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[ CAS No. 956034-03-0 ] {[proInfo.proName]}

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Chemical Structure| 956034-03-0
Chemical Structure| 956034-03-0
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Product Details of [ 956034-03-0 ]

CAS No. :956034-03-0 MDL No. :MFCD12407824
Formula : C11H15NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :OFSPCMNPGVKHEL-UHFFFAOYSA-N
M.W : 241.24 Pubchem ID :52987670
Synonyms :

Calculated chemistry of [ 956034-03-0 ]

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.45
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 60.23
TPSA : 77.77 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.15 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.7
Log Po/w (XLOGP3) : 2.29
Log Po/w (WLOGP) : 2.22
Log Po/w (MLOGP) : 0.52
Log Po/w (SILICOS-IT) : 1.06
Consensus Log Po/w : 1.76

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.6
Solubility : 0.606 mg/ml ; 0.00251 mol/l
Class : Soluble
Log S (Ali) : -3.56
Solubility : 0.0663 mg/ml ; 0.000275 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.65
Solubility : 0.545 mg/ml ; 0.00226 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.21

Safety of [ 956034-03-0 ]

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 [ 956034-03-0 ]

* 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 [ 956034-03-0 ]
  • Downstream synthetic route of [ 956034-03-0 ]

[ 956034-03-0 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 956034-03-0 ]
  • [ 956034-04-1 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: With trifluoroacetic acid In dichloromethane at 20℃; for 5 h;
Stage #2: With sodium hydrogencarbonate In dichloromethane
To a solution of methyl 3-(tert-butoxycarbonylamino)furan-2-carboxylate (7H) (13.5 g,55.96 mmol) in dichloromethane (100 mL) was added TFA (50 mL) and the resulting solution was stirred at room temperature for 5 h. The crude reaction mixture was concentrated under vacuum to dryness. The residue obtained was dissolved in dichloromethane (200 mL) and washed with sat. NaHC03 (3 x 100 mL). The organic layer was dried over MgS04, and concentrated in vacuum to dryness. The residue obtained was purified by flash column chromatography (silica gel, eluting with MeOH/CHCl3 0 to 20percent) to furnish methyl 3- aminofuran-2-carboxylate (7E) (7.89g, 100percent) as a light yellow oil; 1H NMR (300 MHz, CDC13) δ 7.26 (d, J= 1.9 Hz, 1H), 6.13 (d, J= 2.0 Hz, 1H), 4.51 (s, 2H), 3.88 (s, 3H). MS (ES+): 164.2 (M+Na).
100% With trifluoroacetic acid In dichloromethane at 20℃; for 2 h; To a solution of compound 30-g (0.56 g, 2.3 mmoL) in dichloromethane (4 mL) was added trifluoroacetic acid (2.5 mL), the mixture was stirred at room temperature for 2 hours. After the mixture was concentrated under reduced pressure, the residue was treated with aqueous sodium dicarbonate solution (2 N, 6 mL), then extracted with ethyl acetate (5 mL×3). The organic layers were combined, washed with water (10 mL×3) and saturated brine (20 mL) in sequence, dried over anhydrous sodium sulfate, then filtrated, the filtrate was concentrated under reduced pressure to give yellow liquid 30-f (0.35 g, yield: 100percent), which was used directly for the next step without purification.
86% With trifluoroacetic acid In dichloromethane at 20℃; for 3 h; Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml).
Reaction mixture was stirred at room temperature for 3 h, and was then concentrated.
Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3.
The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate.
The combined organic extracts were dried with Na2SO4 and concentrated.
The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate (574 mg, 86percent): MS (Q1) 142 (M)+.
86%
Stage #1: With trifluoroacetic acid In dichloromethane at 20℃; for 3 h;
Stage #2: With sodium hydrogencarbonate In dichloromethane; water
Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86percent) : MS (Ql) 142 (M)+.
86% With trifluoroacetic acid In dichloromethane at 20℃; for 3 h; Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86percent) : MS (Ql) 142 (M)+.
86% With trifluoroacetic acid In dichloromethane at 20℃; for 5 h; To a solution of 3-tert-butoxycarbonylamino-furan-2-carboxylic acid methyl ester (8.05 g, 33.38 mmol) in DCM (5 mL) was added TFA (5 mL) and the mixture stirred at RT for 5 h. The crude reaction mixture was loaded onto an Isolute.(R). SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a brown solid (4.07 g, 86 percent).1H NMR (400 MHz, CDCl3): δ 3.87 (s, 3 H), 4.58 (bs, 2 H), 6.12 (d, J = 2 Hz, 1 H) and 7.25 (d, J = 2 Hz, 1 H).

Reference: [1] Patent: WO2011/79230, 2011, A2, . Location in patent: Page/Page column 56; 57
[2] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0240; 0243
[3] Patent: US2008/76758, 2008, A1, . Location in patent: Page/Page column 77
[4] Patent: WO2008/70740, 2008, A1, . Location in patent: Page/Page column 137
[5] Patent: WO2008/73785, 2008, A2, . Location in patent: Page/Page column 163-164
[6] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7815 - 7833
[7] Patent: WO2008/152394, 2008, A1, . Location in patent: Page/Page column 25; 33-34
  • 2
  • [ 956034-03-0 ]
  • [ 956034-07-4 ]
Reference: [1] Patent: WO2011/79230, 2011, A2,
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7815 - 7833
[3] Patent: US2015/336982, 2015, A1,
[4] Patent: WO2008/152394, 2008, A1,
  • 3
  • [ 56267-48-2 ]
  • [ 616-38-6 ]
  • [ 956034-03-0 ]
YieldReaction ConditionsOperation in experiment
83%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -30 - 0℃; for 1 h;
Stage #2: at -30 - 0℃; for 0.75 h;
To a solution of furan-3-yl-carbamic acid tert-butyl ester (4.2 g, 22.93 mmol) in anhydrous THF (160 mL) was added NJfJT JV-tetramethylethylenediamine (4.3 mL, 28.49 mmol) and the resulting orange solution was cooled to -30 °C. n-Butyl lithium (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added dropwise and the resulting suspension allowed to warm to 0 0C over 1 h. The reaction mixture was cooled to -30 °C and treated with dimethyl carbonate (5.75 mL, 68.24 mmol), then allowed to warm to 0 °C over 45 min. An aqueous solution of HCl (2 M) was added and the mixture was extracted with EtOAc. The organic layer was isolated, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by column chromatography to give the title compound as a pale yellow solid (4.60 g, 83 percent).1H NMR (300 MHz, CDCl3): δ 1.54 (s, 9 H), 3.92 (s, 3 H), 7.22 (bs, 1 H), 7.38 (s, 1 H) and 8.18 (bs, I H).
51%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexanes at -30 - 0℃; for 1 h;
Stage #2: at -30 - 20℃; for 1 h;
To a solution of tert-butyl furan-3-ylcarbamate 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n- butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0 0C and stirred for 1 h, before being cooled back to -30 °C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51percent) : MS (Ql) 242 (M)+.
51%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -30 - 0℃; for 1 h;
Stage #2: at -30 - 20℃; for 1 h;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane
To a solution of tert-butyl furan-3-ylcarbamate 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n- butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0 °C and stirred for 1 h, before being cooled back to -30 °C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51percent) : MS (Ql) 242 (M)+.
49%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexanes at -30 - 0℃; for 1 h;
Stage #2: at -30 - 0℃; for 0.75 h;
To a solution of tert-butyl furan-3-ylcarbamate (7G) (21 g, 114.65 mmol) in THF (800 mL) was added N,N, N'N'-tetramethylene ethylenediamine (21.5 mL, 142.45 mmol). The resulting orange solution was cooled to -30 °C before treating dropwise with ra-BuLi (1.6 M in hexanes, 157 mL, 250 mmol) and allowed to warm to O °C for 1 h after the addition of "-BuLi. The solution was again cooled to -30 °C and treated with dimethyl carbonate (28.75 mL, 341 mmol), allowed to warm to 0 °C over 45 min. The reaction was quenched with 2M HC1 (400 mL) and extracted with ethyl acetate (800, 600, 400 mL). The combined organic layers were dried over MgS04, concentrated to dryness, and purified by flash column chromatography (silica gel, eluting with hexanes/ethyl acetate 0 to 100percent) to give methyl 3-(tert- butoxycarbonylamino)furan-2-carboxylate (7H) (13.5 g, 49percent) as a light brown oil. NMR (300 MHz, DMSO) δ 8.32 (s, 1H), 7.85 (s, 1H), 7.10 (s, 1H), 3.83 (s, 3H), 1.50 (s, 9H); MS (ES+) 264.1 (M+Na).
25%
Stage #1: With N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -40℃; for 0.333333 h;
Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -40 - 0℃; for 1.66667 h;
Stage #3: at 0 - 20℃; for 1 h;
At −40° C., to a solution of compound 30-h (1.7 g, 9.3 mmoL) in anhydrous THF (50 mL) was added N,N-tetramethylethylenediamine (1.8 mL, 12.1 mmoL), after stirred for 20 minutes, a solution of n-BuLi in n-hexane (2.5 N, 8.4 mL, 21 mmoL) was added dropwise and the reaction temperature was maintained at −40° C. After completion of dropping, the mixture was stirred for further 30 minutes. The mixture was warmed slowly to 0° C., and stirred for another 1 hour, then cooled again to −40° C., stirred for 10 minutes, dimethyl carbonate (2.4 mL, 28 mmoL) was added rapidly to the mixture. The reaction mixture was warmed slowly to room temperature, stirred for another 1 hour. Aqueous hydrochloride solution (2 N, 11 mL) and water (100 mL) were added to quench the reaction, then the mixture was extracted with ethyl acetate (100 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, then filtrated, and the filtrate was concentrated under reduced pressure. The residue was purified by silica column chromatography (petroleum ether:ethyl acetate=100:1) to give white solid 30-g (0.56 g, yield: 25percent). LC-MS (ESI): m/z=142 [M+H]+.

Reference: [1] Patent: WO2008/152394, 2008, A1, . Location in patent: Page/Page column 25; 33
[2] Patent: WO2008/70740, 2008, A1, . Location in patent: Page/Page column 137
[3] Patent: WO2008/73785, 2008, A2, . Location in patent: Page/Page column 163
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7815 - 7833
[5] Patent: WO2011/79230, 2011, A2, . Location in patent: Page/Page column 56
[6] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0240; 0242
  • 4
  • [ 616-38-6 ]
  • [ 956034-03-0 ]
YieldReaction ConditionsOperation in experiment
51%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -30 - 0℃; for 1 h;
Stage #2: at -30 - 20℃; for 1 h;
To a solution of tert-butyl furan-3-ylcarbamate (1.7 g, 1.0 eq) in THF (50 ml) at -30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes).
Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to -30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr.
Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl.
Mixture was extracted with ethyl acetate.
The combined organic extracts were dried with Na2SO4 and concentrated.
The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate (1.14 g, 51percent): MS (Q1) 242 (M)+.
Reference: [1] Patent: US2008/76758, 2008, A1, . Location in patent: Page/Page column 77
  • 5
  • [ 956034-04-1 ]
  • [ 24424-99-5 ]
  • [ 956034-03-0 ]
Reference: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 16, p. 6678 - 6696
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