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Structure of 120100-15-4

Chemical Structure| 120100-15-4

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Product Details of [ 120100-15-4 ]

CAS No. :120100-15-4
Formula : C8H8ClNO2
M.W : 185.61
SMILES Code : O=C(OC)C1=CC=CC(N)=C1Cl
MDL No. :MFCD16036890
InChI Key :NKBQKMXNIWIFAE-UHFFFAOYSA-N
Pubchem ID :15132848

Safety of [ 120100-15-4 ]

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

Computational Chemistry of [ 120100-15-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 47.14
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

1.7
Log Po/w (WLOGP)?

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

1.72
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.

1.91
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

1.61
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-2.3
Solubility 0.931 mg/ml ; 0.00501 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.

-2.41
Solubility 0.715 mg/ml ; 0.00385 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

-2.73
Solubility 0.344 mg/ml ; 0.00185 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.

-6.23 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)

1.47

Application In Synthesis of [ 120100-15-4 ]

* 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 [ 120100-15-4 ]

[ 120100-15-4 ] Synthesis Path-Downstream   1~35

  • 2
  • [ 120100-15-4 ]
  • [ 243869-56-9 ]
  • 2-chloro-3-(3,3,3-trifluoro-2-hydroxy-2-methyl-propionylamino)-benzoic acid methyl ester [ No CAS ]
  • 3
  • [ 67-56-1 ]
  • [ 108679-71-6 ]
  • [ 120100-15-4 ]
YieldReaction ConditionsOperation in experiment
92% With sulfuric acid; for 24h;Heating / reflux; (3) methyl 3-amino-2-chlorobenzoate A mixture of 3-amino-2-chlorobenzoic acid (500 mg, 2.91 mmol), conc. 'sulfuric acid (6 ML), and methanol (150 ML) was heated under reflux for 24 hours, and placed under reduced pressure to distill the solvent off.. The residue was neutralized by addition of aqueous saturated sodium hydrogen carbonate.. The neutralized mixture was extracted with toluene, dried over anhydrous magnesium sulfate, and placed under reduced pressure to distill the solvent off.. There was obtained 497 mg (yield 92%) of the desired compound in the form of pale brown oil. 1H NMR (CDCl3, 500 MHz) delta: 3.91 (3H, s), 4.23 (2H, broad s), 6.89 (1H, dd, J=1Hz, 8Hz), 7.10 (1H, dd, J=8Hz, 8Hz), 7.16 (1H, dd, J=1Hz, 8Hz).
  • 4
  • [ 120100-15-4 ]
  • [ 504-02-9 ]
  • [ 247903-17-9 ]
YieldReaction ConditionsOperation in experiment
14.05 g (84%) c) 3-(3-Carbomethoxy-2-chloroanilino)cyclohex-2-en-1-one A mixture of <strong>[120100-15-4]methyl 2-chloro-3-aminobenzoate</strong> (11.11 g, 59.86 mM) and 1,3-cyclohexanedione (9.05 g, 80.8 mM) was heated at 120 C. under a stream of nitrogen for 4 hours. The resultant solid was triturated with hot ethyl acetate, then dried in vacuo to afford 14.05 g (84%) of 3-(3-carbomethoxy-2-chloroanilino)cyclohex-2-en-1-one as a yellow orange solid. 1H NMR (CDCl3) delta 7.6 (dt, 1H, J=1 and 8 Hz), 7.3 (t, 1H, J=8 Hz), 6.6 (br s, 1H), 5.62 (s, 1H), 3.95 (s, 3H), 2.6 (t, 2H, J=6 Hz), 2.4 (t, 2H, J=6 Hz), and 2.1 (m, 2H). IR (CHCl3, cm-1) 3050, 2950, 1729, 1536, 1351, 1299, 1290, 1267, and 1135. MS (ES) m/e 278, 280, 282. Elemental Analyses for C14H14NO3Cl: Calculated: C, 60.11; H, 5.04; N, 5.01. Found: C, 57.51; H, 4.99; N, 4.68.
  • 5
  • sulfided platinum on carbon [ No CAS ]
  • [ 53553-14-3 ]
  • [ 120100-15-4 ]
YieldReaction ConditionsOperation in experiment
8.6 g (100%) In ethyl acetate; b) Methyl 2-chloro-3-aminobenzoate Hydrogen gas was passed through a solution of methyl 2-chloro-3-nitrobenzoate (10.0 g, 46.4 mM) and 1.0 g of 3% sulfided platinum on carbon in 150 mL ethyl acetate for 48 hours at room temperature. The catalyst was removed by filtration through celite. Concentration of the filtrate afforded 8.6 g (100%) of methyl 2-chloro-3-aminobenzoate as a yellow oil. 1H NMR (CDCl3) delta 7.25 (dd, 1H, J=1 and 8 Hz), 7.2 (t, 1H, J=8 Hz), 6.95 (dd, 1H, J=1 and 8 Hz), and 3.9 (s, 3H). IR (CHCl3, cm-1) 3450, 3380, 2980, 2900, 1729, 1615, 1456, 1434, 1322, 1290, and 1268. MS (ES) m/e 186, 188. Elemental Analyses for C8H8NO2Cl: Calculated: C, 51.77; H, 4.34; N, 7.55. Found: C, 51.52; H, 4.17; N, 7.54.
  • 6
  • [ 53553-14-3 ]
  • [ 120100-15-4 ]
YieldReaction ConditionsOperation in experiment
99% With ammonium chloride; zinc; In methanol; at 20 - 60℃; for 3h; To the solution of 213A: (1 g, 4.64 mmol) in MeOH(23.19 ml) was added ammonium chloride (2.481 g, 46.4 mmol) and zinc dust (1.516 g, 23.19 mmol). The reaction was stirred at rt for 2 h, then warmed to 60C for 1 h. The reaction was filtered through a pad of Celite, rinsing withMeOH. The filtrate was concentrated. The residue was partitioned between EtOAc and water and the layers were separated. The organiclayer washed with sat. NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. Purification by silica gel chromatography afforded 213B (0.85 g,99 % yield) as a yellow oil.
98% With hydrogenchloride; iron; In ethanol; water;Reflux; Procedure: The ester (1.06 g, 4.9 mmol, 1 eq.) and HCIaq(1 m, 4.9 ml_, 1 eq.) were dissolved in EtOH (0.25 m) and heated to reflux. Fine powdered iron (302 mg, 5.4 mmol, 1 .1 eq.) was added in portions to the hot solution and the resulting mixture was refluxed until complete consumption of the starting material. The crude mixture was passed through a Celite pad, diluted with EtOAc and the organic layer was washed with water and brine. The combined organic layers were dried over Na2S04, the solvent was removed under reduced pressure and the product was used without further purification.Yield: 1 .06 g, 4.8 mmol, 98% (brown oil).TLC: PE/EtOAc 25%
83.5% With hydrogen; In methanol; at 25℃; under 2585.81 Torr; for 3.5h;Inert atmosphere; To a solution of methyl 2-chloro-3-nitrobenzoate (25 g, 1 16 mmol) in MeOH (150 ml_) was added Raney Ni (3 g). The mixture was stirred under H2 atmosphere (50 psi at 25 C) for 3.5 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the crude product, which was purified by recrystallization in EtOAc to afford the title compound. 69 g (83.5% yield, four batches combined) 1H NMR (400 MHz, CDCIs) delta ppm 6.70-7.25 (m, 3H), 4.40-4.50 (br, 2H), 3.87 (s, 3H).
83.5% With hydrogen;nickel; In methanol; at 25℃; under 2585.81 Torr; for 3.5h; Step B: Methyl 3-amino-2-chlorobenzoate; To a solution of methyl 2-chloro-3-nitrobenzoate (25 g, 116 mmol) in MeOH (150 mL) was added Raney Ni (3 g). The mixture was stirred under H2 atmosphere (50 psi at 25 C.) for 3.5 h. The catalyst was filtered, and the filtrate was concentrated under the reduced pressure to dryness to give the crude product, which was purified by recrystallization in EtOAc to afford the title compound (69 g, 83.5% yield, four batches combined). 1H NMR (400 MHz, CDCl3) delta ppm 6.70-7.25 (m, 3H), 4.40-4.50 (br, 2H), 3.87 (s, 3H).
2.6 g (50%) With sodium hydroxide; stannous chloride; In hydrogenchloride; ethanol; b) Methyl 2-chloro-3-aminobenzoate A solution of stannous chloride (27.0 g, 137.0 mM) in 55 mL of concentrated hydrochloric acid was slowly added to a solution of methyl 2-chloro-3-nitrobenzoate (6.0 g, 27.9 mM) in 75 mL ethanol at 15-20 C. over 1 hour. The mixture was then heated at 50-60 C. for 15 minutes. The mixture was cooled to room temperature and made alkaline by slow addition of solid sodium hydroxide maintaining a temperature of 30-35 C. The resultant mixture was extracted three times with chloroform. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated to afford 2.6 g (50%) of methyl 2-chloro-3-aminobenzoate as a yellow oil, identical in all respects to the material derived via catalytic hydrogenation described above.
1.2 g (33%) With sodium carbonate; In tetrahydrofuran; methanol; water; b) Methyl 2-chloro-3-aminobenzoate A solution of sodium dithionite (14.0 g, 20.0 mM) and sodium carbonate (6.7 g) in 200 mL of water was slowly added to a solution of methyl 2-chloro-3-nitrobenzoate (6.0 g, 27.9 mM) in 40 mL methanol and 40 mL of tetrahydrofuran at 25 C. over 30 minutes. The mixture was stirred at room temperature for an additional 30 minutes, then extracted with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated to afford 1.2 g (33%) of methyl 2-chloro-3-aminobenzoate as a yellow oil, identical in all respects to the material derived via catalytic hydrogenation described above.
With ammonium formate; acetic acid; zinc; In tetrahydrofuran; methanol; at 20℃; for 18h; Step A: methyl 3-amino-2-chlorobenzoate: To a solution of methyl 2-chloro-3-nitrobenzoate (2.1 g, 9.7 mmol) in methanol (100 mL) and THF (20 mL) was added zinc powder (1.9 g, 29 mmol), ammonium formate (3.1 g, 49 mmol), and a few drops of acetic acid. The mixture was allowed to stir at RT for 18 hours. Most of the volatiles were removed under reduced pressure. The residue was redissolved in EtOAc (200 mL), washed with brine, concentrated and purified by MPLC to provide methyl 3-amino-2-chlorobenzoate.
With ammonium formate; acetic acid; zinc; In tetrahydrofuran; methanol; at 20℃; for 18h; Step A: methyl 3-amino-2-chlorobenzoate: To a solution of methyl 2-chloro-3-nitrobenzoate (2.1 g, 9.7 mmol) in methanol (100 mL) and THF (20 mL) was added zinc powder (1.9 g, 29 mmol), ammonium formate (3.1 g, 49 mmol), and a few drops of acetic acid. The mixture was allowed to stir at RT for 18 hours. Most of the volatiles were removed under reduced pressure. The residue was redissolved in EtOAc (200 mL), washed with brine, concentrated and purified by MPLC to provide methyl 3-amino-2-chlorobenzoate.
19 g With iron; ammonium chloride; In methanol; water; at 80℃; for 2h; To a solution of methyl 2-chloro-3-nitrobenzoate (23.0 g, 107 mmol) in MeOH (100 mL) and H2O (20 mL) were added Fe (29.8 g, 533 mmol) and NH4Cl (45.7 g, 853 mmol). The mixture was stirred at 80 C for 2 hours. The mixture was filtered out and the filtrate was concentrated to give a residue. The residue was purified by silica gel chromatography to give methyl 3-amino-2- chlorobenzoate (I-484) (19.0 g) as a yellow oil.

  • 7
  • [ 15568-85-1 ]
  • [ 120100-15-4 ]
  • [ 948573-53-3 ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol; at 80℃; for 0.166667h; The 4-chloro-7-(N-methylcarbamoyl)quinoline used as starting material was prepared as <n="177"/>follows :-5-Methoxymethylene-2,2-dimethyl-l,3-dioxane-4,6-dione (3.24 g) was added to a stirred mixture of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (US Patent No. 6,177,440, columns 227 and 228 thereof; 3.1 g) and isopropanol (75 ml) and the resultant mixture was heated to 80C for 10 minutes. The reaction mixture was cooled to ambient temperature and the precipitate was recovered, washed with diethyl ether and dried under vacuum. There was thus obtained 5-(2-chloro-3-methoxycarbonylanilinomethylene)-2,2-dimethyl- 1 ,3-dioxane-4,6-dione (5 g); 1H NMR: (DMSOd6); 1.7 (s, 6H), 3.89 (s, 3H), 7.56 (m, IH), 7.67 (d, IH), 8.11 (br m, IH), 8.79 (br m, IH); Mass Spectrum: M+H+ 340.
  • 8
  • [ 111-71-7 ]
  • [ 120100-15-4 ]
  • [ 1130798-90-1 ]
  • 9
  • [ 120100-15-4 ]
  • [ 2937-50-0 ]
  • [ 1195768-68-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (29 g, 0.162 mol) in THF (50 ml_) and saturated NaHCO3 (200 ml_) was added 2-propen-1 -yl chloridocarbonate (24 g, 0.194 mol) dropwise at 0 C. The reaction mixture was allowed to warm to room temperature for 2 h. The reaction was extracted with EtOAc (2 x 200 ml_). The organic layer was dried over Na2SO4, and the solvent was removed to give a crude product. 42 g (96.3% yield) 1H NMR (400 MHz, CDCI3) delta ppm 8.30-8.37 (m, 1 H), 7.47-7.51 (m, 1 H), 7.35-7.43 (br, 1 H), 7.28-7.33 (m, 1 H), 5.90-6.06 (m, 1 H), 5.25-5.41 (m, 2H), 4.68-4.70 (m, 2H), 3.91 (s, 3H)
With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 20℃; for 2h; Example 24; N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-chlorophenyl}-2-furansulfonamide; Step A: Methyl 2-chloro-3-[(2-propen-1-yloxy)carbonyl]amino}benzoate; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (29 g, 0.162 mol) in THF (50 mL) and saturated NaHCO3 (200 mL) was added 2-propen-1-yl chloridocarbonate (24 g, 0.194 mol) dropwise at 0 C. The reaction mixture was allowed to warm to rt for 2 h. The reaction was extracted with EtOAc (2×200 mL). The organic layer was dried over Na2SO4, and the solvent was removed to give the crude product of Step A, which was directly used to the next step. (42 g, 96.3% yield). 1H NMR (400 MHz, CDCl3) delta ppm 8.30-8.37 (m, 1H), 7.47-7.51 (m, 1H), 7.35-7.43 (br, 1H), 7.28-7.33 (m, 1H), 5.90-6.06 (m, 1H), 5.25-5.41 (m, 2H), 4.68-4.70 (m, 2H), 3.91 (s, 3H).
  • 10
  • [ 26120-86-5 ]
  • [ 120100-15-4 ]
  • [ 1195768-58-1 ]
  • C22H15Cl2F2NO6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 20℃; Intermediate 45: N-{2-Chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,5-difluorobenzenesulfonamide; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (16.3 g, 88 mmol) in pyridine (150 mL) was added 2,5-difluorobenzenesulfonyl chloride (13.0 ml, 97 mmol) dropwise. The solution was stirred at rt overnight. The crude reaction mixture was concentrated by about half, and 200 mL of water was added. A red oil precipitated from the mixture. The oil was separated, and crystallized upon standing. The crystals were collected by vacuum filtration, washed with ether, and dried in vacuo to generate 16.8 g (46.4 mmol, 52.8% yield) as a white powder. LC/MS indicates that the product is a 2:1 mixture of the desired product and the bis-sulfonamide. The white powder was dissolved in THF (100 mL), and a 1 M solution of LiHMDS in THF (100 mL, 100 mmol) was added. A solution of 2-chloro-4-methylpyrimidine (8.0 g, 62.2 mmol) in THF (10 mL) was added dropwise over 15 minutes. The solution was stirred at 20 C. for an additional 20 minutes, and then the reaction was quenched with MeOH (5 mL). The solvent was removed with a rotary evaporator, and the residue was partitioned between EtOAc and water. The aqueous layer was acidified to pH<9 with saturated aqueous ammonium chloride, and extracted with EtOAc. The combined organic layers were dried over anhydrous NaSO4, filtered, and concentrated to 50 mL. The brown solution was passed through a pad of silica gel (eluting with EtOAc) and concentrated to generate the title compound (6.78 g, 14.8 mmol, 16.8% yield) as a yellow powder. MS (ESI): 458.0 [M+H]+.
  • 11
  • [ 528607-60-5 ]
  • [ 120100-15-4 ]
  • [ 528607-66-1 ]
YieldReaction ConditionsOperation in experiment
71% (4) methyl 2-chloro-3-(3-cyano-4-isobutyloxybenzoylamino)benzoate oxalyl chloride (889 mg, 7.0 mmol) was dropwise added to a solution of 3-cyano-4-isobutyloxybenzoic acid (767 mg, 3.5 mmol) in dichloromethane (10 ML) under cooling with ice.. Subsequently, a catalytic amount of DMF was added.. The mixture was then stirred for one hour at room temperature, heated under reflux for 3 hours, and placed under reduced pressure to distill the solvent off.. To the residue was added toluene, and the solvent was distilled off under reduced pressure.. To the reside were added THF (10 ML) and further a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (497 mg, 2.68 mmol) and triethylamine (1.39 ML, 10 mmol) in THF (10 ML).. The resulting mixture was stirred for 14 hours at room temperature, and toluene and aqueous 1M hydrochloric acid were added.. The organic portion was taken out, washed with aqueous 1M hydrochloric acid and aqueous saturated sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and placed under reduced pressure to distill the solvent off.. The residue was purified by silica gel column chromatography (ethyl acetate/toluene = 1/20), to give 900 mg (purity 82%, yield 71%) of the desired compound as an oil. 1H NMR (CDCl3, 500 MHz) delta: 1.06 (6H, d, J=6Hz), 2.1-2.4 (1H, m), 3.87 (2H, d, J=6Hz), 3.95 (3H, s), 6.93 (1H, d, J=9Hz), 7.1-7.3 (2H, m), 7.83 (1H, dd, J=2Hz, 8Hz), 7.89 (1H, dd, J=2Hz, 9Hz), 7.98 (1H, d, J=2Hz).
  • 12
  • [ 120100-15-4 ]
  • [ 3282-30-2 ]
  • [ 1353575-44-6 ]
YieldReaction ConditionsOperation in experiment
96% With triethylamine; In dichloromethane; at 0 - 20℃; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (2.5 g, 13.5 mmol) andEt3N (3.8 ml, 26.9 mmol) in DCM (50 ml) at 0 C, pivaloyl chloride (1.8 ml, 14.8 mmol) was added. The reaction was allowed to warm to rt overnight. The mixture was diluted withEtOAc. The EtOAc layer was washed with, aqueous 1.0 M HC1 solution, water, saturated aqueous sodium bicarbonate solution, water, brine, and dried (MgSC^). The solution was filtered and concentrated to afford methyl 2-chloro-3-pivalamidobenzoate (3.5 g, 13.0 mmol,96 % yield) as a pale pink oil which was used without further purification:[00124] 1H NMR (400 MHz, CDC13) delta ppm 1.36 (s, 9 H) 3.94 (s, 3 H) 7.33 (t, J=8.0Hz, 1 H) 7.54 (dd, J=7.8, 1.57 Hz, 1 H) 8.24 (br. s., 1 H) 8.60 (dd, 1 H).
  • 13
  • [ 120100-15-4 ]
  • [ 1307272-36-1 ]
  • 14
  • [ 120100-15-4 ]
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  • [ 120100-15-4 ]
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  • [ 120100-15-4 ]
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  • [ 10147-36-1 ]
  • [ 120100-15-4 ]
  • [ 1307272-35-0 ]
YieldReaction ConditionsOperation in experiment
89% With pyridine; at 0 - 30℃; for 6.5h;Inert atmosphere; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (40 g, 216 mmol) in pyridine (45 mL) stirred at 0C was added a solution of propane-1 -sulfonyl chloride (29.1 mL, 259 mmol) dropwise during 30 min. The reaction mixture was stirred at 30 C for 6 h. After 6 h, the reaction mixture was cooled and 80 mL of water and dichloromethane (100 mL) was added. The organic layer was separated and aqueous layer was extracted with dichloromethane(100 mL x 3). The combined organic layers were dried over Na2SO4, and concentrated. The residue was purified silica gel chromatography and was eluted with Hex/EtOAc (4:1 ) to afford methyl 2-chloro-3- (propylsulfonamido)benzoate. (56g, 89 % yield) as a yellow solid MS: 309 [M+H]+
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  • [ 845866-80-0 ]
  • [ 120100-15-4 ]
  • [ 1307272-31-6 ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 20℃; for 40h;Inert atmosphere; To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (20 g, 108 mmol) in pyridine (300 ml_) was added dropwise a solution of 3,3,3-trifluoro-1 - propanesulfonyl chloride (21 .18 g, 108 mmol) in 30 ml_ of pyridine. After 16 hours at room temperature, 3, 3,3-trifluoro-1 -propanesulfonyl chloride (4 g) was added to the reaction mixture. After another 24 hours, the reaction solution was concentrated. The crude residue was partioned between EtOAc and water. The phases were separated. The aqueous phase was further extracted with EtOAc twice more and the combined organic phases were washed with 1 N HCI, water, brine and dried over MgSO4, filtered and concentrated to obtain title compound.
  • 32
  • [ 120100-15-4 ]
  • [ 871224-19-0 ]
YieldReaction ConditionsOperation in experiment
Step B: methyl 3-bromo-2-chlorobenzoate: To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (2.0 g, 11 mmol) in 48% HBr (10 mL) and water (20 mL) was added an aqueous solution of sodium nitrite (0.89 g, 13 mmol) at 0 C. The mixture was allowed to stir at 0 C for 30 minutes before it was added into a suspension of copper(I) bromide (2.3 g, 16 mmol) in water (10 mL) and 48% HBr (5 mL) at 0 C. The reaction was allowed to warm to RT slowly, and then heated to 60 C for 5 minutes. The product was extracted with DCM (100 mL X 2). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC to provide methyl 3-bromo-2-chlorobenzoate. LC-MS (IE, m/z): 251 [M + 1]+
Step B: methyl 3-bromo-2-chlorobenzoate: To a solution of <strong>[120100-15-4]methyl 3-amino-2-chlorobenzoate</strong> (2.0 g, 11 mmol) in 48% HBr (10 mL) and water (20 mL) was added an aqueous solution of sodium nitrite (0.89 g, 13 mmol) at 0 C. The mixture was allowed to stir at 0 C for 30 minutes before it was added into a suspension of copper(I) bromide (2.3 g, 16 mmol) in water (10 mL) and 48% HBr (5 mL) at 0 C. The reaction was allowed to warm to RT slowly, and then heated to 60 C for 5 minutes. The product was extracted with DCM (100 mL X 2). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC to provide methyl 3-bromo-2-chlorobenzoate. LC-MS (IE, m/z) 251 [M + 1]+
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  • [ 120100-15-4 ]
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  • [ 1374574-20-5 ]
 

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Technical Information

Categories

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