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Structure of 152937-04-7

Chemical Structure| 152937-04-7

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Product Details of [ 152937-04-7 ]

CAS No. :152937-04-7
Formula : C7H3BrFNS
M.W : 232.07
SMILES Code : BrC1=NC2=C(S1)C=C(C=C2)F
MDL No. :MFCD07783786
InChI Key :GIANOUBNTGQAID-UHFFFAOYSA-N
Pubchem ID :11492351

Safety of [ 152937-04-7 ]

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

Computational Chemistry of [ 152937-04-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.28
TPSA ?

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

41.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.3
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

3.43
Log Po/w (WLOGP)?

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

3.62
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.

2.69
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

4.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.26

Water Solubility

Log S (ESOL):?

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

-4.05
Solubility 0.0209 mg/ml ; 0.0000901 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-3.97
Solubility 0.0246 mg/ml ; 0.000106 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

-4.11
Solubility 0.0181 mg/ml ; 0.000078 mol/l
Class?

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

Moderately 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

Yes
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.

-5.28 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.

0.55

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

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)

2.34

Application In Synthesis of [ 152937-04-7 ]

* 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 [ 152937-04-7 ]

[ 152937-04-7 ] Synthesis Path-Downstream   1~22

  • 1
  • [ 152937-04-7 ]
  • [ 214337-23-2 ]
  • [ 214337-47-0 ]
  • 2
  • [ 348-40-3 ]
  • [ 7787-70-4 ]
  • [ 152937-04-7 ]
YieldReaction ConditionsOperation in experiment
40% With tert.-butylnitrite; In hexane; ethyl acetate; acetonitrile; (Step 1) Synthesis of 2-bromo-6-fluorobenzothiazole Copper (I) bromide (619 mg, 4.32 mmol) was suspended in acetonitrile (10 ml). To the resulting suspension was added tert-butyl nitrite (640 ael, 5.38 mmol), followed by stirring at 60ØC for 5 minutes. To the reaction mixture was added 2-amino-6-fluorobenzothiazole (605 mg, 3.60 mmol). The resulting mixture was stirred at 60ØC for 10 minutes. After cooling to the room temperature, the reaction mixture was diluted with ethyl acetate. The ethyl acetate solution was washed with 1N HCl, saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ ethyl acetate (5:1, v/v) eluate fractions, 2-bromo-6-fluorobenzothiazole (330 mg, 40%) was obtained as a brown solid. 1H-NMR (CDCl3) delta: 7.19-7.24 (m, 1H), 7.49-7.52 (m, 1H), 7.92-7.96 (m, 1H). MS (ESI) m/z 273.8 (M++1+MeCN).
With sodium nitrite; In water; hydrogen bromide; EXAMPLE 28 [(2-(6-Fluorobenzothiazolyl))carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester STR36 Slurry 2-amino-6-fluorobenzothiazole (0.255 mol) in water (325 mL), heat to reflux and add 48% hydrobromic acid (130 mL). Maintain at reflux for 20 minutes, cool to 0 C. and add a solution of sodium nitrite (17.56 g, 0.255 mol) water (90 mL), maintaining a temperature of 0 C. Stir at 0 C. for 15 minutes and add by dropwise addition (while keeping cold) to a rapidly stirring mixture of copper (I) bromide (42.03 g, 0.293 mol) in 48% hydrobromic acid (86 mL) and water (225 mL). Stir at room temperature for 20 minutes. Allow to stand overnight, extract into methylene chloride and dry (MgSO4). Evaporate the solvent in vacuo and purify by chromatography to give 2-bromo-6-fluorobenzothiazole.
  • 3
  • pyridinium p-toluenesulfonate (PPTS) [ No CAS ]
  • [ 101349-30-8 ]
  • [ 152937-04-7 ]
  • methyl (3-chloro-4-(6-fluoro-2-benzothiazolyl)aminophenyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% In 5,5-dimethyl-1,3-cyclohexadiene; hexane; ethyl acetate; (Step 2) Synthesis of methyl (3-chloro-4-(6-fluoro-2-benzothiazolyl)aminophenyl)acetate In xylene (8 ml), <strong>[152937-04-7]2-bromo-6-fluorobenzothiazole</strong> (330 mg, 1.42 mmol), methyl 4-amino-3-chlorophenylacetate (284 mg, 1.42 mmol), and pyridinium p-toluenesulfonate (PPTS) (107 mg, 0.43 mmol) were heated under reflux for 10 hours. After cooling, the reaction mixture was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ ethyl acetate (6:1, v/v) eluate fractions, methyl (3-chloro-4-(6-fluoro-2-benzothiazolyl)aminophenyl)acetate (158 mg, 32%) was obtained as a pale yellow solid. 1H-NMR (CDCl3) delta: 3.58 (s, 2H), 3.70 (s, 3H), 7.05-7.10 (m, 1H), 7.22-7.25 (m, 1H), 7.34-7.37 (m, 2H), 7.59-7.63 (m, 1H), 8.32-8.34 (m, 1H). MS (ESI) m/z 351 (M++1).
  • 4
  • [ 1005009-98-2 ]
  • [ 152937-04-7 ]
  • 5-(6-fluoro-1,3-benzothiazol-2-yl)-N-methylpyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 100.0℃; for 0.08333330000000001h;Microwave irradiation; A mixture of 5-bromo-N-methylpyridin-2-amine (50 mg, 0.27 mmol), bis(pinacolato)diboron (75 mg, 0.30 mmol), Pd(dprhof)Cl2*DCM (6.5 mg, 0.008 mmol) and S KOAc (79 mg, 0.80 mmol) in DMF (2 mL) was heated at 150 C for 10 minutes in a microwave reactor. Then 2-bromo-6-fluoro-l,3-benzothiazole (93 mg, 0.40 mmol), another batch of Pd(dppf)Cl2*DCM (6.5 mg, 0.008 mmol) and 2 M aq. K2CO3 (0.5 mL) were added and the reaction mixture was heated at 100 C for 5 minutes in a microwave reactor. The mixture was allowed to cool and was partitioned between EtOAc and H2O. The 0 organic phase was washed with water and brine and was dried (Na2SO4). Concentration <n="94"/>under vacuum and purification by HPLC gave the title compound (8 mg). 1H NMR (CHLOROFORM-c/: CD3OD) delta 8.61 (d, 1 H) 8.02 (dd, 1 H) 7.87 (dd, 1 H) 7.57 (dd, 1 H) 7.22-7.15 (m, 1 H) 6.55 (d, 1 H) 2.94 (s, 3 H); MS m/z (M+H) 260, (M-H) 258.
  • 5
  • [ 1280078-65-0 ]
  • [ 152937-04-7 ]
  • [ 1280078-88-7 ]
YieldReaction ConditionsOperation in experiment
52% With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; copper(l) iodide; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100.0℃;Inert atmosphere; General procedure: aryldioxazaboracane (1.2 equiv), arylbromide (1 equiv) PdCl2(PPh3)2 (5 mol %), PPh3 (10 mol %) and copper iodide (10 mol %) in a 4:1 DMF/water mixture (0.2 mmol/mL) under Argon are brought to 100 C until no more aryl bromide is detected. After cooling to RT, water and Et2O are added. The organic and aqueous phases are separated, the aqueous phase is then extracted with ether, and the organic phase is washed with brine, then dried over MgSO4, and filtered. After evaporation the residue is purified by flash column chromatography.
  • 6
  • [ 1280078-66-1 ]
  • [ 152937-04-7 ]
  • [ 1280078-91-2 ]
YieldReaction ConditionsOperation in experiment
63% With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; copper(l) iodide; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100.0℃;Inert atmosphere; General procedure: aryldioxazaboracane (1.2 equiv), arylbromide (1 equiv) PdCl2(PPh3)2 (5 mol %), PPh3 (10 mol %) and copper iodide (10 mol %) in a 4:1 DMF/water mixture (0.2 mmol/mL) under Argon are brought to 100 C until no more aryl bromide is detected. After cooling to RT, water and Et2O are added. The organic and aqueous phases are separated, the aqueous phase is then extracted with ether, and the organic phase is washed with brine, then dried over MgSO4, and filtered. After evaporation the residue is purified by flash column chromatography.
  • 7
  • [ 1280078-67-2 ]
  • [ 152937-04-7 ]
  • [ 1280078-95-6 ]
YieldReaction ConditionsOperation in experiment
82% With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; copper(l) iodide; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100.0℃;Inert atmosphere; General procedure: aryldioxazaboracane (1.2 equiv), arylbromide (1 equiv) PdCl2(PPh3)2 (5 mol %), PPh3 (10 mol %) and copper iodide (10 mol %) in a 4:1 DMF/water mixture (0.2 mmol/mL) under Argon are brought to 100 C until no more aryl bromide is detected. After cooling to RT, water and Et2O are added. The organic and aqueous phases are separated, the aqueous phase is then extracted with ether, and the organic phase is washed with brine, then dried over MgSO4, and filtered. After evaporation the residue is purified by flash column chromatography.
YieldReaction ConditionsOperation in experiment
88% With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 20.0℃; for 0.5h; General procedure: The appropriately substituted 2-aminobenzothiazole (1.0 equiv) was suspended in acetonitrile (0.2 M). To this mixture was added copper (II) bromide (1.0 equiv) followed by t-butyl nitrite (1.3 equiv). After being allowed to stir at room temperature for 30 mm, the reaction mixture was diluted with EtOAc and washed with 1.0 M HC1 followed by brine. The organic phase was dried over MgSO4, filtered and concentrated before being purified by silica gel chromatography to provide the desired material.
  • 9
  • [ 348-40-3 ]
  • [ 152937-04-7 ]
YieldReaction ConditionsOperation in experiment
40% With tert.-butylnitrite; copper(I) bromide; In acetonitrile; at 60.0℃; for 1.0h; General procedure: To a stirred suspension of CuBr (1.57 g, 10.9 mmol) in MeCN (25 ml) was added tBuONO (1.63 ml, 13.7 mmol) and the mixture was stirred at 60 C for 10 min. Then 2-amino-6-methylbenzothiazole (14b) (1.50 g, 9.13 mmol) was added to the mixture, and the reaction mixture was stirred at 60 C for 1 h. After cooled to room temperature, the mixture was poured into 1 N HCl. The resulting precipitate was dissolved into EtOAc, washed with 1 N HCl, brine, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (7:1, v/v) as eluent to give the title compound (703 mg, 34%) as a brown oil.
  • 10
  • [ 101349-30-8 ]
  • [ 152937-04-7 ]
  • methyl (3-chloro-4-(6-fluoro-2-benzothiazolyl)aminophenyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridinium p-toluenesulfonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 10.0h; General procedure: A mixture of 2-bromo-6-methylbenzothiazole (15b) (703 mg, 3.08 mmol), methyl 4-amino-3-chlorophenylacetate (16a) (615 mg, 3.08 mmol), and PPTS (232 mg, 0.92 mmol) in xylene (10 ml) was refluxed for 10 h. After cooled to room temperature, the solvent was evaporated. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (6:1, v/v) as eluent to give methyl [3-chloro-4-(6-methyl-2-benzothiazolyl)aminophenyl]acetate (274 mg, 26%) as a pale yellow oil
  • 11
  • [ 152937-04-7 ]
  • [ 441712-30-7 ]
  • 12
  • [ 152937-04-7 ]
  • [ 441714-88-1 ]
  • 13
  • [ 152937-04-7 ]
  • [3-chloro-4-(6-fluoro-2-benzothiazolyl)aminophenyl]acetic acid [ No CAS ]
  • 14
  • [ 152937-04-7 ]
  • [ 882055-24-5 ]
  • 15
  • [ 152937-04-7 ]
  • [ 882055-31-4 ]
  • 16
  • [ 152937-04-7 ]
  • [ 882054-99-1 ]
  • 17
  • [ 6165-69-1 ]
  • [ 152937-04-7 ]
  • [ 882055-16-5 ]
  • 18
  • [ 1041600-42-3 ]
  • [ 152937-04-7 ]
  • [ 1532593-78-4 ]
  • 19
  • [ 152937-04-7 ]
  • [ 401567-36-0 ]
  • 20
  • [ 152937-04-7 ]
  • (4-(6-fluorobenzo[d]thiazol-2-yl)piperazin-1-yl)(2-(1-(hydroxymethyl)cyclopropyl)methoxy-5-(methylsulfonyl)phenyl)methanone [ No CAS ]
  • 21
  • [ 152937-04-7 ]
  • (4-(6-fluorobenzo[d]thiazol-2-yl)piperazin-1-yl)(2-(1-(fluoromethyl)cyclopropyl)methoxy-5-(methylsulfonyl)phenyl)methanone [ No CAS ]
  • 22
  • [ 57260-71-6 ]
  • [ 152937-04-7 ]
  • tert-butyl4-(6-fluorobenzo[d]thiazol-2-yl)piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With triethylamine; In N,N-dimethyl-formamide; at 120.0℃; for 16.0h; Take 100mL single-mouthed flask, was successively added <strong>[152937-04-7]2-bromo-6-fluorobenzo[d]thiazole</strong> (200mg, 0.86mmol), tert-butyl piperazine-1-carboxylate (0.16g, 0.86mmol), TEA (0.2 mL, 1.3mmol), DMF (3mL), 120 deg. C reaction 16h, concentrated to dryness to give a crude product, purified by column chromatography to give pure product 0.21g, yield: 73%.
 

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