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Chemical Structure| 21606-04-2 Chemical Structure| 21606-04-2
Chemical Structure| 21606-04-2

*Storage: Sealed in dry,Room Temperature.

2-(Methoxycarbonyl)-6-nitrobenzoic acid

CAS No.: 21606-04-2

4.5 *For Research Use Only !

Cat. No.: A133332 Purity: 98%

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Product Details of [ 21606-04-2 ]

CAS No. :21606-04-2
Formula : C9H7NO6
M.W : 225.16
SMILES Code : O=C(O)C1=C([N+]([O-])=O)C=CC=C1C(OC)=O
MDL No. :MFCD00034781
InChI Key :DJMQLZPEBHSABD-UHFFFAOYSA-N
Pubchem ID :4399477

Safety of [ 21606-04-2 ]

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

Calculated chemistry of [ 21606-04-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 4
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 53.5
TPSA ?

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

109.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.85
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

1.08
Log Po/w (WLOGP)?

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

1.08
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.

0.54
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

-0.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.52

Water Solubility

Log S (ESOL):?

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

-1.93
Solubility 2.65 mg/ml ; 0.0118 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.

-2.97
Solubility 0.241 mg/ml ; 0.00107 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

-1.24
Solubility 13.1 mg/ml ; 0.0581 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

No
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.

-6.91 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

0.0
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

2.0 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)

2.26

Application In Synthesis [ 21606-04-2 ]

* 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 [ 21606-04-2 ]

[ 21606-04-2 ] Synthesis Path-Downstream   1~6

  • 2
  • [ 21606-04-2 ]
  • [ 139481-44-0 ]
  • 3
  • [ 21606-04-2 ]
  • [ 121-44-8 ]
  • [ 75-65-0 ]
  • [ 57113-90-3 ]
YieldReaction ConditionsOperation in experiment
86.7% methyl 2-carboxy-3-nitrobenzoate [MNA] obtained in Reference Example 2 (164 kg) was dissolved in dimethylformamide [DMF] (242 kg), diphenylphosphoryl azide [DPPA] (204 kg) was added thereto at room temperature, and triethylamine (87 kg) was added dropwise while maintaining at 20 to 35 C. After stirring at 20 to 30 C for about 3 hours, t-butyl alcohol (930 kg) was added to the reaction solution.. The temperature was risen to 85 to 90 C over 3 to 5 hours, and the solution was stirred for 1 to 2 hours under reflux (85 to 90 C).. The reaction solution was cooled, concentrated, and the residue was dissolved in ethyl acetate (1400 L).. The solution was washed successively with a mixture of 15 % hydrochloric acid (160 L) and water (1890 L), water (660 L), 5 % aqueous sodium bicarbonate solution (1100 kg) and water (660 L), and the organic layer was concentrated under reduced pressure.. methanol (300 kg) was added thereto, and concentrated under reduced pressure.. A seed crystal (15 kg) and methanol (450 kg) were added to the residue, and the mixture was heated to 50 to 60 C to dissolve it.. After cooled to 5 C, crystals were separated, washed with cold methanol (100 L), and dried to give methyl 2-t-butoxycarbonylamino-3-nitrobenzoate [BAN] (187.0 kg, 86.7 %).. The mother liquor and the washing were concentrated under reduced pressure, and cooled.. The precipitated crystals were centrifuged, washed with cold methanol, and dried to give second crystal of BAN. 1H-NMR (200MHz, CDCl3) delta: 1.50(9H, s), 3,96(3H, s), 7.23(1H, t), 8.10(1H, dd), 8.17(1H, dd) IR(KBr) cm-1:3360, 1730, 1705, 1580, 1520, 1490, 1440, 1365, 1355, 1310, 1270, 1240, 1150, 870, 835, 770, 725, 705
  • 4
  • [ 21606-04-2 ]
  • [ 75-65-0 ]
  • [ 57113-90-3 ]
YieldReaction ConditionsOperation in experiment
72.5% Step 1 To a solution of 2-methoxycarbonyl-6-nitrobenzoic acid (18.3 g, 81.3 mmol) in N,N-dimethylformamide (24.1 mL) was added dropwise diphenyl azidophosphonate (22.8 g, 83.0 mmol) at room temperature, and the dropping funnel was washed with N,N-dimethylformamide (1.8 mL). Then, triethylamine (9.75 g, 96.4 mmol) was added dropwise thereto at 22-31 C., and the dropping funnel was washed with N,N-dimethylformamide (1.6 ml). The reaction mixture was stirred at 28-23 C. for 5 hr under a nitrogen atmosphere. The reaction was monitored by HPLC. To the reaction mixture was added dropwise tert-butyl alcohol (104 g) at room temperature, and the reaction mixture was heated to about 85 C. over 5 hr, and stirred at 85-87 C. for 4 hr. The reaction was monitored by HPLC. The reaction mixture was concentrated under reduced pressure at 50 C. or lower, and ethyl acetate (156 mL) and 1.3% hydrochloric acid (229 ml) were added thereto. The organic layer was separated, and washed successively with water (74 mL), 5% aqueous sodium hydrogen carbonate solution (117 ml) and water (74 mL), and concentrated under reduced pressure at 40 C. or lower (solidification). The solid was dissolved in methanol (42.3 ml) at about 55 C. Methanol (63.5 mL) was added to the solution, and the solution was cooled from 50 C. to about 5 C. over 3 hr. During cooling, seed crystals were added thereto at 36 C., and the mixture was stirred at about 5 C. for 2 hr. The crystals were collected by filtration, washed with cold methanol (18 mL), and dried under reduced pressure at 50 C. or lower to give methyl 2-(tert-butoxycarbonylamino)-3-nitrobenzoate (compound 19a, 17.5 g, 72.5%) as pale-yellow crystals. melting point: 92-94 C. IR (KBr): 3368, 1735, 1608, 1540, 1508 cm-1 1H-NMR (CDCl3): delta=9.61 (br s, 1H), 8.16 (dd, J=8.1, 1.5 Hz, 1H), 8.10 (dd, J=8.1, 1.5 Hz, 1H), 7.23 (t, J=8.1 Hz, 1H), to 3.95 (s, 3H), 1.50 (s, 9H) MS: m/z=314 (MNH4+)
  • 5
  • [ 13365-26-9 ]
  • [ 21606-04-2 ]
YieldReaction ConditionsOperation in experiment
> 90% at 20℃; for 2h;Acidic conditions; (1) Put 30 g of 3-nitrophthalic acid into a 500 ml reaction flask and add 300 ml of methanol (1:10, optionally 1:5 to 1:20, preferably 1:10 to 1:15). Sulfuric acid 30g (1:0.5-1:2, preferably 1:1) was warmed at reflux.(2) TLC monitoring, when the formation of the double esterification product exceeds the reduction of the raw material, the refluxing reaction is ended; below 50 C., the methanol is concentrated under reduced pressure to almost no fraction.(3) Add 200ml of water, control the temperature below 25C, add potassium carbonate to neutralize the pH to 7-8, and add 100ml of ethyl acetate to extract.The extract is concentrated and crystallized to obtain <strong>[13365-26-9]dimethyl 3-nitrophthalate</strong>, the aqueous layer is acidified to pH 4-5, stirred at room temperature for 2 hours, and the product is filtered to obtain methyl 3-nitro-2-carboxybenzoate (AM1). , Content more than 98%, yield more than 90%,Drying standby.
  • 6
  • [ 21606-04-2 ]
  • [ 150058-27-8 ]
 

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