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[ CAS No. 957061-21-1 ] {[proInfo.proName]}

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Chemical Structure| 957061-21-1
Chemical Structure| 957061-21-1
Structure of 957061-21-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 957061-21-1 ]

CAS No. :957061-21-1 MDL No. :MFCD03095116
Formula : C7H7BF2O3 Boiling Point : -
Linear Structure Formula :- InChI Key :IWTBPDRQHIEPBQ-UHFFFAOYSA-N
M.W : 187.94 Pubchem ID :4372786
Synonyms :

Calculated chemistry of [ 957061-21-1 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 2
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 42.68
TPSA : 49.69 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.74 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 1.0
Log Po/w (WLOGP) : 0.49
Log Po/w (MLOGP) : 0.87
Log Po/w (SILICOS-IT) : 0.13
Consensus Log Po/w : 0.5

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.84
Solubility : 2.69 mg/ml ; 0.0143 mol/l
Class : Very soluble
Log S (Ali) : -1.63
Solubility : 4.38 mg/ml ; 0.0233 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.98
Solubility : 1.99 mg/ml ; 0.0106 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.3

Safety of [ 957061-21-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 957061-21-1 ]

* 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 [ 957061-21-1 ]

[ 957061-21-1 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 957061-21-1 ]
  • [ 1238196-62-7 ]
  • 2
  • [ 656257-69-1 ]
  • [ 957061-21-1 ]
  • [ 1254162-84-9 ]
YieldReaction ConditionsOperation in experiment
23% bis(tri-tert-butylphosphine)palladium(0); In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; Example 322-(2,3-Difluoro-6-methoxy-phenyl)-Lambda/-methoxy-Lambda/-methyl-isonicotinamideA flask containing 2-bromo-Lambda/-methoxy-Lambda/-methyl-isonicotinamide (Example 25, using method 2) (3.0 g, 12.2 mmol) 2,3-dfluoro-6-methoxyphenylboronic acid (4.6 g, 24.4 mmol)) and 2M aqueous K3PO4 (15 ml_, 30.6 mmol) in 1 ,4-dioxane (40 mL) was successively evacuated and flushed with nitrogen. Pd(P'Bu3)2 (268 mg, 0.48 mmol) was then added and the mixture heated at 90 0C for 2 hours. The mixture was cooled, concentrated in vacuo and then partitioned between EtOAc and sat. aqueous NaHCC>;3 solution. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by SiO2 chromatography (eluting with 30-100% EtOAc/hexane) gave the title compound (0.856 g, 23%). MS(ESI) m/z 309 (M+H)+
  • 3
  • [ 957061-21-1 ]
  • [ 1586044-82-7 ]
  • [ 1586041-15-7 ]
YieldReaction ConditionsOperation in experiment
Example 277 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-difluoro-6-methoxyphenyl)thiazole-4-carboxamide 277 Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 88), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with <strong>[957061-21-1](2,3-difluoro-6-methoxyphenyl)boronic acid</strong> gave 277. 1H NMR (400 MHz, DMSO-d6) delta 9.42 (s, 1H), 7.84 (s, 1H), 7.47 (t, J=9.4 Hz, 1H), 7.39 (s, 2H), 7.01 (ddd, J=9.4, 4.0, 1.9 Hz, 1H), 5.02-4.76 (m, 2H), 4.18-3.93 (m, 2H), 3.92 (s, 3H), 3.72 (s, 3H), 2.23-2.13 (m, 1H), 1.90-1.60 (m, 4H). LCMS (ES+) m/z 497 (M+1).
  • 4
  • [ 3934-20-1 ]
  • [ 957061-21-1 ]
  • 2-chloro-4-(2,3-difluoro-6-methoxyphenyl)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 4h;Inert atmosphere; General procedure: 1.50 g (10.00 mmol) 2,4-dichloropyrimidine was dissolved in 60 ml degassed 1,2-dimethoxyethane under inert atmosphere and stirred for 10 min. 0.23 g (0.20 mmol) tetrakis(triphenylphosphine)palladium(0) was added to the solution and argon was bubbled through the solution for 30 minutes. 1.67 g (11.00 mmol) 2-methoxyphenylboronic acid and the solution of 3.18 g (30.00 mmol) sodium carbonate in 15 ml water were added to the solution, and the mixture was stirred under argon at reflux temperature for 4 hours. The reaction mixture was cooled down to room temperature, and diluted with 150 ml water. The product was extracted three times with 150 ml ethyl acetate. The organic layers were separated, combined, washed with saturated sodium chloride solution and dried over magnesium sulphate. The solvent was removed under reduced pressure. The residual was crystallized from acetonitrile.
  • 5
  • [ 957061-21-1 ]
  • 4-[4-(2,3-difluoro-6-methoxyphenyl)pyrimidin-2-yl]amino}-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide [ No CAS ]
  • 6
  • [ 957061-21-1 ]
  • 4-[4-(2,3-difluoro-6-methoxyphenyl)pyrimidin-2-yl]amino}-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide [ No CAS ]
  • 7
  • [ 957061-21-1 ]
  • tert-butyl (4aR)-10-bromo-11-chloro-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate [ No CAS ]
  • tert-butyl (4aR)-11-chloro-10-(2,3-difluoro-6-methoxyphenyl)-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With methanesulfonato(2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl)(2?-methylamino-1,1?-biphenyl-2-yl)palladium(II); potassium carbonate; ruphos; In 1,4-dioxane; water; at 20 - 100℃; for 2.5h;Inert atmosphere; tert-Butyl (4aR)-11-chloro-10-(2,3-difluoro-6-methoxyphenyl)-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate Atropisomers 1 and 2 RuPhos-Pd-G3 (84 mg, 0.1 mmol) was added to tert-butyl (4aR)-10-bromo-11-chloro-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate (500 mg, 1 mmol), <strong>[957061-21-1](2,3-difluoro-6-methoxyphenyl)boronic acid</strong> (188 mg, 1 mmol), K2CO3 (277 mg, 2 mmol) and RuPhos (46.7 mg, 0.1 mmol) in 1,4-dioxane/H2O (20 mL, 4:1 ratio) at rt. The resulting suspension was stirred at 100 C. for 1 h. Additional <strong>[957061-21-1](2,3-difluoro-6-methoxyphenyl)boronic acid</strong> (188 mg, 1 mmol), K2CO3 (277 mg, 2 mmol), RuPhos (46.7 mg, 0.1 mmol) and RuPhos-Pd-G3 (84 mg, 0.1 mmol) were added and the reaction mixture heated for a further 1.5 h. The solvent was removed in vacuo. The residue obtained was purified by flash silica chromatography (0 to 100% EtOAc in petroleum ether) to afford crude product as a yellow solid. This was purified by preparative chiral-HPLC (Column: CHIRAL ART Cellulose-SB S-5m, 2*25 cm, 5m; Mobile Phase A: Hex (8 mmol/L NH3.MeOH)-HPLC, Mobile Phase B: EtOH-HPLC; Flow rate: 20 mL/min; Gradient: 50 B to 50 B in 15 min; 220/254 nm) to give atropisomer 1 of tert-butyl (4aR)-11-chloro-10-(2,3-difluoro-6-methoxyphenyl)-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate (93 mg, 42%); 1H NMR (300 MHz, DMSO, 30 C.) 1.46 (9H, s), 2.64-2.79 (1H, m), 3.17-3.30 (3H, m), 3.51 (3H, s), 3.77 (3H, s), 3.82-4.00 (2H, m), 4.75 (1H, d), 7.09 (1H, d), 7.56-7.72 (1H, m), 8.13 (1H, s), 9.02 (1H, s); m/z: ES+ [M+H]+=563. This was followed by atropisomer 2 of tert-butyl (4aR)-11-chloro-10-(2,3-difluoro-6-methoxyphenyl)-9-fluoro-6-methyl-5-oxo-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1',2':4,5]pyrazino[2,3-c]quinoline-3-carboxylate (73 mg, 33%); 1H NMR (300 MHz, DMSO, 30 C.) 1.46 (9H, s), 2.63-2.77 (1H, m), 3.18-3.30 (3H, m), 3.51 (3H, s), 3.77 (3H, s), 3.82-3.99 (2H, m), 4.75 (1H, d), 7.08 (1H, d), 7.56-7.72 (1H, m), 8.12 (1H, s), 9.02 (1H, s); m/z: ES+ [M+H]+=563.
  • 8
  • [ 149849-94-5 ]
  • [ 957061-21-1 ]
  • 2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Intermediate 14. 2-(2,3-Difluoro-6-methoxyphenyl)pyrimidine-4-carboxylic acid A mixture of methyl 2-chloropyrimidine-4-carboxylate (300 mg, 1.738 mmol), (3,6-difluoro-2-methoxyphenyl)boronic acid (425 mg, 2.260 mmol), XPhos Pd G2 (68.4 mg, 0.087 mmol) and Hunig's base (607 3.48 mmol) was treated with 1,4-dioxane (5215 muL) and water (579 muL) and the reaction flask was evacuated, back filled with nitrogen, and then stirred at 90 C. for 3 hrs. The reaction mixture was then concentrated and purified by Biotage Isolera to provide the intermediate. This intermediate was then dissolved in a 1:1:1 mixture of THF/water/MeOH, and treated with lithium hydroxide (285 mg, 6.95 mmol) and the reaction mixture heated to 60 C. for 1 hr. IN HCl was added to neutralize the mixture, resulting in the precipitation of the product, which was collected by filtration and air dried. The obtained crude product was used in the next step without further purification.
  • 9
  • [ 149849-94-5 ]
  • [ 957061-21-1 ]
  • N-(4-((2S,4R)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-methylbenzo[d]thiazol-5-yl)-2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxamide [ No CAS ]
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