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Structure of 1231892-80-0

Chemical Structure| 1231892-80-0

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Product Details of [ 1231892-80-0 ]

CAS No. :1231892-80-0
Formula : C12H17BFNO2
M.W : 237.08
SMILES Code : NC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1F
MDL No. :MFCD18383607
InChI Key :JQYPICYMRVGSCU-UHFFFAOYSA-N
Pubchem ID :58164434

Safety of [ 1231892-80-0 ]

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

Computational Chemistry of [ 1231892-80-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 67.28
TPSA ?

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

44.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.33
Log Po/w (WLOGP)?

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

2.14
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.

1.54
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.51

Water Solubility

Log S (ESOL):?

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

-2.97
Solubility 0.252 mg/ml ; 0.00106 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.

-2.9
Solubility 0.296 mg/ml ; 0.00125 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

-3.92
Solubility 0.0282 mg/ml ; 0.000119 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

Yes
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.

-6.09 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

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)

2.96

Application In Synthesis of [ 1231892-80-0 ]

* 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 [ 1231892-80-0 ]

[ 1231892-80-0 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 1231892-80-0 ]
  • [ 1269233-23-9 ]
  • [ 497-19-8 ]
  • [ 1269233-33-1 ]
YieldReaction ConditionsOperation in experiment
With nitrogen;SiO2; In 1,2-dimethoxyethane; n-heptane; ethyl acetate; Preparation of intermediate 3-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-2-fluoroaniline (1-1i) To a microwave vial with stir bar was added 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-1a, step 5, 0.55 g, 1.3 mmol), <strong>[1231892-80-0]2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (0.61 g, 2.6 mmol), 2.0 M aqueous sodium carbonate solution (3.2 mL, 6.4 mmol) and DME (6.4 mL). The resulting mixture was sparged with nitrogen followed by the addition of PdCl2(dppf)·DCM adduct (0.052 g, 0.06 mmol). The reaction was sealed and irradiated in microwave reactor for 20 minutes at 120 C. The reaction mixture was diluted with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4), filtered, concentrated, and adsorbed onto silica gel. Purification by flash chromatography (SiO2, 0-100% EtOAc in heptane) yielded 3-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-2-fluoroaniline (223 mg, 0.48 mmol, 38%) as a viscous yellow oil: LCMS(m/z) 460.1 (MH+), tR=0.95 minute.
  • 2
  • 2-(2-fluoro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • [ 1231892-80-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;palladium 10% on activated carbon; In ethyl acetate; under 760.051 Torr; for 16h; [00202] Intermediate. 2-fluoro-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl) aniline:[00203] A mixture of Intermediate 2-(2-fluoro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (500 mg), 10% palladium on carbon (50 mg) and ethyl acetate (20 ml) was stirred under 1 atmosphere of hydrogen for 16 h. The mixture was sparged with nitrogen and filtered. The filtrate was concentrated to provide the title compound, which was used without further purification. MS m/z 237.1 (M + 1).
  • 3
  • [ 1231892-80-0 ]
  • [ 104-12-1 ]
  • [ 1400220-48-5 ]
YieldReaction ConditionsOperation in experiment
100% In tetrahydrofuran; at 20.0℃; for 23h;Inert atmosphere; Step 3: To a solution of <strong>[1231892-80-0]pinacol 3-amino-2-fluoroboronate</strong> (286 mg, 1.206 mmol) in THF (5 mL) under nitrogen atmosphere was added 4-chlorophenylisocyanate (204 mg, 1.327 mmol). The reaction mixture was stirred at room temperature for 23 h, quenched with a few drops of MeOH and concentrated in vacuo to give 471 mg of l-[2-fluoro-3- (4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-3-(4-chlorophenyl)-urea as a tan solid (quant.): 1H NMR (DMSO-dtf, ppm) delta 1.33 (s, 12H), 7.17 (t, 1H), 7.26 (m, 1H), 7.36 (d, 2H), 7.51 (d, 2H), 8.24 (t, 1H), 8.52 (s, 1H), 9.26 (s, 1H); [M+H]+ m/z 391.
  • 4
  • [ 58534-95-5 ]
  • [ 73183-34-3 ]
  • [ 1231892-80-0 ]
YieldReaction ConditionsOperation in experiment
76% With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 100.0℃; for 23h;Inert atmosphere; Step 2: A flask was charged with 3-bromo-2-fluoroaniline (3.84 g, 20.2 mmol), bis(pinacolato)diboron (6.16 g , 24.25 mmol), potassium acetate (3.96 g, 40.4 mmol), Pd(dppf)Cl2 CH2C12 (495 mg, 0.606 mmol), and DMF (40 mL) under nitrogen atmosphere. After stirring for 23 h at 100 C the reaction mixture was concentrated in vacuo, the residue was triturated with hexanes and filtered through a pad of celite. The filtrate was adsorbed on silica gel. Purification by flash silica gel chromatography using a gradient of 0-30% EtOAc/hexane afforded 3.65 g of pinacol 3-amino-2-fluoroboronate as an off white solid (76% yield): 1H NMR (CDC13, ppm) delta 1.39 (s, 12H), 3.73 (broad s, 2H), 6.91 (dt, 1H), 6.97 (t, 1H), 7.11 (m, 1H).
60.7% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100.0℃; for 16h;Inert atmosphere; [0593] To a solution of compound 138 (500 mg, 2.64 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1,3,2-dioxaborolane) (806 mg, 3.17 mmol) and KOAc (518 mg, 5.29 mmol) in DMF (10 mL) was added Pd(dppf)Cl2 (108 mg, 0.13 mmol) at room temperature under N2 atmosphere. The reaction was stirred under nitrogen protection at 100 oC for 16 hrs. Water (10 mL) was added and the mixture was extracted with ethyl acetate (20 mL x 2). The combined organic phases are washed with brine, dried over anhydrous Na2SO4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with Petroleum ether: Ethyl acetate =40: 1) to give the title compound (380 mg, 60.7% yield) as white solid. LC/MS (ESI) m/z: 238 (M+H) +
803 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90.0℃; for 15h;Inert atmosphere; [0477] A solution of 3-bromo-2-fluoroaniline (0.5g, 2.63 mmol), 4,4,4,4,5,5,5,5?- octamethyl-2,2?-bi(1,3,2-dioxaborane) (1.67g, 6.6 mmol), and KOAc (0.77g) in dioxane (10 mL) was degassed and refilled with argon twice. To this solution was added Pd(dppf)2C12 (289 mg) under an atmosphere of argon. The solution was heated at 90C for 15 h. The reaction mixture was cooled to rt and the volatiles were removed under reduced pressure. The remaining residue was purified by column chromatography to afford S2 (803 mg).
6.9 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 100.0℃; for 7h;Inert atmosphere; A mixture of 3-bromo-2-fluoro-phenylamine (6.52 g, 33.63 mmol), bis(pinacolato)diboron (10.45 g, 41.14 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (1 :1) (1.12 g, 1.37 mmol) and potassium acetate (10.1 g, 103.06 mmol) in dry DMF (65 mL) was heated at 100C under an atmosphere of nitrogen for 7 hours. The reaction was allowed to cool to room temperature, diluted with AcOEt and filtered through celite. The organic was washed with water, brine, dried over Na2SO4 and evaporated. The crude was purified by silica gel chromatography which was eluted with hexane:AcOEt = 8:2 to afford 2-fluoro-3-(4,4,5,5- tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-phenylamine (6.90 g) as white solid.

  • 5
  • [ 58534-94-4 ]
  • [ 1231892-80-0 ]
  • 6
  • [ 2924-09-6 ]
  • [ 1231892-80-0 ]
  • 7
  • [ 2924-09-6 ]
  • [ 348-54-9 ]
  • [ 1231892-80-0 ]
  • 9
  • C12H16BBrFNO2 [ No CAS ]
  • [ 1231892-80-0 ]
  • 10
  • C12H16BBrFNO2 [ No CAS ]
  • [ 348-54-9 ]
  • [ 1231892-80-0 ]
  • 11
  • [ 327-52-6 ]
  • [ 1231892-80-0 ]
  • 2’-chloro-2,4’,5’-trifluoro-[1,1‘-biphenyl]-3-amine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
13.1 g [0478] A solution of 2-fluoro-3 -(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)aniline (26.0 g, 110 mmol), 1-bromo-2,4,5-trifluorobenzene (12.5 g, 60 mmol), and K2C03 (38 g, 275 mmol) in co-solvent of dioxane (250 mL) and water (63 mL) was degassed and refilled with argon twice. To this solution was added Pd(dppf)2C12 (8.04g) under an atmosphere of argon. The solution was refluxed for 15 h. The reaction mixture was cooled to rt and the volatiles were removed under reduced pressure. The remaining residue was purified by column chromatography. The desired product fractions were collected and concentrated, and then the HC1 salt S3 was made by treatment with HC1/MeOH to yield 13.1 g of S3.
  • 12
  • [ 54826-14-1 ]
  • [ 1231892-80-0 ]
  • 1-(3’-amino-6-chloro-2’-fluoro-[1,1‘-biphenyl]-3-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
75.05% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100.0℃; for 16h;Inert atmosphere; [0594] To a solution of compound 137 (600 mg, 2.58 mmol), compound 139 (732 mg, 3.12 mmol) and Na2CO3 (822 mg, 7.74 mmol) in dioxane/H2O (10 mL/3 mL) at room temperature under nitrogen, was added Pd(PPh3)4 (50 mg, 0.043 mmol). The reaction was stirred under nitrogen protection at 100 oC for 16 hrs. The resulting mixture was concentrated and the residue was purified by column chromatography on silica gel (eluted with Petroleum ether: Ethyl acetate =10: 1) to give the title compound (510 mg, 75.05% yield) as white solid. LC/MS (ESI) m/z: 264 (M+H) +.
  • 13
  • [ 54826-14-1 ]
  • [ 1231892-80-0 ]
  • (1R,3S,5R)-tert-butyl 3-((5'-acetyl-2'-chloro-2-fluoro-[1,1'-biphenyl]-3-yl)carbamoyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate [ No CAS ]
  • 14
  • [ 1231892-80-0 ]
  • 5-iodo-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine [ No CAS ]
  • 5-(3-amino-2-fluorophenyl)-7-(tetrahydropyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
39 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,2-dimethoxyethane; water; at 85.0℃; for 5h;Schlenk technique; Inert atmosphere; In a Schlenk tube, to 5-iodo-7-(tetrahydro-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (70 mg, 0.203 mmol), 2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (104 mg, 0.439 mmol), Cs2CO3 (250 mg, 0.767 mmol) and 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (1 :1) (14 mg, 0.017 mmol) were added 1 ,2-dimethoxyethane (DME) (3.6 mL) and water (0.4 mL). The reaction mixture was degassed with nitrogen, heated to 85C for 5 hours and then filtered through a celite pad. The filtrate was evaporated under reduced pressure; the crude was taken up with DCM, washed with saturated aqueous NaHC03, brine and dried over Na2SO4. The solvent was evaporated and the crude was purified by silica gel chromatography which was eluted with DCM:MeOH = 95:5. The solid obtained was triturated with Et.20 to afford the title compound (39 mg) as white solid. HPLC (254 nm): Rt: 4.30 min. HRMS (ESI) calcd for C17H18FN5O [M+H]+ 328.1568, found 328.1575. 1H NMR (401 MHz, DMSO-d6) delta ppm: 1.87 (dd, J=12.33, 2.44 Hz, 2 H) 2.02 - 2.18 (m, 2 H) 3.53 (t, J=1 1.17 Hz, 2 H) 4.00 (dd, J=11.23, 4.03 Hz, 2 H) 4.83 (tt, J=11.93, 3.94 Hz, 1 H) 5.23 (br. s., 2 H) 5.99 (br. s., 2 H) 6.41 - 6.61 (m, 1 H) 6.77 (td, J=8.24, 1.59 Hz, 1 H) 6.88 - 7.02 (m, 1 H) 7.42 (s, 1 H) 8.13 (s, 1 H).
  • 15
  • [ 799293-85-9 ]
  • [ 1231892-80-0 ]
  • 3-(3-amino-2-fluorophenyl)thieno[3,2-c]pyridin-4-ylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of 3-bromo-thieno[3,2-c]pyridin-4-ylamine (80 mg, 0.35 mmol) in DME (3.2 mL) and water (0.32 mL), CS2CO3 (342 mg, 1.05 mmol) and 2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (207 mg, 0.87 mmol) were added. The mixture was sonicated for 5 minutes before adding Pd(dppf)Cl2 (20 mg) and microwave heating at 100 C for 1.5 h. The mixture was diluted with AcOEt and washed with a saturated solution of NaHC03 and brine. The organic layer was dried with Na2SO4 and evaporated to dryness. The residue was purified by flash column chromatography over silica gel eluting with DCM-MeOH 2%. 3-(3-amino-2-fluoro-phenyl)-thieno[3,2-c]pyridin-4-ylamine was so isolated (68 mg). HPLC (254 nm): Rt: 4.55 min. HRMS (ESI) calcd for G3H11 FN3S [M+H]+ 260.0652, found 260.0654. 1H NMR (500 MHz, DMSO-d6) delta ppm 5.38 (s, 4 H) 6.52 (ddd, J=7.44, 6.37, 1.45 Hz, 1 H) 6.88 (td, J=8.27, 1.60 Hz, 1 H) 6.99 (t, J=7.70 Hz, 1 H) 7.26 (d, J=5.64 Hz, 1 H) 7.51 (s, 1 H) 7.81 (d, J=5.64 Hz, 1 H).
  • 16
  • [ 799293-85-9 ]
  • [ 1231892-80-0 ]
  • N-[3-(4-aminothieno[3,2-c]pyridin-3-yl)-2-fluorophenyl]-5-chloro-2-fluoro-4-methoxybenzenesulfonamide [ No CAS ]
  • 17
  • [ 1231892-80-0 ]
  • N-{3-[4-amino-7-(tetrahydropyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl}-4-methoxy-3-methylbenzenesulfonamide [ No CAS ]
  • 18
  • [ 1231892-80-0 ]
  • [ 22952-43-8 ]
  • 3-chloro-N-[2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-4-methoxybenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
250 mg With pyridine; In dichloromethane; at 20.0℃; for 2h; To a solution of 2-fluoro-3-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-phenylamine (163 mg, 0.685 mmol) in DCM (10 mL) were added pyridine (0.28 mL, 3.484 mmol), 3-chloro-4-methoxy-benzenesulfonyl chloride (197 mg, 0.820 mmol) and stirred at room temperature for 2h. The reaction was diluted with DCM and washed with saturated NaHC03, brine and dried over Na2S04. The organic solvent was evaporated under vacuum and the residue was triturated with hexane to give the title compound (250 mg) as a solid. HRMS (ESI) calcd for C19H22BCIFN05S [M+Na]+ 463.0913, found 463.0897. 1H NMR (500 MHz, DMSO-d6) delta ppm: 1.20 - 1.31 (m, 12 H) 3.91 (s, 3 H) 7.13 (t, J=7.63 Hz, 1 H) 7.29 (d, J=8.85 Hz, 1 H) 7.35 - 7.42 (m, 1 H) 7.65 (dd, J=8.85, 2.29 Hz, 1 H) 7.69 (d, J=2.14 Hz, 1 H) 7.93 (t, J=7.63 Hz, 1 H) 10.09 - 10.21 (m, 1 H).
  • 19
  • [ 1231892-80-0 ]
  • 5-[4-chloro-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one [ No CAS ]
  • 5-[3'-amino-2'-fluoro-2-(trifluoromethyl)biphenyl-4-yl]-3,6-dihydro-2H-1,3,4-oxadiazin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
51.0 mg With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); potassium carbonate; XPhos; In 1,4-dioxane; water; at 80.0℃; for 2h;Inert atmosphere; In a reaction vessel, 5-[4-chloro-3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,3,4- oxadiazin-2-one (80.2 mg, 288 muiotaetaomicronIota, Intermediate 64), 2-fluoro-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)aniline (102 mg, 432 muiotaetaomicronIota), potassium carbonate (79.6 mg, 576 muiotaetaomicronIota) and 2-(dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl (8.23 mg, 17.3 muiotaetaomicronIota) were suspended in 740 muIota_ 1,4-dioxane and 220 muIota_ water. The mixture was degassed with nitrogen for 5 min. Then, chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1 '- biphenyl)[2-(2'-amino-1,1 '-biphenyl)]palladium(ll) (6.79 mg, 8.64 muiotaetaomicronIota) was added. Nitrogen was passed through the reaction mixture. It was stirred at 80 for 2 hours in a heating block. The mixture was diluted with water and extracted with ethyl acetate three times. The combined organic layers were dried using a water-resistant filter and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMSO, filtered and purified by preparative HPLC, to give 51.0 mg (95 % purity, 48 % yield) of the title compound. LC-MS (Method 2): R, = 1.04 min; MS (ESIpos): m/z = 354 [M+H]+ 1 H-NMR (400 MHz, DMSO-d6) delta [ppm]: 2.074 (16.00), 2.323 (0.46), 2.327 (0.60), 2.331 (0.45), 2.518 (2.03), 2.522 (1.33), 2.665 (0.44), 2.669 (0.59), 2.673 (0.43), 5.253 (4.94), 5.472 (13.69), 6.369 (0.89), 6.385 (1.64), 6.401 (0.86), 6.797 (0.79), 6.801 (0.82), 6.817 (1.69), 6.821 (1.64), 6.838 (1.19), 6.842 (1.07), 6.896 (1.87), 6.916 (2.66), 6.936 (1.09), 7.493 (2.29), 7.513 (2.43), 7.992 (1.64), 7.995 (1.68), 8.016 (1.57), 8.096 (3.24), 8.099 (3.06).
 

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