Home Cart 0 Sign in  
X

[ CAS No. 4414-87-3 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 4414-87-3
Chemical Structure| 4414-87-3
Chemical Structure| 4414-87-3
Structure of 4414-87-3 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 4414-87-3 ]

Related Doc. of [ 4414-87-3 ]

Alternatived Products of [ 4414-87-3 ]

Product Details of [ 4414-87-3 ]

CAS No. :4414-87-3 MDL No. :MFCD09756053
Formula : C9H7N3 Boiling Point : -
Linear Structure Formula :- InChI Key :KSBVCBLNHLSKFN-UHFFFAOYSA-N
M.W : 157.17 Pubchem ID :21911990
Synonyms :

Calculated chemistry of [ 4414-87-3 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.11
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 45.62
TPSA : 52.47 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.57 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.11
Log Po/w (XLOGP3) : 0.97
Log Po/w (WLOGP) : 1.63
Log Po/w (MLOGP) : 0.67
Log Po/w (SILICOS-IT) : 2.3
Consensus Log Po/w : 1.33

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.91
Solubility : 1.91 mg/ml ; 0.0122 mol/l
Class : Very soluble
Log S (Ali) : -1.66
Solubility : 3.44 mg/ml ; 0.0219 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.39
Solubility : 0.0643 mg/ml ; 0.000409 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.55

Safety of [ 4414-87-3 ]

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

Application In Synthesis of [ 4414-87-3 ]

* 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.

  • Upstream synthesis route of [ 4414-87-3 ]
  • Downstream synthetic route of [ 4414-87-3 ]

[ 4414-87-3 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 4414-87-3 ]
  • [ 5654-93-3 ]
Reference: [1] Journal of the American Chemical Society, 1956, vol. 78, p. 1247,1249
  • 2
  • [ 5654-92-2 ]
  • [ 4414-87-3 ]
YieldReaction ConditionsOperation in experiment
71% With methyl iodide In ethanol; water at 20℃; for 16 h; General procedure: A gramine derivative (1.0 equiv) was dissolved in ethanol (5.5mL for 1.34mmol of starting material) and water (0.55mL for 1.34mmol of starting material). The gramine solution was added to potassium cyanide (2.0 equiv) prepared in a separate flask. Iodomethane (2.6 equiv) was added and the reaction was stirred vigorously at room temperature for 16h. Saturated sodium bicarbonate was added to quench the reaction, followed by extraction with ethyl acetate thrice. The combined organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated in vacuo. Purification by flash silica gel column chromatography afforded the indole-3-acetonitrile derivative product.
Reference: [1] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 344 - 367
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 7, p. 2006 - 2008
  • 3
  • [ 773837-37-9 ]
  • [ 5654-92-2 ]
  • [ 4414-87-3 ]
YieldReaction ConditionsOperation in experiment
52%
Stage #1: With acetic acid In water; N,N-dimethyl-formamide at 110℃; for 8 h;
Stage #2: With potassium carbonate In water; N,N-dimethyl-formamide
To a solution of N,N-dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine 30 (5.60 g, 32.0 mmol) in DMF (20 mL) was added a solution of sodium cyanide (2.35 g, 48.2 mmol) in water (16 mL). Acetic acid (5 mL) was then added to the mixture in a dropwise manner, and the resulting solution was heated to 110 °C for 8 h. After cooling to room temperature, the solution was diluted with saturated aq K2CO3 (30 mL) and extracted with ethyl acetate (3.x.40 mL). The organic extracts were dried over magnesium sulfate, filtered and evaporated under reduced pressure to yield the crude product. Purification by flash column chromatography (ethyl acetate/hexane 50:50) gave the pure product 32 as a white crystalline solid (2.59 g, 52percent): mp 135-137 °C (lit.40 136-138 °C); Rf (50percent ethyl acetate/hexane) 0.19; vmax/cm-1 (KBr) 3089, 2888, 2248, 1611, 1585, 1538, 1420, 1337; δH (300 MHz, CDCl3) 3.85 [2H, s, C-H2], 7.14-7.18 [1H, q, J 7.9, 4.8, C-H5], 7.40 [1H, s, C-H2], 7.97-8.01 [1H, dd, J 7.9, 1.5, C-H4], 8.37-8.39 [1H, dd, J 4.8, 1.5, C-H6], 11.92 [1H, br s, NH]; δC (75 MHz, CDCl3) 14.6 (CH2, CH2CN), 102.8 (C, aromatic C), 116.0 (CH, aromatic CH), 117.8 (C, CH2CN), 119.0 (C, aromatic C), 124.0 (CH, aromatic CH), 127.1 (CH, aromatic CH), 143.1 (CH, aromatic CH), 148.9 (C, aromatic C); m/z (ES+) 158.0 [M+H]+ (100percent).
8 g
Stage #1: With dimethyl sulfate In tetrahydrofuran; methanol at 20℃; for 0.5 h;
Stage #2: at 100℃; for 24 h;
To a solution of compound N,N-dimethyl- l-(lH-pyrrolo[2,3-b]pyridin-3-yl)methanamine (35 g, 199.74 mmol) in THF (180 mL) and MeOH (180 mL) was added Me2S04 (45.85 g, 363.52 mmol). The mixture was stirred for 30 mins at 20°C. The mixture was concentrated under reduced pressure to afford a residue, which was washed three times with PE (50 mL * 3). The residue was treated with H20 (150 mL) and NaCN (27.9 g, 569.26 mmol, 2.85 eq), and the solution was stirred at 100 °C for 24 hours. The reaction mixture was cooled to 20 °C and diluted with H20 (20 mL) and extracted with EA (50 mL * 3). The combined organic layers were washed with brine (50 mL * 2), dried over anhydrous Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Si02, DCM/MeOH=10/l) to give the title compound (8 g, 25.48 percent) as a yellow solid. ^-NMR (400MHz, CDC13), δ = 10.27 - 10.06 (m, 1 H), 8.49 - 8.31 (m, 1 H), 7.98 (dd, J = 0.8, 7.6 Hz, 1 H), 7.38 (s, 1 H), 7.17 (dd, J= 4.8, 7.6 Hz, 1 H), 3.85 (s, 2 H).
Reference: [1] Tetrahedron, 2011, vol. 67, # 25, p. 4601 - 4611
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4752 - 4772
[3] Patent: WO2017/143134, 2017, A1, . Location in patent: Page/Page column 20-21
  • 4
  • [ 271-63-6 ]
  • [ 50-00-0 ]
  • [ 7677-24-9 ]
  • [ 4414-87-3 ]
YieldReaction ConditionsOperation in experiment
28%
Stage #1: With N,N-dimethylammonium chloride In dichloromethane; isopropyl alcohol for 0.333333 h; Reflux
Stage #2: With methyl iodide In dichloromethane; toluene at 20℃; for 12 h; Inert atmosphere
Stage #3: at 20℃; for 4 h; Inert atmosphere
1)
Preparation of 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-acetonitrile
To a solution of 1H-pyrrolo[2,3-b]pyridine (1.5 g, 12.7 mmol, 1.0 eq.) and paraformaldehyde (0.46 g, 15.2 mmol, 1.2 eq.) in isopropanol (20 mL) was added dimethylamine hydrochloride (1.24 g, 15.2 mmol, 1.2 eq).
The mixture was stirred at reflux temperature for 20 minutes and then, quenched with ice and 5 M aqueous sodium hydroxide after cooling to room temperature.
The mixture was extracted with ethyl acetate and the organic layer was dried over MgSO4 and evaporated under reduced pressure.
The gramine residue was taken up in a mixture of anhydrous dichloromethane (40 mL) and toluene (80 mL) and then, methyl iodide (1.26 mL, 20.3 mmol, 1.6 eq.) was added under an argon atmosphere.
The mixture was stirred at room temperature for 12 hours and concentrated.
To the residue taken up in anhydrous THF (120 mL) were added, under an argon atmosphere, TMSCN (2.39 mL, 19.1 mmol, 1.5 eq.) and TBAF (38.1 mL, 1M, 38.1 mmol, 3.0 eq.).
The mixture was stirred at room temperature for 4 hours and then, concentrated under reduced pressure.
The crude was taken up in ethyl acetate and the organic layer was washed with a saturated aqueous sodium bicarbonate solution and then, dried over MgSO4.
The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 50:50) to afford 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-acetonitrile as a white solid (0.56 g, 28percent).
Reference: [1] Patent: US9212138, 2015, B2, . Location in patent: Page/Page column 65; 66
  • 5
  • [ 5654-92-2 ]
  • [ 7677-24-9 ]
  • [ 4414-87-3 ]
YieldReaction ConditionsOperation in experiment
0.56 g
Stage #1: With methyl iodide In dichloromethane; toluene at 20℃; for 12 h;
Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 4 h;
To a solution of 1H-pyrrolo[2,3-b]pyridine (1.5 g, 12.7 mmol, 1.0 eq.)and paraformaldehyde (0.46 g, 15.2 mmol, 1.2 eq.) in isopropanol (20 mL) was addeddimethylamine hydrochloride (1.24 g, 15.2 mmol, 1.2 eq). The reaction mixturewas refluxing for 20 minutes and after cooling to room temperature basified topH 12 with 5M aqueous NaOH solution. The reaction mixture was extracted with EtOAc. The organiclayer was washed with H2O, brine, dried (MgSO4) andevaporated. To a solution of the resulting residue in CH2Cl2 (40mL) and toluene (80 mL) was added methyl iodide (1.3 mL, 20.3 mmol, 1.6 eq.). The reaction mixture was stirred at roomtemperature for 12 hours then evaporated. To a solution of resulting residue inTHF (120 mL) were added successively TMSCN (2.4 mL, 19.1 mmol, 1.5 eq.), thenTBAF (38 mL, 1M, 38.1 mmol, 3.0 eq.). The reaction mixture was stirred at roomtemperature for 4 hours, evaporated under vacuum and extracted with EtOAc. The combined organic layers were washed with saturated aqueous Na2CO3 solution, dried (MgSO4), filtered and evaporated. Silicagel flash-column chromatography of the residue (elution with heptane/EtOAc,50/50) afforded 0.56 g of 7f(28 percent) as an amorphous beige solid. IR νmax(cm-1): 2249 (ν CN). 1H NMR (d6-DMSO, 500 MHz) δ (ppm): 4.07 (2H, s, CH2),7.12 (1H, dd, J5-4 = 7.9 Hz, J5-6 = 4.6 Hz,H5), 7.48 (1H, s, H2), 8.03 (1H, d, J4-5 = 7.9 Hz, H4), 8.26(1H, d, J6-5 = 4.6 Hz, H6), 11.70 (1H, s, H pyrrolic). 13C NMR (d6-DMSO, 75.5 MHz) δ(ppm): 13.8 (CH2), 103.2(C3), 115.9 (C5), 118.7 (C3a), 119.7 (C nitrile), 125.0 (C2), 127.0 (C4), 143.7(C6), 148.9 (C7a). ESI-MS: m/z 158.1 ([M+H]+). HRESI-MS: m/z 158.0714 (calcd for C9H8N3+158.0718).
Reference: [1] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 721 - 734
  • 6
  • [ 7677-24-9 ]
  • [ 87358-28-9 ]
  • [ 4414-87-3 ]
YieldReaction ConditionsOperation in experiment
3.90 g With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 4 h; To a mixture of N,N,N-trimethyl-1 -(1 H-pyrrolo[2,3-b]pyridin-3-yl)methanaminium iodide (5.20 g, 27.33 mmcl) in THE (160 mL) was added TMSCN (4.07 g, 41.0 mmol, 5.15 mL) followed by TBAF (1 M,81 .99 mL). The solution was stirred at 20°C for 4 hours. The reaction solution was concentrated and thethe residue was dissolved in ethyl acetate (200 mL). The organic layer was washed with saturated aqueous Na2003 (200 mL), dried over Na2SO4, filtered and concentrated. The crude product was washed with water (250 mL) and dried in vacuum to give 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)acetonitrile (3.90 g) as a white solid.Ms: (M÷H)1581H NMR (400 MHz, MeOD) 6=3.99 (s, 2H), 7.18-7.14 (m, 1H), 7.41 (s, 1H), 8.08 (d, J= 8.0 Hz, 1H), 8.23 (d, J4.8 Hz, 1H).
Reference: [1] Patent: WO2018/213422, 2018, A1, . Location in patent: Page/Page column 96; 97
  • 7
  • [ 77-78-1 ]
  • [ 4414-87-3 ]
Reference: [1] Patent: US5710164, 1998, A,
  • 8
  • [ 271-63-6 ]
  • [ 4414-87-3 ]
Reference: [1] Tetrahedron, 2011, vol. 67, # 25, p. 4601 - 4611
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4752 - 4772
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 721 - 734
[4] Patent: WO2017/143134, 2017, A1,
[5] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 344 - 367
[6] Patent: WO2018/213422, 2018, A1,
  • 9
  • [ 5654-92-2 ]
  • [ 143-33-9 ]
  • [ 4414-87-3 ]
Reference: [1] Journal of the American Chemical Society, 1956, vol. 78, p. 1247,1249
  • 10
  • [ 5654-92-2 ]
  • [ 4414-87-3 ]
Reference: [1] Patent: WO2018/213422, 2018, A1,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 4414-87-3 ]

Nitriles

Chemical Structure| 517918-95-5

[ 517918-95-5 ]

1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile

Similarity: 0.87

Chemical Structure| 344327-11-3

[ 344327-11-3 ]

4-Cyano-7-azaindole

Similarity: 0.84

Chemical Structure| 1159982-14-5

[ 1159982-14-5 ]

4-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Similarity: 0.78

Chemical Structure| 920965-87-3

[ 920965-87-3 ]

4-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Similarity: 0.78

Chemical Structure| 1190309-69-3

[ 1190309-69-3 ]

3-Bromo-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

Similarity: 0.73

Related Parent Nucleus of
[ 4414-87-3 ]

Other Aromatic Heterocycles

Chemical Structure| 325975-67-5

[ 325975-67-5 ]

3-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

Similarity: 0.90

Chemical Structure| 517918-95-5

[ 517918-95-5 ]

1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile

Similarity: 0.87

Chemical Structure| 824-52-2

[ 824-52-2 ]

5-Methyl-1H-pyrrolo[2,3-b]pyridine

Similarity: 0.86

Chemical Structure| 267876-25-5

[ 267876-25-5 ]

(1H-Pyrrolo[2,3-b]pyridin-5-yl)methanamine

Similarity: 0.85

Chemical Structure| 625386-57-4

[ 625386-57-4 ]

3-(Piperazin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

Similarity: 0.84