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[ CAS No. 870063-60-8 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 870063-60-8
Chemical Structure| 870063-60-8
Chemical Structure| 870063-60-8
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Product Details of [ 870063-60-8 ]

CAS No. :870063-60-8 MDL No. :MFCD11656367
Formula : C6H6FNO Boiling Point : -
Linear Structure Formula :- InChI Key :DEGCNYCNQMSEKG-UHFFFAOYSA-N
M.W : 127.12 Pubchem ID :49760376
Synonyms :

Calculated chemistry of [ 870063-60-8 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 30.32
TPSA : 33.12 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.03 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.32
Log Po/w (XLOGP3) : 0.07
Log Po/w (WLOGP) : 0.98
Log Po/w (MLOGP) : 0.31
Log Po/w (SILICOS-IT) : 1.63
Consensus Log Po/w : 0.86

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.1
Solubility : 10.1 mg/ml ; 0.0795 mol/l
Class : Very soluble
Log S (Ali) : -0.32
Solubility : 60.9 mg/ml ; 0.479 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.09
Solubility : 1.03 mg/ml ; 0.00807 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.26

Safety of [ 870063-60-8 ]

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 [ 870063-60-8 ]

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

  • Upstream synthesis route of [ 870063-60-8 ]
  • Downstream synthetic route of [ 870063-60-8 ]

[ 870063-60-8 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 372-47-4 ]
  • [ 68-12-2 ]
  • [ 870063-60-8 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -65 - -60℃; Inert atmosphere
Stage #2: at -60℃; for 1 h;
Stage #3: at 0℃; for 1 h;
[0122] A mechanically stirred solution of 3-fluoropyridine (600 g, 6.18 mol) in dry THE (6 L) was cooled to -65°C under N2 atmosphere. Lithium diisopropylamine solution in THE (3.4 L, 6.5 mol) was added over 2 hours while keeping the temperature below -60°C, and the reaction mixture was allowed to stir an additional hour below -60°C. Neat DME (804 mL, 10.4 mol) was then added over a one hour period at a rate as to maintain the temperature below -60°C. The reaction mixture was monitored by TLC for the complete consumption of 3-fluoropyridine starting material. Upon completion, the reaction mixture was then warmed to -10°C, and H20 (1.1 Kg, 62 mol) was added. Sodium borohyd ride (234 g, 6.18 mol) was then added in two portions over several minutes at 0°C with stirring. Then 6 M HCI (5.6 L) was added over 1 h while maintaining the reaction quenching temperature between 0-25°C. The reaction mixture was then heated to 40°C and stirred at this temperature overnight. To the mixture 6 M NaOH was then slowly added at 0-15°C to adjust the pH to 12. The aqueous layer was extracted with isopropylacetate (500 mL x 1, 1 Lx 3). The combined organic layers were washed with brine, dried over Na2504 and concentrated in vacuo. To the crude product was added heptane-isopropylacetate (1.2 L, v/v = 5/1), and the mixture was stirred at 0 °C for 30 mm. The product crystallized as a pale-yellow solid during stirring. The mixture was filtered, the filter cake was extracted with cooled heptane (250 mL x 1), collected and dried under vacuum to give the title compound as a pale-yellow solid (688 g, 88percent). 1H NMR (400 MHz, CDCI3) 6 8.42 (d, i = 4.8 Hz, 1H), 8.40 (d, i = 1.6 Hz, 1H), 7.49 (t, i = 4.8 Hz, 1H), 4.85 (s, 2H), 2.35 (br s, 1H).
88%
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -65 - -60℃; for 3 h; Inert atmosphere
Stage #2: at -60℃; for 1 h; Inert atmosphere
Stage #3: With sodium tetrahydroborate; water In tetrahydrofuran at -10 - 0℃; Inert atmosphere
Step 1. (3-fluoropyridin-4-yl)methanol [0171] A mechanically stirred solution of 3-fluoropyridine (600 g, 6.18 mol) in dry THF (6 L) was cooled to -65 °C under N2 atmosphere. Lithium diisopropylamine solution in THF (3.4 L, 6.5 mol) was added over 2 hours while keeping the temperature below -60 °C, and the reaction mixture was allowed to stir an additional hour below -60 °C. Neat DMF (804 mL, 10.4 mol) was then added over a one hour period at a rate as to maintain the temperature below -60 °C. The reaction mixture was monitored by TLC for the complete consumption of 3-fluoropyridine starting material. Upon completion, the reaction mixture was then warmed to -10 °C, and H20 (1.1 Kg, 62 mol) was added. Sodium borohydride (234 g, 6.18 mol) was then added in two portions over several minutes at 0 °C with stirring. Then 6 M HCI (5.6 L) was added over 1 h while maintaining the reaction quenching temperature between 0-25 °C. The reaction mixture was then heated to 40 °C and stirred at this temperature overnight. To the mixture 6 M NaOH was then slowly added at 0-15 °C to adjust the pH to 12. The aqueous layer was extracted with isopropylacetate (500 m L x 1, 1 L x 3). The combined organic layers were washed with brine, dried over Na2S04 and concentrated in vacuo. To the crude product was added heptane-isopropylacetate (1.2 L, v/v = 5/1), and the mixture was stirred at 0 °C for 30 min. The product crystallized as a pale-yellow solid during stirring. The mixture was filtered, the filter cake was extracted with cooled heptane (250 m L x 1), collected and dried under vacuum to give the title compound as a pale-yellow solid (688 g, 88percent). 1H N M R (400 M Hz, CDCI3) δ 8.42 (d, J = 4.8 Hz, 1H), 8.40 (d, J = 1.6 Hz, 1H), 7.49 (t, J = 4.8 Hz, 1H), 4.85 (s, 2H), 2.35 (br s, 1H).
Reference: [1] Patent: WO2016/49048, 2016, A1, . Location in patent: Paragraph 0122
[2] Patent: WO2016/100349, 2016, A2, . Location in patent: Paragraph 0171
  • 2
  • [ 393-53-3 ]
  • [ 870063-60-8 ]
YieldReaction ConditionsOperation in experiment
46%
Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1 h;
Stage #2: With sodium hydroxide; water In tetrahydrofuran at 0℃;
Examples CL, CM, CN, and CO; (3-Fluoro-pyridin-4-yl)-methanol:; At 0° C. LAH (200 mg, 4 eq.) was added to 3-fluoro-isonicotinic acid (186 mg, 1.32 mmol, 1 eq.) suspension in 25 mL THF. The reaction was stirred at 0° C. for 1 hour. The reaction was quenched by adding 0.2 mL water, followed by 0.4 mL 10percent NaOH aqueous solution and 0.6 mL water at 0° C. Ethyl acetate was added to the reaction crude and washed with brine. n-Butanol was used to extract back from the brine. The organic layers were combined and concentrated down and purified (silica gel, 0-15percent MeOH/DCM) to give colorless oil (78 mg, 46percent). 1H NMR (300 MHz, CD3OD): δ 8.39 (m, 2H), 7.61 (m, 1H), 4.86 (s, 2H).
Reference: [1] Patent: US2008/70920, 2008, A1, . Location in patent: Page/Page column 104-105
[2] Journal of the American Chemical Society, 2018, vol. 140, # 9, p. 3322 - 3330
  • 3
  • [ 876919-08-3 ]
  • [ 870063-60-8 ]
YieldReaction ConditionsOperation in experiment
54%
Stage #1: With sodium tetrahydroborate; calcium chloride In tetrahydrofuran; methanol at -20 - 20℃;
Stage #2: With ammonium chloride In tetrahydrofuran; ethanol; water
General Procedure: To a 50 mL round bottom flask equipped with a stir bar were added calcium chloride (96 percent, 1.12 g, 9.67 mmol), tetrahydrofuran (5 mL) and ethanol (5 mL). The suspension was cooled to -20° C and sodium borohydride (96 percent, 699 mg, 17.73 mmol) was added. The reaction mixture was stirred at -20° C for 20 minutes and then a solution of 3- fluoro-isonicotinic acid methyl ester (500 mg, 3.22 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at -20° C for 15 minutes and then at room temperature over the weekend. The reaction was quenched with cold saturated aqueous <n="68"/>ammonium chloride (40 mL) and extracted with diethyl ether (3x60 mL). The combined organic layer was washed with brine (75 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel using dichloromethane: ethyl acetate = 80:20 to 60:40 in a gradient fashion, to give the desired product as a white solid (223 mg, 54 percent). 1H NMR (300 MHz, CDCl3): δ 8.43 (m, 2H), 7.50 (t, IH)54.86 (d, 2H), 2.25 (t, IH).
Reference: [1] Journal of the American Chemical Society, 2018, vol. 140, # 9, p. 3322 - 3330
[2] Patent: WO2007/87135, 2007, A2, . Location in patent: Page/Page column 66
  • 4
  • [ 40273-47-0 ]
  • [ 870063-60-8 ]
YieldReaction ConditionsOperation in experiment
1.12 g for 3 h; Cooling with ice Reference Production Example 5
To a mixture of 1.2 g of 3-fluoroisonicotinaldehyde and 5 ml of ethanol was gradually added 0.36 g of sodium borohydride under ice-cooling, and the mixture was stirred under ice-cooling for 3 hours.
Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate.
The organic layers were combined and washed with saturated brine and dried over magnesium sulfate.
The resulting mixture was concentrated under reduced pressure to obtain 1.12 g of (3-fluoropyridin-4-yl)methanol.
1H-NMR (CDCl3) δ: 8.43-8.41 (m, 1H), 8.40 (d, J=1.7 Hz, 1H), 7.51-7.47 (m, 1H), 4.85 (d, J=5.1 Hz, 2H), 2.35-2.30 (br m, 1H)
Reference: [1] Patent: WO2006/69287, 2006, A1, . Location in patent: Page/Page column 25; 26-27
[2] Tetrahedron, 2009, vol. 65, # 44, p. 8987 - 8994
[3] Patent: WO2010/132999, 2010, A1, . Location in patent: Page/Page column 97
[4] Patent: US2013/90353, 2013, A1, . Location in patent: Paragraph 0758; 0759
  • 5
  • [ 1289010-50-9 ]
  • [ 870063-60-8 ]
YieldReaction ConditionsOperation in experiment
91% With methanol; sodium tetrahydroborate In tetrahydrofuranReflux To a 50 mL conical vial equipped with a condenser was added 3-fluoroisonicotinaldehyde (0.5 ml, 5.02 mmol, 1.0 eq), tetrahydrofuran (20.06 mL, 0.25 M), sodium borohydride (0.190 g, 5.02 mmol, 1.0 eq.), and MeOH (4.01 mL, 1.25 M). The reaction was heated to reflux and stirred overnight. The reaction was cooled to room temperature, extracted with ethyl acetate, washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting white solid was intermediate 50, (3-fluoropyridin-4-yl)methanol (0.580 g, 91.0percent)
Reference: [1] Patent: US2011/105509, 2011, A1, . Location in patent: Page/Page column 52
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