[ CAS No. 64622-16-8 ] {[proInfo.proName]}

Name: 64622-16-8|2-Bromo-6-chlorobenzaldehyde|97%
Brand: Ambeed
SKU: A175452
Price: 5.0 USD
Availability: InStock
Rating: 96 (29 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 64622-16-8

Structure of 64622-16-8 * Storage: {[proInfo.prStorage]}

Please Login or Create an Account to: See VIP prices and availability

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

For Research Only 120K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 64622-16-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 64622-16-8 ]

SDS Specification

Alternatived Products of [ 64622-16-8 ]

Product Details of [ 64622-16-8 ]

CAS No. :	64622-16-8	MDL No. :	MFCD00266792
Formula :	C₇H₄BrClO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NUGMENVSVAURGO-UHFFFAOYSA-N
M.W :	219.46	Pubchem ID :	13524042
Synonyms :

Calculated chemistry of [ 64622-16-8 ] Expand+

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.54
TPSA :	17.07 Å²

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) :	-5.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.81
Log Po/w (XLOGP3) :	2.7
Log Po/w (WLOGP) :	2.92
Log Po/w (MLOGP) :	2.79
Log Po/w (SILICOS-IT) :	3.3
Consensus Log Po/w :	2.7

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.28
Solubility :	0.115 mg/ml ; 0.000525 mol/l
Class :	Soluble
Log S (Ali) :	-2.71
Solubility :	0.426 mg/ml ; 0.00194 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.82
Solubility :	0.0331 mg/ml ; 0.000151 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.4

Safety of [ 64622-16-8 ]

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 [ 64622-16-8 ]

* 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 [ 64622-16-8 ]
Downstream synthetic route of [ 64622-16-8 ]

[ 64622-16-8 ] Synthesis Path-Upstream 1~4

1
[ 108-37-2 ]
[ 68-12-2 ]
[ 64622-16-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: With magnesium chloride In 2-methyltetrahydrofuran Stage #2: With lithium diisopropyl amide In tetrahydrofuran; 2-methyltetrahydrofuran; n-heptane at -78 - -75℃; for 1 h;	The thermal characteristics of this reaction were studied using an HEL Simular reaction calorimeter. The calorimeter was equipped with a double-jacketed, 0.8-liter, glass reactor (6 bars). The inner jacket contained a heat-transfer fluid and the outer jacket was evacuated to insulate the system. A quantity of 26.5 g (0.139 moles, 1 equivalent) of 3-bromochlorobenzene (10), 200 ml of 2-methyltetrahydrofuran (Me-THF) and 15.0 g (0.158 moles, 1.1 equivalents) of anhydrous magnesium chloride was charged to this reactor. The slurry was then cooled to -78° C. A quantity of 91.2 ml (0.158 moles, 1.3 equivalents) of lithium diisopropylamide (LDA, 2M in heptane/THF) was charged into the batch, keeping the temp <--75° C. The batch was held for an hour after LDA addition. A quantity of 15.0 ml (0.194 moles, 1.4 equivalents) of N,N-dimethylformamide was charged into the batch at -78° C., keeping the temperature <--75° C. The mixture was stirred for an hour and gradually warmed to 0° C. At 0° C., the reaction was quenched with 150 ml of 0.5M citric acid solution. The layers were separated and the organic layer was collected and concentrated to dryness. The desired product (12) was isolated in 80percent yield and 99percent purity by GC.
59%	Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -70℃; for 1 h; Stage #2: at -70℃; for 1 h;	i). Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b) To a solution of 1-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70° C. The mixture was stirred at -70° C. for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70° C. The reaction was stirred vigorously at -70° C. for 1 h. Warmed to -30° C., the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL*3). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated in vacuo to afford the title compound (3.6 g, yield: 59percent). LCMS (ESI) calc'd for C₇H₄BrClO [M+H]⁺: 219. found: 219.
53%	Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78 - 0℃; for 1.16667 h;	A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a STIRRER, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0 °C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0 °C for ten minutes, then cooled to-78 °C. Upon cooling, a solution of L-BROMO-3- chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at-78 °C for one hour. Anhydrous dimethylformamide (636 GEL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9: 1 hexanes: ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53 percent yield). NMR (300 MHz, CDC13): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H).

3.6 g

Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -70℃; for 1 h;
Stage #2: for 1 h;

Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b). To a solution of l-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70 °C. The mixture was stirred at -70 °C for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70 °C. The reaction was stirred vigorously at -70 °C for 1 h. Warmed to -30 °C, the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were dried over anhydrous Na₂S0₄ and concentrated in vacuo to afford the title compound (3.6 g, yield: 59 percent). LCMS (ESI) calc'd for C₇H₄BrC10 [M+H]⁺: 219, found: 219.

Reference： [1] Organic Process Research and Development, 2014, vol. 18, # 1, p. 228 - 238
[2] Patent: US2009/118546, 2009, A1, . Location in patent: Page/Page column 6
[3] Patent: US2015/210687, 2015, A1, . Location in patent: Paragraph 0244
[4] Patent: WO2004/99164, 2004, A1, . Location in patent: Page 62-63; 21/22
[5] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 3, p. 670 - 684
[6] Patent: WO2014/28591, 2014, A2, . Location in patent: Page/Page column 45

2
[ 89-98-5 ]
[ 64622-16-8 ]

Reference： [1] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 888 - 896

3
[ 6630-33-7 ]
[ 64622-16-8 ]

Reference： [1] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 888 - 896

4
[ 62356-27-8 ]
[ 64622-16-8 ]

Reference： [1] Patent: DE213502, , ,

[ 64622-16-8 ] Synthesis Path-Downstream 1~108

1
[ 64622-16-8 ]
[ 105-45-3 ]
[ 1673-76-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1965,p. 5976 - 5983

2
[ 64622-16-8 ]
[ 6421-05-2 ]
[ 103408-99-7 ]

Reference： [1]European Journal of Medicinal Chemistry,1985,vol. 20,p. 333 - 337

3
[ 64622-16-8 ]
[ 149-73-5 ]
1-bromo-3-chloro-2-(dimethoxymethyl)benzene [ No CAS ]

Reference： [1]New Journal of Chemistry,2007,vol. 31,p. 144 - 154

4
[ 64622-16-8 ]
3-chloro-2-carbaldehyde phenylboronic acid [ No CAS ]

Reference： [1]New Journal of Chemistry,2007,vol. 31,p. 144 - 154

5
[ 64622-16-8 ]
[ 1692-15-5 ]
[ 793706-90-8 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; acetonitrile; at 150℃; for 0.0833333h;Microwaves irradiation;	2-Chloro-6-bromobenzaldehyde (200 mg, 0. 91 mmol), pyridine-4-boronic acid (125 mg, 1.0 mmol), dichlorobis (triphenylphosphine) palladium (II) (5 mol%, 30 mg), acetonitrile (2 ML) and aqueous sodium carbonate (2 molar solution, 2 mL) were combined in a microwave vial and sealed with a crimp seal. The mixture was microwaved at 150 C for 5 min. The crude reaction mixture was then poured over Celite and washed with acetonitrile. The mixture was concentrated under reduced pressure and taken up in ethyl acetate. This organic solution was successively washed with water and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 98: 2 methylene chloride: methanol to provide 2-chloro-6- (4-pyridyl) benzaldehyde (100 mg, 51% yield). NMR (300 MHz, CDC13) : 10.3 (s, 1H), 8.65 (m, 2H), 7.55 (m, 2H), 7.2 ppm (m, 3H).Step 2 2-Chloro-6-bromobenzaldehyde (1.0 equivalent), appropriately substituted boronic acid (1.1 equivalents), dichlorobis (triphenylphosphine) palladium (II) (5 mol%), acetonitrile and aqueous sodium carbonate (1-2 molar solution) were combined in a microwave vial and sealed with a crimp seal. The mixture was microwaved at 150 C for 5-20 min. The crude reaction mixture was then poured over Celite and washed with acetonitrile. The mixture was concentrated under reduced pressure and taken up in ethyl acetate. This organic solution was successively washed with water and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with methylene chloride-methanol to provide the substituted aldehyde.

Reference： [1]Patent: WO2004/99164,2004,A1 .Location in patent: Page 60; 63; 21/22

6
[ 108-37-2 ]
[ 68-12-2 ]
[ 64622-16-8 ]

Yield	Reaction Conditions	Operation in experiment
80%		The thermal characteristics of this reaction were studied using an HEL Simular reaction calorimeter. The calorimeter was equipped with a double-jacketed, 0.8-liter, glass reactor (6 bars). The inner jacket contained a heat-transfer fluid and the outer jacket was evacuated to insulate the system. A quantity of 26.5 g (0.139 moles, 1 equivalent) of 3-bromochlorobenzene (10), 200 ml of 2-methyltetrahydrofuran (Me-THF) and 15.0 g (0.158 moles, 1.1 equivalents) of anhydrous magnesium chloride was charged to this reactor. The slurry was then cooled to -78 C. A quantity of 91.2 ml (0.158 moles, 1.3 equivalents) of lithium diisopropylamide (LDA, 2M in heptane/THF) was charged into the batch, keeping the temp ?75 C. The batch was held for an hour after LDA addition. A quantity of 15.0 ml (0.194 moles, 1.4 equivalents) of N,N-dimethylformamide was charged into the batch at -78 C., keeping the temperature ?75 C. The mixture was stirred for an hour and gradually warmed to 0 C. At 0 C., the reaction was quenched with 150 ml of 0.5M citric acid solution. The layers were separated and the organic layer was collected and concentrated to dryness. The desired product (12) was isolated in 80% yield and 99% purity by GC.
59%		i). Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b) To a solution of 1-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70 C. The mixture was stirred at -70 C. for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70 C. The reaction was stirred vigorously at -70 C. for 1 h. Warmed to -30 C., the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL*3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound (3.6 g, yield: 59%). LCMS (ESI) calc'd for C7H4BrClO [M+H]+: 219. found: 219.
53%		A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a STIRRER, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0 C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0 C for ten minutes, then cooled to-78 C. Upon cooling, a solution of L-BROMO-3- chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at-78 C for one hour. Anhydrous dimethylformamide (636 GEL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9: 1 hexanes: ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53 % yield). NMR (300 MHz, CDC13): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H).

3.6 g

Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b). To a solution of l-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70 C. The mixture was stirred at -70 C for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70 C. The reaction was stirred vigorously at -70 C for 1 h. Warmed to -30 C, the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were dried over anhydrous Na2S04 and concentrated in vacuo to afford the title compound (3.6 g, yield: 59 %). LCMS (ESI) calc'd for C7H4BrC10 [M+H]+: 219, found: 219.

Reference： [1]Organic Process Research and Development,2014,vol. 18,p. 228 - 238
[2]Patent: US2009/118546,2009,A1 .Location in patent: Page/Page column 6
[3]Patent: US2015/210687,2015,A1 .Location in patent: Paragraph 0244
[4]ACS Medicinal Chemistry Letters,2020,vol. 11,p. 114 - 119
[5]Patent: WO2004/99164,2004,A1 .Location in patent: Page 62-63; 21/22
[6]Journal of Heterocyclic Chemistry,2018,vol. 55,p. 670 - 684
[7]Patent: WO2014/28591,2014,A2 .Location in patent: Page/Page column 45

7
[ 1242156-53-1 ]
[ 64622-16-8 ]
[ 1242156-54-2 ]

Yield	Reaction Conditions	Operation in experiment
60%	With copper(l) iodide; potassium carbonate; In tetrahydrofuran; N,N-dimethyl-formamide; at 70 - 120℃;Inert atmosphere of nitrogen;Product distribution / selectivity;	In a 1 L reactor, 6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one (65 g, 0.32 mol), <strong>[64622-16-8]2-bromo-6-chlorobenzaldehyde</strong> (84.2 g, 0.38 mol), copper(I) iodide (12.2 g, 64.0 mmol) and potassium carbonate (88.4 g, 0.64 mol) were charged. The reactor was evacuated and backfilled with Nitrogen. This sequence was repeated three times. Then, DMF (650 ml) was added and the resulting mixture was heated to 120 C. for 20 hr. The reaction mixture was cooled down to about 70 C., and THF (975 ml) was added. Then, the resulting mixture was allowed to cool down to ambient temperature, followed by filtration through Celite pad. The filtrate was concentrated down under vacuum with distilling THF off. Crystallization was performed with DMF/IPA/H2O (10/5/2) at around 60 C., and the material was aged overnight with slow cooling. The desired product was collected by filtration and washed with IPA/H2O. The filter cake was dried under vacuum at 70 C. overnight to afford 65.4 g of the title compound (60% isolated yield) as a yellow solid. MS (ESI) 341, 343 (M+H)-.
2.7 g	With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 24h;Inert atmosphere;	Under nitrogen atmosphere, <strong>[64622-16-8]2-bromo-6-chlorobenzaldehyde</strong> (3.65 g, 16.63 mmol), potassium carbonate (3.54 g, 25.6 mmol) and copper(I) iodide (0.49 g, 2.56 mmol) were added to a solution of 6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one (2.6 g, 12.8 mmol) in DMF (25 mL), and stirred at 110 C. for 1 day. The reaction mixture was diluted with ethyl acetate (200 mL), filtered to remove insoluble material, and then the filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by chromatography on silica gel, eluted with hexane/ethyl acetate to afford 2-chloro-6-(6-cyclopropyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)benzaldehyde (2.7 g). 1H NMR (400 MHz, DMSO-d6) delta10.18 (s, 1H), 7.84-7.78 (m, 1H), 7.75 (dd, J=8.2, 1.3 Hz, 1H), 7.49 (dd, J=7.8, 1.2 Hz, 1H), 7.41 (d, J=7.5 Hz, 1H), 7.27 (d, J=1.6 Hz, 1H), 7.00 (dd, J=13.3, 1.6 Hz, 1H), 6.64 (dd, J=7.5, 2.2 Hz, 1H), 2.14-2.01 (m, 1H), 1.14-1.06 (m, 2H), 0.92-0.83 (m, 2H); LCMS (m/z): 342.1 [M+H]+.
2.7 g	With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 24h;Inert atmosphere;	Under nitrogen atmosphere, <strong>[64622-16-8]2-bromo-6-chlorobenzaldehyde</strong> (3.65 g, 16.63 mmol), potassium carbonate (3.54 g, 25.6 mmol) and copper(I) iodide (0.49 g, 2.56 mmol) were added to a solution of 6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one (2.6 g, 12.8 mmol) in DMF (25 mL), and stirred at 110 C. for 1 day. The reaction mixture was diluted with ethyl acetate (200 mL), filtered to remove insoluble material, and then the filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by chromatography on silica gel, eluted with hexane/ethyl acetate to afford 2-chloro-6-(6-cyclopropyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)benzaldehyde (2.7 g).

2.7 g

With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 24h;Inert atmosphere;

To a solution of 6-cyclopropyl-8-fluoroisoquinolin-1 (2H)-one (2.6 g, 12.8 mmol) in DMF (25 mE), 2-bromo-6- chlorobenzaldehyde (3.65 g, 16.63 mmol), potassium carbonate (3.54 g, 25.6 mmol) and copper (I) iodide (0.49 g, 2.56 mmol) were added under nitrogen atmosphere and stirred at 110 C. for 1 day. The reaction mixture was diluted with ethyl acetate (200 mE), filtered to remove insoluble material, andthen the filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by chromatography on silica gel, eluted with hexane/ethyl acetate to afford 2-chloro-6-(6-cyclopropyl-8- fluoro- 1 -oxoisoquinolin-2 (1 H)-yl)benzaldehyde (2.7 g).j0116] ?H NMR (400 MHz, DMSO-d5) oe 10.18 (s, 1H), 7.84-7.78 (m, 1H), 7.75 (dd, J=8.2, 1.3 Hz, 1H), 7.49 (dd, J=7.8, 1.2Hz, 1H), 7.41 (d, J=7.5 Hz, 1H), 7.27 (d, J=1 .6Hz, 1H), 7.00 (dd, J=13.3, 1.6 Hz, 1H), 6.64 (dd, J=7.5, 2.2 Hz, 1H), 2.14-2.01 (m, 1H), 1.14-1.06 (m, 2H), 0.92-0.83 (m, 2H); ECMS (mlz): 342.1 [M+H].

Reference： [1]Patent: US2010/222325,2010,A1 .Location in patent: Page/Page column 59
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 8917 - 8933
[3]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 145 - 151
[4]Journal of Medicinal Chemistry,2015,vol. 58,p. 512 - 516
[5]Patent: US2016/168122,2016,A1 .Location in patent: Paragraph 0086; 0087
[6]Patent: KR2016/41946,2016,A .Location in patent: Paragraph 0136; 0137
[7]Patent: US2016/207906,2016,A1 .Location in patent: Page/Page column 9

8
[ 23755-73-9 ]
[ 64622-16-8 ]
[ 1243602-09-6 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 6632 - 6638

9
[ 64622-16-8 ]
[ 1034-49-7 ]
[ 1243601-90-2 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 6632 - 6638

10
[ 625-53-6 ]
[ 64622-16-8 ]
[ 141-97-9 ]
C₁₆H₁₈BrClN₂O₂S [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1 - 10

11
[ 625-52-5 ]
[ 64622-16-8 ]
[ 141-97-9 ]
[ 1263357-63-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1 - 10

12
[ 64622-16-8 ]
[ 141-97-9 ]
[ 598-50-5 ]
[ 1263357-62-5 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1 - 10

13
[ 64622-16-8 ]
[ 1296216-50-6 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502
[3]Patent: WO2015/9742,2015,A2

14
[ 64622-16-8 ]
[ 1296216-51-7 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

15
[ 64622-16-8 ]
[ 1296216-53-9 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

16
[ 64622-16-8 ]
[ 1296216-54-0 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

17
[ 64622-16-8 ]
[ 1296216-56-2 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

18
[ 64622-16-8 ]
6-chloro-9-aza-tricyclo[6.3.1.0(2,7)]dodeca-2,4,6,10-tetraene-9-carboxylic acid benzylester [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

19
[ 64622-16-8 ]
C₃₀H₂₇ClN₂O₄ [ No CAS ]
C₃₀H₂₉ClN₂O₄ [ No CAS ]
C₃₀H₂₉ClN₂O₄ [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

20
[ 64622-16-8 ]
[ 1296216-47-1 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502
[3]Patent: WO2015/9742,2015,A2

21
[ 64622-16-8 ]
6-chloro-9-aza-tricyclo[6.3.1.0(2,7)]dodeca-2,4,6-triene-9-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

22
[ 64622-16-8 ]
benzyl 9-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,5-methanobenzo[c]azepine-2(3H)-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

23
[ 64622-16-8 ]
6-phenyl-9-aza-tricyclo[6.3.1.0(2,7)]dodeca-2,4,6-triene-9-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

24
[ 64622-16-8 ]
6-morpholin-4-yl-9-aza-tricyclo[6.3.1.0(2,7)]dodeca-2,4,6-triene-9-carboxylic acidbenzyl ester [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

25
[ 64622-16-8 ]
[ 1296216-84-6 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

26
[ 64622-16-8 ]
[ 1296216-87-9 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

27
[ 64622-16-8 ]
[ 1296216-89-1 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

28
[ 64622-16-8 ]
[ 1296216-90-4 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

29
[ 64622-16-8 ]
[ 1296216-91-5 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593

30
[ 64622-16-8 ]
9-benzyl-6-morpholin-4-yl-9-aza-tricyclo[6.3.1.0(2,7)]dodeca-2,4,6-triene [ No CAS ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

31
[ 64622-16-8 ]
[ 107-11-9 ]
[ 1296217-03-2 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 20℃; for 12h;Molecular sieve; Inert atmosphere;	A mixture of allylamine (971 mg, 1.27 mL, 17.0 mmol), 2-bromo-6- chlorobenzaldehyde (1.87 g, 8.51 mmol) and 4 A molecular sieves (2.0 g) was stirred in CH2C12 (20 mL) for 12 h at room temperature. The sieves were removed by filtration through Celite, and the filtrate was concentrated under reduced pressure to afford 2.20 g (ca. 100%) of crude imine, which was used directly in the next step.

Reference： [1]Organic Letters,2011,vol. 13,p. 2590 - 2593
[2]Patent: WO2015/9742,2015,A2 .Location in patent: Paragraph 0324

32
2-bromo-6-chlorobenzaldehyde O-methyloxime [ No CAS ]
[ 64622-16-8 ]

Reference： [1]Journal of Organic Chemistry,2011,vol. 76,p. 6414 - 6420

33
[ 64622-16-8 ]
[ 20439-47-8 ]
[ 1346661-54-8 ]

Reference： [1]Journal of Organic Chemistry,2011,vol. 76,p. 9900 - 9918

34
[ 1360057-31-3 ]
[ 64622-16-8 ]
[ 1360057-32-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 4.5h;Inert atmosphere;	Step 4. Preparation of 2-Chloro-6-[8-fluoro-6-(2-fluoro-1,1-dimethyl-ethyl)-1-oxo-1H-isoquino-lin-2-yl]-benzaldehyde-6,8-difluoro-3,4-dihydro-2H-isoquinolin-1-one In a 250 mL round-bottomed flask, 8-fluoro-6-(1-fluoro-2-methylpropan-2-yl)isoquinolin-1(2H)-one (92 mg, 388 mumol), <strong>[64622-16-8]2-bromo-6-chlorobenzaldehyde</strong> (136 mg, 620 mmol) and potassium carbonate (107 mg, 776 mumol) were combined with DMSO (1.23 ml) to give a yellow suspension. The mixture was degassed with argon for 5 min. Copper(I) iodide (73.9 mg, 13.1 mul, 388 mumol) was added and the resulting mixture was placed in a oil bath at 110 C. The reaction mixture was heated to 110 C. and stirred for 1.5 h. Reaction was not complete by LCMS. More <strong>[64622-16-8]2-bromo-6-chlorobenzaldehyde</strong> (70 mg) was added. The reaction mixture was heated to 110 C. and stirred for 3 h, then allowed to cool to ambient. The crude reaction mixture was filtered through a plug of celite and washed through with EtOAc. The combined filtrate and washes were added to a separatory funnel with 25 ml of 1:1 diluted sat NH4Cl/water. The organic phase was collected and washed with an equal volume of brine. The aqueous phase was extracted (2*20 ml EtOAc). The combined organic phase was dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by preparative tlc: 2 plates; eluted with 2% MeOH/DCM to afford the desired product (106 mg) as a light yellow semi-solid. (M+H)+=376 m/e.

Reference： [1]Patent: US2012/40949,2012,A1 .Location in patent: Page/Page column 145-146

35
[ 64622-16-8 ]
[ 1393462-81-1 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 5718 - 5722

36
[ 64622-16-8 ]
(E)-1-bromo-2-(2-bromo-2-(p-tolyl)vinyl)-3-chlorobenzene [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 5718 - 5722

37
[ 64622-16-8 ]
[ 1393462-45-7 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 5718 - 5722

38
[ 64622-16-8 ]
[ 1393462-63-9 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 5718 - 5722

39
[ 64622-16-8 ]
[ 1393462-78-6 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 5718 - 5722

40
[ 64622-16-8 ]
[ 107-11-9 ]
C₁₈H₁₆BrClNO₂⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

41
[ 64622-16-8 ]
C₂₆H₂₂F₃NO₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

42
[ 64622-16-8 ]
C₁₉H₁₈F₃N [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

43
[ 64622-16-8 ]
C₂₁H₂₀F₃NO₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

44
[ 64622-16-8 ]
C₂₅H₂₂F₃NO₃S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

45
[ 64622-16-8 ]
C₂₇H₂₅F₃N₂S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

46
[ 64622-16-8 ]
C₂₂H₂₀F₃NO₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

47
[ 64622-16-8 ]
C₂₆H₂₅NO₃ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

48
[ 64622-16-8 ]
C₂₅H₂₂F₃N [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

49
[ 64622-16-8 ]
C₁₁H₁₀ClN [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

50
[ 64622-16-8 ]
C₁₈H₁₆F₃N [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 496 - 502

51
[ 67-56-1 ]
[ 64622-16-8 ]
1-bromo-3-chloro-2-(dimethoxymethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; In ethyl acetate; at 20℃; for 7h;	General procedure: a mixture of aldehyde (1, 0.01 mol), methanol (2a, 3-5 vol), and T3P (10 mol %, 50% solution in EtOAc) was stirred at room temperature for 4-7 h. When the reaction was completed (monitored by TLC), the solvent was removed under vacuum and the residue was diluted with water (20 mL). The product was extracted with ethyl acetate (2 15 mL) and the combined organic extracts were washed with saturated NaHCO3 solution (1 10 mL) and brine. The organic phase was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the crude product was passed through a small plug of neutral alumina to afford the dimethoxy acetals (3a-i) in good purity and yield

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 5030 - 5033

52
[ 64622-16-8 ]
[ 1422359-46-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 996 - 1000

53
[ 64622-16-8 ]
C₂₁H₁₇BrClF₃N₂O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 996 - 1000

54
[ 64622-16-8 ]
[ 1422358-98-2 ]
C₁₉H₁₃ClF₃N₃O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 996 - 1000

55
[ 64622-16-8 ]
[ 1422359-31-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 996 - 1000

56
[ 64622-16-8 ]
[ 830-43-3 ]
[ 1422359-14-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 996 - 1000

57
[ 64622-16-8 ]
[ 96-32-2 ]
(Z)-2-bromo-3-(2-bromo-6-chlorophenyl)acrylic acid methyl ester [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 8065 - 8072

58
[ 64622-16-8 ]
[ 1562195-11-2 ]