisopropylphenyl)phthalimide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In hexane; dichloromethane; ethyl acetate;	Synthesis Example 10 Synthesis of N-(2,6-diisopropylphenyl)-5-tert-butyl phthalimide (Compound No.173 as Described Hereinafter) 0.605 g of <strong>[32703-79-0]4-tert-butylphthalic anhydride</strong> and 0.630 g of 2,6-diisopropylaniline were mixed, and the mixture was reacted at a temperature of 200 C. for 1 hour. After the reaction was finished, the reaction mixture was dissolved in ethyl acetate, washed with sodium hydrogen carbonate aqueous solution, washed with water, and washed with saturated aqueous sodium chloride. Then, it was dried over anhydrous magnesium sulfate and subjected to filtration. The filtrate was concentrated and dried and solidified. Then, it was recrystallized by using a mixture of hexane and dichloromethane, to obtain 0.7055 g of the specified substance having a melting point of 234.0-234.8 C.

References: [1]Patent: US6429212,2002,B1 .

46
[ 219508-60-8 ]
[ 32703-79-0 ]
[ 219507-25-2 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;	EXAMPLE 17 Preparation of N-(6-Indazolyl)-2-(5-t-butyl-1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)benzamide To a stirring solution of 2-amino-N-(1-Boc-6-indazolyl)benzamide (1 g, 2.8 mmol) in THF (30 mL) was added <strong>[32703-79-0]4-t-butylphthalic anhydride</strong> (1.2 g, 5.9 mmol) and the solution was heated to reflux. After 72 h, the vessel was cooled and the volume was reduced to about 10 mL in vacuo. The mixture was diluted with diethyl ether (20 mL) and after sonication, a white solid was collected. This solid was processed by methods substatially equivalent to those described in Example 2-F to give 200 mg of N-(6-indazolyl)-2-(5-t-butyl-1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)benzamide. 1H NMR FD-MS, m/e 438.2 (M+) Anal. for C26H22N4O3.0.5H2O: Calc: C, 69.79; H, 5.18; N, 12.51. Found: C, 69.69; H, 5.48; N, 11.56.

References: [1]Patent: US6372759,2002,B1 .

47
[ 247157-95-5 ]
[ 32703-79-0 ]
[ 886592-55-8 ]
[ 886592-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; dichloromethane; for 72h;	EXAMPLE 18; 5-tert-Butyl-2-{2-r2-(4-methylpiperazin-1-yl)phenv?ethyl>isoindole-1,3-dione.PP5 (0.10 g, 0.455 mmol) and <strong>[32703-79-0]4-t-butylphthalic anhydride</strong> (0.094 g, 0.460 mmol) were stirred vigorously in CH2CI2 (6 ml_)/ THF (4 ml_) for 3 days. The reaction was concentrated and the residual solid was triturated with EtOAc to give 108 mg (56%) of a 1 :1 mixture of regioisomeric acids, 4-tert-butyl-N-{2-[2-(4-methylpiperazin-1 -yl)phenyl]-ethyl}-phthalamic acid and 5-tert-butyl-N-{2-[2-(4-methylpiperazin-1-yl)phenyl]-ethyl}-phthalamic acid. This mixture was refluxed in glacial HOAc (3 ml.) for 4 hrs, cooled and concentrated to give 70 mg of orange oil. Chromatography with 10% MeOH/ EtOAc gave 33mg (35%) of Example 18 as an oil, the HCI salt of which had: mp 153-157C; NMR (MeOH-d4) 7.85-7.82 (m, 2H), 7.72 (d, J =7.9 Hz, 1 H), 7.21-7.19 (m, 3H), 7.05 (m, 1 H), 3.89, (t, J = 7.5 Hz, 2H), 3.59-3.56 (m, 2H),3.48-3.42 (m, 3H), 3.28-3.14 (m, 3H), 3.01 (s, 3H), 2.99-2.95 (m, 2H) 1.36 (s, 9H).

References: [1]Patent: WO2006/48727,2006,A1 .Location in patent: Page/Page column 56.

48
[ 1445-45-0 ]
[ 32703-79-0 ]
dimethyl 4-amino-5-t-butylphthalate [ No CAS ]
dimethyl 4-nitro-5-t-butylphthalate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; nitric acid; In methanol;	EXAMPLE I Preparation of dimethyl 4-amino-5-t-butylphthalate A mixture of 70 g. of <strong>[32703-79-0]4-t-butylphthalic anhydride</strong> and 65 ml. of concentrated sulfuric acid was stirred at room temperature while adding 60 ml. of 90% nitric acid. The rate of addition was slow and controlled such that the temperture of the mixture did not go above 60 C, although the nitration reaction can be carried out at any temperature within the range of -20 to 120 C. After the addition was complete (2 hours) an additional 50 ml. of concentrated nitric acid was added over a 20 minute period. The reaction mixture was allowed to cool and was then stirred for 4 days. The mixture was then poured onto 800 g. of ice and the layers allowed to separate. The upper layer (water and acid) was decanted off and the residue dissolved in 500 ml. of ether. The ether solution was washed five times with 100 ml. of water, dried with MgSO4, filtered, and the ether removed under reduced pressure. The residual oil was esterified with 150 ml. of trimethyl orthoacetate by mixing the two and distilling off methanol, methyl acetate, and the excess reagent. The crude product was mixed with 400 ml. of methanol and cooled to 10 C. for 20 hours. Filtering and drying gave 33.2 g. of crystalline material. Recrystallization from methanol (125 ml.) gave 30.1 g. of pure dimethyl 4-nitro-5-t-butylphthalate, m.p. 80 -81 C.

References: [1]Patent: US4078142,1978,A .

49
[ 32703-79-0 ]
[ 57-13-6 ]
tin(ll) chloride [ No CAS ]
[ 83218-80-8 ]

References: [1]Chemische Berichte,1982,vol. 115,p. 2836 - 2853.

50
[ 32703-79-0 ]
copper(l) chloride [ No CAS ]
[ 39001-64-4 ]

References: [1]Monatshefte fur Chemie,1986,vol. 117,p. 475 - 490.

51
[ 32703-79-0 ]
[ 7646-79-9 ]
[ 70619-85-1 ]

References: [1]Inorganic Chemistry,1984,vol. 23,p. 1065 - 1071.

52
tin(II) iodide [ No CAS ]
[ 32703-79-0 ]
[ 57-13-6 ]
[ 83218-81-9 ]

References: [1]Chemische Berichte,1982,vol. 115,p. 2836 - 2853.

53
[ 32703-79-0 ]
nickel dichloride [ No CAS ]
[ 146442-33-3 ]
[ 146442-34-4 ]

References: [1]Journal of the Chemical Society. Chemical communications,1993,p. 58 - 60.

54
[ 32703-79-0 ]
[ 141-43-5 ]
[ 104638-94-0 ]

References: [1]European Journal of Medicinal Chemistry,2009,vol. 44,p. 1650 - 1663.

Historical Records

Technical Information

• Acyl Group Substitution • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Ester Cleavage • Fischer Indole Synthesis • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions with Organometallic Reagents • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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CAS No.: 32703-79-0

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CAS No.: 32703-79-0

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[ 32703-79-0 ] Synthesis Path-Downstream 1~54

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