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[ CAS No. 261732-38-1 ] {[proInfo.proName]}

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Chemical Structure| 261732-38-1
Chemical Structure| 261732-38-1
Structure of 261732-38-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 261732-38-1 ]

CAS No. :261732-38-1 MDL No. :MFCD08059280
Formula : C13H16BrNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :UOCVSZYBRMGQOL-UHFFFAOYSA-N
M.W :298.18 Pubchem ID :21865438
Synonyms :

Calculated chemistry of [ 261732-38-1 ]

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.46
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 75.08
TPSA : 29.54 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.71 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.33
Log Po/w (XLOGP3) : 3.39
Log Po/w (WLOGP) : 3.37
Log Po/w (MLOGP) : 3.19
Log Po/w (SILICOS-IT) : 2.85
Consensus Log Po/w : 3.23

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.89
Solubility : 0.0386 mg/ml ; 0.00013 mol/l
Class : Soluble
Log S (Ali) : -3.69
Solubility : 0.061 mg/ml ; 0.000204 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.03
Solubility : 0.0281 mg/ml ; 0.0000942 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.41

Safety of [ 261732-38-1 ]

Signal Word:Warning Class:
Precautionary Statements:P280-P305+P351+P338 UN#:
Hazard Statements:H317-H319 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 261732-38-1 ]

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

  • Upstream synthesis route of [ 261732-38-1 ]
  • Downstream synthetic route of [ 261732-38-1 ]

[ 261732-38-1 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 22190-33-6 ]
  • [ 24424-99-5 ]
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YieldReaction ConditionsOperation in experiment
95% at 20℃; for 18 h; To a solution of 5-bromo-2,3-dihydro-1H-indole (2.11 g, 10.7 mmol) in 40 mL of THF was added Boc2O (2.56 g, 11.7 mmol).
The reaction mixture was stirred at room temperature for 18 hours, and then concentrated under reduced pressure.
Purification of the residue via flash chromatography (8percent EtOAc in hexane) afforded 5-bromo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (2.59 g, 95percent) as a white solid; MS (M+H)=298.
89% With sodium hydroxide In 1,4-dioxane; water Part 1.
To a solution of 5-bromoindoline (1.0 g, 5 mmol) in 10 ml of dioxane was added 5 mL of a 1N NaOH solution and 5 mL of water.
This mixture was cooled with an ice bath, and di-tert-butyl dicarbonate (1.2 g, 5.5 mmol) was added in one portion.
The reaction was allowed to warm to room temperature, stirred for 4 hours, and then concentrated.
The residue was extracted with ethyl acetate (2*25 mL), and the combined organic phases were washed with water (2*25 mL), saturated aqueous NaCl (2*25 ml), then dried over MgSO4.
Filtration and concentration in vacuo gave N-Boc-5-bromoindoline (1.33 g, 89percent) as a light brown powder after drying. 1H NMR (CDCl3) δ: 1.541 (s, 9H); 3.03-3.08 (t, 2H); 3.92-3.96 (t, 2H); 7.23-7.27 (m, 3H).
80% With potassium carbonate In tetrahydrofuran; water at 20℃; for 2 h; Step 1: tert-butyl 5-bromoindoline-l-carboxylateTo a solution of 5-bromoindoline (280 mg, 1.41 mmol) in THF (15 mL) and H20 (5 mL) was added k2C03 (293 mg, 2.12 mmol), followed by di-tert-butyl dicarbonate (617 mg, 2.82 mmol) and the resulting mixture was stirred at room temperature for 2 hours. The mixture was diluted with water and extracted with EtOAc. The combined extract was washed with brine, dried and concentrated to afford desired product (338 mg, 80percent). 1H NMR (OMSO-d6): δ 7.59 (1H, br), 7.38 (1H, s), 7.30-7.32 (2H, m), 3.90 (2H, t, / = 8.8 Hz), 3.07 (2H, t, / = 8.8 Hz), 1.50 (9H, s).
73% With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16 h; To a solution of 5-bromoindoline (3.3 g, 16.7 mmol) in DCM (33 mL) at room temperaturewas added 4-dimethylaminopyridine (0.21 g, 1.7 mmol), di-iso-propylethyl amine (4.3 g,33.4 mmol) and di-tert-butyldicarbonate (5.8 g, 26.7 mmol). The resulting mixture was stirred at room temperature for 16 h and then concentrated in vacuo. The crude residue was purified by silica gel chromatography (petroleum ether / EtOAc = 9: 1) to give the title compound (3.63 g, 73percent) as a white solid.
55% at 20℃; A solution of 5-bromo-2,3-dihydro-1H-indole (4.97 g, 25.1 mmol), di-tert-butyl dicarbonate (6.0 g, 27.5 mmol) and 4-dimethylaminopyridine (catalytic) in dichloromethane (70 mL) was stirred at room temperature until the starting material was consumed. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on silica gel, eluted with ethyl acetate/hexane to give the product, 4.1 g (55percent). 1H NMR (CDCI3) : δ 1.55 (s, 9 H), 3.06 (t, 2 H), 3.97 (t, 2 H), 7.23-7.27 (m, 2 H) and 7.72 (br m, 1 H).
38% With dmap In acetonitrile at 20℃; for 16 h; 5-Bromoindoline (3.96 g, 20 mmol), di-t-butylcarbonate (4.37 g, 20 mmol), 4-dimethylaminopyridine (2.69 g, 22 mmol) and CH3CN (50 mL) were mixed and stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc (300 mL) and the organic solution was washed successively with water (50 mL), a 1 N HCl solution (50 mL), a saturated NaHCO3 solution (2.x.50 mL) and brine (25 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford a solid. Trituration with hexane and drying in vacuo provided a white solid (2.26 g, 38percent yield): 1H NMR (DMSO-d6, 300 MHz): 7.36 (s, 1H), 7.29 (d, 2H, J=7), 3.86 (t, 2H, J=7), 3.04 (t, 2H, J=7), 1.48 (s, 9H).
Ca. 28.5 g With dmap In acetonitrile at 20℃; for 3 h; 1,1-Dimethylethyl 5-bromo-2,3-dihvdro-1 H-indole-1-carboxylate
To a stirred solution of 5-bromo-2,3-dihydro-1 H-indole (30 g, 151 mmol) and DMAP (0.4 g, 3.27 mmol, 0.02 equiv) in 150 mL of MeCN at room temperature was added Boc20 (43 g, 197 mmol, 1.3 equiv) in one portion. The mixture was stirred at room temperature. After 10 min, the mixture gradually became a suspension. After 3 hours, the suspension was filtered. The cake was washed with cold MeCN (60 mL), and dried under house vacuum for 5 hours to give 1 ,1-Dimethylethyl 5-bromo-2,3-dihydro-1 H-indole-1- carboxylate (ca. 28.5 g prior to drying). LCMS (ES) m/z = 244, 242 as prominent fragments. 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (s, 9 H), 3.06 (t, J=8.7 Hz, 2 H),3.91 (t, J=8.7 Hz, 2 H), 7.31 (dd, J=8.5, 1.9 Hz, 1 H), 7.38 (s, 1 H), 7.51 - 7.71 (br s, 0.6 H).

Reference: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3892 - 3909
[2] Patent: US2008/45543, 2008, A1, . Location in patent: Page/Page column 28
[3] Patent: US6534535, 2003, B1,
[4] Patent: WO2012/103806, 2012, A1, . Location in patent: Page/Page column 47
[5] Patent: WO2016/86200, 2016, A1, . Location in patent: Page/Page column 300
[6] Journal of Medicinal Chemistry, 2012, vol. 55, # 16, p. 7193 - 7207
[7] Patent: US2005/26944, 2005, A1,
[8] Patent: WO2004/69792, 2004, A2, . Location in patent: Page 165
[9] Patent: US2006/63799, 2006, A1, . Location in patent: Page/Page column 11
[10] Patent: US2004/220194, 2004, A1, . Location in patent: Page 20; 21
[11] Patent: US2005/239795, 2005, A1, . Location in patent: Page/Page column 19
[12] Patent: EP1571154, 2005, A1,
[13] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 17, p. 4823 - 4827
[14] Patent: WO2011/119663, 2011, A1, . Location in patent: Page/Page column 86
[15] Patent: US2012/329649, 2012, A1, . Location in patent: Page/Page column 46
[16] Patent: US2014/171314, 2014, A1, . Location in patent: Page/Page column
[17] Patent: WO2014/100163, 2014, A1, . Location in patent: Page/Page column 85
[18] Patent: US2014/171308, 2014, A1, . Location in patent: Paragraph 0413
[19] Journal of Medicinal Chemistry, 2014, vol. 57, # 12, p. 5179 - 5189
[20] Patent: WO2014/100206, 2014, A1, . Location in patent: Page/Page column 86
[21] Patent: US2014/171312, 2014, A1, . Location in patent: Paragraph 0579
[22] Patent: WO2015/56180, 2015, A1, . Location in patent: Page/Page column 73; 74
[23] Patent: US9211280, 2015, B2, . Location in patent: Page/Page column 86
[24] Patent: WO2016/22644, 2016, A1, . Location in patent: Page/Page column 81
  • 2
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Reference: [1] Patent: WO2004/65351, 2004, A1, . Location in patent: Page 82
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  • [ 22190-33-6 ]
  • [ 261732-38-1 ]
Reference: [1] Patent: US6608084, 2003, B1,
  • 4
  • [ 10075-50-0 ]
  • [ 261732-38-1 ]
Reference: [1] Patent: US2012/329649, 2012, A1,
[2] Patent: US2014/171314, 2014, A1,
[3] Patent: WO2014/100163, 2014, A1,
[4] Patent: US2014/171308, 2014, A1,
[5] Patent: WO2014/100206, 2014, A1,
[6] Patent: US2014/171312, 2014, A1,
[7] Patent: US9211280, 2015, B2,
  • 5
  • [ 261732-38-1 ]
  • [ 68-12-2 ]
  • [ 879887-32-8 ]
  • [ 143262-10-6 ]
YieldReaction ConditionsOperation in experiment
18%
Stage #1: With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 2.08333 h;
Stage #2: With acetic acid In tetrahydrofuran; pentane at -78 - 20℃; for 2 h;
5-Bromo-1-t-butyloxycarbonylindoline (2.0 g, 6.7 mmol) and DMF (0.53 mL, 6.7 mmol), were dissolved in THF (30 mL) and the resulting solution was cooled to -78° C. with stirring under a nitrogen atmosphere. A solution of t-butyllithium in pentane (1.7 M, 10.3 mL, 17.5 mmol) was added dropwise over 5 min. The reaction mixture was stirred for 2 h; then HOAc (3 mL) was added. The cloudy mixture was warmed to ambient temperature over 30 min and diluted with EtOAc (100 mL). Successive washings with a saturated Na2CO3 solution (2.x.10 mL) and then brine (10 mL) were performed. Drying over Na2SO4, filtration and removal of solvent in vacuo gave an oil. Column chromatography (EtOAc:hexane: 1:9, then 1:1) and removal of solvent in vacuo provided two products, both were white solids: (1) 1-t-butyloxycarbonylindoline (270 mg, 18percent yield): 1H NMR (CDCl3, 300 MHz): 7.18-7.10 (m, 2H), 6.92 (t, 1H, J=7), 3.97 (t, 2H, J=7), 3.08 (t, 3H, J=7), 1.57 (s, 9H); MS (APCI+): 220 (C13H18NO2, M++H) and (2) the title product (650 mg, 39percent yield): 1H NMR (CDCl3, 300 MHz): 9.86 (s, 1H), 7.9 (br s, 1H), 7.70-7.65 (m, 2H), 4.06 (t, 2H, J=7), 3.15 (t, 2H, J=7), 1.58 (s, 9H); MS (ES+): 248 (C14H18NO3, M++H).
Reference: [1] Patent: US2006/63799, 2006, A1, . Location in patent: Page/Page column 11
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Reference: [1] Patent: WO2012/103806, 2012, A1,
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  • [ 1337531-36-8 ]
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 16, p. 7193 - 7207
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