Home Cart Sign in  
Chemical Structure| 166599-84-4 Chemical Structure| 166599-84-4

Structure of 166599-84-4

Chemical Structure| 166599-84-4

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 166599-84-4 ]

CAS No. :166599-84-4
Formula : C9H6O3
M.W : 162.14
SMILES Code : OC(=O)C1=CC=CC2=C1C=CO2
MDL No. :MFCD10000600
InChI Key :WFAPIZKLEVLUMX-UHFFFAOYSA-N
Pubchem ID :22324117

Safety of [ 166599-84-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 166599-84-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 43.17
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

50.44 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.5
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.85
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.13
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.08
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.66

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.5
Solubility 0.513 mg/ml ; 0.00316 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.53
Solubility 0.478 mg/ml ; 0.00295 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.65
Solubility 0.363 mg/ml ; 0.00224 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.98 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.18

Application In Synthesis of [ 166599-84-4 ]

* 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.

  • Downstream synthetic route of [ 166599-84-4 ]

[ 166599-84-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 41019-56-1 ]
  • [ 166599-84-4 ]
YieldReaction ConditionsOperation in experiment
99% With water; lithium hydroxide; In tetrahydrofuran; methanol; at 20℃; for 16h; A solution of LiOH (1.44 g, 34.3 mmol) in water (20 mL) was added to a solution of 131 (2.02 g, 11.4 mmol) in THF (20mL) and MeOH (20 mL) and the solution was stirred at r.t. for 16 h and then evaporated. The residue was dissolved in water (50 mL) and acidified with cone. HC1 and the precipitate was filtered and dried to give 132 (1.83 g, 99%). 1H NMR (DMSO-d6) δ 13.10 (s, 1H), 8.14 (d, J = 2.1 Hz, 1H), 7.85-7.91 (m, 2H), 7.43 (t, J = 7.9 Hz, 1H), 7.33 (dd, J = 2.1, 1.0 Hz, 1H). Found: [M-H] = 161.1.
99% A solution of LiOH (1.44 g, 34.3 mmol) in water (20 mL) wasadded to a solution of the above ester (2.02 g, 11.4 mmol) in THF(20 mL) and MeOH (20 mL) and the solution was stirred at 20 Cfor 16 h and then evaporated. The residue was dissolved in water(50 mL) and acidified with conc. HCl and the precipitate was filteredand dried to give benzofuran-4-carboxylic acid (1.83 g,99%). 1H NMR (DMSO d6) d 13.10 (s, 1H), 8.14 (d, J = 2.1 Hz, 1H),7.85-7.91 (m, 2H), 7.43 (t, J = 7.9 Hz, 1H), 7.33 (dd, J = 2.1, 1.0 Hz,1H). Found: [MH] = 161.1.
  • 2
  • [ 166599-84-4 ]
  • [ 380899-56-9 ]
YieldReaction ConditionsOperation in experiment
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 19 - 20℃; for 2.5h; All volumes and weights refer to the weight of Intermediate 12. The reactor was charged with Intermediate 1 1 (1.0 eq) and DMF (0.025 vol, 0.14 eq) in dichloromethane (1.9 vol) at 20 0C. A solution of oxalyl chloride (0.20 vol, 1.0 eq) in dichloromethane (2.1 vol) was added at 20-19 0C over 30 minutes. The mixture was stirred 2 hours at 19-20 0C. Solvent (2.8 vol) was removed at a maximum jacket temperature of 45 0C under reduced pressure. The solution was stored under nitrogen in a feed tank. The reactor was cleaned, dried under vacuum and charged with Intermediate 12 (1.0 eq, 1 wt) and dichloromethane (7.0 vol). Trifluoroacetic acid (3.05 wt, 12 eq) was added at 19-20 0C over 18 minutes. The mixture was stirred overnight at 20-21 0C. The mixture was split in 2 equal portions. Each portion was washed with half saturated aqueous Na2CO3 (8.6 vol) at 20 0C. The combined organic phases were dried over MgSO4 (0.45 wt). After filtration the filtrate was transferred into the cleaned and dried reactor. Dichloromethane (1.3 vol) and triethylamine (0.96 vol, 3eq) were added.The acid chloride solution was added at 1-5 0C over 25 minutes and the mixture was stirred at 19-22 0C overnight. The mixture was split in 2 equal portions. Each portion was washed with saturated aqueous NaHCO3 (7.3 vol) at 20 0C. The combined organic phases were concentrated in the cleaned reactor. The mixture was filtered through a plug of silica gel (0.78 wt) conditioned with ethyl acetate and eluted with ethyl acetate (8.8 vol). The filtrate was concentrated in the cleaned reactor and a solvent change to iPrOAc was performed. The resulting suspension was heated to obtain a clear solution. The solution was cooled and seed crystals (obtained by cooling of about 1 vol% of the clear solution) was added at 57C. The resulting suspension was concentrated, cooled to 100C, stirred overnight and filtered. The filter cake was washed with iPrOAc and IPA and dried at a max. jacket temperature of 50 0C and reduced pressure at the rotavap to give intermediate grade title compound. Yield (% theory): 48%
With thionyl chloride; for 2h;Heating / reflux; A mixture of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> [Eissenstat, et al., J. Medicinal Chemistry, 38 (16) 3094-3105 (1995)] (2.8 g, 17.4 mmol) and thionyl chloride (25 mL) was heated to reflux for 2 h and then concentrated in vacuo. The solid residue was dissolved in ethyl acetate (50 mL) and a solution of N,O-dimethylhydroxylamine hydrochloride (2.8 g) in saturated NaHCO3 (60 mL) was added with stirring. After stirring for 1.5 h, the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with saturated NaHCO3 and concentrated in vacuo to give an oil (3.2 g, 95.4%).
  • 3
  • [ 166599-84-4 ]
  • [ 75-65-0 ]
  • [ 412336-05-1 ]
  • 4
  • (1R*,2S*,5S*)-2-aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester [ No CAS ]
  • [ 166599-84-4 ]
  • (1R*,2S*,5S*)-2-[(benzofuran-4-carbonyl)-amino]-methyl}-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 0.166667h; A.9 Synthesis of N-substituted (IR ,2S ,5S )-2-(amino-methyl)-3-aza- bicyclo [3.1.0] -hexane derivativesA.9.1 Synthesis of (lR*,2S*,5S*)-2-(aroylamino-methyl)-3-aza-bicyclo[3.1.0]- hexane-3-carboxylic acid tert-butyl ester derivatives (general procedure); To a solution of the respective carboxylic acid (3.2 mmol, l.lOeq) in DMF (5.0 mL) is added successively DIPEA (8.8 mmol, 3.0eq) and a solution of TBTU (3.7 mmol,1.25eq) in DMF (5.0 mL). The obtained mixture is added to a solution of(IR ,2S ,5S )-2-aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (2.9 mmol, l.Oeq) in DMF (5.0 mL). After 10 min sat. aq. NaHCO3 solution and ether are added, the layers are separated and the organic layer is washed with sat. NaHCO3 solution, citric acid (5% in water) and water. After drying over Na2SO4 and removal of solvents in vacuo the desired amides are obtained which are used without further purification.
  • 6
  • [ 166599-84-4 ]
  • 4-(4-benzofuranylamino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline [ No CAS ]
  • 7
  • [ 79250-46-7 ]
  • [ 166599-84-4 ]
  • 8
  • [ 79950-39-3 ]
  • [ 166599-84-4 ]
  • 9
  • [ 166599-84-4 ]
  • Benzofuran-4-yl-[1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl]-methanone [ No CAS ]
  • 10
  • [ 166599-85-5 ]
  • [ 166599-84-4 ]
YieldReaction ConditionsOperation in experiment
62% A solution of Intermediate 10 in toluene (1 wt in 6.6 vol) was added to a refluxing mixture of p-toluenesulfonic acid (0.03 eq., 0.03 wt) in toluene (3.8 vol) over 43 minutes. The mixture was stirred under reflux for 33 minutes then solvent (1.1 vol) was withdrawn at 130 0C jacket temperature under slightly reduced pressure (1000- 880 mbar). The mixture was further stirred at reflux. 4.25 hours after the addition of Intermediate 10 the mixture was cooled to 25 0C. The mixture was filtered over silica gel (1.1 wt) that had been conditioned with toluene (4.1 vol). The silica plug was further washed with toluene (8.2 vol). The product containing fractions were combined (total volume 10.8 vol). Solvent (8.6 vol) was withdrawn at 80 0C jacket temperature under reduced pressure. Toluene (0.6 vol) and 1.0 M NaOH (1.5 eq., 7.7 vol) was added and the two-phase mixture was stirred at 60 0C for 9 hours. After cooling to 20 0C the phases were separated and 32% HCI (1.7 vol) was added at 2- 14C to the aqueous phase. After addition of 9.4 vol toluene the mixture was stirred under reflux for 14.5 hours. The suspension was cooled to 20 0C and THF (5.3 vol) was added. The phases were separated and the organic layer was washed two times with a mixture of 5.6 vol water and 0.6 vol THF. 10.3 vol of solvent was distilled off at 80 0C jacket temperature and reduced pressure before 3.2 vol toluene was added. The mixture was refluxed for 33 minutes (ambient pressure), cooled to 0 0C over 3 hours and stirred at that temperature for 2.5 days. The precipitate was filtered, dried for 2 hours in a stream of nitrogen and dried in a rotavap at 50 0C to give the title compound as an off-white solid. Yield (% theory): 62%
  • 11
  • [ 166599-84-4 ]
  • [ 209256-40-6 ]
YieldReaction ConditionsOperation in experiment
83% With hydrogen;palladium 10% on activated carbon; In acetic acid; under 3102.97 Torr; for 12h; Benzofuran-4-carboxylic acid [] [Eissenstat, et al, J. Medicinal Chemistry, 38 (16) 3094-3105 (1995)] (10.0 g, 61.7 mmol) was hydrogenated (60 psi) in acetic acid (100 mL) over 10% Pd/C (2 g) for 12 hr. The mixture was filtered and the filtrate was diluted with water (500 mL) to give 2,3-dihydro<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> as a white powder (8.4 g, 83%). A sample was recrystallized from isopropanol to give fine white needles (mp: 185.5-185.5C).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3000.3 Torr; for 16h; Benzofuran-4-carboxylic acid (30.8 mmol, M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 1H-NMR (DMSO-dβ): δ = 3.45 (t, J = 8.79 Hz, 2H); 4.55 (t, J = 8.79 Hz, 2H); 6.99 (d, J = 7.78 Hz, IH); 7.21 (t, J = 7.91 Hz, IH); 7.39 (d, J = 7.78 Hz, IH); 12.9 (bs, IH).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3000.3 Torr; for 16h; Benzofuran-4-carboxylic acid (30.8 mmol, M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 1H-NMR (DMSO-d6): δ = 3.45 (t, J = 8.79 Hz, 2H); 4.55 (t, J = 8.79 Hz, 2H); 6.99 (d, J = 7.78 Hz, IH); 7.21 (t, J = 7.91 Hz, IH); 7.39 (d, J = 7.78 Hz, IH); 12.9 (bs, IH).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3000.3 Torr; for 16h; Benzofuran-4-carboxylic acid (30.8 mmol, M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 1H-NMR (DMSO-de): δ = 3.45 (t, J = 8.79 Hz, 2H); 4.55 (t, J = 8.79 Hz, 2H); 6.99 (d, J = 7.78 Hz, IH); 7.21 (t, J = 7.91 Hz, IH); 7.39 (d, J = 7.78 Hz, IH); 12.9 (bs, IH).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3000.3 Torr; for 16h; Benzofuran-4-carboxylic acid (30.8 mmol, M. A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 1H-NMR (DMSO-d6): δ=3.45 (t, J=8.79 Hz, 2H); 4.55 (t, J=8.79 Hz, 2H); 6.99 (d, J=7.78 Hz, 1H); 7.21 (t, J=7.91 Hz, 1H); 7.39 (d, J=7.78 Hz, 1H); 12.9 (bs, 1H).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3000.3 Torr; for 16h; A.2 Synthesis of 2,3-dihydro-<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> Benzofuran-4-carboxylic acid (30.8 mmol, M. A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 1H-NMR (DMSO-d6): δ=3.45 (t, J=8.79 Hz, 2H); 4.55 (t, J=8.79 Hz, 2H); 6.99 (d, J=7.78 Hz, 1H); 7.21 (t, J=7.91 Hz, 1H); 7.39 (d, J=7.78 Hz, 1H); 12.9 (bs, 1H).
With hydrogen;palladium 10% on activated carbon; In acetic acid; under 3102.97 Torr; for 12h; Benzofuran-4-carboxylic acid (10.0 g, 61.7 mmol) was hydrogenated (60 psi) in acetic acid (100 mL) over 10% Pd/C (2 g) for 12 hr. The mixture was filtered and the filtrate was diluted with water (500 mL) to give 2,3-dihydro<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> as a white powder (8.4 g, 83%). A sample was recrystallized from isopropanol to give fine white needles (mp: 185.5-187.5C).
With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; under 2585.81 Torr; for 12h; A third exemplary Intermediate B, Intermediate B-3, may be used to synthesize compounds of formula I wherein Z is O, n is one, X is C(R5)2, - is a single bond and one R3 is chlorine. To a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (900 mg, 5.55 mmol, 1 equiv) in MeOH (9.00 mL) was added palladium on activated carbon (20.0 mg, 555 pmol, 10.0 wt %, 0.10 equiv) under nitrogen. The vessel was evacuated and purged with hydrogen several times. The mixture was stirred at 25 C for 12 h under hydrogen (50.0 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to afford 2, 3-dihydro<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (750 mg, 3.66 mmol, 65.9% yield, 80.0% purity) as a white solid. 1H NMR (400MHz, DMSO-d6) d = 7.38 (d, J=8.0 Hz, 1H), 7.20 (t, =8.0 Hz, 1H), 6.97 (d, =8.0 Hz, 1H), 4.54 (t, =8.8 Hz, 2H), 3.45 (br t, =8.8 Hz, 2H).
With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; under 2585.81 Torr; for 12h; To a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (900 mg, 5.55 mmol, 1 equiv) in MeOH (9.00 mL) was added palladium on activated carbon (20.0 mg, 555 μmol, 10.0 wt %, 0.10 equiv) under nitrogen. The vessel was evacuated and purged with hydrogen several times. The mixture was stirred at 25 C for 12 h under hydrogen (50.0 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to afford 2,3-dihydrobenzofuran-4- carboxylic acid (750 mg, 3.66 mmol, 65.9% yield, 80.0% purity) as a white solid. [0271] 1H NMR (400MHz, DMSO-d6) d = 7.38 (d, J = 8.0 Hz, 1H), 7.20 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 4.54 (t, J = 8.8 Hz, 2H), 3.45 (br t, J = 8.8 Hz, 2H).
With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; under 2585.81 Torr; for 12h; To a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (900 mg, 5.55 mmol, 1 equiv) in MeOH (9.00 mL) was added palladium on activated carbon (20.0 mg, 555 mol, 10.0 wt %, 0.10 equiv) under nitrogen. The vessel was evacuated and purged with hydrogen several times. The mixture was stirred at 25 C for 12 h under hydrogen (50.0 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to afford 2,3-dihydro<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (750 mg, 3.66 mmol, 65.9 % yield, 80.0% purity) as a white solid. [0186] 1H NMR (400MHz, DMSO-d6) d = 7.38 (d, J=8.0 Hz, 1H), 7.20 (t, J=8.0 Hz, 1H), 6.97 (d, J=8.0 Hz, 1H), 4.54 (t, J=8.8 Hz, 2H), 3.45 (br t, J=8.8 Hz, 2H).

  • 12
  • [ 79950-39-3 ]
  • [ 166599-84-4 ]
  • [ 412336-05-1 ]
YieldReaction ConditionsOperation in experiment
With diphenylphosphoranyl azide; triethylamine; In tert-butyl alcohol; Using analogous procedures to those described in J. Med. Chem., 1995, 38, 3102-3103, methyl 2-allyl-3-hydroxybenzoate was converted in three steps via methyl 2-hydroxy-2,3-dihydrobenzofuran-4-carboxylate and methyl benzofuran-4-carboxylate into <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong>. A mixture of benzofuran-4carboxylic acid (0.5 g), diphenylphosphoryl azide (1.2 ml), triethylamine (0.79 ml) and tert-butanol (1.5 ml) were stirred and heated to reflux for 18 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic phase was washed in turn with water and brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography using methylene chloride as eluent. There was thus obtained tert-butyl benzofuran-4-carbamate (0.8 g) as an oil; Mass Spectrum: M+Na+ 256.
  • 13
  • [ 188111-79-7 ]
  • [ 166599-84-4 ]
  • [ 1030389-11-7 ]
YieldReaction ConditionsOperation in experiment
82% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; A.2.4 Synthesis of (R)-3-[(benzofuran-4-carbonyl)-amino]-piperidine-l- carboxylic acid tert-buty ester; A mixture of (R)-3-amino-l-N-Boc-piperidine (1 g), <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (809 mg), PyBOP (2.6g), DIEA (1.96 mL) in dry DMF (10 mL) was stirred at RT under nitrogen for 20 h. The reaction mixture was diluted with EA, washed with water. The aqueous phase was extracted twice with EA, the combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to yield a crude light brown oil. FC (EA/ n-heptane: 1/1 to EA) gave 1.41 g (82%) of the title compound as an oil. LC-MS: tR = 0.93 min; [M+H]+ = 345.
82% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; A mixture of (R)-3-amino-1-N-Boc-piperidine (1 g), <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (809 mg), PyBOP (2.6 g), DIEA (1.96 mL) in dry DMF (10 mL) was stirred at RT under nitrogen for 20 h. The reaction mixture was diluted with EA, washed with water. The aqueous phase was extracted twice with EA, the combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to yield a crude light brown oil. FC (EA/n-heptane: 1/1 to EA) gave 1.41 g (82%) of the title compound as an oil.LC-MS: tR=0.93 min; [M+H]+=345.
  • 14
  • [ 1038509-56-6 ]
  • [ 166599-84-4 ]
  • [ 1038509-59-9 ]
YieldReaction ConditionsOperation in experiment
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; for 2h; TBTU (1.24 mmol, 1.05eq) is added to a solution of the respective carboxylic acid (1.18 mmol, l.Oeq), (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (1.18 mmol, l.Oeq) and DIPEA (1.77 mmol, 1.5eq) in DCM, DMF or acetonitrile (10 mL). After 2h the mixture is washed with water, hydrochloric acid (0.5 M) and water. The organic layer is dried over Na2SO4, the solvents are removed in vacuo and the residue is purified by prep. HPLC or by flash chromatography (EtO Ac/heptane).(lS,3S,5S)-3-[(benzofuran-4-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2- carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2- carboxylic acid tert-butyl ester with <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105). LC-MS (acidic): tR = 1.00 min; [M+H]+ = 357.1. 1H- NMR (CDCl3): δ = 0.58 (bs, IH); 0.80-0.86 (m, IH); 1.52 (s, 9H); 1.52-1.59 (m, IH); 1.79 (bd, J = 13.3 Hz, IH); 2.51-2.60 (m, IH); 3.24-3.30 (m, IH); 3.60-3.64 (m, 2H); 4.45-4.52 (m, IH); 7.32 (t, J = 7.9 Hz, IH); 7.47 (bs, IH); 7.61 (d, J = 8.2 Hz, IH); 7.65 (d, J = 7.5 Hz, IH); 7.70 (bs, IH); 8.43 (bs, IH).
  • 15
  • [ 1108172-95-7 ]
  • [ 166599-84-4 ]
  • [ 1108172-98-0 ]
YieldReaction ConditionsOperation in experiment
To a solution of the respective carboxylic acid (0.85 mmol) in DMF (4.0 mL) is added successively DIPEA (2.40 mmol) and TBTU (0.97 mmol). The obtained mixture is stirred for 10 min and treated with a solution of (lS,2S,5R)-2-Aminomethyl-3-aza- bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (0.84 mmol) in DMF (1.5 mL). After LC-MS indicated complete conversion (10 min - 16 h) sat. aq. NaHCOs solution and ether (50 mL) are added, the layers are separated and the aq. layer is extracted twice with ether. The combined organic layers are washed twice with sat. NaHCC>3 solution, twice with citric acid (5% in water) and once with brine. After drying over MgSO4 and removal of solvents in vacuo the respective amide is obtained which is either purified by FC (EtO Ac/heptane) or used without further purification.; (lS,2S,5R)-2-[(Benzofuran-4-carbonyl)-amino]-methyl}-3-aza- bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (method A) prepared by reaction of (lS,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane- 3-carboxylic acid tert-butyl ester with <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105). LC-MS (basic): tR = 0.91 min; [M+H]+ = 357.2.
  • 16
  • [ 1117693-67-0 ]
  • [ 166599-84-4 ]
  • [ 1117693-63-6 ]
YieldReaction ConditionsOperation in experiment
22% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; (RS)-2-Cyclopropyl-2-[methyl-(2-methyl-5-phenyl-thiazole-4-carbonyl)-amino]-ethyl- ammonium chloride (0.17 mmol, 1.0 eq.) was suspended in DMF (0.2 ml) and a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (0.135 mmol, 0.79 eq.) and DIPEA (0.57 mmol, 3.4 eq.) in DMF (0.54 ml) was added. Finally a solution of HATU (0.135 ml, 0.79 eq.) was added and the mixture was shaken overnight. The solvent was stripped off and the residue was purified by preparative HPLC yielding the desired product (0.0134 g, 22%)LC-MS: tR = 0.99; [M+H]+ = 460.18
  • 17
  • [ 1181573-42-1 ]
  • [ 166599-84-4 ]
  • [ 1181573-44-3 ]
YieldReaction ConditionsOperation in experiment
B.2 Synthesis of (lR^S^SJ-S-Acylaminomethyl-l-aza-bicycloβ.l.ljheptane derivatives; B.2.1 Synthesis of (lR^S^SJ-S-Acylaminomethyl^-aza-bicycloβJ.llheptane^- carboxylic acid tert-butyl ester derivatives; (general procedure); TBTU (0.73 mmol, 1.1 Oeq) is added to a solution of the respective carboxylic acid (0.70 mmol, 1.05eq) and DIPEA (1.66 mmol, 2.5eq) in DCM (1.0 mL) and DMF (0.25 mL). After 10 min a solution of (lR,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2- carboxylic acid tert-butyl ester (0.66 mmol, l.Oeq) in DCM (1.0 mL) is added and the mixture is stirred for 2h and washed twice with water (1.0 mL). The organic layer is dried over MgSO4, the solvents are removed in vacuo and the residue is purified by prep. HPLC to give the respective amide.; (lR,3S,4S)-3-[(Benzofuran-4-carbonyl)-amino]-methyl}-2-aza-bicyclo[2.2.1]heptane- 2-carboxylic acid tert-butyl ester prepared by reaction of (lR,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2- carboxylic acid tert-butyl ester with <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (M.A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105). LC-MS (basic): tR = 0.97 min; [M+H]+ = 371.1.
  • 18
  • [ 166599-84-4 ]
  • [ 1061591-03-4 ]
YieldReaction ConditionsOperation in experiment
23% a) 2-Iodo-<strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> To a cold (-78 C.) solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (100 mg) in dry diethyl ether (1.2 mL), was added dropwise tert-butyl lithium (1.7 M in pentane, 0.8 mL, 2.2 eq). The reaction mixture was stirred at -78 C. for 30 min. under nitrogen, then a solution of iodine (172.2 mg, 1.2 eq) in ether (1.9 mL) was added dropwise. The reaction was stirred at -78 C. for 30 min. and allowed to warm to rt. The reaction mixture was partitioned between sat. NH4Cl and diethyl ether, the aqueous phase was extracted once again with diethyl ether. The combined organic extracts were washed with sat. sodium thiosulfate, water, dried (Na2SO4), filtered and concentrated to yield a crude brown solid. FC (DCM/MeOH: 99/1 to 97/3) afforded the title compound as a pink solid (40 mg, 23%). LC-MS: tR=0.89 min; [m+H]+=288.99.
  • 19
  • [ 391248-13-8 ]
  • [ 166599-84-4 ]
  • [ 1061591-40-9 ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; A.4.1 Synthesis of 4-[acyl-amino]-methyl}-thiazolidine-3-carboxylic acid tert-butyl ester Derivatives (General Procedure)To a solution of the respective carboxylic acid R1COOH, wherein R1 is as defined for formula (I), (4.6 mmol, 1.0 eq.), 4-aminomethyl-thiazolidine-3-carboxylic acid tert-butyl ester (4.6 mmol, 1.0 eq.) and DMAP (2.3 mmol, 1.0 eq.) in DCM (25 mL) was added under stirring solid EDC (4.7 mmol, 1.02 eq.). Stirring continued over night. Then sat. aq. NaHCO3 solution (6 mL) was added to the reaction mixture and stirring continued for 30 min. The organic phase was separated, the solvent was stripped off yielding the crude corresponding 4-[acyl-amino]-methyl}-thiazolidine-3-carboxylic acid tert-butyl ester derivative.
  • 20
  • [ 1007873-74-6 ]
  • [ 166599-84-4 ]
  • [ 1007873-72-4 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; To a mixture of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (Eissenstat M. A. et al, J. Med. Chem. 1995, 38, 16, 3094-3105 (61 mg), PyBOP (196 mg), DIEA (0.15 mL) in dry DMF (0.5 mL), was added a solution of (2RS)-(2-aminomethyl-azetidin-1-yl)-biphenyl-2-yl-methanone (100 mg) in dry DMF (0.5 mL). The resulting reaction mixture was stirred at RT for 20 h. The reaction mixture was diluted with EA, washed with water. The aqueous phase was extracted once again with EA, the combined organic extracts were dried (MgSO4), filtered and concentrated to yield the crude product as light brown oil.FC (EA) gave 140 mg (71%) of the title compound as a light yellow oilLC-MS: rt=0.99 min, 411 [M+H]+.
  • 21
  • [ 1007873-82-6 ]
  • [ 166599-84-4 ]
  • [ 1007873-83-7 ]
YieldReaction ConditionsOperation in experiment
78% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; To a mixture of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (11 mg), PyBOP (35 mg), DIEA (0.030 mL) in dry DMF (0.15 mL), was added a solution of (2RS)-(2-aminomethyl-azetidin-1-yl)45-(4-fluoro-phenyl)-2-methyl-thiazol-4-A-methanone (20 mg) in dry DMF (0.1 mL). The resulting reaction mixture was stirred at RT for 20 h. The reaction mixture was diluted with EA, washed with water. The aqueous phase was extracted once again with EA, the combined organic extracts were dried (MgSO4), filtered and concentrated to yield a crude light brown oil.FC (EA to DCM/MeOH: 98/2) gave 23 mg (78%) of the title compound as a white solid.LC-MS: rt=0.94 min, 450 [M+H]+.
  • 22
  • [ 1007873-90-6 ]
  • [ 166599-84-4 ]
  • [ 1007873-91-7 ]
YieldReaction ConditionsOperation in experiment
30% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;Inert atmosphere; To a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (548.5 mg), TBTU (1.41 g) DIEA (1.73 mL) in dry DMF (6 mL) was added dropwise a solution of (2S)-aminomethyl-azetidine-1-carboxylic acid tert-butyl ester (630 mg) in dry DMF (2 mL). The reaction mixture was stirred under nitrogen for 72 h. The reaction mixture was diluted with EA, washed with water, the aqueous phase was extracted twice again with EA. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to yield a crude oil.FC (EA/n-heptane: 1/1) gave 336 mg (30%) of the title compound as a white solid.LC-MS: rt=0.95 min, 331 [M+H]+.
  • 23
  • [ 1007873-77-9 ]
  • [ 166599-84-4 ]
  • [ 1007873-75-7 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; To a mixture of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (Eissenstat M. A. et al, J. Med. Chem. 1995, 38, 16, 3094-3105 (63.3 mg), PyBOP (203 mg), DIEA (0.116 mL) in dry DMF (1.5 mL), was added a solution of (2RS)-[1-(biphenyl-2-sulfonyl)-azetidin-2-yl]-methylamine (118 mg) in dry DMF (0.5 mL). The resulting reaction mixture was stirred at RT for 20 h. The reaction mixture was diluted with EA, washed with water. The aqueous phase was extracted once again with EA, the combined organic extracts were dried (MgSO4), filtered and concentrated to yield the crude product as light brown oil.FC (EA) gave 118 mg (67%) of the title compound as a light yellow oil.LC-MS: rt=1.04 min, 447 [M+H]+.
  • 24
  • [ 1238071-95-8 ]
  • [ 166599-84-4 ]
  • [ 1312557-94-0 ]
YieldReaction ConditionsOperation in experiment
78% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 20h; b Benzofuran-4-carboxylic acid ((S)-1-benzyl-2-cyano-ethyl)-methyl-amide(S)-3-Methylamino-4-phenyl-butyronitrile hydrochloride (2.2 g, 10.4 mmol), benzofuran-4- carboxylic acid (2.03 g, 12.5 mmol), HOBt (1.9 g, 12.5 mmol), EDC x HCI (3.0 g, 15.7 mmol), and triethylamine (5.82 ml, 41.8 mmol) were dissolved in DCM (50 ml) and the reaction was stirred at rt for 20h. The mixture was diluted with EtOAc, washed with NaHC03- and NaCI- soln., dried (Na2S04), filtered and concentrated. The crude product was purified by chromatography (Flashmaster, Hex to Hex:EtOAc 2:3 over 60 min; Hex:EtOAc 2:3 for 5 min) to yield 2.59 g (78%) of the title compound as yellowish oil. [1 H-NMR (DMSO, 600 MHz, rotamers) 7.97/7.94 (s, 1 H), 7.61/7.58 (d, 1 H), 7.36-6.86 (m, 7H), 6.46/6.16 (s, 1 H), 5.25/4.02 (br s, 1 H), 3.14-2.68 (m, 4H), 3.05/2.61 (s, 3H); LCMS RtA = 2.729 min; [M+H]+ = 319.2].
  • 25
  • (RS)-2-cyclopropyl-2-[methyl-(2-methyl-5-phenyl-thiazole-4-carbonyl)amino]ethyl-ammonium chloride [ No CAS ]
  • [ 166599-84-4 ]
  • [ 1117693-63-6 ]
YieldReaction ConditionsOperation in experiment
22% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; (RS)-2-Cyclopropyl-2-[methyl-(2-methyl-5-phenyl-thiazole-4-carbonyl)-amino]-ethyl-ammonium chloride (0.17 mmol, 1.0 eq.) was suspended in DMF (0.2 ml) and a solution of <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (0.135 mmol, 0.79 eq.) and DIPEA (0.57 mmol, 3.4 eq.) in DMF (0.54 ml) was added. Finally a solution of HATU (0.135 ml, 0.79 eq.) was added and the mixture was shaken overnight. The solvent was stripped off and the residue was purified by preparative HPLC yielding the desired product (0.0134 g, 22%) LC-MS: tR=0.99; [M+H]+=460.18
  • 26
  • [ 1396788-43-4 ]
  • [ 166599-84-4 ]
  • C28H29N3O4S [ No CAS ]
  • 27
  • C18H22FN3OS [ No CAS ]
  • [ 166599-84-4 ]
  • C27H26FN3O3S [ No CAS ]
  • 28
  • rac-((2S,3R)-2-(aminomethyl)-3-methylpiperidin-1-yl)(2-methyl-5-phenylthiazol-4-yl)methanone [ No CAS ]
  • [ 166599-84-4 ]
  • C27H27N3O3S [ No CAS ]
  • 29
  • C18H20F3N3OS [ No CAS ]
  • [ 166599-84-4 ]
  • C27H24F3N3O3S [ No CAS ]
  • 30
  • [ 166599-84-4 ]
  • 1-(benzofuran-4-ylmethyl)-N5-cyclopropyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide [ No CAS ]
  • 31
  • [ 166599-84-4 ]
  • [ 173470-67-2 ]
YieldReaction ConditionsOperation in experiment
With borane-THF; In tetrahydrofuran; at 20℃; for 1h; To <strong>[166599-84-4]benzofuran-4-carboxylic acid</strong> (50 mg, 0.308 mmol, commercially available from, for example, J&W PharmLab) in THF (1 mL), borane tetrahydrofuran complex (0.47 mL, 1M in THF, 0.470 mmol) was added and the reaction stirred at rt for 1 h. The reaction was quenched with NaHCO3 (20 mL)and extracted with EtOAc (3 x 10 mL). The organic layers were dried over a hydrophobic frit and concentrated to give 50 mg of a colourless oil. This was purified bychromatography on 5i02 (Biotage SNAP 10 g cartridge, eluting with O-5O% EtOAc/cyclohexane), theappropriate fractions were concentrated to give benzofuran-4-ylmethanol (37 mg, 0.225 mmol, 72.9 % yield) as a white solid.LCMS (2 mm Formic): Rt = 0.72 mi [M-OH] = 131.1.
  • 32
  • [ 166599-84-4 ]
  • 4-(bromomethyl)benzofuran [ No CAS ]
  • 33
  • [ 6638-79-5 ]
  • [ 166599-84-4 ]
  • [ 209256-39-3 ]
YieldReaction ConditionsOperation in experiment
93% Oxalyl chloride (1.14 mL, 13.5 mmol) was added to a suspension of 132 (1.82 g, 11.2 mmol) in DCM (100 mL, anhydrous) and DMF (0.2 mL, 2.5 mmol) at r.t.. The mixture was stirred at r.t. for 1 h to give a colourless solution which was cooled to 0 C. Ν,Ο- Dimethylhydroxylamine hydrochloride (1.31 g, 13.5 mmol) and pyridine (2.72 mL, 33.6 mmol) were added sequentially and the mixture was stirred at r.t. for 18 h, then partitioned between DCM and water. Column chromatography with 95:5 DGVLEtOAc gave 133 (2.13 g, 93%). 1H MR (CDC13) δ 7.68 (d, J = 2.2 Hz, 1H), 7.59 (dt, J = 8.3, 0.8 Hz, 1H), 7.51 (dd, J = 7.5, 0.9 Hz, 1H), 7.32 (t, J = 7.9 Hz, 1H), 6.95 (dd, J = 2.2, 0.9 Hz, 1H), 3.56 (s, 3H). 3.40 (s, 3H). Found: [M+H]=206.2
93% Oxalyl chloride (1.14 mL, 13.5 mmol) was added to a suspensionof thew above acid (1.82 g, 11.2 mmol) in DCM (100 mL, anhydrous)and DMF (0.2 mL, 2.5 mmol) at 20 C. The mixture wasstirred at 20 C for 1 h to give a colourless solution which wascooled to 0 C. N,O-Dimethylhydroxylamine hydrochloride (1.31g, 13.5 mmol) and pyridine (2.72 mL, 33.6 mmol) were addedsequentially and the mixture was stirred at 20 C for 18 h, thenpartitioned between DCM and water. Column chromatographywith 95:5 DCM:EtOAc gave N-methoxy-N-methylbenzofuran-4-carboxamide (2.13 g, 93%). 1H NMR (CDCl3) d 7.68 (d, J = 2.2 Hz,1H), 7.59 (dt, J = 8.3, 0.8 Hz, 1H), 7.51 (dd, J = 7.5, 0.9 Hz, 1H),7.32 (t, J = 7.9 Hz, 1H), 6.95 (dd, J = 2.2, 0.9 Hz, 1H), 3.56 (s, 3H).3.40 (s, 3H). Found: [M+H] = 206.2.
  • 35
  • [ 166599-84-4 ]
  • 1-(benzofuran-4-yl)-3-(dimethylamino)propan-1-one [ No CAS ]
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 166599-84-4 ]

Carboxylic Acids

Chemical Structure| 90721-27-0

A146937 [90721-27-0]

Benzofuran-5-carboxylic acid

Similarity: 0.94

Chemical Structure| 77095-51-3

A255852 [77095-51-3]

Benzofuran-6-carboxylic acid

Similarity: 0.94

Chemical Structure| 57598-51-3

A114705 [57598-51-3]

2-Ethyl-3-methoxybenzoic acid

Similarity: 0.90

Chemical Structure| 37934-89-7

A233849 [37934-89-7]

2,6-Dimethyl-4-methoxybenzoic acid

Similarity: 0.90

Chemical Structure| 19692-24-1

A236639 [19692-24-1]

4-Ethoxy-1-naphthoic acid

Similarity: 0.89

Related Parent Nucleus of
[ 166599-84-4 ]

Benzofurans

Chemical Structure| 90721-27-0

A146937 [90721-27-0]

Benzofuran-5-carboxylic acid

Similarity: 0.94

Chemical Structure| 77095-51-3

A255852 [77095-51-3]

Benzofuran-6-carboxylic acid

Similarity: 0.94

Chemical Structure| 26537-68-8

A287325 [26537-68-8]

Benzofuran-3-carboxylic acid

Similarity: 0.88

Chemical Structure| 90484-22-3

A106998 [90484-22-3]

Benzofuran-7-carboxylic acid

Similarity: 0.87

Chemical Structure| 69716-04-7

A262340 [69716-04-7]

2-(6-Hydroxybenzofuran-3-yl)acetic acid

Similarity: 0.87