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Structure of 89878-14-8

Chemical Structure| 89878-14-8

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Product Details of [ 89878-14-8 ]

CAS No. :89878-14-8
Formula : C9H14BN
M.W : 147.03
SMILES Code : CCB(CC)C1=CC=CN=C1
MDL No. :MFCD00012348
InChI Key :OJKBCQOJVMAHDX-UHFFFAOYSA-N
Pubchem ID :642851

Safety of [ 89878-14-8 ]

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

Computational Chemistry of [ 89878-14-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.44
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 50.97
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.09
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.82
Log Po/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.

1.8
Log Po/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

1.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.6

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.9
Solubility 0.183 mg/ml ; 0.00125 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.

-3.03
Solubility 0.138 mg/ml ; 0.000937 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

-3.63
Solubility 0.0346 mg/ml ; 0.000236 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

No
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.

-5.0 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

2.0
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

1.0 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)

2.76

Application In Synthesis of [ 89878-14-8 ]

* 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 [ 89878-14-8 ]

[ 89878-14-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 32138-69-5 ]
  • [ 89878-14-8 ]
  • [ 154229-19-3 ]
YieldReaction ConditionsOperation in experiment
74.1% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In ethanol; water; at 70 - 75℃; for 22h; 40 g of compound VIII, dissolved in 1200 ml of ethanol, 15.5 g of diethyl (3-pyridyl) borane, 720 mg of bis (triphenylphosphine) palladium dichloride, and 53.6 g of sodium carbonate were added to 240 ml of water The solution was heated to 70-75 C for 22 hours. The mixture was cooled and filtered. The filtrate was concentrated under reduced pressure. The mixture was stirred at room temperature with 1200 ml of water and filtered to give crude IX. HPLC purity: 86.1% X 0.9%.The crude cake was stirred at about 65 C for 1 hour, cooled and filtered. The filter cake was dried under reduced pressure at about 50 C to give Compound IX 26 g; HPLC purity: 98.6%, containing impurities X0.5% ; Yield: 74.1%.
72.1% With bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; for 24h;Reflux; Autoclave; Large scale; 100L in the reaction kettle, by adding KOH (3.36 kg, 60 . 0mol) and 32 kg water stirring dissolves clear, adding THF32L, 17-iodo-androst -5,16-diene -3 beta- mellow vinegar ester (7.96 kg, 20 . 0mol), b (triphenylphosphine) palladium chloride [Pd (PPh3)2Cl2] (140g, 0.2mol), diethyl (3-pyridyl) borane (2.94 kg, 20 . 0mol) heating to reflux, stirring for 24 hours. Decompression concentrating reaction solution, removing THF, precipitating a large amount of solid. Then added to the reaction kettle 80L water, continue to stir 20 minutes. Centrifugal separation to obtain a large number of light gray color solid, solid to pH7-8 eluviation of a large amount of water, the resulting solid for 50-60 C drying, to crude abiraterone 7.23 kg. 2.1 purification of crude abiraterone 1 produced in the added to crude abiraterone 200L in the reaction kettle, add isopropanol 145L, heating and stirring, to be completely dissolve, then adding activated carbon 723g reflux decolourizations and a half hours, to take advantage of heat filtering, removing the activated carbon. Adding the filtrate 70L water, stirring separating out crystal, when the system is cooled to the room temperature to continue stirring 2 hours, and then cooling to-5-5 C stirring 8 hours. Centrifugal drying, with 10L freezing of isopropanol and water mixed solution (volume ratio of 1:1) washing the filter cake, getting white crystalline solid, for 50-60 C vacuum drying 5 hours, shall be abiraterone 5.74 kg, yield quality of 72.1%.
71.2% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; at 80℃;Inert atmosphere; At room temperature, under nitrogen protection, a mixed solution of tetrahydrofuran (30 mL) and water (10 mL) was added to a mixture of 17-iodoandrost-5,16-diene-3beta-alcohol (2.00 g, 5.02 mmol), 3-diethylboranylpyridine (900 mg, 6.02 mmol), bis(triphenylphosphine)palladium (II) chloride (180 mg, 0.26 mmol), and sodium carbonate (2.12 g, 20.08 mmol). The reaction solution was kept at 80C overnight (16 hrs). After cooled to room temperature, the reaction was quenched with water (25 mL), and filtered through celite, and the filtrate was extracted with ethyl acetate (60 mL x 3). The organic layers were combined, washed with brine (60 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the concentrate was purified by column chromatography (eluent: PE/EtOAc (v/v) = 1/1) to give 1.25 g of a pale yellow solid, yield: 71.2%, purity: 96.25%, LC -MS (APCI): m/z = 350.1 (M+1)+. 1H NMR (300 MHz, MeOD-d4) (delta/ppm) 8.54 (s, 1H), 8.40 (d, J=4.0 Hz, 1H), 7.86 (d, J=8.1 Hz, 1H), 7.39 (dd, J=7.8, 4.9Hz, 1H), 6.10(s, 1H), 5.41 (d, J=5.0Hz, 1H), 3.49-3.37 (m, 1H), 2.36-2.21 (m, 3H), 2.17 - 2.00 (m, 3H), 1.95-1.78 (m, 3H), 1.76-1.62 (m, 4H), 1.56-1.44 (m, 2H), 1.15-1.06 (m, 8H).
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; water; for 50h;Inert atmosphere; Reflux; 17-Iodoandrosta-5, 16-dien-3 -ol [Organic Preparations and Procedures Int., 29, 123- 134 (1997)] (90 g) in tetrahydrofuran (1.0 L), in an inert gas environment, is added with diethyl(3-pyridyl)borane (40 g), bis(triphenylphosphine)palladium II chloride (1.5 g) and a 2M sodium carbonate aqueous solution (450 mL). The resulting mixture is refluxed until the reaction is complete (about 50 h), then cooled to room temperature, and tetrahydrofuran (1 L) is added. The organic phase is separated and washed with a 5% sodium chloride aqueous solution, then dried over magnesium sulphate. The residue is then concentrated under vacuum, and the concentrate is taken up in tert-butyl methyl ether (about 600 mL) to obtain a sandy solid, which is isolated by filtration (at 0-5 C) and dried under vacuum at 40C for 16 h. The crude abiraterone thus obtained (about 64 g) is taken up in methylene chloride (350 mL), and the resulting mixture, cooled to a temperature of -5 to 0C, is added with acetic anhydride (130 mL) and then with triethylamine (190 mL), maintaining the temperature at -5 to 0C. The mixture is stirred at room temperature for about 25 h, then washed with water and concentrated under vacuum, taking up the residue in acetone (250 mL). The resulting solid is isolated by filtration (at 0-5C) and dried under vacuum at 40C for 16 h (about 46 g; purity: 82.5%; assay: about 73%). A second fraction of crude abiraterone acetate, as an oil, is obtained by concentration of the mother liquor under vacuum (54 g, purity: 74%, assay: about 45%).
81.5 g (3f)-l7-iodo-androsta-5,16-dien-3-ol compound of formula-2 (100 gin) was added to a mixture of tetrahydrofuran (700 ml) and methanol (500 ml) at 25-30C and stirred the reaction mixture for 10 mm at the same temperature. 3-(diethylboryl)pyridune compound of formula-3 (42.5 gm) and Pd(PPh3)2C12 (2 gin) were added to the reaction mixture at 25-30Cand stirred for 10 mm at the same temperature. Aq.sodium carbonate solution (prepared by dissolving 148.5 gm of sodium carbonate in 700 ml of water) was slowly added to the reaction mixture at 25-30C. Heated the reaction mixture to 60-70C and stirred for 2 brs at the same temperature. After completion of the reaction, reduced the temperature of the reaction mixture to 25-30C. Dichioromethane and water were added to the reaction mixtureat 25-30C and stirred for 10 miii at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichioromethane. Combined the organic layers and dried over sodium sulfate. Charcoal (20 gm) was added to the organic layer at 25-30C and stirred for 2 hrs at the same temperature. Filtered the reaction mixture through hyflow bed and washed the hyflow bed with dichloromethane. Distilled off the solvent completely from the filtrate and co-distilled with ethyl acetate. Cooled the obtainedcompound to 25-30C, ethyl acetate (150 ml) was added and stirred the reaction mixture for10 mm at the same temperature. Pet ether (1500 ml) was added to the reaction mixture at25-30C and stirred for 15 mm at the same temperature. Further cooled the reaction mixture to 0-5C and stirred for 1 hr at the same temperature. Filtered the precipitated solid, washed with pet ether and then dried to get the title compound.Yield: 81.5 gm; Purity by HPLC: 99.36%; Water content by KFR: 0.5% w/w.
30 g With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In tetrahydrofuran; methanol; water; at 60 - 65℃; for 10h; A 2 lit round bottom flask fitted with a mechanical stirrer, thermometer socket was charged 30% methanol and tetrahydrofuran (1 lit), 17-Iodo-androsta-5,16-diene-3 -ol of Formula III (50 gm), aqueous sodium carbonate (53.2 gm dissolved in 300 ml water), bis (triphenyl phosphine)Pd (II) chloride (1.75 gm) and diethyl (3- pyridyl)borane (18.45 gm) at 25-30C and heated to 60-65C and stirred for 10 hr at same temperature. After completion of the reaction, cooled the reaction mass to 25- 35C and charged reaction mass in to 10% methanol in water (2.5 lit) at same .temperature and stirred for 2 hr at same temperature. Filtered the obtained solids and washed with water (100 ml); wet wt: 60 gm. The XRPD is set forth in Figure- 1 Palladium recovery: To a '2 lit round bottom flask charged 2-methoxy ethanol (1250 ml) and above wet compound (60 gm) at 25-35C and allowed to stir for 10 min. The reaction mass temperature was raised to 85-90C and allowed to stir for 2 hrs. Reaction mass cooled to 60-65 C and filtered to obtain palladium metal, distilled the obtained filterate up to 2 volumes remains in the flask under vacuum at 60-65C. Cooled the reaction mass to 25-35 C and stirred for 1 hr at same temperature. Filtered the obtained solids and washed with 2-methoxy ethanol (50 ml); wt: 35 gm. Purity by HPLC: 98% - - The XRPD is set forth in Figure-2- Purification of abiraterone: To a 2 lit round bottom flask charged the above obtained wet compound (35 gm) and tetrahydrofuran (800 ml) at 25-35C and heated to reflux. Filtered the clear solution through micron filter and distilled out the reaction mass to 2 volumes remains in the . flask at 45-50C. Cooled the reaction mass to 25-35C and stirred for 1 hr at same temperature. Filtered the obtained solids and washed with tetrahydrofuran (25 ml) and dryed under vacuum for lhr and dryed under vacuum at 45-50C for 6 hr to obtain pure abiraterone. Yield: 30 gm Purity by HPLC: 99.5% The XRPD is set forth in Figure-3.
39.2 kg With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 70 - 80℃;Large scale; The 110L NMP was added to the 3L three-necked flask with stirring followed by adding 7.5kg 17-iodoandrosta-5,16-dien-3beta-ol, 132g bis(triphenylphosphine)palladium chloride and 29.6kg diethyl (3-pyridyl)borane, and finally adding 500L 2mol / L Na2CO3 solution. Maintain the internal temperature of about 70-80 C, TLC monitored the reaction was complete. The reaction was cooled to room temperature, the reaction mixture was added to 220 L of water, stirred for 30min, filtered, washed with water. Blast drying, abiraterone was 39.2kg.
With potassium phosphate; palladium on activated charcoal; In N,N-dimethyl-formamide; at 90℃; for 6h; In 1000 ml of the magneton with stirring, of the reflux condensation tube of three compounds are added to a reaction flask 17 - iodine male steroid - 5, 16 - diene - 3 beta - hydroxy 39.8 g (0.10 muM, 1.0 equiv), diethyl (3 - pyridyl) borane 16.2 g (0.11 muM, 1.1 equiv), palladium/carbon (to palladium) 0.106 g (0.001 muM, 0 . 01 equiv), adding phosphoric acid potassium 31.8 g (0.15 muM, 1.5 equiv), adding N, N - dimethyl formamide 500 ml as the solvent, nitrogen replacement heating to 90 C reaction 6 hours. After the reaction, distilled under reduced pressure (the distillation temperature is 90 C, vacuum degree is -0.08 mpa) to remove the solvent, by adding dichloromethane 500 ml and triethylamine 11.1 g (0.11 muM, 1.1 equiv) solution, adding 4 - dimethyl aminopyridine 0.62 g (0.005 muM, 0 . 05 equiv) as catalyst, lowering the temperature to 0 C, slowly dropping vinegar anhydride 15.3 g (0.15 muM, 1.5 equiv), the end of the [...], raising the temperature to 25 C after three hours to continue the reaction after the palladium/carbon catalyst filter recovery, organic layer is 500 ml water, 500 mL1N sodium bicarbonate solution and then concentrated under reduced pressure (the distillation temperature is 30 C, vacuum degree is -0.07 mpa) to dry, adding 120 g acetone heating [...] after two hours the temperature slowly to 0 C to crystallize, get acetate 30.7 g, purity of 99.3%, the molar yield is 78.0%,

  • 2
  • Et2 [ No CAS ]
  • [ 32138-69-5 ]
  • [ 89878-14-8 ]
  • [ 154229-19-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; (c) 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol diethyl(3-pyridyl)borane (3.23g, 22 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 17-iodo-androsta-5,16-dien-3beta-ol (7.96g, 20 mmol) in THF (120ml) containing bis(triphenylphosphine)palladium (II) chloride (140mg. 0.2 mmol). An aqueous solution of sodium carbonate (2M, 50ml) was then added and the mixture heated, with stirring, by an oil bath at 80C for 48h, and allowed to cool. The mixture was partitioned between Et2 and water the organic phase was separated, dried (Na2O3 and twice concentrated from Et2 by evaporation to remove THF (with Et2). The residual solid was then washed with Et2 (100ml), the Et2 solution decanted off, and the remaining white solid recrystallized from toluene (3.94g, 56%). Notes
  • 3
  • [ 56427-54-4 ]
  • [ 89878-14-8 ]
  • [ 702682-38-0 ]
YieldReaction ConditionsOperation in experiment
97% With sodium carbonate; DavePhos;palladium diacetate; In tetrahydrofuran; water; for 6.0h;Heating / reflux; 5-chloro-2-methylbenzoic acid (5.04 g, 29.5 mmol) was dissolved in 100 mL ethanol in a 250 mL round bottom flask fitted with a water condenser. 0.5 mL concentrated sulfuric acid was added and the solution heated to reflux. The solution was heated for 48 h and cooled to ambient temperature. The ethanol was removed under reduced pressure. The resultant oil was taken up in 300 mL diethyl ether and washed with saturated aqueous sodium bicarbonate (2 x 300 mL). The organic layer was dried over NA2SO4, filtered and concentrated under reduced pressure to yield 5.12 (87%) of <strong>[56427-54-4]ethyl 5-chloro-2-methylbenzoate</strong> as a clear oil. 'H NMR (400 MHz, CDC13) 8 7.88 (d, 1H), 7.35 (dd, 1H), 7.18 (d, 1H), 4.36 (q, 2H), 2.56 (s, 3H), 1.40 (t, 3H). Ethyl 5-chloro-2-methylbenzoate (16.60 g, 83.56 mmol) and diethyl- (3- pyridyl) borane (13.52 g, 91.92 mmol) were dissolved in 100 mL tetrahydrofuran in a 500 mL round bottom flask equipped with a magnetic stirrer. Sodium carbonate (26.57 g, 250.69 mmol) and 50 mL water were added followed by palladium acetate (0.38g, 1.67 mmol) and (2'-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (AmPhos, 0.92g, 2.51 mmol) and 25 mL ethanol. The mixture was heated at reflux for 6 h then cooled to ambient temperature. The mixture was diluted with 600 mL water and extracted with diethyl ether (2 x 300 mL). The organic phases were combined and extracted with 1 N HCI (3 x 200 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (3 x 500 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 19.57g (97%) of ethyl 5- (3-PYRIDYL)-2-METHYLBENZOATE as a brown oil. MS (LC-MS) 242.2 (M + H) +. 'H NMR (400 MHz, CDCI3) 8 8.87 (d, 1H), 8.61 (dd, 1H), 8.13 (d, 1H), 7.95 (dd, 1 H), 7.62 (dd, 1 H), 7.44 (dd, 1 H), 7.37 (d, 1 H), 4.40 (t, 2H), 2.65 (s, 3H), 1.42 (q, 3H). A 500 mL hydrogenation vessel was charged with 2. 0g PLATINUM (II) oxide and purged with nitrogen. Ethyl 5- (3-PYRIDYL)-2-METHYLBENZOATE (19.57g, 81.10 mmol) was added as a solution in 200 mL acetic acid. The suspension was hydrogenated at 45 psi for 18 h. The catalyst was filtered through celite and the filter plug was washed with 200 mL acetic acid. The filtrate was concentrated under reduced pressure. The resultant oil was taken up in 500 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 500 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was taken up in 200 mL hot ethanol. L- (+)-tartaric acid (12.17g, 81.1 mmol) was added into the ethanol solution and was allowed to stir at ambient temperature for 48 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H2O/ETHANOL (300 mL) and then from 350 mL hot 20% H20/ETHANOL to yield 11.25g (35%, 95.8% ee) of (S)-ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-L-TARTARIC acid salt as a white solid. The mother liquors were combined and concentrated under reduced pressure. The resultant oil was taken up in 300 mL water and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with ethyl acetate (2 x 300 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was taken up in 200 mL hot ethanol. D- (-)-tartaric acid (6.82g, 45.4 mmol) was added into the ethanol solution and was allowed to stir at ambient temperature for 48 h, forming a white precipitate that was collected by filtration. The white solid was recrystallized from hot 5% H20/ETHANOL (300 mL) and then from 350 mL hot 20% H20/ETHANOL to yield 13. 51g (42%, 100% ee) of (R)-ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-D-TARTARIC acid salt as a white solid. MS (LC-MS) 248.2 (M + H) +. 1H NMR (400 MHZ, CDCI3) 6 7. 73 (d, 1H), 7.24 (dd, 1H), 7.18 (d, 1H), 4.35 (q, 2H), 3.18 (t, 2H), 2.78 (t, 1H), 2.68 (m, 2H), 2.54 (s, 3H), 2.38 (br, 1H), 2.01 (d, 1H), 1.82 (m, 1 H), 1.64 (6,2H), 1.40 (t, 3H). HPLC analysis: Chiralcel AD, 1 mL/min, 10% ethanol/heptane 0.025% diethylamine, rt = 8.36 min, 9.00 min (R)-Ethyl 5- (3-PIPERIDINYL)-2-METHYLBENZOATE-D-TARTARIC acid (2.02 g, 5.08 mmol) was dissolved in 100 mL ethyl acetate and washed with 100 mL saturated aqueous NAHCO3. The organic phase was dried over NA2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 10 mL toluene and imidazole-1-carboxylic acid 4-trifluoromethyl-benzyl ester (1.37 g, 5.08 mmol) was added. The reaction was stirred for 72 h at room temperature under nitrogen. The reaction was diluted with water (200 mL), acidified with 1 N aqueous hydrochloric acid and extracted with diethyl ether (2 x 150 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentr...
  • 4
  • [ 60-29-7 ]
  • [ 32138-69-5 ]
  • [ 89878-14-8 ]
  • [ 154229-19-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In tetrahydrofuran; bis(triphenylphosphine)palladium(II) dichloride; (c) 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol Diethyl(3-pyridyl)borane (3.23 g, 22 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 17-iodo-androsta-5,16-dien-3beta-ol (7.96 g, 20 mmol) in THF (120 ml) containing bis(triphenylphosphine)palladium (II) chloride (140 mg, 0.2 mmol). An aqueous solution of sodium carbonate (2M, 50 ml) was then added and the mixture heated, with stirring, by an oil bath at 80 C. for 48 h, and allowed to cool. The mixture was partitioned between Et2 O and water the organic phase was separated, dried (Na2 CO3) and twice concentrated from Et2 O by evaporation to remove THF (with Et2 O). The residual solid was then washed with Et2 O (100 ml), the Et2 O solution decanted off, and the remaining white solid recrystallized from toluene (3.94 g, 56%).
  • 5
  • [ 13667-12-4 ]
  • [ 89878-14-8 ]
  • [ 1064194-22-4 ]
  • 6
  • [ 32138-69-5 ]
  • [ 89878-14-8 ]
  • (3β)-17-(3-pyridyl)androst-5,16-dienyl d3-acetate [ No CAS ]
  • 7
  • [ 32138-69-5 ]
  • [ 89878-14-8 ]
  • [ 154229-18-2 ]
 

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