Home Cart 0 Sign in  

[ CAS No. 16817-43-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 16817-43-9
Chemical Structure| 16817-43-9
Structure of 16817-43-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 16817-43-9 ]

Related Doc. of [ 16817-43-9 ]

Alternatived Products of [ 16817-43-9 ]

Product Details of [ 16817-43-9 ]

CAS No. :16817-43-9 MDL No. :MFCD00078659
Formula : C7H6BrClO Boiling Point : -
Linear Structure Formula :- InChI Key :UAMVKOTWSHJOSY-UHFFFAOYSA-N
M.W :221.48 Pubchem ID :2769567
Synonyms :

Calculated chemistry of [ 16817-43-9 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 45.64
TPSA : 9.23 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) : -5.23 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.46
Log Po/w (XLOGP3) : 3.41
Log Po/w (WLOGP) : 3.11
Log Po/w (MLOGP) : 3.15
Log Po/w (SILICOS-IT) : 3.14
Consensus Log Po/w : 3.05

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.74
Solubility : 0.0404 mg/ml ; 0.000182 mol/l
Class : Soluble
Log S (Ali) : -3.28
Solubility : 0.115 mg/ml ; 0.00052 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.0
Solubility : 0.0221 mg/ml ; 0.0001 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.69

Safety of [ 16817-43-9 ]

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

Application In Synthesis of [ 16817-43-9 ]

* 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 [ 16817-43-9 ]
  • Downstream synthetic route of [ 16817-43-9 ]

[ 16817-43-9 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 16817-43-9 ]
  • [ 13726-14-2 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With magnesium; ethylene dibromide In tetrahydrofuranInert atmosphere
Stage #2: With C10H17NO In tetrahydrofuran; toluene at -78℃; for 3 h; Inert atmosphere
General procedure: To a flame-dried 25 mL round bottom flask was charged activated Mg (7.5 mmol, 1.5 eq.) and 5 mL anhydrous THF. To this suspension was added 2 drops of 1,2-dibromoethane. After 5 min, a solution of Aryl bromide (5 mmol, 1.0 eq.) in 5 mL anhydrous THF was slowly added to the suspension of Mg at room temperature. The reaction was mildly exothermic. The Grignard reagent was titrated and 1 mmol of this reagent was added to a flame-dried reaction vial. The solution was diluted with 3 mL anhydrous toluene and after cooling to the target temperature T, a solution of oxaziridine (1.2 mmol, 1.2 eq.) in 1 mL anhydrous toluene was added. The reaction was maintained at the targeted temperature T for time t before being quenched with saturated aqueous NH4Cl. (The actual temperature/reaction time is listed for each substrate.)
Reference: [1] Nature Chemistry, 2017, vol. 9, # 7, p. 681 - 688
[2] Patent: US2018/57444, 2018, A1, . Location in patent: Paragraph 0098; 0134; 0135; 0184
  • 2
  • [ 183802-98-4 ]
  • [ 77-78-1 ]
  • [ 16817-43-9 ]
Reference: [1] Journal of Organic Chemistry, 1947, vol. 12, p. 213,215
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 9, p. 2450 - 2454[3] Angew. Chem., 2018, vol. 130, # 9, p. 2475 - 2479,5
  • 3
  • [ 71-43-2 ]
  • [ 16817-43-9 ]
Reference: [1] Journal of Organic Chemistry, 1947, vol. 12, p. 213,215
  • 4
  • [ 13726-14-2 ]
  • [ 16817-43-9 ]
Reference: [1] Journal of medicinal chemistry, 1967, vol. 10, # 6, p. 1008 - 1014
  • 5
  • [ 59557-91-4 ]
  • [ 16817-43-9 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 1977, vol. 42, # 5, p. 1705 - 1722
  • 6
  • [ 18282-59-2 ]
  • [ 124-41-4 ]
  • [ 16817-43-9 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1930, vol. 49, p. 1082,1087
  • 7
  • [ 16817-43-9 ]
  • [ 13726-16-4 ]
Reference: [1] Patent: US2004/102360, 2004, A1,
  • 8
  • [ 16817-43-9 ]
  • [ 89694-47-3 ]
YieldReaction ConditionsOperation in experiment
65%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane; toluene at -78℃; for 0.5 h;
Stage #2: With Trimethyl borate In tetrahydrofuran; hexane; toluene at -78 - 20℃;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water; toluene
To 4-bromo-1-chloro-2-methoxybenzene (2.2 g, 9.9 mmol) in toluene/THF (16/6 mL) at -78° C. was added n-butyl lithium (8.7 mL, 1.6 M in hexane, 14 mmol) dropwise. The reaction was stirred at -78° C. for 30 min, then trimethylborate (2.2 mL, 19.8 mmol) was added. The reaction was allowed to warm to rt and stirred overnight and then quenched with 1 M HCl (15 mL). The organic layer was separated and dried over sodium sulfate. The solvent was removed and the crude product was purified by flash column chromatography to give 25A (1.2 g, 65percent yield) as a white solid. 1H NMR (400 MHz, CDOD3) δ ppm 3.87 (m, 3H) 7.11 (d, J=7.83 Hz, 1H) 7.20 (s, 1H) 7.29 (d, J=7.83 Hz, 1H).
65%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane; toluene at -78℃; for 0.5 h;
Stage #2: With Trimethyl borate In tetrahydrofuran; hexane; toluene at -78 - 20℃;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane; toluene
To 4-bromo-1-chloro-2-methoxybenzene (2.2 g, 9.9 mmol) in toluene/THF (16/6 mL) at -78° C. was added n-butyl lithium (8.7 mL, 1.6 M in hexane, 14 mmol) dropwise. The reaction was stirred at -78° C. for 30 min., then trimethylborate (2.2 mL, 19.8 mmol) was added. The reaction was allowed to warm to rt and stirred overnight and then quenched with 1 M HCl (15 mL). The organic layer was separated and dried over sodium sulfate. The solvent was removed and the crude product was purified by flash column chromatography to give 79A (1.2 g, 65percent yield) as a white solid. 1H NMR (400 MHz, Methanol-d4) δ ppm 3.87 (m, 3 H) 7.11 (d, J=7.83 Hz, 1 H) 7.20 (s, 1 H) 7.29 (d, J=7.83 Hz, 1 H).
900 mg
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.5 h;
Stage #2: With Triisopropyl borate In diethyl ether; hexane at -78 - 20℃; for 1 h;
Stage #3: With hydrogenchloride In diethyl ether; hexane; water at 0℃; for 1 h;
To a stuffed solution of 4-bromo-i-chloro-2-methoxybenzene (2 g, 9.03 mmol) in diethyl ether (20 mL) was added n-BuLi (2 M in hexane; 5.2 mL, 10.4 mmol) at -78 °C dropwise. The reaction was allowed to stir at -78 °C for 30 mm, and then triisopropyl borate (2.4 mL, 10.40 mmol) was slowly added to the reaction mixture at -78 °C. The temperature of the reaction mixture was gradually raised to RT over a period of 1 h, and then the reaction was stirred at RT for 30 mm. After 30 mm, 3 N HC1 (100 mL) was slowly added to the reaction mixture at 0 °C and the reaction was stirred for further 1 h. The progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was extracted with EtOAc (2x200 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate and concentrated to obtain a crude product. The residue obtained was triturated with hexane (2x25 mL) to afford 4-chloro-3-methoxyphenylboronic acid (900 mg) as a white solid.
Reference: [1] Patent: US2010/227894, 2010, A1, . Location in patent: Page/Page column 35
[2] Patent: US2007/3539, 2007, A1, . Location in patent: Page/Page column 77
[3] Patent: WO2015/58084, 2015, A1, . Location in patent: Paragraph 0331
  • 9
  • [ 121-43-7 ]
  • [ 16817-43-9 ]
  • [ 89694-47-3 ]
YieldReaction ConditionsOperation in experiment
31%
Stage #1: With n-butyllithium In tetrahydrofuran; toluene at -78℃; for 0.5 h; Inert atmosphere
Stage #2: at 20℃; for 16 h;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; toluene
5-bromo-2-chloro anisole (leq) in toluene (8vol) and THF (3vol) at -78oC was added n-BuLi (1.5eq) drop wise. The resulting mixture was stirred at -78oC for 30 minutes under an atmosphere of N2.Trimethylborate (2eq) was then added to the reaction mixture and this was allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was quenched with 1M HC1 and the organic layer was separated. The organic layer was washed with saturated aqueous NaCl (20vol), dried over Na2S04, filtered and the solvent removed in vacuum. The resulting residue was purified by flash column chromatography (eluent:[1 : 1] EtOAc: heptane) to afford the required target compound (1.15g, 31percent).
Reference: [1] Patent: WO2013/33085, 2013, A1, . Location in patent: Paragraph 00170
  • 10
  • [ 16817-43-9 ]
  • [ 13659-23-9 ]
Reference: [1] Patent: US5985853, 1999, A,
  • 11
  • [ 16817-43-9 ]
  • [ 183802-98-4 ]
YieldReaction ConditionsOperation in experiment
98%
Stage #1: With boron tribromide In dichloromethane at 0 - 20℃; for 20.6667 h;
Stage #2: With water In dichloromethane at 0℃; for 0.5 h;
Preparation 5: 5 -Bromo-2-chloro-phenol; A solution of 5 -bromo-2-chloroanisole (20 g, 90.3 mmol) in dichloromethane (100 ml) at 0 "C under nitrogen was treated with borontribromide (1M in dichloromethane, 100 mL, 0.1 mol) dropwise over 2.5 hours. After 10 minutes the reaction was allowed to warm to RT and stirred for 18 hours. The reaction mixture was poured into water (200 mL) and ice (200 mL) and stirred for 30 minutes, dichloromethane (100 mL) was added and the organics separated. The aqueous phase was saturated with sodium chloride and re -extracted with dichloromethane (2x 200 mL). The combined organics were dried (MgSO 4) to furnish a white solid (18.34 g, 98 percent).
96%
Stage #1: With boron tribromide In dichloromethane at 0 - 20℃; for 14 h;
Stage #2: With potassium carbonate In water at 0℃;
Stage #3: With hydrogenchloride In water
EXAMPLE I
5-bromo-2-chloro-phenol
96 ml of a 1 M solution of boron tribromide in dichloromethane are added to an ice-cooled solution of 20 g 5-bromo-2-chloro-anisol in 300 ml dichloromethane.
The reaction solution is stirred for 14 h at ambient temperature and then cooled in the ice bath.
The cooled solution is combined with aqueous saturated potassium carbonate solution, the aqueous phase is acidified with 1 M hydrochloric acid and extracted with dichloromethane.
The combined organic phases are dried over sodium sulphate and the solvent is eliminated completely.
Yield: 17.9 g (96percent of theory)
Mass spectrum (ESI+): m/z=205/207/209 (bromine+chlorine) [M+H]+
96%
Stage #1: With boron tribromide In dichloromethane at 0 - 20℃; for 14 h;
Stage #2: With water; potassium carbonate In dichloromethane
Stage #3: With hydrogenchloride In water
EXAMPLE I
5-bromo-2-chloro-phenol
96 ml of a 1 M solution of boron tribromide in dichloromethane are added to an ice-cooled solution of 20 g 5-bromo-2-chloro-anisol in 300 ml dichloromethane.
The reaction solution is stirred for 14 h at ambient temperature and then cooled in the ice bath.
The cooled solution is combined with aqueous saturated potassium carbonate solution, the aqueous phase is acidified with 1 M hydrochloric acid and extracted with dichloromethane.
The combined organic phases are dried over sodium sulphate and the solvent is eliminated completely.
Yield: 17.9 g (96percent of theory)
Mass spectrum (ESI+): m/z=205/207/209 (bromine+chlorine) [M+H]+
95%
Stage #1: With boron tribromide In dichloromethane at 0 - 20℃; for 4 h;
Stage #2: With sodium hydroxide; water In dichloromethane
Stage #3: With hydrogenchloride In water
Example 128: 1-(5-Chloro-4-cyclopropylmethoxy-2-f(E)-3-(at)7(at)4-fluoro-benzyl)-3-oxa-7 9(at) diaza-bicvdo13.3. llnon-9-vll-3-oxo-DroDenvl)-Dhenvl)-3-methvl-urea; a) 5-Bromo-2-chlorophenol; BBr3 (8.2ml; 84.9mmol) is added under stirring at 0-5°C to a solution of 5-bromo-2- chloroanisol (18.26g; 82.4mmol) in CH2CI2 (45 ml). The reaction mixture is stirred for 4h at room temp. , then poured on 2N NaOH/ice and washed with TBME twice. The aqueous phase is acidified with 2N HCI and extracted with TBME twice. The combined organic phases are dried over Na2S04, evaporated to dryness and rendered the title compound as colorless crystals (16.35 g; 95 percent). 1 H-NMR (400MHz; DMSO-d6), 8 (ppm) : 6.97 (dd, 1 H); 7.09 (d, 1 H); 7.26 (d, 1 H); 10.65 (bs, 1 H, OH).. MS (m/z) ES+: 210 (15) ; 208 (70, M+) ; 206 (50) ; 179 (20) ; 177 (15) ; 63 (100).

Reference: [1] Patent: WO2007/91152, 2007, A1, . Location in patent: Page/Page column 43
[2] Patent: US2006/25349, 2006, A1, . Location in patent: Page/Page column 17
[3] Patent: US2006/35841, 2006, A1, . Location in patent: Page/Page column 18
[4] Patent: WO2005/103054, 2005, A2, . Location in patent: Page/Page column 158-159
[5] Patent: WO2003/105853, 2003, A1, . Location in patent: Page 57
  • 12
  • [ 16817-43-9 ]
  • [ 183802-98-4 ]
  • [ 108-95-2 ]
Reference: [1] Patent: US2004/162282, 2004, A1,
  • 13
  • [ 16817-43-9 ]
  • [ 915201-06-8 ]
Reference: [1] Patent: WO2015/58084, 2015, A1,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 16817-43-9 ]

Aryls

Chemical Structure| 50638-47-6

[ 50638-47-6 ]

4-Bromo-2-chloro-1-methoxybenzene

Similarity: 0.96

Chemical Structure| 637022-52-7

[ 637022-52-7 ]

4-Bromo-1-chloro-2-isopropoxybenzene

Similarity: 0.91

Chemical Structure| 174913-10-1

[ 174913-10-1 ]

1-Bromo-3-chloro-2-methoxybenzene

Similarity: 0.91

Chemical Structure| 183802-98-4

[ 183802-98-4 ]

5-Bromo-2-chlorophenol

Similarity: 0.90

Chemical Structure| 201849-21-0

[ 201849-21-0 ]

4-Bromo-2-chloro-1-isopropoxybenzene

Similarity: 0.87

Bromides

Chemical Structure| 50638-47-6

[ 50638-47-6 ]

4-Bromo-2-chloro-1-methoxybenzene

Similarity: 0.96

Chemical Structure| 637022-52-7

[ 637022-52-7 ]

4-Bromo-1-chloro-2-isopropoxybenzene

Similarity: 0.91

Chemical Structure| 174913-10-1

[ 174913-10-1 ]

1-Bromo-3-chloro-2-methoxybenzene

Similarity: 0.91

Chemical Structure| 183802-98-4

[ 183802-98-4 ]

5-Bromo-2-chlorophenol

Similarity: 0.90

Chemical Structure| 201849-21-0

[ 201849-21-0 ]

4-Bromo-2-chloro-1-isopropoxybenzene

Similarity: 0.87

Chlorides

Chemical Structure| 50638-47-6

[ 50638-47-6 ]

4-Bromo-2-chloro-1-methoxybenzene

Similarity: 0.96

Chemical Structure| 637022-52-7

[ 637022-52-7 ]

4-Bromo-1-chloro-2-isopropoxybenzene

Similarity: 0.91

Chemical Structure| 174913-10-1

[ 174913-10-1 ]

1-Bromo-3-chloro-2-methoxybenzene

Similarity: 0.91

Chemical Structure| 183802-98-4

[ 183802-98-4 ]

5-Bromo-2-chlorophenol

Similarity: 0.90

Chemical Structure| 201849-21-0

[ 201849-21-0 ]

4-Bromo-2-chloro-1-isopropoxybenzene

Similarity: 0.87

Ethers

Chemical Structure| 50638-47-6

[ 50638-47-6 ]

4-Bromo-2-chloro-1-methoxybenzene

Similarity: 0.96

Chemical Structure| 637022-52-7

[ 637022-52-7 ]

4-Bromo-1-chloro-2-isopropoxybenzene

Similarity: 0.91

Chemical Structure| 174913-10-1

[ 174913-10-1 ]

1-Bromo-3-chloro-2-methoxybenzene

Similarity: 0.91

Chemical Structure| 201849-21-0

[ 201849-21-0 ]

4-Bromo-2-chloro-1-isopropoxybenzene

Similarity: 0.87

Chemical Structure| 174913-12-3

[ 174913-12-3 ]

1-Bromo-3-chloro-5-methoxybenzene

Similarity: 0.86