[ CAS No. 10035-16-2 ]

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Cat. No.: {[proInfo.prAm]}
2D
Chemical Structure| 10035-16-2
Chemical Structure| 10035-16-2
Structure of 10035-16-2

Quality Control of [ 10035-16-2 ]

Purity: {[proInfo.showProBatch.pb_purity]}

Related Doc. of [ 10035-16-2 ]

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Product Details of [ 10035-16-2 ]

CAS No. :10035-16-2MDL No. :MFCD03411182
Formula :C9H6O2Boiling Point :251.5°C at 760 mmHg
Linear Structure Formula :-InChI Key :LLLBDLDNTMMZHL-UHFFFAOYSA-N
M.W :146.14Pubchem ID :2773875
Synonyms :

Computed Properties of [ 10035-16-2 ]

TPSA : 30.2 H-Bond Acceptor Count : 2
XLogP3 : 1.8 H-Bond Donor Count : 0
SP3 : 0.00 Rotatable Bond Count : 1

Safety of [ 10035-16-2 ]

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H302-H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 10035-16-2 ]

  • Upstream synthesis route of [ 10035-16-2 ]
  • Downstream synthetic route of [ 10035-16-2 ]

[ 10035-16-2 ] Synthesis Path-Upstream   1~15

  • 1
  • [ 55745-70-5 ]
  • [ 10035-16-2 ]
YieldReaction ConditionsOperation in experiment
75% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chlorobenzene at 20 - 80℃; for 1.00 h; Inert atmosphere NBS (0.656 g, 3.69 mmol) and AIBN (8.10 mg, 49.2 lmol) wereadded to a solution of 107 (0.364 g, 2.46 mmol) in chlorobenzene(7.3 mL) at room temperature under an argon atmosphere. Afterstirring for 1 h at 80 C, the mixture was cooled to room temperatureand diluted with EtOAc. The organic layers were washed withsaturated aqueous NaHCO3 and brine, dried (Na2SO4), filtered, andconcentrated in vacuo. The residue was purified by silica gel CC(EtOAc/hexane, 3:97) to afford benzofuran-5-carbaldehyde (108)(0.268 g, 1.84 mmol, 75percent) as a colorless oil: 1H-NMR (CDCl3,400 MHz) d: 6.82 (d, J = 2.0 Hz, 1H, furan-H), 7.54 (d, J = 8.8 Hz,1H, Ar–H), 7.65 (d, J = 2.0 Hz, 1H, furan-H), 7.79 (d, J = 8.8 Hz, 1H,Ar–H), 8.07 (s, 1H, Ar–H), 9.99 (s, 1H, –CHO); spectroscopic datawere consistent with those reported in the literature (van Otterloet al., 2005).
60% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chlorobenzene at 80℃; for 1.00 h; To a solution of 2,3-dihydrobenzofuran-5-carbaldehyde (1 g, 6.75 mmol, A) in Chlorobenzene (20 mL), NBS (1.44 g, 8.10 mmol), AIBN (22 mg, 0.13 mmol) were added and the mixture was stirred at 80° C. for 1 h. After cooling the reaction mixture to room temperature, it was washed with aqueous NaHCO3. The organic layer was separated and the aqueous layer was washed with CH2Cl2. The organic layers were combined, dried over Na2SO4 and concentrated under vacuum on a rotary evaporator. The crude product was purified via gradient column chromatography using hexanes and ethyl acetate (100:1 to 1:1) to obtain the desired aldehyde B as brown syrup (60percent) which solidifies at 0° C. [0076] 1H NMR (500 MHz, CDCl3): δ 10.07 (s, 1H), 8.15 (d, J=1.2 Hz, 1H), 7.87 (dd, J=1.5, 8.6 Hz, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 6.90 (m, 1H). [0077] 13C NMR (125 MHz, CDCl3): δ 191.7, 158.2, 146.7, 132.2, 125.7, 124.6, 112.1, 107.2
55% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chlorobenzene at 80℃; for 4.00 h; Cooling with ice To an ice-cold stirred solution of compound A (500 mg, 3.37 mmol, leq) in chlorobenzene (10 ml) were added NBS (721 mg, 4.05 mmol, 1.2 eq) in portions and AIBN (11 mg, 0.07 mmol, 0.02 eq) and the resulting solution was stirred at 80 °C for 4 h. The reaction mixture was cooled to RT, concentrated in vacuo and the residue was washed with saturated aq. NaHCC>3 solution (20 ml). The organic components were extracted with ethyl acetate (50 ml) and the ethyl acetate layer was concentrated in vacuo. The crude material was purified by flash chromatography (Combiflash) using 100-200 mesh silica gel eluting with 5percent ethyl acetate/hexane to obtain the compound B (270 mg, 55percent) as white solid. [0176] FontWeight="Bold" FontSize="10" H NMR (400 MHz, OMSO-d6) δ 10.06 (s, 1 H), 8.28 (s, 1 H), 8.16-8.16 (m, 1 H), 7.89-7.87 (m, 1 H), 7.81-7.79 (m, 1 H), 7.16-7.15 (m, 1 H); (0181) [0177] LCMS: m/z = 147.4 [M+H], RT = 2.99 minutes; (Program Rl, Column Y).
Reference: [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 20, p. 6270 - 6286
[2] Phytochemistry, 2013, vol. 96, p. 132 - 147
[3] Patent: US2014/309427, 2014, A1. Location in patent: Paragraph 0074; 0075; 0076; 0077
[4] Patent: WO2018/64135, 2018, A1. Location in patent: Paragraph 0174-0177
  • 2
  • [ 79002-39-4 ]
  • [ 10035-16-2 ]
YieldReaction ConditionsOperation in experiment
78%
Stage #1: With diisobutylaluminium hydride In n-heptane; dichloromethane at -20 - -15℃; for 0.17 h;
Stage #2: With hydrogenchloride; water In n-heptane; dichloromethane
EXAMPLE 20
Preparation of 1-benzofuran-5-carbaldehyde
To a solution of 1-benzofuran-5-carbonitrile (5.0 g, 34.9 mmol) in CH2Cl2 under nitrogen at -15 to -20° C. was added DIBAL-H (41.9 mL, 41.9 mmol, 1 M/heptane) and the temperature was maintained below -15° C.
After addition was complete, the reaction mixture was stirred at -15 to -20° C. for an additional 10 min.
The reaction mixture was quenched via dropwise addition of aqueous 2N HCl.
The organic layer was separated and washed with water, dried over sodium sulfate, and concentrated to give 4.0 g (78percent) of 1-benzofuran-5-carbaldehyde as a yellow oil.
78%
Stage #1: With diisobutylaluminium hydride In n-heptane; dichloromethane at -20 - -15℃; for 0.17 h;
Stage #2: With hydrogenchloride; water In n-heptane; dichloromethane at 20℃;
EXAMPLE 15:PREPARATION OF 5-(5-FORMYL-I -BENZOFURAN-2-YL)-6-METHYL-4-[(4- METHYL-1 H-INDOL-5-YL)AMINO]NICOTINONITRILEStep a): Preparation of 5-formylbenzofuran.To a -150C to -2O0C solution of 1-benzofuran-5-carbonitrile (5 g, 34.9 mmol) in 50 mL of dichloromethane under nitrogen was added DIBAL-H (41.9 mL, 41.9 mmol, 1.0M in heptane) such that the temperature was less than or equal to -150C. The reaction mixture was stirred for an additional 10 min at -150C to -2O0C and quenched by adding 2.0 N HCI dropwise such that the temperature was less than or equal to room temperature. The organic layer was then separated, washed with water, dried over sodium sulfate and concentrated to give 4 g (78percent) of the title compound as a yellow oil, which was used in the next step without further purification.
Reference: [1] Patent: US2007/287738, 2007, A1. Location in patent: Page/Page column 25
[2] Patent: WO2009/76571, 2009, A1. Location in patent: Page/Page column 41
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 19, p. 5799 - 5802
  • 3
  • [ 68-12-2 ]
  • [ 10035-16-2 ]
YieldReaction ConditionsOperation in experiment
67%
Stage #1: With tert.-butyl lithium In diethyl ether at -78℃; for 0.33 h;
Stage #2: at -25 - 20℃; for 3.00 h;
To a solution of the product from Step B (2g) in ether (20MI) AT-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred AT-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MGS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent); A solution of 5-bromobenzofuran (950 mg, 4.82 MMOL) in anhydrous ether (12 mL) was cooled to-78 °C. 1.7 M TERT-BULI solution in pentane (6 mi, 10.2 MMOL) was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 V/V) to give the title compound as a pale yellow solid (490 mg, 70percent).
67%
Stage #1: With tert.-butyl lithium In diethyl ether at -78℃; for 0.33 h;
Stage #2: at -25 - 20℃;
To a solution ol the product from Step B (2 g) in ether (20 ml) at -78 C. was added t-BuLi dropwise. Alter stirring lor 20 min, DMF (950 mg) was added dropwise and the mixture was stirred at -25 C. lor 3 hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgSO4, filtered and concentrated in vacuo to give 980 mg ol crude product (67percent).
Reference: [1] Patent: WO2004/33440, 2004, A1. Location in patent: Page 239-240; 348
[2] Patent: US2004/147559, 2004, A1. Location in patent: Page 122
  • 4
  • [ 23145-07-5 ]
  • [ 68-12-2 ]
  • [ 10035-16-2 ]
YieldReaction ConditionsOperation in experiment
75%
Stage #1: With tert.-butyl lithium In diethyl ether; pentane at -78℃; for 2.00 h;
Stage #2: for 1.00 h;
Weigh (950 mg, 4.82 mmol)Soluble12 mL anhydrous ether and cooled to -78 ° C. 1.3 M tert-butyllithium in pentane (7.85 mL, 10.2 mmol) was added dropwise to the supernatant. The reaction was stirred at -78 ° C for 2 hours,DMF (0.8 mL, 10.3 mmol) and diethyl ether (1 mL). After 1 h reaction, quench with ammonium chloride at -78 ° C. Ethyl acetate extraction, anhydrous sulfur Sodium sulfate dried, concentrated, and passed through a silica gel column to give a yield of 75percent.
70% With tert.-butyl lithium In diethyl ether; pentane at -78 - 8℃; for 0.83 h; A solution of 5-bromobenzofuran (950 mg, 4.82 [MMOL)] in anhydrous ether (12 mL) was cooled to-78 [°C.] 1.7 M [TELT-BULI] solution in pentane (6 [ML,] 10.2 [MMOL)] was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 [V/V)] to give the title compound as a pale yellow solid (490 mg, [70percent).]
70%
Stage #1: With tert.-butyl lithium In diethyl ether; pentane at -78℃; for 0.33 h;
Stage #2: at -78 - 20℃; for 0.50 h;
A solution of 5-bromobenzofuran (950 mg, 4.82 mmol) in anhydrous ether (12 mL) was cooled to-78 °C. 1.7 M tert-BuLi solution in pentane (6 ml, 10.2 mmol) was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 v/v) to give the title compound as a pale yellow solid (490 mg, 70percent).
67% With ammonium chloride; tert.-butyl lithium In benzene at -25 - 20℃; for 3.00 h; To a solution of the product from Step B (2 g) in ether (20 ml) at -78 C. was added t-BuLi dropwise. After stirring for 20 min, DMF (950 mg) was added dropwise and the mixture was stirred at ?25 C. for 3 hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgSO4, filtered and concentrated in vacuo to give 980 mg of crude product (67percent).
67%
Stage #1: With tert.-butyl lithium In diethyl ether at -78℃; for 0.33 h;
Stage #2: at -25 - 20℃;
Step C; To a solution of the product from Step B (2g) in ether (20mut) at-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred at-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent).
67%
Stage #1: With tert.-butyl lithium In diethyl ether at -78℃; for 0.33 h;
Stage #2: at -25 - 20℃;
To a solution of the product from Step B (2g) in ether (20ml) at-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred at-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent).
54%
Stage #1: With iodine In tetrahydrofuran for 2.50 h; Heating / reflux
Stage #2: at -40 - 20℃; for 12.00 h;
A mixture [OF 5-BROMO-1-BENZOFURAN (0. 5G),] Mg (0.92g, 0. [038MOL), I2] (1 crystal) in dry THF (2. [5ML)] under N2 atmosphere was refluxed for 30min. To this was added a solution of 5- [BROMO-1-BENZOFURAN] (4. [5G)] in 25mL of dry THF) as soon as [THE I2 COLOR] disappear and refluxed for another 2h. The reaction mixture was then cooled to-40°C and added dry DMF (3.6g) drop-wise and slowly warmed to RT for a period of 12h. The reaction mixture was then cooled to 0°C and acidified with 3N HCl to pH=2 and stirred for 30min. The reaction mixture was then diluted with water [(500ML),] extracted with ethylacetate [(2X200ML),] washed with brine and dried. The solvent was removed under vacuum and purified by column chromatography over silica gel (pet. [ETHER/CH2CL2)] to give 5-formyl-1- [BENZOFURAN] (2g, 54percent) as a liquid. LC-MS: M/Z ESI: 1.47 min, [14734 (M+1).]

Reference: [1] Patent: CN107266413, 2017, A. Location in patent: Paragraph 0188; 0190; 0191; 0192
[2] Patent: WO2004/11418, 2004, A1. Location in patent: Page 161
[3] Patent: WO2005/68460, 2005, A1. Location in patent: Page/Page column 318
[4] Patent: US2004/106794, 2004, A1. Location in patent: Page 123
[5] Patent: WO2005/66147, 2005, A1. Location in patent: Page/Page column 209
[6] Patent: WO2005/68460, 2005, A1. Location in patent: Page/Page column 203
[7] Patent: WO2004/7491, 2004, A1. Location in patent: Page 52
[8] Journal of Medicinal Chemistry, 1997, vol. 40, # 3, p. 322 - 330
  • 5
  • [ 23145-07-5 ]
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Reference: [1] Patent: US5229381, 1993, A
[2] Patent: EP125059, 1991, B1
  • 6
  • [ 863659-50-1 ]
  • [ 10035-16-2 ]
Reference: [1] Tetrahedron, 2005, vol. 61, # 32, p. 7746 - 7755
  • 7
  • [ 160625-49-0 ]
  • [ 10035-16-2 ]
Reference: [1] Heterocycles, 1994, vol. 38, # 11, p. 2463 - 2472
  • 8
  • [ 112598-18-2 ]
  • [ 10035-16-2 ]
Reference: [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 3, p. 322 - 330
  • 9
  • [ 23145-07-5 ]
  • [ 106-41-2 ]
  • [ 2032-35-1 ]
  • [ 10035-16-2 ]
Reference: [1] Patent: US4664693, 1987, A
  • 10
  • [ 41052-88-4 ]
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Reference: [1] Tetrahedron, 2005, vol. 61, # 32, p. 7746 - 7755
  • 11
  • [ 40663-68-1 ]
  • [ 10035-16-2 ]
Reference: [1] Tetrahedron, 2005, vol. 61, # 32, p. 7746 - 7755
  • 12
  • [ 136433-45-9 ]
  • [ 10035-16-2 ]
Reference: [1] Tetrahedron, 2005, vol. 61, # 32, p. 7746 - 7755
  • 13
  • [ 621-59-0 ]
  • [ 10035-16-2 ]
Reference: [1] Heterocycles, 1994, vol. 38, # 11, p. 2463 - 2472
  • 14
  • [ 160625-48-9 ]
  • [ 10035-16-2 ]
Reference: [1] Heterocycles, 1994, vol. 38, # 11, p. 2463 - 2472
  • 15
  • [ 157790-73-3 ]
  • [ 10035-16-2 ]
Reference: [1] Heterocycles, 1994, vol. 38, # 11, p. 2463 - 2472
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