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Product Details of [ 80058-84-0 ]

CAS No. :80058-84-0 MDL No. :MFCD09743895
Formula : C12H18BrN Boiling Point : -
Linear Structure Formula :H2NC6H2(Br)(CH(CH3)2)2 InChI Key :QAQRHTYPYQPBSX-UHFFFAOYSA-N
M.W : 256.18 Pubchem ID :11780114
Synonyms :

Calculated chemistry of [ 80058-84-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.5
Num. rotatable bonds : 2
Num. H-bond acceptors : 0.0
Num. H-bond donors : 1.0
Molar Refractivity : 67.71
TPSA : 26.02 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -4.89 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.03
Log Po/w (XLOGP3) : 4.18
Log Po/w (WLOGP) : 4.29
Log Po/w (MLOGP) : 4.0
Log Po/w (SILICOS-IT) : 3.79
Consensus Log Po/w : 3.86

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.25
Solubility : 0.0145 mg/ml ; 0.0000566 mol/l
Class : Moderately soluble
Log S (Ali) : -4.44
Solubility : 0.0094 mg/ml ; 0.0000367 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -4.54
Solubility : 0.00739 mg/ml ; 0.0000288 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.71

Safety of [ 80058-84-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P501-P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312 UN#:N/A
Hazard Statements:H302+H312+H332-H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 80058-84-0 ]

* 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.

  • Upstream synthesis route of [ 80058-84-0 ]
  • Downstream synthetic route of [ 80058-84-0 ]

[ 80058-84-0 ] Synthesis Path-Upstream   1~2

  • 1
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  • [ 80058-84-0 ]
YieldReaction ConditionsOperation in experiment
100% With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 5℃; for 0.333333 h; Inert atmosphere A solution of NBS (24.59 g, 137 mmol) in DMF (160 mL) was added slowly to a solution of 2,6-diisopropylaniline (25 g, 137 mmol) in DMF (300 mL) at 0-5°C under a nitrogen atmosphere over a period of 20 minutes. The reaction mixture was stirred at 0-5°C. After the reaction was complete, water was added and the oil suspension was stirred at rt. The aqueous layer was decanted out and the remaining oil was dissolved in ethyl acetate. The organic layer was separated, washed water and brine.Evaporation gave light brown oil (35.1 g, 100percent yield).
99% With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 2 h; To a stirred solution of 2,6-diisopropylaniline (14 g, 78.97 mmol, 1.00 equiv) in N,N-dimethylformamide (200 mL) at 0° C. was added a solution of NBS (14 g, 78.65 mmol, 1.00 equiv) in N,N-dimethylformamide (100 mL) dropwise in 60 min.
The reaction was stirred for another hour at 0° C. then water (900 mL) was added.
The resulting mixture was extracted with 300 mL of ethyl acetate.
The combined organic layers was washed with 3*100 mL of saturated NH4Cl solution and 1*100 mL of water then dried over anhydrous sodium sulfate and concentrated under vacuum to give 20.05 g (99percent) of 4-bromo-2,6-diisopropylaniline as a red oil. 1H NMR (400 MHz, DMSO-d6): δ 6.95 (s, 2H), 4.77 (s, 2H), 5.47-5.39 (m, 1H), 3.04-2.98 (m, 1H), 1.13 (d, J=6.8 Hz, 12H) ppm.
97% With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 20℃; for 48 h; Synthesis of 4-bromo-2,6-diisopropylaniline (0199) A three neck round bottom flask was charged with 2,6-diisopropylaniline (22.96 g, 130 mmol) and DMF (Volume: 250 ml). A solution of 1-bromopyrrolidine-2,5-dione (23.05 g, 130 mmol) in 100 ml DMF was added into reaction mixture drop wise at 0° C. After addition was over; reaction mixture was stirred for 2 days at room temperature. The reaction mixture was poured into 500 ml deionized water and extracted with 3×150 ml ether. The combined extracts were washed with 150 ml deionized water, 150 ml 10percent lithium chloride, dried over MgSO4 and evaporated to dryness. The residue was purified by vacuum distillation to yield 4-bromo-2,6-diisopropylaniline (32.3 g; 97percent).
95% With tetra-N-butylammonium tribromide In tetrahydrofuran at 0℃; 40.8 g (85 mmol) of tetra-n-butylammonium tribromide are added, at 0° C. and portionwise, to a solution of 15 g (85 mmol) of 2,6-diisopropylphenyl-amine in 200 ml of tetrahydrofuran.
The medium is stirred for 2 h.
It is then poured into a saturated aqueous solution of sodium thiosulphate and extracted with ethyl acetate.
The organic phases are combined and washed with water.
They are dried over sodium sulphate.
The residue is purified by silica gel chromatography (80/20 heptane/ethyl acetate).
20.6 g of 4-bromo-2,6-diisopropylphenylamine are obtained in the form of a yellow oil (yield=95percent).
82% With tetra-N-butylammonium tribromide In tetrahydrofuran at 20℃; Preparative Example P16Step 1 : 4-Bromo-2,6-diisopropylaniline (PI 6a)To a solution of 2,6-diisopropylaniline (12.5 g, 70.6 mmol) in THF was added (C4H9)4NBr3 (47 g, 85 mmol) at rt and stirred overnight. Then sat. NaHS03 solution (30 mL) was added and the mixture was extracted with Et20 (3 x 250 mL). The organic layer was washed with brine, dried over Na2S04 and concentrated to give compound P16a (19 g, 82percent).
79% With bromine In methanol at 20℃; A solution of 2, [6-DIISOPROPYLANILINE] (2.0 mL, 11 mmol) in methanol (80 mL) was treated dropwise with bromine (543 μL, 10.6 mmol). The solution was stirred at room temperature for 15 min. Chloroform and 0.1 N [NAOH] were added and the organic layer was dried (Na2SO4), filtered and concentrated to an orange liquid. Kugelrohr distillation [(110 °C COMMAT; ] 0.06 Torr) afforded a colorless liquid (2.22 g 79percent): 1H NMR (400 MHz) 8 1.25 (d, J= 6.4 Hz, 12H), 2. 88 (m, 2H), 3.70 (brs, 2H), 7.11 (s, 2H) [; 13C NMR 8] 22.1, 27.9, 111.0, 125.6, 134.5, 139.3 ; Anal calcd for [C12HIGBRN] : C, 56.26 ; H, 7. 08 ; Br, 31.19 ; Found, C, 56.24 ; H, 7.07 ; Br, 30.98
72% With bromine In methanol; dichloromethane at 20℃; for 24 h; A solution of Br2(2.1 ml, 41.0 mmol, 1.05 eq.) in CH2Cl2/MeOH (100 ml, 1:1 v/v)was added to a stirring solution of 2,6-diisopropylaniline (7.4 ml,39.0 mmol, 1.0 eq.) in CH2Cl2/MeOH (200 ml, 1:1 v/v) at r.t. over2 h. The orange-red solution was stirred for 1 day. The solvents were evaporated and the resultant pink solid was washed with PE and further recristallized from CH2Cl2/PE to give the title compound as light orange-red solid (7.8 g, 28.1 mmol, 72percent).1H-NMR (300 MHz,CDCl3) [ppm]: 10.08 (s, 2H), 7.36 (s, 2H), 3.80–3.62 (m, 2H), 1.29(d, J = 6.7 Hz, 12H). The analytical data are in accordance with theliterature.
42% With potassium hydroxide; bromine In water; acetic acid 4-Bromo-2,6-diisopropylaniline
To a solution of 80.0 g (0.452 mol) of 2,6-diisopropylaniline in 2000 cm3 of glacial acetic acid, 23.3 ml (72.3 g, 0.452 mol) of bromine were added dropwise, while vigorously stirring, over 20 minutes.
This mixture was stirred additionally for 2 hours at 40° C.
The white precipitate that formed was filtered off, washed with 100 ml of acetic acid, and dried in air.
The resulting white solid was added to a solution of 150 g of potassium hydroxide in 600 ml of water.
This mixture was stirred for 30 minutes.
The product was extracted with 3*100 ml of methyl-tert-butyl ether.
The combined organic fractions were washed with Na2SO4 and evaporated to dryness.
Fractional distillation gave a yellowish oil, b.p. 112-115° C./1 mm Hg. Yield 48.8 g (42percent).
Anal. calc. for Cl2H18BrN: C, 56.26; H, 7.08. Found: C, 56.11; H, 7.13.
1H NMR (CDCl3): δ 7.10 (s, 2H, 3,5-H), 3.69 (br.s, 2H, NH2), 2.86 (sept, J=6.8 Hz, 2H, CHMe2), 1.23 (d, J=6.8 Hz, 12H, CHMe2).
13C{1H}NMR (CDCl3): δ 139.3, 134.5, 125.6, 111.0, 27.9, 22.1.
540 g With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 20℃; for 18 h; Apparatus set-up:A 10 L 3-necked round-bottomed flask, equipped with a mechanical overhead stirrer, nitrogen inlet and exhaust.Experimental Procedure:1. 2, 6-Diisopropyl aniline (500 g, 2.8202 mol) was dissolved in dry N, N-dimethyl formamide.It was cooled to 0 °C using an ice bath.2. N-Bromosuccinimide (501.9 g, 2.8202 mol) was added slowly portion wise.3. The reaction mixture was stirred at the room temperature for 18 h.4. After 18 h, TLC showed complete conversion of starting material.5. To the mixture, 10percent NaHCO3 solution (4 L) was added and extracted with ethyl acetate (3 x2L).6. The combined organic phase was washed with water (1 L), brine (1 L), dried over sodium sulphate and concentrated.7. The crude product was purified by silica column chromatography using 8 percent ethyl acetate in hexane as an eluent to get 540 g with 95.75 percent HPLC purity. 1H-NMR (300 MHz, CDCl3): δ[ppm] 1.26 (d, J = 6.78 Hz, 12H), 2.84 - 2.93 (m, 2H), 3.72 (br, s, 2H), 7.12 (s, 2H).

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[14] Journal of Molecular Catalysis A: Chemical, 2017, vol. 426, p. 572 - 585
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[27] Patent: WO2018/91684, 2018, A1, . Location in patent: Page/Page column 55
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Reference: [1] Journal of Organometallic Chemistry, 2005, vol. 690, # 5, p. 1314 - 1323
[2] Journal of Organometallic Chemistry, 1993, vol. 459, # 1-2, p. 185 - 198
[3] Journal of Physical Organic Chemistry, 2013, vol. 26, # 2, p. 144 - 150
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