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Chemical Structure| 146394-99-2 Chemical Structure| 146394-99-2

Structure of 146394-99-2

Chemical Structure| 146394-99-2

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Product Details of [ 146394-99-2 ]

CAS No. :146394-99-2
Formula : C9H18N2O2
M.W : 186.25
SMILES Code : O=C(OC(C)(C)C)NC/C=C/CN
MDL No. :MFCD09752966
InChI Key :BWNIUPOJWUXWMX-SNAWJCMRSA-N
Pubchem ID :18947920

Safety of [ 146394-99-2 ]

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

Computational Chemistry of [ 146394-99-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 6
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 52.12
TPSA ?

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

64.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.27
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

0.3
Log Po/w (WLOGP)?

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

1.03
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.

0.84
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

0.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-0.79
Solubility 30.4 mg/ml ; 0.163 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.21
Solubility 11.4 mg/ml ; 0.0611 mol/l
Class?

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

Very 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

-1.37
Solubility 7.89 mg/ml ; 0.0424 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

No
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.

-7.22 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.

0.55

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

1.0 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)

2.69

Application In Synthesis of [ 146394-99-2 ]

* 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 [ 146394-99-2 ]

[ 146394-99-2 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 24424-99-5 ]
  • trans-but-2-ene-1,4-diamine dihydrochloride [ No CAS ]
  • [ 146394-99-2 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In methanol; at 20℃;Heating / reflux; (E)-l,4-diaminobut-2-ene dihydrochloride (8.0 g, 50mrnol) was suspended in 10% TEA/ MeOH solution (120ml). To the above suspension TEA (14ml) was added. A solution of di-tert-butyldicarbonate (3.7g, 16.8mmol) in methanol (10ml) was added drop- wise to the vigorously stirred mixture. The reaction mixture was refluxed for 3 h, and stirred at room temperature overnight. After the removal of the precipitate, the filtrate was evaporated to dryness. The crude residue was purified by column chromatography with CH2Cl2-MeOH (20:1) to give 1.5g of the desired product.
  • 2
  • [ 667936-71-2 ]
  • [ 146394-99-2 ]
  • [ 905301-61-3 ]
YieldReaction ConditionsOperation in experiment
70% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃; To a solution of <strong>[146394-99-2](4-amino-but-2-enyl)-carbamic acid tert-butyl ester</strong> (1.Og, 5.36mmol) in dry CH2Cl2 (40 ml) was added 6,6-bis-(4-fluorophenyl)-hexanoic acid (1.62g, 5.36mmol) under nitrogen. To the reaction was added EDC (2.04g, 10.72mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temperature overnight. The reaction was then concentrated under reduced pressure. The residue dissolved in ethyl acetate: water (10:1) (150ml). The organic was washed with water (30ml, 2x) and 10% NaOH (30 ml) and dried over MgSO4 and evaporated to dryness. The resulting residue was purified by column chromatography using CH2C12:CH3OH (15:1) to give the desired product in 70% yield.
  • 3
  • [ 146394-99-2 ]
  • 4-chloro-3-(3-methoxypropoxy)-5-nitrobenzamide [ No CAS ]
  • (E)-tert-butyl (4-((4-carbamoyl-2-(3-methoxypropoxy)-6-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tert-buty (4-aminobut-2-en-l-yl)carbamate (1.45 g, 7.81 mmol) and DIEA (3.41 mL, 19.5 mmol). The reaction was heated to 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange precipitate was collected by filtration and washed with EtOH to provide the title compound (2.1 g, 5.5 mmol, 85 % yield). LCMS (LCMS Method D): Rt = 0.96 min, [M+H]+ = 439.2
85% With di-tert-butyl diisopropylphosphoramide; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH(25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.45 g, 7.81 mmol) andDIEA (3.41 mL, 19.5 mmol). The reaction was heated to 120 C in a sealed tube overnightand allowed to cool to RT. The resulting orange precipitate was collected by filtration andwashed with EtOH to provide the title compound (2.1 g, 5.5 mmol, 85 % yield). LCMS (LCMSMethod D): Rt = 0.96 mi [M+H] = 439.2
  • 4
  • [ 146394-99-2 ]
  • [ 349-02-0 ]
  • (E)-tert-butyl (4-((4-carbamoyl-2-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With potassium carbonate; In dimethyl sulfoxide; at 20℃; A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (E)-tert-buty (4- aminobut-2-en-l-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3 (15.01 g, 109 mmol) in DMSO (200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 min, [2M+H]+ = 700.5
96% With potassium carbonate; In dimethyl sulfoxide; at 20℃; A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (£)-fert-butyl (4- aminobut-2-en-l-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3 (15.01 g, 109 mmol) in DMSO (200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound ( 18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 min, [2M+H]+ = 700.5
96% With potassium carbonate; In dimethyl sulfoxide; at 20℃; A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), <strong>[146394-99-2](E)-tert-butyl (4-aminobut-2-en-1-yl)carbamate</strong> (10.62 g, 57.0 mmcl) and K2C03 (15.01 g, 109 mmcl) in DMSO(200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 mm. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 mi [2M+H] = 700.5
96% With potassium carbonate; In dimethyl sulfoxide; at 20℃; A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (E)-tert-butyl (4- aminobut-2-en-1-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3(15.01 g, 109 mmol) in DMSO (200 mL) was stirred at room temperature overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96% yield). LCMS [2M+H]+= 700.5

  • 5
  • [ 146394-99-2 ]
  • (E)-tert-butyl (4-((2-amino-4-carbamoylphenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
  • 6
  • [ 146394-99-2 ]
  • (E)-tert-butyl (4-(2-amino-5-carbamoyl-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)carbamate [ No CAS ]
  • 7
  • [ 146394-99-2 ]
  • (E)-tert-butyl (4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)carbamate [ No CAS ]
  • 8
  • [ 146394-99-2 ]
  • 4-chloro-3-methoxy-5-nitrobenzamide [ No CAS ]
  • (E)-tert-butyl (4-((4-carbamoyl-2-methoxy-6-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (B-tert-buty (4-aminobut-2-en-l-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). *H NMR (400 MHz, DMSO-t) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H); LCMS (LCMS Method D): Rt = 0.89 min, [M-t- Bu+H]+ = 325.1
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.454 g, 7.81 mmol) and DIPEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight andallowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). 1H NMR (400 MHz, DMSOd6) ppm 8.19 Cd, J=l.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 Ct, J=6.08 Hz, 1 H) 7.55 Cd, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 Ct, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 Cs, 3 H) 3.48 (br. s., 2 H) 1.35 Cs, 9 H). LCMS (LCMS Method D): Rt = 0.89 mi [M-t-Bu+H] =325.1
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (£)-tert-butyl (4-aminobut-2-en-l-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). NMR (400 MHz, DMSO-tfc) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H); LCMS (LCMS Method D): Rt = 0.89 min, [M-i-Bu+H]+ = 325.1
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed withEtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). 1H NMR (400 MHz, DMSO-d6) ppm 8.19 Cd, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 Ct, J=6.08 Hz, 1 H) 7.55 Cd, J=1.52 Hz, 1 H) 7.34 Cbr. 5., 1 H) 6.95 Ct, J=5.45 Hz, 1 H) 5.53 Cbr. 5., 2 H) 4.09 Cbr. 5., 2 H)3.88 Cs, 3 H) 3.48 Cbr. s., 2 H) 1.35 Cs, 9 H); LCMS CLCMS Method D): Rt = 0.89 mi [M-tBu+H] = 325.1
85% With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added <strong>[146394-99-2](E)-tert-butyl (4-aminobut-2-en-1-yl)carbamate</strong> (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to room temperature. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H). LCMS (m/z): 325.1 [M-t-Bu + H]+.

  • 9
  • [ 146394-99-2 ]
  • tert-butyl (E)-(4-((2-amino-6-bromophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
  • 10
  • [ 146394-99-2 ]
  • tert-butyl (E)-(4-(7-bromo-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)carbamate [ No CAS ]
  • 11
  • [ 146394-99-2 ]
  • [ 58534-94-4 ]
  • tert-butyl (E)-(4-((2-bromo-6-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 25℃; for 96.0h; To a solution of <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (2.2 g, 11.81 mmol) and DIEA (4.37 mL, 25.00 mmol) in isopropanol (30 mL) at 25 C was added 1-bromo-2- fluoro-3-nitrobenzene (2.5 g, 11.36 mmol). The reaction mixture was then stirred at 25 C for 4 days. The reaction mixture was concentrated. The resulting material was partitioned between water and EtOAc. The aqueous layer was separated and extracted with EtOAc (1x). The combined organic layers were then washed with brine, dried with magnesium sulfate, and concentrated to obtain the tert-butyl (E)-(4-((2-bromo-6-nitrophenyl)amino)but- 2-en-1-yl)carbamate (4.6 g, 12 mmol, 100% yield) as a yellow solid. The isolated material was used without any further purification. LCMS (m/z): 332.0 ([M + H]+- t-butyl).
  • 12
  • [ 146394-99-2 ]
  • 3-(3-((tert-butyldimethylsilyl)oxy)propoxy)-4-chloro-5-nitrobenzamide [ No CAS ]
  • tert-butyl (E)-(4-((2-(3-((tert-butyldimethylsilyl)oxy)propoxy)-4-carbamoyl-6-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃;Sealed tube; To a vial was added 3-(3-((tert-butyldimethylsilyl)oxy)propoxy)-4-chloro-5-nitrobenzamide (1.004 g, 2.58 mmol), <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (Ark Pharm, cat No.AK308564: 0.481 g, 2.58 mmol), DMSO (12.91 ml), and DIPEA (2.254 ml, 12.91 mmol). The mixture was sealed, then heated at 100 C. overnight with stirring. After cooling to rt, the mixture was diluted with water and extracted with CHCl3/IPA (3:1). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to provide the desired product as a brown oil. LC-MS calculated for C25H43N4O7Si (M+Na)+: m/z=561.3; found 561.3.
  • 13
  • [ 146394-99-2 ]
  • 4-fluoro-3-methoxy-5-nitrobenzamide [ No CAS ]
  • (E)-tert-butyl (4-((4-carbamoyl-2-methoxy-6-nitrophenyl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In dimethyl sulfoxide; at 70℃; for 12.0h; To a solution of 4-fluoro-3-methoxy-5-nitrobenzamide (300.0 mg, 1.401 mmol), <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (391 mg, 2.101 mmol) in dry DMSO (2335 mul) was added K2CO3 (387 mg, 2.80 mmol). The resulting solution was heated at 70 C. for 12 h. The mixture was concentrated under reduced pressure, and then extracted with DCM and water. The combined organic layers were dried, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel column to afford the desired product. LC-MS calculated for C17H24N4NaO6 (M+Na)+: m/z=403.2; found 403.2.
  • 14
  • [ 146394-99-2 ]
  • 4-fluoro-3-methyl-5-nitrobenzamide [ No CAS ]
  • (E)-tert-butyl 4-(4-carbamoyl-2-methyl-6-nitrophenylamino)but-2-enylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 1.0h; To a solution of 4-fluoro-3-methyl-5-nitrobenzamide (0.400 g, 2.019 mmol) and <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (0.376 g, 2.019 mmol) (Ark Pharm, cat No.AK308564) in dry DMSO (2.019 ml) was added K2CO3 (0.614 g, 4.44 mmol). The resulting yellow solution was stirred at room temperature for 1 h. The reaction mixture was diluted with water (15 mL) dropwise. The precipitated solid was filtered and then washed with water (10 mL). The resulting solid residue was dried to provide the desired product as a yellow solid. LC-MS calculated for C17H24N4NaO5 (M+Na)+: m/z=387.2; found 387.2.
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 1.0h; To a solution of 4-fluoro-3-methyl-5-nitrobenzamide (0.400 g, 2.019 mmol) and <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (0.376 g, 2.019 mmol) (Ark Pharm, cat No.AK308564) in dry DMSO (2.019 mL) was added K2CO3 (0.614 g, 4.44 mmol).;The resulting yellow solution was stirred at room temperature for 1 h. The reaction mixture was diluted with water (15 mL) dropwise. The precipitated solid was filtered and then washed with water (10 mL). The resulting solid residue was dried to provide the desired product as a yellow solid. LC-MS calculated for C17H24N4NaO5 (M+Na)+: m/z=387.2; found 387.2.
  • 15
  • [ 146394-99-2 ]
  • 7-chloro-6-nitrobenzofuran-4-carboxamide [ No CAS ]
  • tert-butyl (E)-(4((4-carbamoyl-6-nitrobenzofuran-7-yl)amino)but-2-en-1-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In ethanol; at 80 - 120℃;Sealed tube; To a vial was added <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (Ark Pharm, cat No.AK308564: 0.140 g, 0.752 mmol), 7-chloro-6-nitrobenzofuran-4-carboxamide (Example 2, Step 5, 0.181 g, 0.752 mmol), a stir bar, EtOH (3.76 mL), and DIPEA (0.656 mL, 3.76 mmol). The resulting mixture was sealed and heated at 80 C. overnight, then 120 C. for 8 h. After cooling to rt, the mixture was concentrated and used directly in the next step. LC-MS calculated for C18H22N4O6Na (M+Na)+: m/z=413.2; found 413.2.
 

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