[ CAS No. 94278-68-9 ]

Name: 94278-68-9|2-(Bromomethyl)-1,3-difluoro-5-methoxybenzene|98%
Brand: Ambeed
SKU: A460074
Rating: 98 (30 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

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

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

type	HazMat fee
Excepted Quantity	Free
Inaccessible (Haz class 6.1), Domestic	USD 41.00
Inaccessible (Haz class 6.1), International	USD 64.00
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 83.00
Accessible (Haz class 3, 4, 5 or 8), International	USD 133.00

DV 2D 3D

3d Animation Molecule Structure of 94278-68-9

Structure of 94278-68-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 88K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 94278-68-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 94278-68-9 ]

SDS

Alternatived Products of [ 94278-68-9 ]

Product Details of [ 94278-68-9 ]

CAS No. :	94278-68-9	MDL No. :	MFCD04115925
Formula :	C₈H₇BrF₂O	Boiling Point :	210.4°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	237.04 g/mol	Pubchem ID :	-
Synonyms :

Calculated chemistry of of [ 94278-68-9 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	45.69
TPSA :	9.23 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.86 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.52
Log Po/w (XLOGP3) :	2.65
Log Po/w (WLOGP) :	3.56
Log Po/w (MLOGP) :	3.44
Log Po/w (SILICOS-IT) :	3.67
Consensus Log Po/w :	3.17

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.22
Solubility :	0.144 mg/ml ; 0.000607 mol/l
Class :	Soluble
Log S (Ali) :	-2.49
Solubility :	0.758 mg/ml ; 0.0032 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.35
Solubility :	0.0107 mg/ml ; 0.000045 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.78

Safety of [ 94278-68-9 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 94278-68-9 ]

* 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.

Downstream synthetic route of [ 94278-68-9 ]

[ 94278-68-9 ] Synthesis Path-Downstream 1~31

1
[ 79538-27-5 ]
[ 94278-68-9 ]

Yield	Reaction Conditions	Operation in experiment
66%	With phosphorus(V) oxybromide In tetrahydrofuran at 20℃; for 2h;	56.3 Step3: Step3: To a cold stirring solution of (2,6-difluoro-4-methoxyphenyl)MeOH (0.5 g, 2.87 mmol, 1 eq) in THF (20 ml) was portion wise added ROB FontWeight="Bold" FontSize="10" (1.65 g, 5.74 mmol, 2 eq). The reaction mixture then stirred for 2 h at RT. The reaction mixture was quenched by saturated NaHCCb solution under cooling conditions. The organic layer was separated and aqueous layer was extracted by EtOAc (50 ml). The combined organic layer was washed by water (30 ml) and brine (30 ml). [71] The organic layer was dried over anhydrous Na2SC>4, concentrated under reduced pressure to get the crude material which was purified by silica gel (230-400 mesh silica gel; 10% EtO Ac/hexane; R value-0.5) to afford 2-(bromomethyl)-1,3-difluoro-5-methoxybenzene (0.45 g, 66%) as color less liquid.
	With hydrogen bromide; acetic acid for 0.75h; Heating;

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2019/170904, 2019, A1 Location in patent: Page/Page column 69-73
[2]Pascal, Robert A.; Chen, Y.-C. Jack [Journal of Organic Chemistry, 1985, vol. 50, # 3, p. 408 - 410]

2
[ 79538-28-6 ]
[ 94278-68-9 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 408 - 410

3
[ 84937-82-6 ]
[ 94278-68-9 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 408 - 410

4
potassium cyanide [ No CAS ]
[ 94278-68-9 ]
[ 886499-03-2 ]

Yield	Reaction Conditions	Operation in experiment
48%	In water; N,N-dimethyl-formamide at 20℃; for 0.5h;	56.4 Step4: Step4: To a cold stirring solution of 2-(bromomethyl)-l,3-difluoro-5-methoxybenzene (9.5 g, 40.08 mmol, 1 eq) in DMF (38 ml) was slowly added a solution of KCN (3.23 g, 49.7 mmol, 1.24 eq) in water (7.34 ml). The reaction mixture then stirred for 30 min at RT. Water (48 ml) and NaHCCb solution (48 ml) were added to the reaction mixture. The reaction mixture was then extracted by Et20 (2 x 200 ml). The combined organic layer was washed by water (4 x 80 ml) followed by brine (200 ml). The organic layer was dried over anhydrous Na2SC>4, concentrated under reduced pressure to get the crude material, which was purified by silica gel (230-400 mesh silica gel; 10% EtOAc/hexane; Rvalue-0.4) to afford 2-(2,6-difluoro-4-methoxyphenyl)acetonitrile (3.5 g, 48%) as color less liquid.
	In water; N,N-dimethyl-formamide Cooling with water bath;	3.A Step A: Preparation of 2,6-Difluoro-4-methoxybenzeneacetonitrileA solution of KCN (0.88 g, 13 mmol) dissolved in water (2 mL) was added dropwise to a water-bath-cooled solution of 2,6-difluoro-4-methoxybenzyl bromide (2.50 g, 10.5 mmol) in Λ/,Λ/-dimethylformamide (10 mL). The reaction mixture was stirred for 20 min. Water was added (20 mL) and then the reaction mixture was poured into saturated aqueous NaΗCC>;3 solution (20 mL) and extracted with ether (50 mL). The organic phase was washed with water (5 x 25 mL), dried over MgSOφ and concentrated to give an oil, which crystallized on standing to provide the title compound as a white solid (1.9 g). 1H NMR δ 6.50 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H)
	In water; N,N-dimethyl-formamide for 0.333333h;	2.A A solution of KCN (0.88 g, 13 mmol) dissolved in water (2 mL) was added dropwise to a water-bath-cooled solution of 2,6-difluoro-4-methoxybenzyl bromide (2.50 g, 10.5 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was stirred for 20 min. Water was added (20 mL) and then the reaction mixture was poured into saturated aqueous NaHCC^ solution (20 mL) and extracted with ether (50 mL). The organic phase was washed with water (5 x 25 mL), dried over MgSC^, and concentrated to give an oil, which crystallized on standing to provide the title compound as a white solid (1.9 g)..H NMR δ 6.50 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H).

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2019/170904, 2019, A1 Location in patent: Page/Page column 69-73
[2]Current Patent Assignee: FMC CORP - WO2010/101973, 2010, A1 Location in patent: Page/Page column 58
[3]Current Patent Assignee: FMC CORP - WO2012/31061, 2012, A2 Location in patent: Page/Page column 48

5
[ 94278-68-9 ]
[ 1242015-79-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide; water / 0.33 h 2: sodium ethanolate / ethyl acetate; ethanol; xylene / 4 h / 50 °C 3: acetic acid / ethanol / 16 h / Reflux 4: copper(ll) bromide; tert.-butylnitrite / acetonitrile / 20 °C / Cooling with ice 5: potassium carbonate / palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / 1,4-dioxane / 22 h / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: FMC CORP - WO2012/31061, 2012, A2

6
[ 94278-68-9 ]
[ 1242020-16-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide; water / 0.33 h 2: sodium ethanolate / ethyl acetate; ethanol; xylene / 4 h / 50 °C

Reference： [1]Current Patent Assignee: FMC CORP - WO2012/31061, 2012, A2

7
[ 94278-68-9 ]
[ 1242020-17-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; water / 0.33 h 2: sodium ethanolate / ethyl acetate; ethanol; xylene / 4 h / 50 °C 3: acetic acid / ethanol / 16 h / Reflux

Reference： [1]Current Patent Assignee: FMC CORP - WO2012/31061, 2012, A2

8
[ 94278-68-9 ]
[ 1242020-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N,N-dimethyl-formamide; water / 0.33 h 2: sodium ethanolate / ethyl acetate; ethanol; xylene / 4 h / 50 °C 3: acetic acid / ethanol / 16 h / Reflux 4: copper(ll) bromide; tert.-butylnitrite / acetonitrile / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: FMC CORP - WO2012/31061, 2012, A2

9
[ 1534390-60-7 ]
[ 94278-68-9 ]
[ 1534389-48-4 ]

Yield	Reaction Conditions	Operation in experiment
58 mg	With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 5h;	4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethylpyridin-3-yl)-2H-1 ,2,4- benzothiadiazin-3(4H)-one 1 ,1 -dioxide (178) 4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethylpyridin-3-yl)-2H-1 ,2,4- benzothiadiazin-3(4H)-one 1 ,1 -dioxide (178) The title compound (58 mg, 0.13 mmol) was prepared from 2-(5,6-dimethylpyridin-3- yl)-2/-/-1 ,2,4-benzothiadiazin-3(4/-/)-one 1 , 1-dioxide (lntA29) (150 mg, 0.49 mmol), 2,6-difluoro-4-methoxybenzyl bromide (129 mg, 0.54 mmol) and K2C03 (102 mg, 0.74 mmol) in DMF (3 mL) at 50°C using the methods of (115). LCMS (Method B): m/z 460.0 (M+H)+ (ES+), at 4.32 min, 95% 1H NMR: (400 MHz, CDCI3) δ: 2.38 (s, 3H), 2.60 (s, 3H), 3.77 (s, 3H), 5.45 (s, 2H), 6.43-6.51 (m, 2H), 7.35 (t, J=7.5, 1 H), 7.49-7.51 (m, 1 H), 7.62-7.73 (m, 2H), 7.93 (dd, J=7.8, 1.5, 1 H), 8.37 (d, J=2.3, 1 H)

Reference： [1]Current Patent Assignee: SOSEI GROUP CORPORATION - WO2014/6402, 2014, A1 Location in patent: Page/Page column 119

10
[ 1534390-00-5 ]
[ 94278-68-9 ]
[ 1534390-52-7 ]

Yield	Reaction Conditions	Operation in experiment
301 mg	With potassium carbonate In N,N-dimethyl-formamide at 20 - 27℃; for 5h;	1 Step 1 : Preparation of te/f-butyl {6-[4-(2,6-difluoro-4-methoxybenzyl)-1 , 1-dioxido-3- oxo-3,4-dihydro-2/-/-1 ,2,4-benzothiadiazin-2-yl]-3-methoxypyridin-2- yl}methyl carbamate Step 1 : Preparation of te/f-butyl {6-[4-(2,6-difluoro-4-methoxybenzyl)-1 , 1-dioxido-3- oxo-3,4-dihydro-2/-/-1 ,2,4-benzothiadiazin-2-yl]-3-methoxypyridin-2- yl}methyl carbamate The title compound (301 mg, 0.51 mmol) was prepared from te/f-butyl [6-(1 , 1- dioxido-3-oxo-3,4-dihydro-2H-1 ,2,4-benzothiadiazin-2-yl)-3-methoxypyridin-2- yl]methylcarbamate (lntA31) (343 mg, 0.79 mmol), 2,6-difluoro-4-methoxybenzyl bromide (225 mg, 0.95 mmol) and K2C03 (164 mg, 1.19 mmol) in DMF (4 ml_) at rt using the methods of (1 15). LCMS (Method B): m/z 591.2 (M+H)+ (ES+), at 5.04 min, 100%

Reference： [1]Current Patent Assignee: SOSEI GROUP CORPORATION - WO2014/6402, 2014, A1 Location in patent: Page/Page column 119-120

11
[ 1534389-78-0 ]
[ 94278-68-9 ]
[ 1534389-13-3 ]

Yield	Reaction Conditions	Operation in experiment
38 mg	With potassium carbonate In N,N-dimethyl-formamide at 100℃; Sealed tube;

Reference： [1]Christopher, John A.; Aves, Sarah J.; Brown, Jason; Errey, James C.; Klair, Suki S.; Langmead, Christopher J.; Mace, Oliver J.; Mould, Richard; Patel, Jayesh C.; Tehan, Benjamin G.; Zhukov, Andrei; Marshall, Fiona H.; Congreve, Miles [MedChemComm, 2015, vol. 6, # 5, p. 947 - 955]

12
[ 1534389-82-6 ]
[ 94278-68-9 ]
[ 1534389-16-6 ]

Yield	Reaction Conditions	Operation in experiment
92 mg	With potassium carbonate In N,N-dimethyl-formamide at 100℃; Sealed tube;

13
[ 1534389-81-5 ]
[ 94278-68-9 ]
[ 1534389-20-2 ]

Yield	Reaction Conditions	Operation in experiment
38 mg	With potassium carbonate In N,N-dimethyl-formamide at 100℃; Sealed tube;

14
[ 941882-18-4 ]
[ 94278-68-9 ]
[ 1534388-69-6 ]

Yield	Reaction Conditions	Operation in experiment
59 mg	With potassium carbonate In N,N-dimethyl-formamide at 100℃; Sealed tube;

15
(S)-methyl-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate [ No CAS ]
[ 94278-68-9 ]
(S)-Methyl 1-(2,6-difluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: (S)-methyl-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 5℃; for 0.25h; Inert atmosphere; Stage #2: 4-(bromomethyl)-3,5-difluorophenyl methyl ether In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h;	149 Preiaration 51: (8)-Methyl 1-(2,6-difluoro-4-methoxybenzyfl-,4-dimethyl-2-oxo-1,2,,4-tetrahydro1uinazoline-7-carboxylate To a stirred solution of (S)-methyl 3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7- carboxylate (Preparation 14) (o.i g, 0.43 mmol) in DMF ( mL) was added NaH (0.014g, 60% suspension in mineral oil) at 0-5 oC under an inert atmosphere and the whole allowed to stir for 15 mm. Then, 2-(bromomethyl)-1,3-difluoro-5-methoxybenzene (0.119 g, 0.47 mmol) was added into the reaction mixture which was allowed to further stir at RT for 2 h. The progress of the reaction was monitored by TLC and LCMS and after completion the mixture was quenched with a saturated solution of NH4C1 andextracted with EtOAc. The organics were washed with cold water followed by brine, dried over anhydrous Na2SO4 and evaporated under reduced pressure to give titled compound (0.166 g, 100% yield and purity >95%) as a white solid. LCMS m/z: 391.14 [M+H].

Reference： [1]Current Patent Assignee: CURADEV PHARMA PRIVATE LTD - WO2018/234808, 2018, A1 Location in patent: Page/Page column 185; 186

16
[ 94278-68-9 ]
(S)-1-(4-(allyloxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 0 - 5 °C / Inert atmosphere 1.2: 2 h / 20 °C 2.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 2 h / 20 °C 3.1: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0.25 h / 10 - 15 °C 3.2: 1 h / 20 °C 4.1: boron tribromide / dichloromethane / 2 h / 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C