Home Cart 0 Sign in  

[ CAS No. 889858-12-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 889858-12-2
Chemical Structure| 889858-12-2
Structure of 889858-12-2 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 889858-12-2 ]

Related Doc. of [ 889858-12-2 ]

Alternatived Products of [ 889858-12-2 ]

Product Details of [ 889858-12-2 ]

CAS No. :889858-12-2 MDL No. :MFCD08703426
Formula : C11H12BrFO2 Boiling Point : -
Linear Structure Formula :- InChI Key :ZPGZHSAOCVWZMR-UHFFFAOYSA-N
M.W : 275.11 Pubchem ID :46738774
Synonyms :

Calculated chemistry of [ 889858-12-2 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.36
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 59.84
TPSA : 26.3 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.16 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.92
Log Po/w (XLOGP3) : 3.97
Log Po/w (WLOGP) : 3.96
Log Po/w (MLOGP) : 3.93
Log Po/w (SILICOS-IT) : 3.55
Consensus Log Po/w : 3.67

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.14
Solubility : 0.0197 mg/ml ; 0.0000716 mol/l
Class : Moderately soluble
Log S (Ali) : -4.22
Solubility : 0.0165 mg/ml ; 0.0000598 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -4.43
Solubility : 0.0103 mg/ml ; 0.0000374 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.81

Safety of [ 889858-12-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P210-P261-P305+P351+P338 UN#:N/A
Hazard Statements:H227-H302-H315-H319-H335-H412 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 889858-12-2 ]

* 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.

  • Upstream synthesis route of [ 889858-12-2 ]
  • Downstream synthetic route of [ 889858-12-2 ]

[ 889858-12-2 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 112704-79-7 ]
  • [ 75-65-0 ]
  • [ 889858-12-2 ]
YieldReaction ConditionsOperation in experiment
95.5% With dmap; di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran at 80℃; for 13 h; Step 1 : Preparation of tert-butyl 4-bromo-2-fluoro-benzoate To a solution of 4-bromo-2-fluoro-benzoic acid (100.0 g, 0.46 mol) in THF/t-BuOH (800 mL/400 mL) was added Boc20 (150.0 g, 0.69 mol) and DMAP (5.6 g, 46.0 mmol), the mixture was stirred at 80°C for 13h. TLC (PE:EtOAc=10:1 ) showed the reaction was completed. After removal of the solvent, the residue was dissolved in water and extracted with EtOAc (500 mL x 3), the organic layer was dried over Na2S04 and concentrated to give the crude product, which was purified by column chromatography (PE:EtOAc=100:1 ) to give the title compound (120.0 g, 95.5percent) as a colorless oil. H-NMR (400 MHz, CDCI3): δ = 7.69 - 7.78 (m, 1 H) 7.26 - 7.34 (m, 2 H) 1 .58 (s, 9 H)
80%
Stage #1: With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 1.5 h;
Stage #2: With pyridine In dichloromethane at 20℃; for 64 h;
Step 1.
tert-Butyl 4-bromo-2-fluorobenzoate
To a stirred solution of 4-bromo-2-fluorobenzoic acid (60 g, 274 mmol) in anhydrous THF (700 mL) at 0° C. was added DMF (2 mL) followed by oxalyl chloride (48 mL, 548 mmol) portionwise over 1 hour.
The mixture was stirred at 0° C. for 30 min, and then at room temperature for 1 hour.
The solvent was removed under reduced pressure, and the residue dissolved in DCM (700 mL).
tert-Butyl alcohol (97 g, 1315 mmol) and pyridine (150 mL) were added, and the reaction mixture was stirred at room temperature for 64 h.
The mixture was transferred to a separating funnel and washed with water (400 mL), 2 N NaOH aqueous solution (400 mL) and brine (2*200 mL), dried over magnesium sulfate, filtered and concentrated under vacuum.
The residue was purified by flash chromatography on silica gel (0 to 5percent ethyl acetate in heptane over 30 min) to give tert-butyl 4-bromo-2-fluorobenzoate (60 g, 80percent) as an oil. LCMS (m/z): 218/220 (MH+ (-tBu)), 1.11 min; 1H NMR (500 MHz, CDCl3) δ ppm 7.81-7.71 (m, 1H) 7.39-7.30 (m, 2H) 7.29 (s, 1H) 1.68-1.55 (m, 9H).
74%
Stage #1: With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5 h;
Stage #2: With pyridine In tetrahydrofuran at 0 - 50℃; for 23 h;
4-Bromo-2-fluorobenzoic acid (1 ) (10 g, 46 mmol) was suspended in DCM (100 mL), treated with oxalyl chloride (12.0 mL, 137 mmol) followed by DMF (36 μ, 0.46 mmol) and the mixture was stirred at RT for 5 h. The mixture was concentrated in vacuo to give a yellow oil which was redissolved in THF and added dropwise to a mixture of pyridine (5.5 mL, 68 mmol) and 'BuOH (8.7 mL, 91 mmol) in THF (100 mL) at 0°C. The mixture was then warmed to RT, stirred at RT for 18 h, then at 50°C for 5 h. The mixture was cooled to RT, concentrated in vacuo and the residue was purified by silica gel chromatography (220 g, 0-10percent EtOAc in isohexane) to afford the title compound (2) (0862) (9.3 g, 74percent) as a colourless oil: 1 H NMR (400 MHz, CDCI3) δ: 7.76 - 7.72 (1 H, m), 7.34 - 7.28 (2H, m), 1 .58 (9H, s)
Reference: [1] Patent: WO2016/102482, 2016, A1, . Location in patent: Page/Page column 114
[2] Patent: US9242996, 2016, B2, . Location in patent: Page/Page column 248; 251
[3] Patent: WO2016/97004, 2016, A1, . Location in patent: Page/Page column 108
  • 2
  • [ 151982-51-3 ]
  • [ 75-65-0 ]
  • [ 889858-12-2 ]
Reference: [1] Patent: US2006/194801, 2006, A1, . Location in patent: Page/Page column 43
  • 3
  • [ 24424-99-5 ]
  • [ 105931-73-5 ]
  • [ 889858-12-2 ]
Reference: [1] Patent: US2014/275540, 2014, A1, . Location in patent: Paragraph 0137
  • 4
  • [ 24424-99-5 ]
  • [ 112704-79-7 ]
  • [ 889858-12-2 ]
Reference: [1] Patent: WO2015/110467, 2015, A1, . Location in patent: Page/Page column 14
  • 5
  • [ 112704-79-7 ]
  • [ 115-11-7 ]
  • [ 889858-12-2 ]
Reference: [1] Patent: US9242996, 2016, B2, . Location in patent: Page/Page column 382; 383
  • 6
  • [ 24424-99-5 ]
  • [ 1435-52-5 ]
  • [ 889858-12-2 ]
Reference: [1] Organic Syntheses, 2012, vol. 89, p. 460 - 470
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 889858-12-2 ]

Venetoclax Intermediates

Chemical Structure| 392-09-6

[ 392-09-6 ]

Methyl 2-fluoro-4-nitrobenzoate

Chemical Structure| 98549-88-3

[ 98549-88-3 ]

1H-Pyrrolo[2,3-b]pyridin-5-ol

Chemical Structure| 106614-28-2

[ 106614-28-2 ]

Methyl 2,4-difluorobenzoate

Chemical Structure| 105931-73-5

[ 105931-73-5 ]

4-Bromo-2-fluoro-1-iodobenzene

Chemical Structure| 1235865-77-6

[ 1235865-77-6 ]

2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid

Similar Product of
[ 889858-12-2 ]

Chemical Structure| 1958100-37-2

A816723[ 1958100-37-2 ]

TERT-BUTYL 4-BROMO-2-FLUOROBENZOATE-1,2,3,4,5,6-13C6

Reason: Stable Isotope

Related Functional Groups of
[ 889858-12-2 ]

Fluorinated Building Blocks

Chemical Structure| 612835-53-7

[ 612835-53-7 ]

Ethyl 5-bromo-2-fluorobenzoate

Similarity: 0.94

Chemical Structure| 955887-09-9

[ 955887-09-9 ]

tert-Butyl 4-bromo-2,6-difluorobenzoate

Similarity: 0.93

Chemical Structure| 1255208-34-4

[ 1255208-34-4 ]

5-Bromo-7-fluoroisobenzofuran-1(3H)-one

Similarity: 0.93

Chemical Structure| 1427409-40-2

[ 1427409-40-2 ]

Methyl 4-bromo-2-fluoro-6-methylbenzoate

Similarity: 0.91

Chemical Structure| 57381-59-6

[ 57381-59-6 ]

Methyl 5-bromo-2-fluorobenzoate

Similarity: 0.91

Aryls

Chemical Structure| 612835-53-7

[ 612835-53-7 ]

Ethyl 5-bromo-2-fluorobenzoate

Similarity: 0.94

Chemical Structure| 955887-09-9

[ 955887-09-9 ]

tert-Butyl 4-bromo-2,6-difluorobenzoate

Similarity: 0.93

Chemical Structure| 1427409-40-2

[ 1427409-40-2 ]

Methyl 4-bromo-2-fluoro-6-methylbenzoate

Similarity: 0.91

Chemical Structure| 57381-59-6

[ 57381-59-6 ]

Methyl 5-bromo-2-fluorobenzoate

Similarity: 0.91

Chemical Structure| 1214362-62-5

[ 1214362-62-5 ]

Ethyl 2-bromo-6-fluorobenzoate

Similarity: 0.90

Bromides

Chemical Structure| 612835-53-7

[ 612835-53-7 ]

Ethyl 5-bromo-2-fluorobenzoate

Similarity: 0.94

Chemical Structure| 955887-09-9

[ 955887-09-9 ]

tert-Butyl 4-bromo-2,6-difluorobenzoate

Similarity: 0.93

Chemical Structure| 1255208-34-4

[ 1255208-34-4 ]

5-Bromo-7-fluoroisobenzofuran-1(3H)-one

Similarity: 0.93

Chemical Structure| 1427409-40-2

[ 1427409-40-2 ]

Methyl 4-bromo-2-fluoro-6-methylbenzoate

Similarity: 0.91

Chemical Structure| 57381-59-6

[ 57381-59-6 ]

Methyl 5-bromo-2-fluorobenzoate

Similarity: 0.91

Esters

Chemical Structure| 612835-53-7

[ 612835-53-7 ]

Ethyl 5-bromo-2-fluorobenzoate

Similarity: 0.94

Chemical Structure| 955887-09-9

[ 955887-09-9 ]

tert-Butyl 4-bromo-2,6-difluorobenzoate

Similarity: 0.93

Chemical Structure| 1255208-34-4

[ 1255208-34-4 ]

5-Bromo-7-fluoroisobenzofuran-1(3H)-one

Similarity: 0.93

Chemical Structure| 1427409-40-2

[ 1427409-40-2 ]

Methyl 4-bromo-2-fluoro-6-methylbenzoate

Similarity: 0.91

Chemical Structure| 57381-59-6

[ 57381-59-6 ]

Methyl 5-bromo-2-fluorobenzoate

Similarity: 0.91