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Chemical Structure| 847818-74-0
Chemical Structure| 847818-74-0
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Product Details of [ 847818-74-0 ]

CAS No. :847818-74-0 MDL No. :MFCD05861380
Formula : C10H17BN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :HLXOVAMYQUFLPE-UHFFFAOYSA-N
M.W : 208.07 Pubchem ID :4912908
Synonyms :

Calculated chemistry of [ 847818-74-0 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.7
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 59.97
TPSA : 36.28 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.68 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 1.25
Log Po/w (WLOGP) : 0.72
Log Po/w (MLOGP) : 0.3
Log Po/w (SILICOS-IT) : 0.29
Consensus Log Po/w : 0.51

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.1
Solubility : 1.66 mg/ml ; 0.00798 mol/l
Class : Soluble
Log S (Ali) : -1.61
Solubility : 5.1 mg/ml ; 0.0245 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.4
Solubility : 0.823 mg/ml ; 0.00395 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.02

Safety of [ 847818-74-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 847818-74-0 ]

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

  • Upstream synthesis route of [ 847818-74-0 ]
  • Downstream synthetic route of [ 847818-74-0 ]

[ 847818-74-0 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 930-36-9 ]
  • [ 61676-62-8 ]
  • [ 847818-74-0 ]
YieldReaction ConditionsOperation in experiment
77%
Stage #1: With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 1 h;
Stage #2: at -78 - 0℃; for 1.25 h;
Stage #3: With ammonium chloride In tetrahydrofuran
To a solution of 1-methyl pyrazole (4.1 g, 50 mmole) in THF (100 mL) at 00C was added n-BuLi (2.2M in THF, 55 mmole). The reaction solution was stirred for 1 hour at RT and then cooled to -78°C [J. Heterocyclic Chem. 41 , 931 (2004)]. To the reaction solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (12.3 mL, 60 mmole). After 15 min at -78°C, the reaction was allowed to warm to 00C over 1 hour. The reaction <n="32"/>was diluted with saturated NH4CI solution and extracted with DCM. The organic fractions were washed with H2O (2 x 100 ml_), dried over Na2SO4 and concentrated under vacuum to afford a tan solid (8.0 g, 77percent) which was used without further purification. LCMS (ES) m/z 127 (M+H)+ for [RB(OH)2]; 1H NMR (CDCI3, 400 MHz) δ 7.57 (s, 1 H), 6.75 (s, 1 H), 4.16 (s, 3H), and 1.41 (s, 12H).
77%
Stage #1: With n-butyllithium In tetrahydrofuran at 0 - 20℃;
Stage #2: at -78℃;
Preparation 2 Preparation of 1-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 /-/-pyrazoleTo a solution of 1-methyl pyrazole (4.1 g, 50 mmole) in THF (100 mL) at 00C was added n-BuLi (2.2M in THF, 55 mmole). The reaction solution was stirred for 1 hour at RT and then cooled to -78°C [J. Heterocyclic Chem. 41 , 931 (2004)]. To the reaction solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (12.3 mL, 60 mmole). After 15 min at -78°C, the reaction was allowed to warm to 00C over 1 hour. The reaction was diluted with saturated NH4CI solution and extracted with DCM. The organic fractions were washed with H2O (2 x 100 mL), dried over Na2SO4 and concentrated under vacuum to afford a tan solid (8.0 g, 77percent) which was used without further purification. LCMS (ES) m/z 127 (M+H)+ for [RB(OH)2]; 1H NMR (CDCI3, 400 MHz) δ 7.57 (s, 1 H), 6.75 (s, 1 H), 4.16 (s, 3H), and 1.41 (s, 12H).
76%
Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 1 h;
Stage #2: at -78 - 0℃; for 1.25 h;
To a solution of 1 -methyl pyrazole (4.1 g, 50 mmole) in THF (100 mL) at 00C was added n-BuLi (2.2M in THF, 55 mmole). The reaction solution was stirred for 1 hour at RT and then cooled to -78°C [J. Heterocyclic Chem. 41 , 931 (2004)]. To the reaction solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (12.3 mL, 60 mmole). After 15 min at -78°C, the reaction was allowed to warm to 00C over 1 hour. The reaction was diluted with saturated NH4CI solution and extracted with DCM. The organics were dried over Na2SO4 and concentrated under vacuum to afford a tan solid (8.0 g, 76percent) which was used without further purification. LCMS (ES) m/z 127 (M+H)+ for [RB(OH)2]; 1H NMR (CDCI3, 400 MHz) δ 7.57 (s, 1 H), 6.75 (s, 1 H), 4.16 (s, 3H), and 1.41 (s, 12H).
Reference: [1] Patent: WO2009/158372, 2009, A1, . Location in patent: Page/Page column 30; 31
[2] Patent: WO2009/158374, 2009, A2, . Location in patent: Page/Page column 30
[3] Patent: WO2008/98105, 2008, A1, . Location in patent: Page/Page column 36
[4] Patent: US2010/216843, 2010, A1, . Location in patent: Page/Page column 20-21
[5] Patent: WO2008/121786, 2008, A1, . Location in patent: Page/Page column 42-43
[6] Drugs of the Future, 2014, vol. 39, # 8, p. 541 - 546
  • 2
  • [ 5419-55-6 ]
  • [ 847818-74-0 ]
YieldReaction ConditionsOperation in experiment
51%
Stage #1: With n-butyllithium In tetrahydrofuran; hexanes at -78 - 20℃; for 1 h;
Stage #2: for 1 h;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexanes
EXAMPLE 27; 2-r4-ri-methyl-lH-pyrazol-5-vnphenyll-N-fflRVl-r5-r2.2.2-trifluoroethoxy')pyridin-2- yli ethyl > acetamide; To a 5°C solution of 5.00 mL (60.9 mmol) n-methylpyrazole in 100 ml THF was added dropwise 381 mL (60.9 mmol) 1.6M n-BuLi in hexanes. The reaction mixture was warmed to room temperature, and after lhr at room temperature, the reaction mixture was cooled to -78°C. 18.4 mL (79.0 mmol) isopropyl borate was added. After 1.00 h at -78°C, the reaction mixture was quenched with 12.OmL of 2N HCl. The resulting solution was concentrated in vacuo and azotroped with toluene. The resulting crude material was dissolved in 11 ImL THF.6.57g (55.6mmol) pincol and 1.0Og of molecular sieves were added. After 24.0 hr at room temperature, the reaction mixture was filtered and concentrated. The resulting residue was dissolved in 10OmL hexanes, washed twice with water, dried over NaSO4, filtered, and concentrated in vacuo to afford 5.9Og (51percent) l-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan- <n="64"/>2-yl)-lH-pyrazole. IH NMR (CD3OD, 400 MHz) 7.45(d, IH, J = 1-92); 7.67 (d, 2H, J = 1.92Hz); 4.04 (s, 3H); 1.35 (s, 12H). ESMS+1 for Ci0HnBN2O2: 209.1.
Reference: [1] Patent: WO2007/120729, 2007, A2, . Location in patent: Page/Page column 62-63
  • 3
  • [ 76-09-5 ]
  • [ 720702-41-0 ]
  • [ 847818-74-0 ]
YieldReaction ConditionsOperation in experiment
67% at 20℃; for 48 h; Molecular sieve A solution of 1-methylpyrazole (25.0 g, 305 mmol) in tetrahydrofuran (THF) (600 mL) was cooled to 0 °C. n-Butyl lithium (1.6 M in hexanes, 209 mL, 335 mmol) was added drop-wise over 1 h, keeping the temperature below 7 °C. The solution was stirred at room temperature (rt) for 3 h before cooling to −70 °C. B(OMe)3 (44.4 mL, 0.40 mol) was slowly added, keeping the reaction temperature below −65 °C. The resulting mixture was allowed to warm to rt, before it was quenched with 15percent aqueous (aq) NH4Cl (450 mL). The mixture was extracted with THF (3 × 500 mL), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellowish solid (15.6 g, 41percent). The aq layer was concentrated in vacuo, and the resulting solid was repeatedly extracted with THF (5 × 250 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo, yielding a yellow solid (20.3 g, 52percent). The combined yield of   (1-methyl-1H-pyrazol-5-yl)boronic acid was 35.9 g (93percent), and 20.3 g (161 mmol) of this material was esterified with   pinacole (28.4 g, 240 mmol) in   THF (200 mL). 4 Å molecular sieves (6.0 g dried in vacuo at 50 °C) were added, and the resulting mixture was stirred at rt for 2 days. The sieves were filtered off, and the filtrate was concentrated in vacuo. The resulting crude product was dissolved in heptane (500 mL) and washed with water (2 × 250 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a white solid. This material was recrystallized from acetonitrile yielding white   crystals (22.5 g, 67percent). Mp 71.0–71.6 °C (Ivachtchenko et al.,21 74–76 °C). 1H NMR (500 MHz, DMSO-d6): δ, 7.46 (d, J = 1.9 Hz, pyrazole H-3), 6.62 (d, J = 1.9 Hz, pyrazole H-4), 3.98 (s, N-methyl), 1.30 (s, pinacol methyl groups, 12H). 13C NMR (126 MHz, DMSO-d6): δ, 138.3, 115.9, 84.4 (2C), 41.9, 24.9 (4C). Anal. calcd for C10H17BN2O2: C, 57.73; H, 8.24; N, 13.46. Found: C, 57.72; H, 8.08; N, 13.40.#10;
Reference: [1] Journal of Heterocyclic Chemistry, 2004, vol. 41, # 6, p. 931 - 939
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 196 - 204
  • 4
  • [ 844501-71-9 ]
  • [ 74-88-4 ]
  • [ 1020174-04-2 ]
  • [ 847818-74-0 ]
Reference: [1] Patent: US2012/316166, 2012, A1, . Location in patent: Page/Page column 71
  • 5
  • [ 930-36-9 ]
  • [ 25015-63-8 ]
  • [ 847818-74-0 ]
Reference: [1] Organometallics, 2018, vol. 37, # 10, p. 1567 - 1574
  • 6
  • [ 844501-71-9 ]
  • [ 74-88-4 ]
  • [ 1020174-04-2 ]
  • [ 847818-74-0 ]
Reference: [1] Patent: US2012/316166, 2012, A1, . Location in patent: Page/Page column 71
  • 7
  • [ 847818-74-0 ]
  • [ 942070-88-4 ]
Reference: [1] Chemistry - A European Journal, 2015, vol. 21, # 34, p. 11976 - 11979
  • 8
  • [ 847818-74-0 ]
  • [ 1258861-20-9 ]
YieldReaction ConditionsOperation in experiment
92% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 74℃; for 12 h; Inert atmosphere A solution of 10 (0.20 g, 0.43 mmol, 1.0 equiv.) in a mixture of toluene(18 mL), ethanol (6 mL) and H2O (6 mL) was treated with Na2CO3(0.09 g, 0.86 mmol, 2.0 equiv.) and 1-methyl-1H-pyrazole-5-boronicacid pinacol ester (0.10 g, 0.47 mmol, 1.1 equiv.) and the mixture waspurged with nitrogen for 20 min. Pd(PPh3)4 (60 mg) was added andthe mixture was stirred at 74 °C for 12 h. After monitoring by TLC,the reaction mixture was cooled to room temperature and diluted withDCM. The organic portion was washed with sat. sodium chloridesolution, and dried over anhydrous Na2SO4 and concentrated underreduced pressure. The resulting residue was purified by flash silica gelchromatography (dichloromethane/MeOH, 30:1) to provide Taladegibas a yellow foam. Yield 0.20 g, 92percent; m.p. 95 °C; 1H NMR (300 MHz,CDCl3) δ 8.09 (dd, J = 7.6, 7.7 Hz, 2H), 7.90–7.80 (m, 2H), 7.65 (d,J = 1.8 Hz, 1H), 7.47–7.28 (m, 3H), 6.59 (d, J = 1.8 Hz, 1H), 4.97–4.89(m, 1H), 4.21–4.08 (m, 2H), 4.05 (s, 3H), 3.44–3.35 (m, 2H), 2.76 (s,3H), 2.35–2.11(m, 2H), 2.04–1.88 (m, 2H); 13C NMR (75 MHz, CDCl3)δ 168.0, 163.8, 159.9, 147.4, 138.2, 136.7, 132.0, 131.9, 131.5, 129.4,129.0, 128.0, 126.3, 124.6, 121.4, 119.5, 114.5, 109.1, 56.9, 51.4, 38.3,31.8, 29.7, 28.4; MS calcd for C26H24F4N6O [M + H]+: 513.2026; found:513.2018.
92% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 74℃; for 12 h; Inert atmosphere Compound 10 (0.2 g, 0.429 mmol, 1 eq.) Was dissolved in a mixed solution of 18 mL of toluene, 6 mL of ethanol and 6 mL of water,To the solution were added 0.091 g (0.858 mmol, 2 eq.) Of sodium carbonate and 0.098 g (0.472 mmol, 1.1 eq.) Of 1 -methyl- lH-pyrazole-5-boronic acid pinacol ester (CAS No. 847818- 74-0),After degassing with nitrogen for 20 min, 60 mg of tetrakis (triphenylphosphine) palladium was added, and the mixture was degassed with nitrogen for 10 min. After the reaction was stirred uniformly, the reaction was refluxed at 74 ° C. for 12 h.After the reaction was completed, the mixture was cooled to room temperature, diluted with dichloromethane, washed three times with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product.Purification by column chromatography (eluent dichloromethane / methanol, 30: 1 by volume) gave LY-2940680 (0.202 g, 92percent yield) as a pale yellow foam.
Reference: [1] Journal of Chemical Research, 2017, vol. 41, # 2, p. 112 - 115
[2] Patent: CN106279114, 2017, A, . Location in patent: Paragraph 0037; 0061; 0062
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