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Chemical Structure| 120157-97-3 Chemical Structure| 120157-97-3

Structure of 120157-97-3

Chemical Structure| 120157-97-3

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Product Details of [ 120157-97-3 ]

CAS No. :120157-97-3
Formula : C13H18BrNO2
M.W : 300.19
SMILES Code : CC(C)(C)OC(=O)NCCC1=CC=C(Br)C=C1
MDL No. :MFCD08443684
InChI Key :MRQBIMZMDWOQLF-UHFFFAOYSA-N
Pubchem ID :14221818

Safety of [ 120157-97-3 ]

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

Computational Chemistry of [ 120157-97-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.46
Num. rotatable bonds 6
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 72.46
TPSA ?

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

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.15
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

3.58
Log Po/w (WLOGP)?

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

3.52
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.

3.32
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

3.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.34

Water Solubility

Log S (ESOL):?

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

-3.82
Solubility 0.0453 mg/ml ; 0.000151 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.

-4.07
Solubility 0.0255 mg/ml ; 0.0000849 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-5.0
Solubility 0.00301 mg/ml ; 0.00001 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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

Yes
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.

-5.59 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

0.0 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)

2.09

Application In Synthesis of [ 120157-97-3 ]

* 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.

  • Downstream synthetic route of [ 120157-97-3 ]

[ 120157-97-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 73918-56-6 ]
  • [ 41840-28-2 ]
  • [ 120157-97-3 ]
  • 2
  • [ 120157-97-3 ]
  • [ 120158-10-3 ]
  • 3
  • [ 16532-79-9 ]
  • [ 24424-99-5 ]
  • [ 120157-97-3 ]
  • 4
  • [ 24424-99-5 ]
  • [ 73918-56-6 ]
  • [ 120157-97-3 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In isopropyl alcohol; at 20℃; for 2h;Inert atmosphere; PREPARATION D : [2-(4-Bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester; [Show Image] Under argon, a 100 mL one-necked round bottomed flask was charged with 4-bromophenethylamine (2.0 g, 10.0 mmol) in iPrOH (50.0 mL). (Boc)2O (2.2 g, 10.0 mmol) was then added followed by triethylamine (2.8 mL, 20.0 mmol). The reaction mixture was stirred at ambient temperature during 2 hours. The reaction mixture was concentrated then diluted with a saturated solution of sodium hydrogenocarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, evaporated in vacuo and dried under high vacuum yielding [2-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (3.4 g, quant.) as a white powder. 1H NMR (300 MHz, CDCl3-d): delta 7.42 (dd, 2H, J=6.6 Hz, J=1.7 Hz), 7.06 (d, 2H, J=8.3 Hz), 4.51 (bs, 1H), 3.33 (m, 2H), 2.75 (m, 2H), 1.43 (s, 9H).
100% In tetrahydrofuran; at 0 - 20℃; To a pre-cooled 0 C. solution of 112 (2.0 g, 10 mmol) in THF (10 mL) was added (Boc)2O (2.2 g, 10 mmol) portionwise. The reaction mixture was stirred at room temperature over night. It was concentrated in vacuo to yield 113 (3 g, 100%) as a white solid which was used in the next step without further purification.
100% With potassium carbonate; In dichloromethane; 4-Bromophenethylamine (2 mE, 13 nmol) in DCM(12 mE) was treated with K2C03 (2.7 g, 20 nmol, 1.5 eq.) and13oc20 (3.1 g, 14 mmol, 1.1 eq.). The mixture was diluted withwater, extracted with MTBE, washed with brine, dried onNa2SO4, and concentrated to give clean N-l3oc-4-bro-mophenethylamine (4 g, quant.).
100% With triethylamine; In dichloromethane; at 0 - 25℃; 1. BOC2O (818 mg, 3.75 mmol, 1.5 eq.) was added to a stirred solution of 2-(4- bromophenyl)ethanamine (500 mg, 2.5 mmol, 1.0 eq.) and TEA (1.5 ml, 7.5 mmol, 3.0 eq.) in DCM (25 ml) at 0 0C and resulting reaction mixture is stirred at 25 0C for 6 h. The reaction mixture was diluted with DCM (75 ml), washed with water (2 x 50 ml) and brine (50 ml) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the residue triturated with hexanes to yield the desired product as an off white solid.Yield: 100 % (750 mg, 2.5 mmol)
98% In dichloromethane; at 20℃; for 3h; 4-bromophenethylamine (10 g, 50 mm) was dissolved in 250 ml of methylene chloride, di-tert-butyl dicarbonate (12 g, 55 mmol) was added, and the mixture was stirred at room temperature for 3 hours.successively with saturated ammonium chloride solution, saturated aqueous solution of sodium bicarbonate, water, saturated salt water to wash the reaction solution, the organic phase is water-free magnesium sulfate drying reciprocation to dryness to obtain the crude product. In the title compound crystallized to obtain ethyl ether (white solid, 14.70 g, 98% yield).
96.3% With triethylamine; In tetrahydrofuran; at 0 - 20℃; t°lambdatf-Butyl [2-(4-bromophenyl)ethyl]carbamate; [2-(4-Bromophenyl)ethyl] amine (2.2Og, ll.OOmmol) was dissolved in dry THF (77mL) and TEA (1.1 Ig, ll.OOmmol) was added. The mixture was cooled in an ice-bath. Di-tert-butyl dicarbonate (2.4Og, ll.OOmmol) was added. The mixture was stirred for Ih at O0C and left at rt overnight. The solvent was evaporated and column chromatography of the crude product EPO <DP n="185"/>(ISOLUTE SI (2Og), Heptane/EtOAc (90:10)) afforded the title compound (3.18g, 96.3%). 1H NMR (500MHz, CD3OD): delta 1.42 (s, 9H), 2.73 (t, 2H), 3.25 (t, 2H), 7.14 (d, 2H), 7.43 (d, 2H).
95% With triethylamine; In dichloromethane; at 25℃; To a solution of 2-(4-bromophenyl)ethan-l-amine (5.00 g, 25.0 mmol) in anhydrous dichloromethane (50 mL) was added Boc20 (6.57 g, 30.1 mmol) followed by EtsN (10.4 mL, 74.9 mmol). The resulting solution was stirred overnight at 25 C and then concentrated in vacuo. The crude product was purified by FCC eluting with ethyl acetate/petroleum ether (4-bromophenethyl)carbamate as a white solid (7.1 g, 95%), LCMS (ESI, m/z): 300 [M+H]+
95% With triethylamine; In dichloromethane; at 25℃; (0935) [00330] To a solution of 2-(4-bromophenyl)ethan-l -amine (5.00 g, 25.0 mmol) in anhydrous dichlorometha e (50-raL) was added B0C2O (6,57 g, 30.1 mmol) followed by EtaN (10.4 mL, 74.9 mmol). The resulting solution was stirred overnight at 25 C and then concentrated in vacuo. The resulting crude product was purified by FCC eluting with ethyl acetate/petroleum ether (PE/EA=3 : 1) to afford fert-butyl (4-bromophenethyl)carbamate as a white solid (7.1 g, 95%). LCMS (ESI, m/z) 300 [M+H]+.
91% In dichloromethane; at 0 - 20℃; for 3h; Example 3C:; Part A:; A mixture of 4-bromophenethylamine (11) (0.5 g, 2.5 mmol) and di-te/t-butyl dicarbonate (0.65 g, 3 mmol) at 00C in DCM (5 mL) was warmed to room temperature and stirred for 3 hours. LC-MS analysis indicated the reaction was complete. Oichloromethane (5 mL) was added and the solution washed with 1 lambda/ HCI (10 mL). Drying over magnesium sulfate, concentration and purification by flash column chromatography (Sitheta2, 12.5 % ethyl acetate in hexanes) afforded compound 12 as a white solid (0.68 g, 91 % yield). HPLC- MS tR = 2.13 min (UV254 nm); mass calculated for formula C13Hi8BrNO2299.1 , observed LCMS m/z 244.1 (M+H-'Bu).
90% With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃; for 5.5h; 2-(4-Bromophenyl)-ethylamine (13, 10.0g, 50mmol) and NaOH (3.0g, 75mmol) were dissolved in the mixture of dioxane (150mL) and H2O (150mL). The reaction mixture was cooled to 0C. The solution of di-tert-butyl dicarbonate (16.36g, 75mmol) in dioxane (72mL) was added dropwise to the reaction mixture, which was stirred at room temperature for 5.5h. Dioxane was removed in vacuo and the residue was extracted with ethyl acetate 3 times. The combined organic layer was washed with water and brine, and then dried over anhydrous Na2SO4. Filtration and removal of solvent provided the crude product, which was purified by Combiflash chromatography (5-10% of ethyl acetate in hexane). The title compound 5 (13.5g, 90.0%) was obtained as a white solid; mp 59-60C. 1H NMR (300MHz, chloroform-d): delta=7.42 (d, J=8.0Hz, 2H), 7.07 (d, J=8.0Hz, 2H), 4.51 (br. s, 1H), 3.40-3.27 (m, 2H), 2.75 (t, J=6.9Hz, 2H), 1.43 (s, 9H). MS (EI): m/z=300.1 (M++H).
90% With triethylamine; In dichloromethane; at 20℃; for 6h;Cooling with ice; Dissolve p-bromophenethylamine (2.0 g, 10 mmol) in a 100 mL round bottom flask under ice bathAfter dissolving 20 mL of dichloromethane, triethylamine (3.0 g, 30 mmol) was added, and then di-tert-butyl dicarbonate (3.3 g) was gradually added dropwise.20 mL of a solution of 15 mmol) of dichloromethane (DCM) was allowed to react at room temperature for 6 hours after the addition. After the reaction is completed, the solvent is distilled off under reduced pressure.40 mL of water was added, and the mixture was extracted with ethyl acetate. Distill the solvent and then silica gel column chromatographyFrom purification, eluent: petroleum ether (PE) / ethyl acetate (EA) = (20:1). A white solid (2.7 g, 90%) was obtained.
89% With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; To a stirred solution of 2-(4-bromophenyl)ethan-l -amine (3.0 g, 14.99 mmol) in dry DCM (30 ml) was added TEA (4.55 g, 44.98 mmol) at 0 C. Boc anhydride (3.92 g, (0366) 17.98 mmol) was added dropwise at 0 C and the resulting reaction mixture was allowed to come to room temperature over a period of 2 hours. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (2 x 30 ml). The combined organic layers were washed with brine (50 ml), dried over anhydrous Na2S04 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford the title compound (4.0 g, 89 %) as off-white solid. 1H NMR (400 MHz, DMSO-d6): 1.36 (s, 9H), 2.66 (t, J = 7.2 Hz, 2H), 3.10-3.15 (m, 2H), 6.89 (S, 1H, -NH), 7.16 (d, J = 8.4Hz, 2H), 7.47 (d, J = 8.4Hz, 2H). LCMS: m/z = 244.1 [M+l -56] and 246.1 [M+2 -56].
88% To a solution of 4-bromophenethylamine (5.00 g, 25.0 mmol), potassium carbonate (5.18 g, 37.5 mmol) in CH2Cl2 (125 ml) was stirred for 15 min at room temperature, and boc anhydride was added (6.04 mL, 26.3 mmol). After 16 h, the reaction mixture was washed with H2O (125 mL 3) and brine (75 mL). The organic layer was dried with anhydrous Na2SO4 and concentrated in vacuo. The residue was washed with n-hexane and gave 13 as a white solid (6.63 g, 88%); Rf = 0.50 (EtOAc 1: n-Hexane 3); 1H NMR (300 MHz, DMSO-d6) delta 1.43 (s, C(CH3)3), 2.75 (t, J = 6.6 Hz, NHCH2CH2), 3.34-3.35(m, NHCH2CH2), 7.06 (d, J = 8.0 Hz, 2 ArH), 7.42 (d, J = 8.2 Hz, 2 ArH); 13C NMR (75 MHz, DMSO-d6) delta 28.4 (C(CH3)3), 35.7 (NHCH2CH2), 41.6 (NHCH2CH2), 79.3 (C(CH3)3), 120.2, 130.6, 131.6, 138.0 (6 ArC), 155.8 (C(O)).
88% In tetrahydrofuran; at 0 - 20℃; for 18h; Di-te/f-butyl dicarbonate (3.93 g, 18.0 mmol) was added to a cooled (0C) stirred solution of 2-(4-bromophenyl)ethanamine (3.00 g, 15.0 mmol) in THF (20 ml). The resulting solution was allowed to warm to RT then stirred at RT for 18 h. The reaction mixture was partitioned between EtOAc (30 ml) and saturated aqueous NaHC03 solution (50 ml). The phases were separated then the aqueous phase was extracted with EtOAc (15 ml). The combined organic phases were washed with brine (50 ml), dried over MgS04, then concentrated in vacuo. The crude material was dissolved in the minimum volume of CH2CI2, pre-adsorbed onto silica, then purified by flash column chromatography on a silica column (25 g). The column was eluted with EtOAc: heptane, using the following gradient (%EtOAc, column volumes): 0%, 1 CV; 0-8%, 2.5 CV; 8-12%, 1 CV; 12%, 3.5 CV; 12- 27%, 5.5 CV; 27-30%, 0.5 CV; 30%, 2 CV; 30-90%, 4 CV; 100% 1 CV. The desired fractions were combined and concentrated in vacuo to afford the product as a white solid (3.99 g, 88%). 1 H NMR (500 MHz, DMSO-cfe) delta 7.50 - 7.42 (m, 2H), 7.19 - 7.1 1 (m, 2H), 6.86 (t, J = 5.3 Hz, 1 H), 3.12 (q, J = 6.6 Hz, 2H), 2.70 - 2.63 (m, 2H), 1.41 - 1.26 (m, 9H). LC/MS (System A): Rt = 1.27 min, UV purity = 99%.
88% In tetrahydrofuran; at 0 - 20℃; for 18h; Di-teit-butyl dicarbonate (3.93 g, 18.0 mmol) was added to a cooled (0C) stirred solution of 2-(4-bromophenyl)ethanamine (3.00 g, 15.0 mmol) in THF (20 ml). The resultingsolution was allowed to warm to RT then stirred at RT for 18 h. The reaction mixture waspartitioned between EtOAc (30 ml) and saturated aqueous NaHCO3 solution (50 ml). The phases were separated then the aqueous phase was extracted with EtOAc (15 ml). The combined organic phases were washed with brine (50 ml), dried over Mg504, then concentrated in vacuo. The crude material was dissolved in the minimum volume of CH2CI2, pre-adsorbed onto silica, then purified by flash column chromatography on a silica column (25 g). The column was eluted with EtOAc:heptane, using the following gradient (%EtOAc, column volumes): 0%, 1 CV; 0-8%, 2.5 CV; 8-12%, 1 CV; 12%, 3.5CV; 12-27%, 5.5 CV; 27-30%, 0.5 CV; 30%, 2 CV; 30-90%, 4 CV; 100% 1 CV. Thedesired fractions were combined and concentrated in vacuo to afford the product as a white solid (3.99 g, 88%).1H NMR (500 MHz, DMSO-d6) O 7.50- 7.42 (m, 2H), 7.19-7.11 (m, 2H), 6.86 (t, J = 5.3Hz, 1H), 3.12 (q, J= 6.6 Hz, 2H), 2.70-2.63(m, 2H), 1.41- 1.26(m, 9H). LC/MS (System A): R = 1.27 mi UV purity = 99%.
85% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; Intermediate 991 ,1 -Dimethylethyl [2-(4-bromophenyl)ethyl]carbamate Bis(1 ,1 -dimethylethyl) dicarbonate (240 mg, 1.100 mmol) was added to a mixture of [2-(4- bromophenyl)ethyl]amine 2-(4-bromophenyl)ethanamine (200 mg, 1 .000 mmol) and DIPEA (0.524 mL, 3.00 mmol) in dichloromethane (DCM) (5 mL). The resulting mixture was stirred under nitrogen at room temperature for 2 h then concentrated in vacuo. The residue was partitioned between AcOEt (20 mL) and water (15 mL) and the layers were separated. The aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgS04 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 5 to 25% AcOEt in hexanes) gave 1 ,1 -dimethylethyl [2-(4-bromophenyl)ethyl]carbamate (256mg, 0.853mmol, 85%) as a white solid.LCMS (method G): Retention time 1.22 min, [M+H-t-Bu]+ = 244.0 (1 Br)
85% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; Bis(1,1-dimethylethyl) dicarbonate (240 mg, 1.100 mmol) was added to a mixture of [2-(4-bromophenyl)ethyl]amine 2-(4-bromophenyl)ethanamine (200 mg, 1.000 mmol) and DIPEA (0.524 mL, 3.00 mmol) in dichloromethane (DCM) (5 mL). The resulting mixture was stirred under nitrogen at room temperature for 2 h then concentrated in vacuo. The residue was partitioned between AcOEt (20 mL) and water (15 mL) and the layers were separated. The aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 5 to 25% AcOEt in hexanes) gave 1,1-dimethylethyl [2-(4-bromophenyl)ethyl]carbamate (256 mg, 0.853 mmol, 85%) as a white solid.LCMS (method G): Retention time 1.22 min, [M+H-t-Bu]+=244.0 (1 Br)
84% In dichloromethane; at 25℃; for 4h; To a suspension of 2-(4-bromophenyl)ethan-1-amine (1) (3.1?mL, 20?mmol) in CH2Cl2 (30?mL) was added dropwise (Boc)2O (5.97?mL, 26?mmol) at 25?C and the solution was stirred for 4?h. After the reaction completed, the solvent was removed under reduced pressure. The residue was dissolved in water, then the aqueous solution was extracted with ethyl acetate (50?mL?*?3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give the crude product, which was purified by column chromatography to give tert-butyl(4-bromophenethyl)-carbamate (2) (5.0?g, 84% yield) as a white solid. 1H NMR (400?MHz, CDCl3) delta: 7.42 (d, J?=?8.2?Hz, 2H), 7.07 (d, J?=?8.1?Hz, 2H), 4.52 (s, 1H), 3.35 (s, 2H), 2.75 (t, J?=?6.9?Hz, 2H), 1.43 (s, 9H).
65% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h;Inert atmosphere; [000449] Synthesis of tert-butyl (4-bromophenethyl) carbamate (547): To a stirred solution of 2-(4-bromophenyl) ethan-1-amine 546 (500 mg, 2.50 mmol) in CH2C12 (5 mL) under argon atmosphere were added Boc-anhydride (594 mg, 2.75 mmol), diisopropyl ethyl amine (1 mL, 7.50 mmol) at RT and stirred for 4 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (25 mL) and extracted with CH2C12 (235 mL). The combined organic extracts were washed with water (25 mL), dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 5-8% EtOAc/ hexanes to afford compound 547 (500 mg, 65%) as white solid. TLC: 10% EtOAc/ hexanes (R 0.5); 1H-NMR (DMSO-d6, 400 MHz): oe 7.46 (d, J= 8.0 Hz, 2H), 7.12 (d, J= 8.0 Hz, 2H), 6.86-6.82 (m, 1H), 3.12-3.08 (m, 2H), 2.68-2.64 (m, 2H), 1.32 (s, 9H).
53% Example 1 Synthesis of tert-butyl 4-bromophenethylcarbamate Bromophenethylamine (50 g, 250 mmol) and triethylamine (105 mL, 750 mmol) were stirred in dichloromethane (DCM; 1.5 L), and cooled to 0 C. Boc anhydride (82 g, 375 mmol) was added and the reaction mixture stirred at room temperature overnight. The reaction mixture was washed with water (1 L), brine (500 mL), dried (MgSO4) and concentrated to give an orange oil. The crude residue was crystallized from hexane (250 mL) to give a white solid, tert-butyl 4-bromophenethylcarbamate (39.85 g, 133 mmol, 53%).
50% In tetrahydrofuran; at 20℃; for 1.5h; A solution of di-tert-butyl dicarbonate (0.36 g, 1.6 mmol) in tetrahydrofuran (5 mL) was added to a solution of 4-bromophenethylamine (0.30 g, 1.5 mmol) in tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 1.5 hours. After the reaction mixture was concentrated, the resultant solid was washed with hexane (3 mL), and dried under reduced pressure to give the title Reference compound (0.23 g) as a colorless solid (yield 50 %). tert-Butyl N-[2-(4-bromophenyl)ethyl]carbamate (Reference compound 30-1) [Show Image] 1H-NMR (500 MHz, CDCl3) delta 1.43 (s, 9H), 2.75 (t, J = 6.9 Hz, 2H), 3.3 5(q, J = 6.9 Hz, 2H), 4.52 (s, 1H), 7.07 (dd, J = 6.6, 1.7 Hz, 2H), 7.42 (dd, J = 6.6, 1.7 Hz, 2H)
22% With dmap; In dichloromethane; at 20 - 24℃; for 18h; To a stirring solution of 4-dimethylaminopyridine (0.19 g, 1.5 mmol) and di-tert-butyl dicarbonate (2.6 g, 12 mmol) in dichloromethane (40 mL) was added 4-bromophenethylamine (1.6 mL, 10 mmol) and stirred at room temperature for 48 hours. The reaction mixture directly adsorbed onto silica gel and purified by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent to afford the title compound as a white solid (0.68 g, 22%): mp 58-59 C.; 1H NMR (400 MHz, CDCl3) delta 7.42 (d, J=8.3 Hz, 2H), 7.07 (d, J=8.3 Hz, 2H), 4.51 (s, 1H), 3.43-3.27 (m, 2H), 2.75 (t, J=7.0 Hz, 2H), 1.43 (s, 9H); 13C NMR (101 MHz, CDCl3) delta 155.79, 137.97, 131.62, 130.55, 120.25, 77.21, 41.58, 35.65, 28.39; EIMS m/z 301 ([M]+).
With triethylamine; In methanol; water; Step 1 A solution of 4-bromophenethylamine (10 g, 50 mmol), di-tert-butyldicarbonate (21.82 g, 100 mmol), triethylamine (13.9 ml, 100 mmol), and anhydrous methanol (350 ml) was refluxed for 2 h. The reaction mixture was concentrated in vacuo and the residue was stirred with water, filtered, washed with water and air dried to give N-(tert-butoxycarbonyl)-4-bromophenethylamine (15 g).
EXAMPLE 63C 4-Bromo-(N-tert-butoxycarbonyl)phenethylamine 4-Bromophenethylamine and di-t-butyldicarbonate were subjected to the conditions described in Synthesis, 48, 1986 to provide the title compound. MS (DCI/NH3) m/e 319 (M+NH4)+.
EXAMPLE 63C 4-Bromo-(N-tert-butoxycarbonyl)phenethylamine 4-Bromophenethylamine and di-t-butyldicarbonate were subjected to the conditions described in Synthesis, 48, 1986 to provide the title compound. MS (DCI/NH3) m/e 319 (M+NH4)+.
In tetrahydrofuran; Preparation 74 Di-tert-butyl dicarbonate (2.18 g) was added to a solution of 2-(4-bromophenyl)ethanamine (2.0 g) in tetrahydrofuran (5 ml) under ice water cooling over 10 minutes and the mixture was stirred at room temperature for further 1 hour. The reaction mixture was evaporated in vacuo to give tert-butyl 2-(4-bromophenyl)ethylcarbamate (2.98 g) as a colorless foam. NMR (CDCl3, delta): 1.43 (9H, s), 2.75 (2H, t, J=8 Hz), 3.36 (2H, t, J=8 Hz), 7.00-7.10 (2H, m), 7.30-7.50 (2H, m)
In tetrahydrofuran; for 0.166667h; To 7.03 g (35.1 mmol) of 4-bromophenethylamine (Sigma-Aldrich) in 60 mL of THF was added 8.6 g (39.4 mmol) of di-tert-butyldicarbonate. After 10 minutes, the solution was concentrated under reduced pressure, and the residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The ethyl acetate phase was washed with brine, dried over MgSO4, filtered, and concentrated to give compound X as a white solid.
With triethylamine; In methanol; for 2h;Heating / reflux; A solution of 4-bromophenethylamine (10 g, 50 mmol), di-tert-butyldicarbonate (21.82 g, 100 mmol), triethylamine (13.9 ml, 100 mmol), and anhydrous methanol (350 ml) was refluxed for 2 h.. The reaction mixture was concentrated in vacuo and the residue was stirred with water, filtered, washed with water and air dried to give N-(tert-butoxycarbonyl)-4-bromophenethylamine (15 g).
With triethylamine; In DMF (N,N-dimethyl-formamide); at 50℃; for 0.25h; To a solution of 4-BROMOPHENETHYLAMINE (10G, 48. 98mmol) in anhydrous DMF (150mL), containing anhydrous triethylamine (35mL, 244.9 mol), was added BOC2O. The reaction mixture was heated for 15 minutes at 50C. After cooling to room temperature, brine (100ML) and HCI (1N, 100ML) were added subsequently, and the mixture was extracted several times with ether. The recombined organic layer was washed again with brine, dried over sodium sulfate, filtered and evaporated. The crude was flashed with 10% ethyl acetate in hexanes to give the [2- (4-BROMO-PHENYL)-ETHYL]-CARBAMIC acid tert-butyl ester.'H NMR (CDCI3, 300MHZ) : 1.41 (s, 9H); 2.22 (t, J=7. 1HZ, 2H); 3.31 (m, 2H); 4.67 (s, broad, 1 H); 7.03 (d, J=8.2Hz, 2H); 7.38 (d, J=8.2Hz, 2H). A mixture of the above mentioned compound (1. 00g, 3. 33MMOL), 3, 4-DIMETHOXYPHENYLBORONIC acid (1. 21 G, 6. 66MMOL), and potassium hydroxide (2N, 5mL, 10MMOL) in THF (15mL) was degassed using argon for 5 minutes. Palladium tetrakis-triphenylphosphine (200mg, 0. 167MMOL) was added and the mixture was heated at 85C. After 24 hours, the reaction mixture was allowed to cool to room temperature. Brine (20mL) was added and the reaction mixture was extracted several times with ether. The recombined organic phase was extracted with brine, dried over sodium sulfate, filtered, and evaporated. Silica gel chromatography of the crude using 20% ethyl acetate/n-hexane afforded [2- (3', 4'-DIMETHOXY-BIPHENYL-4YL)-ETHYLAMINE]-CARBAMIC acid tert-butyl ester as a white SOLID. 1H-NMR (CDCI3, 300MHZ) : 1.44 (s, 9H); 2.82 (t, J=6.9Hz, 2H); 3.39 (m, 2H); 3.91 (s, 3H); 3.93 (s, 3H); 4.67 (s, broad, 1H) ; 6.92 (d, J=8.2Hz, 1 H) ; 7.11 (m, 2H); 7.25 (m, 2H); 7.48 (d, J=8. 1 Hz, 2H). A solution of the above mentioned compound (1.14g, 3. 19mmol) in anhydrous methanol (50mL) was cooled in ice bath and then treated drop wise with acetyl chloride. Stirring was continued for 30 minutes at the same temperature followed by overnight stirring at room temperature. About 30mL of the solvent was removed by evaporation and the mixture was diluted with 200mL of ether. The entitled product was collected as a white solid by filtration, followed by washing with anhydrous ether and drying under high VACUUM.'H-NMR (D20, 300MHZ) : 2.80 (t, J=6.9Hz, 2H); 3.40 (m, 2H); 3.91 (s, 3H); 3.93 (s, 3H); 4.77 (s, broad, 1H) ; 7.00 (d, J=8.2Hz, 1H) ; 7.15 (m, 2H); 7.26 (m, 2H); 7.50 (d, J=8. 1HZ, 2H)
With triethylamine; In dichloromethane; at 20℃; for 16h; Dissolved 2-(4-bromophenyl)ethanamine (25.0 g, 124.95 mmol) in DCM (500 mL). Charged with di-tert-butyl dicarbonate (32.7 g, 149.94 mmol) and triethylamine (52 mL, 373.08 mmol). Stirred at room temperature for 16 hours. Removed solvent and used crude without further purification.

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  • 5
  • [ 1993-03-9 ]
  • [ 120157-97-3 ]
  • [ 257299-28-8 ]
  • 6
  • [ 120157-97-3 ]
  • [ 73183-34-3 ]
  • [ 360792-43-4 ]
YieldReaction ConditionsOperation in experiment
100% With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃; for 18h; A mixture of tert-butyl 4-bromophenethylcarbamate (C48) (0.68 g, 2.3 mmol), bis(pinacolato)diborane (0.89 g, 3.5 mmol), potassium acetate (0.69 g, 7.0 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.10 g, 0.14 mmol), and 1,1'-bis(diphenylphosphino)ferrocene (0.075 g, 0.14 mmol) in anhydrous dioxane (7 mL) was heated at 80 C. for 18 hours. The reaction was cooled, diluted with ethyl acetate, and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The crude compound was adsorbed onto silica gel and purified by flash column chromatography using 0-60% ethyl acetate/hexanes as eluent to afford the title compound as a clear oil (0.86 g, 104%): 1H NMR (400 MHz, CDCl3) delta 7.75 (d, J=7.9 Hz, 2H), 7.23-7.17 (m, 2H), 4.51 (s, 1H), 3.46-3.28 (m, 2H), 2.81 (t, J=7.1 Hz, 2H), 1.43 (s, 9H), 1.34 (s, 12H); ESIMS m/z 348 ([M+H]+).
85% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 12h;Inert atmosphere; Under argon protection,Compound (h) (600 mg, 2.0 mmol) was added sequentially to a 50 mL two-necked flask.Anhydrous potassium acetate (588 mg, 6 mmol),Diterpenoid borate (607mg, 2.4mmol) and PdCl2 (dppf)(44mg, 0.06mmol),Add 20 mL of anhydrous dioxane (1:1 by volume),The mixture was reacted at 120 C for 12 hours.After the reaction was completed, it was cooled to room temperature. Filtered with suction and the filtrate was extracted with ethyl acetate.Wash with water and wash with saturated NaCl.The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure.Separation by column method, eluent:Petroleum ether (PE) / ethyl acetate (EA) = (20:1),A white solid (566 mg, 85%) was obtained.
40.58 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; at 65℃; for 16h; Dissolved <strong>[120157-97-3]tert-butyl N-[2-(4-bromophenyl)ethyl]carbamate</strong> (?124.95 mmol) in THF (500 mL). Added bis(pinacolato)diboron (44.0 g, 174.93 mmol), palladium chloride diphenyl phosphine ferrocene (10.2 g, 10 mol %) and potassium acetate (36.8 g, 374.85 mmol). Heated to 65 C. for 16 hours. Removed solvent and purified using normal phase chromatography (0-100% EtOAc in heptanes) to yield 40.58 g of product; 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.35 (s, 12H) 1.44 (s, 9H) 2.82 (t, J=6.74 Hz, 2H) 3.38 (d, J=5.86 Hz, 2H) 4.18-4.71 (m, 1H) 7.21 (d, J=7.42 Hz, 2H) 7.76 (d, J=7.61 Hz, 2H).
  • 7
  • [ 120157-97-3 ]
  • 2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethylamine; hydrochloride [ No CAS ]
  • 8
  • [ 120157-97-3 ]
  • [ 913181-88-1 ]
  • 9
  • [ 120157-97-3 ]
  • <i>N</i>-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-guanidine; compound with trifluoro-acetic acid [ No CAS ]
  • 10
  • [ 16532-79-9 ]
  • 1-nitro-cyclohexene-(1) [ No CAS ]
  • [ 120157-97-3 ]
  • 11
  • [ 120157-97-3 ]
  • [ 211315-64-9 ]
  • 12
  • [ 120157-97-3 ]
  • propane-2-sulfonic acid [2-(2'-fluoro-biphenyl-4-yl)-ethyl]-amide [ No CAS ]
  • 13
  • [ 120157-97-3 ]
  • [ 74860-13-2 ]
  • 14
  • [ 120157-97-3 ]
  • [ 156-43-4 ]
  • [ 1055276-57-7 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 95℃; for 16h;Heating / reflux; To a flask containing 1.2 g (4.1 mmol) of compound X, 0.72 g (5.3 mmol) of para-phenetidine (4-ethoxyaniline, Sigma-Aldrich), 0.19 g (0.35 mmol) of tris(dibenzylidineacetone)dipalladium(0), 0.38 g (0.61 mmol) of rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and 0.51 g (5.3 mmol) of sodium tert-butoxide, was added 35 mL of toluene, and the mixture was heated at 95 C. for 16 hours under an nitrogen atmosphere. The mixture was partitioned between 1.0 M aqueous NaHSO4 and diethyl ether. The diethyl ether phase was washed once each with saturated NaHCO3 and brine, dried over MgSO4, filtered, and concentrated to a dark oil. The oil was purified by silica gel chromatography, using 15% EtOAc/85% hexanes as eluant, to give compound Y as a dark orange oil.
  • 15
  • [ 92028-21-2 ]
  • [ 120157-97-3 ]
  • [ 530084-75-4 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 90℃; for 2.5h;Heating / reflux; Under nitrogen, compound X (from Example 38 part a) (5.0 g, 16.7 mmol) was mixed with toluene (80 mL) and 4-methoxy-3-phenylaniline hydrochloride (4.3 g, 18.3 mmol) was added to form a slurry. 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (1.6 g, 2.5 mmol) was added, followed by tris(dibenzylideneacetone)dipalladium(0) (760 mg, 0.83 mmol) and finally sodium tert-butoxide (5.3 g, 55 mmol). The mixture was heated at 90 C. for 150 min and then cooled to room temperature. Water (150 mL) was added followed by ethyl acetate (150 mL) and the phases partitioned. The aqueous layer was extracted with ethyl acetate (150 mL) and the combined organics washed three times with 0.5 M sodium bisulfate (200 mL), once with saturated sodium bicarbonate (150 mL) and twice with saturated sodium chloride (150 mL). The organics were dried over magnesium sulfate (50 g) and the volatiles removed under vacuum to give N-tert-butoxycarbonyl-2-[4-(3-[phenyl-4-methoxyphenyl)aminophenyl]ethylamine (LL) (8.4 g) which was used without further purification.
  • 16
  • [ 122775-35-3 ]
  • [ 120157-97-3 ]
  • [ 708269-37-8 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 20 - 85℃; for 24.0833h; To a solution of 4-BROMOPHENETHYLAMINE (10G, 48. 98mmol) in anhydrous DMF (150mL), containing anhydrous triethylamine (35mL, 244.9 mol), was added BOC2O. The reaction mixture was heated for 15 minutes at 50C. After cooling to room temperature, brine (100ML) and HCI (1N, 100ML) were added subsequently, and the mixture was extracted several times with ether. The recombined organic layer was washed again with brine, dried over sodium sulfate, filtered and evaporated. The crude was flashed with 10% ethyl acetate in hexanes to give the [2- (4-BROMO-PHENYL)-ETHYL]-CARBAMIC acid tert-butyl ester.'H NMR (CDCI3, 300MHZ) : 1.41 (s, 9H); 2.22 (t, J=7. 1HZ, 2H); 3.31 (m, 2H); 4.67 (s, broad, 1 H); 7.03 (d, J=8.2Hz, 2H); 7.38 (d, J=8.2Hz, 2H). A mixture of the above mentioned compound (1. 00g, 3. 33MMOL), 3, 4-DIMETHOXYPHENYLBORONIC acid (1. 21 G, 6. 66MMOL), and potassium hydroxide (2N, 5mL, 10MMOL) in THF (15mL) was degassed using argon for 5 minutes. Palladium tetrakis-triphenylphosphine (200mg, 0. 167MMOL) was added and the mixture was heated at 85C. After 24 hours, the reaction mixture was allowed to cool to room temperature. Brine (20mL) was added and the reaction mixture was extracted several times with ether. The recombined organic phase was extracted with brine, dried over sodium sulfate, filtered, and evaporated. Silica gel chromatography of the crude using 20% ethyl acetate/n-hexane afforded [2- (3', 4'-DIMETHOXY-BIPHENYL-4YL)-ETHYLAMINE]-CARBAMIC acid tert-butyl ester as a white SOLID. 1H-NMR (CDCI3, 300MHZ) : 1.44 (s, 9H); 2.82 (t, J=6.9Hz, 2H); 3.39 (m, 2H); 3.91 (s, 3H); 3.93 (s, 3H); 4.67 (s, broad, 1H) ; 6.92 (d, J=8.2Hz, 1 H) ; 7.11 (m, 2H); 7.25 (m, 2H); 7.48 (d, J=8. 1 Hz, 2H). A solution of the above mentioned compound (1.14g, 3. 19mmol) in anhydrous methanol (50mL) was cooled in ice bath and then treated drop wise with acetyl chloride. Stirring was continued for 30 minutes at the same temperature followed by overnight stirring at room temperature. About 30mL of the solvent was removed by evaporation and the mixture was diluted with 200mL of ether. The entitled product was collected as a white solid by filtration, followed by washing with anhydrous ether and drying under high VACUUM.'H-NMR (D20, 300MHZ) : 2.80 (t, J=6.9Hz, 2H); 3.40 (m, 2H); 3.91 (s, 3H); 3.93 (s, 3H); 4.77 (s, broad, 1H) ; 7.00 (d, J=8.2Hz, 1H) ; 7.15 (m, 2H); 7.26 (m, 2H); 7.50 (d, J=8. 1HZ, 2H)
  • 17
  • [ 288-32-4 ]
  • [ 120157-97-3 ]
  • [ 1056950-87-8 ]
YieldReaction ConditionsOperation in experiment
With 1,10-Phenanthroline; caesium carbonate;copper(I) trifluoromethanesulfonate benzene; 1,5-diphenyl-1,4-pentadiene-3-one; In o-xylene; at 120℃; for 96h; Tert-butyl 2- (4-BROMOPHENYL)- ethylcarbamate (500 mg, 1.67 mmol), imidazole (170 mg, 2.50 mmol), (CuOTf) 2. PHH (84 mg, 0.17 mmol), 1, 10-PHENANTHROLINE (360 mg, 2.00 mmol), dba (39 mg, 0.17 mmol), and CS2CO3 (650 mg, 1.99 mmol) were mixed together in a flask and o-xylene (10 ML) was added. Resulting solution was heated to 120C and stirred for four days. Reaction mixture was then cooled, poured into water (20 mL) and extracted with EtOAc (3 x 20 mL). Combined organics were washed with water (1 x 20 mL) and brine (2 x 20 mL), dried over sodium sulfate, filtered, and concentrated. Crude product was purified by flash chromatography eluting with 25% Hexanes in ETOAC to pure EtOAc to give tert-butyl 2- [4- (LH-IMIDAZOL-1-YL) PHENYL] ETHYLCARBAMATE. HCL (G) was bubbled into a solution of tert-butyl 2-[4-(1H-imidazol-1-yl)phenyl]- ethylcarbamate in EtOAc cooled to 0C until saturated. Reaction stirred for one hour at 0C and was then concentrated to give 2- [4- (lH-imidazol-1-yl) phenyl] ethanamine, which was used without further purification. LCMS (ES) 188. 3 711JZ (M + H) +.
With tris-(dibenzylideneacetone)dipalladium(0); 1,10-Phenanthroline; Cu2(OTf)2; caesium carbonate; In o-xylene; at 120℃; for 96h; Ter<strong>[120157-97-3]t-butyl 2-(4-bromophenyl)ethylcarbamate</strong> (500 mg, 1.67 mmol), imidazole (170 mg, 2.50 mmol), (CuOTf)2.PhH (84 mg, 0.17 mmol), 1,10-Phenanthroline (360 mg, 2.00 mmol), dba (39 mg, 0.17 mmol), and Cs2CO3 (650 mg, 1.99 mmol) were mixed together in a flask and o-xylene (10 mL) was added. Resulting solution was heated to 120 C. and stirred for four days. Reaction mixture was then cooled, poured into water (20 mL) and extracted with EtOAc (3×20 mL). Combined organics were washed with water (1×20 mL) and brine (2×20 mL), dried over sodium sulfate, filtered, and concentrated. Crude product was purified by flash chromatography eluting with 25% Hexanes in EtOAC to pure EtOAc to give tert-butyl 2-[4-(1H-imidazol-1-yl)phenyl]ethylcarbamate
  • 19
  • [ 898270-98-9 ]
  • [ 120157-97-3 ]
  • 2-tert-butyl-5-phenyl-4-[2-(pyridin-3-yloxy)ethyl]amino}isothiazol-3(2H)-one 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35.7% With potassium carbonate; In acetonitrile; at 120℃; for 0.25h;Microwave irradiation; Example 102; 2-fe/f-ButyI-5-phenyl-4-[2-(pyridin-3-yloxy)ethyl]amino}isothiazol-3(2H)-one l,l- dioxide30 2-[(2-tert-Butyl-l,l-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]ethyl 4- methylbenzenesulfonate (150mg, 0.313mmol) was dissolved in dry MeCN (3mL) under nitrogen atmosphere. Pyridin-3-ol (33mg, 0.345mmol) was added followed by potassium carbonate (217mg, 1.567mmol). The reaction mixture was heated in a microwave reactor at EPO <DP n="246"/>120C for 15 mins. Potassium carbonate was filtered off and the reaction mixture was evaporated to dryness in a vacuum centrifuge. The crude product was purified by preparative HPLC affording the title compound (46mg, 35.7%). 1H NMR (CDCl3, 500MHz): delta 1.74 (s, 9H), 3.30 (q, 2H), 3.92 (t, 2H), 5.64 (t, IH), 7.12-7.14 (m, IH), 7.22-7.24 (m, IH), 7.46-7.48 (m, 3H), 7.53-7.55 (m, 2H), 8.26-8.28 (m, 2H); 13C NMR (CDCl3, 125MHz): delta 27.84, 43.32, 61.90, 66.37, 108.51, 121.55, 124.15, 125.03, 129.09, 130.10, 131.69, 135.11, 137.90, 143.23, 154.51, 159.64; Mass Spectrum: M+H4" 402.1.
  • 20
  • [ 557-21-1 ]
  • [ 120157-97-3 ]
  • [ 172348-86-6 ]
YieldReaction ConditionsOperation in experiment
88.9% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 150℃; for 0.333333h;Microwave irradiation; tert-Butyl [2-(4-cyanophenyl)ethyl]carbamate; tert-Butyl [2-(4-bromophenyl)ethyl]carbamate (0.52g, 1.73mmol) was dissolved in dry DMF (17mL) under nitrogen atmosphere. Zinc cyanide (0.41g, 3.46mmol) and tetrakis(triphenylphosphine)palladium (O.l?g, 0.14mmol) was added. The reaction mixture was heated in a microwave reactor at 150C for 20mins. The procedure was repeated two more times with equal amount of starting material and the resulting three mixtures were combined. The mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and water, dried with Na2SO4, filtered and evaporated. The crude product was purified using Biotage Horizon HPFC system (40+M column, isocratic run DCM/MeOH (99.5:0.5, 96OmL), gradient run DCM/MeOH (99.5:0.5-92:8, 24OmL), isocratic run DCM/MeOH (92:8, 72OmL)) affording the title compound (1.14g, 88.9%). 1H NMR (500MHz, CDCl3): 6 1.44 (s, 9H), 2.88 (t, 2H), 3.40 (q, 2H), 4.58 (bs, IH), 7.32 (d, 2H), 7.61 (d, 2H); Mass Spectrum: M+it 247.
31% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 150℃; for 0.333333h;Microwave irradiation; t-Butyl 2-(4-cyanophenyl)ethylcarbamate (114) Compound 113 (530 mg, 1.8 mmol) was dissolved in dry DMF (17 mL) under N2. Zn(CN)2 (416 mg, 3.6 mmol) and Pd(PPh3)4 (200 mg, 0.18 mmol) was added. The reaction mixture was stirred and heated at 150 C. in a microwave instrument (CEM Discover) for 20 min and the reaction mixture was then concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluding with EtOAc/hexanes (20~80%) to yield 114 (540 mg, 31%) as a white solid. MS (APCI, negative): m/z 245 [M-H]+.
  • 21
  • [ 24424-99-5 ]
  • [ 73918-56-6 ]
  • [ 144-55-8 ]
  • [ 120157-97-3 ]
YieldReaction ConditionsOperation in experiment
14.6 g (97%) In chloroform; water; Preparation 41 2-(4-bromophenyl)-N-(t-butoxycarbonyl)ethylamine To a room temperature solution of 10.0 g (50.0 mmol) of 4-bromophenethylamine and 11.0 g (50.0 mmol) of di-tert-butyl dicarbonate in 100 mL of chloroform was added 100 mL of saturated aqueous sodium bicarbonate. The mixture was stirred at room temperature for 1.5 hours and diluted with 100 mL of water. The organic layer was separated and the aqueous layer was extracted two times with 100 mL each of chloroform. The combined organics were washed once with 100 mL of 10% aqueous sodium bisulfate, dried (NaSO4), filtered and concentrated in vacuo to afford 14.6 g (97%). Mass Spectrum: M+1=301.
In chloroform; water; PREPARATION 41 2-(4-bromophenyl)-N-(t-butoxycarbonyl)ethylamine To a room temperature solution of 10.0 g (50.0 mmol) of 4-bromophenethylamine and 11.0 g (50.0 mmol) of di-tert-butyl dicarbonate in 100 mL of chloroform was added 100 mL of saturated aqueous sodium bicarbonate. The mixture was stirred at room temperature for 1.5 hours and diluted with 100 mL of water. The organic layer was separated and the aqueous layer was extracted two times with 100 mL each of chloroform. The combined organics were washed once with 100 mL of 10% aqueous sodium bisulfate, dried (NaSO4), filtered and concentrated in vacuo to afford 14.6 9 (97%). Mass Spectrum: M+1=301.
  • 22
  • [ 120157-97-3 ]
  • [ 132690-91-6 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; carbon dioxide; In hexane; water; Step 2 To a 0 C. solution of <strong>[120157-97-3]N-(tert-butoxycarbonyl)-4-bromophenethylamine</strong> (12.82 g, 42.6 mmol) in anhydrous ether (200 ml) under argon was added dropwise n-butyllithium (34 ml, 85.2 mmol, 2.5 M in hexane). The slightly yellow solution turned milky white and was stirred 15 min., at 0 followed by one hour at room temperature. The resulting mixture was cooled to -78 C. in a dry ice-acetone bath. Dry carbon dioxide was bubbled through the stirring reaction mixture for 30 min., and then the reaction mixture was allow to slowly warm to room temperature over 30 min. Water (100 ml) was added, the pH adjusted to 8 with dilute aqueous potassium carbonate solution, and the aqueous layer was separated and extracted with ethyl acetate. The aqueous layer was then cooled to 0 C. and acidified to pH 3 with 3 N aqueous hydrochloric acid. The resulting white precipitate was filtered, washed with water and air dried to provide 4-[2-(N-tert-butoxycarbonylamino)ethyl]benzoic acid (7.8 g).
  • 23
  • [ 87199-18-6 ]
  • [ 120157-97-3 ]
  • [ 921625-82-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3h;Micro wave conditions; A mixture of [2-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (500 mg), 3-hydroxy- benzeneboronic acid (296 mg), sodium carbonate (265 mg), palladium (II) acetate (7 mg) and tricyclohexylphosphine (10 mg) in water (3 ml) and dioxane (12 ml) is kept at 90C under micro wave conditions for 180 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column (Varian) with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (15Og) with cyclohexane /EtOAc 5/1 to afford pure [2-(3'-hydroxy-biphenyl-4-yl)-ethyl]-carbamic acid tert-butyl ester.MS (ESI+): 336 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28.
  • 24
  • [ 124-38-9 ]
  • [ 120157-97-3 ]
  • [ 132690-91-6 ]
YieldReaction ConditionsOperation in experiment
To a 0 C. solution of <strong>[120157-97-3]N-(tert-butoxycarbonyl)-4-bromophenethylamine</strong> (12.82 g, 42.6 mmol) in anhydrous ether (200 ml) under argon was added dropwise n-butyllithium (34 ml, 85.2 mmol, 2.5 M in hexane).. The slightly yellow solution turned milky white and was stirred 15 min., at 0 followed by one hour at room temperature.. The resulting mixture was cooled to -78 C. in a dry ice-acetone bath.. Dry carbon dioxide was bubbled through the stirring reaction mixture for 30 min., and then the reaction mixture was allow to slowly warm to room temperature over 30 min.. water (100 ml) was added, the PH adjusted to 8 with dilute aqueous potassium carbonate solution, and the aqueous layer was separated and extracted with ethyl acetate.. The aqueous layer was then cooled to 0 C. and acidified to PH 3 with 3 N aqueous hydrochloric acid.. The resulting white precipitate was filtered, washed with water and air dried to provide 4-[2-(N-tert-butoxycarbonylamino)ethyl]benzoic acid (7.8 g).
  • 25
  • [ 17997-47-6 ]
  • [ 120157-97-3 ]
  • [ 1418212-16-4 ]
YieldReaction ConditionsOperation in experiment
[2- (4-Bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (1. 5g, 4.99 mmol) was dissolved in toluene (0.2 M) in a 100 mL round-bottom flask. To this was added LiCl (10.6 mg, 0.25 mmol, 0. 05eq) and the resulting solution was flushed under nitrogen for 2-3 minutes. PdCl2 (PPh3) 2 (175.4 mg, 0. 25mmol, 0. 05eq) was added to the reaction mixture and the solution was again flushed under nitrogen for 2-3 minutes. 2-Tributylstannanyl-pyridine, from Frontier (1. 84g, 4.99mmol, leq) was added last and the reaction mixture was heated to 110C overnight. The solvent was removed under vacuum. The crude material was purified on column chromatography (silica gel), and eluted with EtOAc-Hexanes 15: 85 to afford [2- (4-Pyridin-2-yl-phenyl)-ethyl]-carbamic acid tert-butyl ester in good yield.
  • 26
  • [ 110-91-8 ]
  • [ 120157-97-3 ]
  • [ 1235711-35-9 ]
YieldReaction ConditionsOperation in experiment
40% With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 110℃; for 16h;Inert atmosphere; PREPARATION E : [2-(4-Morpholin-4-yl-phenyl)-ethyl] -carbamic acid tert-butyl ester; [Show Image] Under argon, a 10 mL one-necked round bottomed flask was charged with [2-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (Preparation D) (300 mg, 1.0 mmol) in dioxane (3.0 mL). Morpholine (218 muL, 2.5 mmol) was added followed by 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl (124 mg, 0.2 mmol) and cesium carbonate (978 mg, 3.0 mmol). The reaction mixture was purged with argon during 10 minutes and palladium II acetate (23 mg, 0.1 mmol) was added. The reaction mixture was stirred at 110C during 16 hours and diluted with dichloromethane. This mixture was absorbed on silica gel and purified by flash chromatography (Hex:EtOAc 100:0 to 0:100). The isolated compound was dried under high vacuum yielding [2-(4-morpholin-4-yl-phenyl)-ethyl]-carbamic acid tert-butyl ester (120 mg, 40%) as a pale brown powder. 1H NMR (300 MHz, CDCl3-d): delta 7.10 (AB system, 2H, J=8.6 Hz), 6.86 (AB system, 2H, J=8.6 Hz), 4.51 (bs, 1H), 3.86 (t, 4H, J=4.8 Hz), 3.33 (m, 2H), 3.13 (t, 4H, J=4.8 Hz), 2.72 (t, 2H, J=6.9 Hz), 1.43 (s, 9H). MS (ESI+) m/z: 307.38 (M+H)+.
  • 27
  • [ 557-21-1 ]
  • [ 120157-97-3 ]
  • [ 172348-86-6 ]
YieldReaction ConditionsOperation in experiment
73% With 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;tris-(dibenzylideneacetone)dipalladium(0); In N,N-dimethyl-formamide; at 100℃; for 18h; 2. A mixture of tert-butyl 4-bromophenethylcarbamate (750 mg, 2.5 mmol, 1.0 eq.) and Zn(CN)2 (439 mg, 3.75 mmol, 1.5 eq.) in dry DMF (15 ml) was degassed with argon for 15 min. Xanthphos (290 mg, 0.5 mmol, 0.2 eq.) and Pd2(dba)3 (229 mg, 0.25 mmol, 0.1 eq.) were added to the reaction mixture and it was heated to 100 C for 18 h. The reaction mixture was diluted with water (40 ml) and extracted with ethyl acetate (2 x 50 ml). The organic layer was washed with brine (50 ml) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (neutral alumina, 10 % ethyl acetate in hexanes) to yield the desired product as a reddish solid. Yield: 73 % (450 mg, 1.83 mmol)
  • 28
  • [ 120157-97-3 ]
  • [ 74-88-4 ]
  • [ 1191063-30-5 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 18h; This carbamate was dissolved in DMF (40 mE) andtreated with 60% NaR dispersion (1.7 g, 42 mmol, 3.0 eq.)and Mel (1.7 mE, 28 mmol, 2.0 eq.). After stirring at ambient temperature 18 h, the reaction mixture is extracted from 0.1 MNaOH into MTBE, dried on Na2 SO4, and concentrated toclean N-Boc-N-methyl-4-bromophenethylamine (4.67 g,quant.). 1 g of this bromide (3.2 mmol) was converted viaMethod 3 to N-l3oc-N-methyl-4-boronophenethylaminepinacol ester (981 mg, 85%).
59% Intermediate 981 ,1 -Dimethylethyl [2-(4-bromophenyl)ethyl]methylcarbamateSodium hydride (60% in mineral oil, 134 mg, 3.35 mmol) was added portionwise to a solution of 1 ,1 -dimethylethyl [2-(4-bromophenyl)ethyl]carbamate (for a preparation see Intermediate 99) (914 mg, 3.04 mmol) in tetrahydrofuran (THF) (25 mL). The reaction mixture was stirred at room temperature for 15 min, then methyl iodide (0.952 mL, 15.22 mmol) was slowly added to the mixture which was stirred under nitrogen for a further 2 h. An extra portion of methyl iodide (0.952 mL, 15.22 mmol) was then added to the mixture which was stirred at the same temperature for 2 more hours before being treated with methanol (1 mL). Most of the solvent was removed in vacuo and the residue partitioned between AcOEt (50 mL) and water (30 mL). The layers were separated and the aqueous phase was extracted with AcOEt (20 mL). The combined organic phases were washed with brine, dried over MgS04 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 5 to 15% AcOEt in Hexanes) gave 1 ,1 - dimethylethyl [2-(4-bromophenyl)ethyl]methylcarbamate (566 mg, 1.801 mmol, 59%) as a colourless oil. LCMS (method G): Retention time 1.35 min, [M+H]+ = 315.9 (1 Br)
59% Sodium hydride (60% in mineral oil, 134 mg, 3.35 mmol) was added portionwise to a solution of 1,1-dimethylethyl [2-(4-bromophenyl)ethyl]carbamate (for a preparation see Intermediate 99) (914 mg, 3.04 mmol) in tetrahydrofuran (THF) (25 mL). The reaction mixture was stirred at room temperature for 15 min, then methyl iodide (0.952 mL, 15.22 mmol) was slowly added to the mixture which was stirred under nitrogen for a further 2 h. An extra portion of methyl iodide (0.952 mL, 15.22 mmol) was then added to the mixture which was stirred at the same temperature for 2 more hours before being treated with methanol (1 mL). Most of the solvent was removed in vacuo and the residue partitioned between AcOEt (50 mL) and water (30 mL). The layers were separated and the aqueous phase was extracted with AcOEt (20 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 5 to 15% AcOEt in Hexanes) gave 1,1-dimethylethyl [2-(4-bromophenyl)ethyl]methylcarbamate (566 mg, 1.801 mmol, 59%) as a colourless oil. LCMS (method G): Retention time 1.35 min, [M+H]+=315.9 (1 Br)
  • 29
  • [ 120157-97-3 ]
  • [ 1301198-76-4 ]
  • 30
  • [ 1301198-32-2 ]
  • [ 120157-97-3 ]
  • [ 1301198-58-2 ]
YieldReaction ConditionsOperation in experiment
31% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); at 100℃; for 0.833333h;Inert atmosphere; Intermediate 87 1 -Methylethyl ((2S,4 ?)-1 -acetyl-6-{4-[2-([(1 ,1 - dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1 ,2,3,4-tetrahydro-4- quinolinyl)carbamateA mixture of 1 -methylethyl [(2S,4R)-1 -acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 ,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 52) (125 mg, 0.300 mmol), 1 ,1 -dimethylethyl [2-(4- bromophenyl)ethyl]carbamate (90 mg, 0.300 mmol), potassium carbonate (104 mg, 0.751 mmol) and tetrakis(triphenylphosphine)palladium(0) (17.35 mg, 0.015 mmol) was degassed under house vacuum for 15 min and quenched several times with nitrogen, then was then stirred at 100C under nitrogen for 50 min before being cooled to room temperature. Most of the solvent was removed in vacuo and the residue was partitioned between AcOEt (20 mL) and water (15 ml_). The layers were separated and the aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgS04 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 50 to 75% AcOEt in Hexanes) gave 1 -methylethyl ((2S,4R)-1 -acetyl-6-{4-[2-([(1 ,1 - dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1 ,2,3,4-tetrahydro-4- quinolinyl)carbamate (50 mg, 0.093 mmol, 31 %) as a colourless oil.LCMS (method G): Retention time 1.16 min, [M+H-Boc]+ = 410.3
31% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); at 100℃; for 0.833333h;Inert atmosphere; A mixture of 1-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 52) (125 mg, 0.300 mmol), 1,1-dimethylethyl [2-(4-bromophenyl)ethyl]carbamate (90 mg, 0.300 mmol), potassium carbonate (104 mg, 0.751 mmol) and tetrakis(triphenylphosphine)palladium(0) (17.35 mg, 0.015 mmol) was degassed under house vacuum for 15 min and quenched several times with nitrogen, then was then stirred at 100 C. under nitrogen for 50 min before being cooled to room temperature. Most of the solvent was removed in vacuo and the residue was partitioned between AcOEt (20 mL) and water (15 mL). The layers were separated and the aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 50 to 75% AcOEt in Hexanes) gave 1-methylethyl ((2S,4R)-1-acetyl-6-{4-[2-([(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (50 mg, 0.093 mmol, 31%) as a colourless oil.LCMS (method G): Retention time 1.16 min, [M+H-Boc]+=410.3
  • 31
  • [ 1301198-32-2 ]
  • [ 120157-97-3 ]
  • [ 1301198-91-3 ]
  • 32
  • [ 120157-97-3 ]
  • [ 163105-89-3 ]
  • [ 1417540-98-7 ]
YieldReaction ConditionsOperation in experiment
58% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; at 90℃; for 18h;Inert atmosphere; Example 6 Synthesis of tert-Butyl 4-(6-oxo-1,6-dihydropyridin-3-yl)phenethylcarbamate IMS (600 mL) and water (250 mL) were degassed thoroughly. tert-Butyl 4-bromophenethylcarbamate (32.7 g, 109 mmol), sodium carbonate (46.2 g, 436 mmol), palladium tetrakis (12.6 g, 11.0 mmol) and 2-methoxypyridine boronoic acid (25.0 g, 163 mmol) were added and the reaction mixture heated to 90 C. for 18 hours. The reaction was cooled to room temperature, filtered and the residue washed with IMS (100 mL) and ethyl acetate (1 L). The filtrate was washed with water (500 mL), dried (MgSO4) and concentrated to give a brown solid. The crude residue was subject to column chromatography (0 to 1.5% MeOH in DCM) to give a white solid, tert-butyl 4-(6-oxo-1,6-dihydropyridin-3-yl)phenethylcarbamate (20.95 g, 63.8 mmol, 58% yield).
  • 33
  • [ 120157-97-3 ]
  • [ 89641-18-9 ]
  • [ 1417540-94-3 ]
YieldReaction ConditionsOperation in experiment
91% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; at 90℃; for 18h;Inert atmosphere; Example 2 Synthesis of tert-butyl 4-(2,4-dimethoxypyrimidin-5-yl)phenethylcarbamate Industrial methylated spirits (IMS; 15 mL) and water (5 mL) were degassed thoroughly. tert-butyl 4-bromophenethylcarbamate (1.08 g, 3.63 mmol), sodium carbonate (1.54 g, 14.52 mmol), palladium tetrakis (0.42 g, 0.36 mmol) and 2,4-dimethoxy-5-pyrimidinylboronic acid (1.00 g, 5.44 mmol) were added and the reaction mixture heated to 90 C. for 18 hours. No starting material was observed by LCMS. Water (100 ml) and ethyl acetate (300 ml) were added and the organic layer separated. The organic layer was washed with water (100 ml), dried (MgSO4) and concentrated to give a yellow oil. The crude residue was subject to column chromatography (20 to 60% ethyl acetate/hexane) to give a yellow oil, tert-butyl 4-(2,4-dimethoxypyrimidin-5-yl)phenethylcarbamate, which crystallized on standing (1.18 g, 3.28 mmol, 91%).
  • 34
  • [ 761446-45-1 ]
  • [ 120157-97-3 ]
  • [ 1417540-96-5 ]
YieldReaction ConditionsOperation in experiment
95% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; at 90℃;Inert atmosphere; Example 4 Synthesis of tert-Butyl 4-(6-oxo-1,6-dihydropyridin-3-yl)phenethylcarbamate IMS (50 mL) and water (16 mL) were degassed thoroughly. tert-Butyl 4-bromophenethylcarbamate (3.52 g, 11.7 mmol), sodium carbonate (5.0 g, 46.9 mmol), palladium tetrakis (1.35 g, 1.2 mmol) and 1-benzyl-1H-pyrazole-4-boronic acid pinacol ester (5.0 g, 17.6 mmol) were added and the reaction mixture heated to 90 C. overnight. The reaction was partitioned between ethyl acetate (500 mL) and water (250 mL) and brine (250 mL), then dried (MgSO4). Filtration and removal of the solvent gave the crude residue which was subject to column chromatography (50% ethyl acetate/heptane) to give tert-butyl 4-(6-oxo-1,6-dihydropyridin-3-yl)phenethylcarbamate (4.2 g, 11.1 mmol, 95% yield).
 

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