[ CAS No. 1146699-64-0 ]

Name: 1146699-64-0|3-(4-(Bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole|97%
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Quality Control of [ 1146699-64-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1146699-64-0 ]

CAS No. :	1146699-64-0	MDL No. :	MFCD13181201
Formula :	C₉H₆BrFN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZBKXTEJUTGXVJL-UHFFFAOYSA-N
M.W :	257.06	Pubchem ID :	57672367
Synonyms :

Calculated chemistry of [ 1146699-64-0 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	11
Fraction Csp3 :	0.11
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.53
TPSA :	38.92 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) :	-6.12 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.43
Log Po/w (XLOGP3) :	2.46
Log Po/w (WLOGP) :	3.04
Log Po/w (MLOGP) :	2.53
Log Po/w (SILICOS-IT) :	3.31
Consensus Log Po/w :	2.75

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.43
Solubility :	0.0949 mg/ml ; 0.000369 mol/l
Class :	Soluble
Log S (Ali) :	-2.92
Solubility :	0.308 mg/ml ; 0.0012 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.92
Solubility :	0.00307 mg/ml ; 0.0000119 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.44

Safety of [ 1146699-64-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1146699-64-0 ]

* 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 [ 1146699-64-0 ]
Downstream synthetic route of [ 1146699-64-0 ]

[ 1146699-64-0 ] Synthesis Path-Upstream 1~4

1
[ 1146699-65-1 ]
[ 1146699-64-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; for 0.25 h; Stage #2: With phosphonic acid diethyl ester In tetrahydrofuran at 20℃; for 1 h;	A 200 mL round bottom flask was charged with 3-(4-(dibromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (8.37 g, 25 mmol) and THF (60 mL). The mixture was cooled to 0° C. and diisopropyl ethyl amine (3.48 g, 27 mmol) was added dropwise over 15 minutes, followed by diethyl phosphite (3.7 g, 26.8 mmol). The mixture was stirred at room temperature for 60 minutes and quenched with 40 mL of water. The aqueous layer was extracted with ether (2*80 mL). The combined organic layer was washed with 20 mL of sat aq. NH₄Cl and 20 mL of saturated sodium chloride solution. The organic layer was dried over sodium sulfate, filtered and concentrated on a rotovap to give a crude solid which was purified by a short silica pad to afford 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (6.03 g, 94percent). mp 87.3° C. ¹H-NMR (CDCl₃, 400 MHz) δ 8.80 (s, 1H), 7.94 (dd, 1H), 7.87 (dd, 1H), 7.58 (t, 1H), 4.57 (s, 2H); ¹³C-NMR (CDCl₃, 400 MHz) δ 166.97, 166.95, 165.45, 162.29, 159.73, 132.34, 132.30, 128.99, 128.90, 128.81, 124.04, 124.01, 115.56, 115.32, 25.22, 25.18; ¹⁹F-NMR (CDCl₃, 400 MHz) δ -115.81, -115.84, -115.86. Anal. Calcd for C₉H₆BrFN₂O: C, 42.05; H, 2.35; N, 10.90. Found: C, 42.17; H, 2.17; N, 10.63.

Reference： [1] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 6; 18
[2] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 18
[3] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 18

2
[ 1146699-63-9 ]
[ 1146699-64-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: With sodium bromate In water; ethyl acetate at 20℃; Stage #2: With sodium hydrogensulfite In water; ethyl acetate at 20℃; for 2 h;	Method C: Sodium bromate Bromination (Direct Isolation); Sodium bromate (2.54 g) was dissolved in water (8.4 mL). To this solution was added a solution of 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole (1.0 g) in EtOAc (12 mL) at rt. A solution of NaHSO₃(1.75 g) in water (17 mL) was added dropwise (CAUTION: EXOTHERMIC). The mixture was stirred at rt for 2 h, and then kept in a cold room overnight. The organic layer was separated, washed with 10percent Na₂S₂O₃and water, and then concentrated. The resulting solid was dissolved in EtOAc (6 mL). Heptane was added slowly (30 mL). The slurry was stirred at rt for 3 h, and then filtered. The solid was washed with heptane (15 mL), then dried giving 0.74 g (51percent) ofthe title compound: HPLC: 99.42AP. Second crop recovery: the filtrate was concentrated to a volume 30 mL and the resulting slurry was filtered to give the title compound as a white solid 0.23 (16percent) with HPLC 97.09 AP.

Reference： [1] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 18

3
[ 1146699-63-9 ]
[ 1146699-64-0 ]
[ 1146699-65-1 ]

Reference： [1] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 18
[2] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 18

4
[ 1146699-64-0 ]
[ 1146699-67-3 ]
[ 1146699-66-2 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydroxylamine; tetra-(n-butyl)ammonium iodide; caesium carbonate In acetonitrile at 15 - 35℃;	Step B, Procedure 2 To a suitable vessel was added (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide (2.68 kg, 7.77 mol, 1 eq), 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (2.00 kg, 7.78 mol, 1 eq), cesium carbonate (1.65 kg, 5.06 mol, 0.65 eq), tetrabutylammonium iodide (0.29 kg, 0.78 mol, 0.1 eq) and acetonitrile (12.0 L 4.5 L/kg). The reaction was heated to 35° C. until complete by HPLC (3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole <0.5 relative AP by HPLC). The reaction was cooled to 15° C. and water (10.72 L, 4 L/kg) was added with stirring followed by glacial acetic acid (0.22 kg) to bring the pH of the reaction to <6.5. The stirring was stopped and the phases were separated (the top layer contained the product). To the product rich layer was added toluene (26.8 kg, 31 L, 10 kg/kg) followed by brine solution (20percent w/w, 6.39 kg, 2 L/kg) and the layers were separated (the top layer contained the product). The mixture was distilled at ~50° C. under vacuum (200 mbar) until acetonitrile was removed. The concentration was adjusted with additional toluene if needed after distillation to ensure total volume in the reactor was ~10 L/kg. Isopropyl alcohol (0.48 kg, 0.2 L/kg) was charged and the batch was cooled to 15° C. to initiate crystallization. The resulting slurry was filtered and washed with cold toluene (18.65 kg, 21.56 L, 8 L/kg). The crude cake was tray dried under vacuum at 50° C. until loss on drying was <1.0percent. The dry cake was added to a 100 L reactor along with isopropyl alcohol (27.34 kg, 34.8 L, 13 L/kg) and hydroxylamine (50percent aqueous solution, 0.05 kg, 1.51 mol, 0.2 eq). The mixture was heated to 65° C. and monitored by HPLC until (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide was <0.4 AP. The reaction was then distilled (pot temperature ~50° C., vacuum 300 mbar) until reaction volume was ~60percent of original. Acetonitrile (5.36 kg, 2 L/kg) was charged and the reaction temperature was increased to 70° C. to achieve complete dissolution. Water (11.26 L, 4.2 L/kg) was charged slowly while keeping the reaction temperature >65° C. The reaction was cooled to 15° C. over 2 hours and crystallization occurred. The slurry was filtered and washed with cold aqueous isopropyl alcohol (2:1 IPA:water by volume). The cake was dried in a vacuum oven until loss on drying was <1percent. The product was then recrystallized by dissolving in acetonitrile (2 L/kg based on weight of input of dried cake) and methanol (6 L/kg) and then heated to 50° C. Water (4 L/kg) was added slowly, keeping the reaction temperature >50° C. The reaction was cooled to 15° C. over 2 hours. The resulting slurry was filtered and washed with a solution of methanol:acetonitrile:water (6:2:4, 5 L/kg) to give (2R)-2-[[(4-chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoropentanamide (2.02 kg, 50percent yield) as a white solid.

Reference： [1] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 21-22
[2] Patent: US2009/111858, 2009, A1, . Location in patent: Page/Page column 20-21

[ 1146699-64-0 ] Synthesis Path-Downstream 1~5

1
[ 1146699-64-0 ]
[ 1146699-67-3 ]
[ 1146699-66-2 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydroxylamine; tetra-(n-butyl)ammonium iodide; caesium carbonate; In acetonitrile; at 15 - 35℃;Product distribution / selectivity;	Step B, Procedure 2 To a suitable vessel was added (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide (2.68 kg, 7.77 mol, 1 eq), 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (2.00 kg, 7.78 mol, 1 eq), cesium carbonate (1.65 kg, 5.06 mol, 0.65 eq), tetrabutylammonium iodide (0.29 kg, 0.78 mol, 0.1 eq) and acetonitrile (12.0 L 4.5 L/kg). The reaction was heated to 35 C. until complete by HPLC (3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole <0.5 relative AP by HPLC). The reaction was cooled to 15 C. and water (10.72 L, 4 L/kg) was added with stirring followed by glacial acetic acid (0.22 kg) to bring the pH of the reaction to <6.5. The stirring was stopped and the phases were separated (the top layer contained the product). To the product rich layer was added toluene (26.8 kg, 31 L, 10 kg/kg) followed by brine solution (20% w/w, 6.39 kg, 2 L/kg) and the layers were separated (the top layer contained the product). The mixture was distilled at ~50 C. under vacuum (200 mbar) until acetonitrile was removed. The concentration was adjusted with additional toluene if needed after distillation to ensure total volume in the reactor was ~10 L/kg. Isopropyl alcohol (0.48 kg, 0.2 L/kg) was charged and the batch was cooled to 15 C. to initiate crystallization. The resulting slurry was filtered and washed with cold toluene (18.65 kg, 21.56 L, 8 L/kg). The crude cake was tray dried under vacuum at 50 C. until loss on drying was <1.0%. The dry cake was added to a 100 L reactor along with isopropyl alcohol (27.34 kg, 34.8 L, 13 L/kg) and hydroxylamine (50% aqueous solution, 0.05 kg, 1.51 mol, 0.2 eq). The mixture was heated to 65 C. and monitored by HPLC until (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide was <0.4 AP. The reaction was then distilled (pot temperature ~50 C., vacuum 300 mbar) until reaction volume was ~60% of original. Acetonitrile (5.36 kg, 2 L/kg) was charged and the reaction temperature was increased to 70 C. to achieve complete dissolution. Water (11.26 L, 4.2 L/kg) was charged slowly while keeping the reaction temperature >65 C. The reaction was cooled to 15 C. over 2 hours and crystallization occurred. The slurry was filtered and washed with cold aqueous isopropyl alcohol (2:1 IPA:water by volume). The cake was dried in a vacuum oven until loss on drying was <1%. The product was then recrystallized by dissolving in acetonitrile (2 L/kg based on weight of input of dried cake) and methanol (6 L/kg) and then heated to 50 C. Water (4 L/kg) was added slowly, keeping the reaction temperature >50 C. The reaction was cooled to 15 C. over 2 hours. The resulting slurry was filtered and washed with a solution of methanol:acetonitrile:water (6:2:4, 5 L/kg) to give (2R)-2-[[(4-chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoropentanamide (2.02 kg, 50% yield) as a white solid.
	With tetra-(n-butyl)ammonium iodide; caesium carbonate; In acetonitrile; at 38℃;Product distribution / selectivity;	Step B, Procedure 1 A suitable vessel was charged with 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (492.14 g, 1.10 equiv, 1.914 mol), (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide (600 g, 1.00 equiv; 1.74 mol) cesium carbonate (312.22 g, 0.55 equiv; 0.98 mol), tetra-n-butylammonium iodide (64.29 g, 0.10 equiv; 0.17 mmoles), and acetonitrile (9 mL/g; 5.4 L). The jacket was heated to 40 C. (internal 38 C.). The reaction was monitored by HPLC until (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide was <5 AP. The vessel was cooled to an internal temperature of 20 C. and water (5.4 L) was added. The phases were separated and the product rich layer was on the top. The bottom layer was discarded. Water (3.7 L) was charged over 18 minutes, and the reaction was held for 20 h at 20 C. and then filtered. Water (6 L) was added to the vessel and agitated to assist in transfer of solid stuck to agitator and vessel walls. The crude cake was washed once with the water used to rinse the reactor. The crude cake was dried in trays under vacuum at 50 C. The dry, crude cake weighed 699 g. The cake was transferred to a 10 L reactor and THF was charged (2.025 L) followed by hydroxylamine solution (50% in water) (42.97 mL, 0.40 equiv, 0.696 mol). The reactor jacket was heated to 40 C. The reaction was monitored by HPLC until (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide was <0.4 AP. The reaction was cooled to 20 C., water (2 L) was added and the reaction was stirred at 20 C. for 30 minutes. The phases were separated and the organic phase was treated with heptane (8 L) while stirring and the reaction oiled, then precipitated. The slurry was allowed to stand at 20 C. for 2 h, and the reaction was filtered and the cake was washed with heptane (2 L). The crude cake was tray dried under vacuum at 40-50 C. and weighed 613 g after drying to <1% loss on drying. The crude product was transferred back to the vessel along with MeOH (3.678 L) and MeCN (1.226 L). The jacket was heated to 60 C. (internal 52 C.) to effect complete dissolution, and water (2.023 L) was added at that temperature slowly, maintaining an internal temperature of >50 C. When water addition was complete, the solution was cooled to an internal temperature of 15 C. over 4 hours while crystallization occurred. Additional water was charged to the reactor (400 mL) and the reaction was filtered and the mother liquor was returned to the vessel. The mother liquor was agitated for 2 minutes to free any stuck product in the vessel. The crude cake was washed with mother liquor followed by heptanes (1.500 L). The product was tray dried under vacuum at 40-50 C. until loss on drying was <0.5% to give (2R)-2-[[(4-Chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoropentanamide as a shiny, off white solid (577.6 g, 63.76% yield.).

Reference： [1]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 21-22
[2]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 20-21

2
[ 1146699-63-9 ]
[ 1146699-64-0 ]

Yield	Reaction Conditions	Operation in experiment
51%		Method C: Sodium bromate Bromination (Direct Isolation); Sodium bromate (2.54 g) was dissolved in water (8.4 mL). To this solution was added a solution of 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole (1.0 g) in EtOAc (12 mL) at rt. A solution of NaHSO3 (1.75 g) in water (17 mL) was added dropwise (CAUTION: EXOTHERMIC). The mixture was stirred at rt for 2 h, and then kept in a cold room overnight. The organic layer was separated, washed with 10% Na2S2O3 and water, and then concentrated. The resulting solid was dissolved in EtOAc (6 mL). Heptane was added slowly (30 mL). The slurry was stirred at rt for 3 h, and then filtered. The solid was washed with heptane (15 mL), then dried giving 0.74 g (51%) ofthe title compound: HPLC: 99.42AP. Second crop recovery: the filtrate was concentrated to a volume 30 mL and the resulting slurry was filtered to give the title compound as a white solid 0.23 (16%) with HPLC 97.09 AP.

Reference： [1]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 18

3
[ 1146699-63-9 ]
[ 1146699-64-0 ]
[ 1146699-65-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In acetonitrile; at 20 - 70℃; for 2h;Product distribution / selectivity;	Method B. Alternative One-Pot Bromination 3-(3-Fluoro-4-methylphenyl)-1,2,4-oxadiazole (101.8 g, 0.57 mol) and N-bromosuccinimide (206 g, 1.16 mol) were dissolved in acetonitrile (~1 L) and azobisisobutyronitrile (4.2 g, 26 mmol) was added at room temperature. The mixture was heated to 70 C. for 2 hours at which point HPLC showed complete conversion of the starting material to a mixture of the monobromide and dibromide. The mixture was cooled to 0 C. and diisopropyl ethyl amine (73 mL, 54.2 g, 0.42 mol) was added while maintaining the reaction temperature below 5 C. Diethyl phosphite (54.7 mL, 58.6 g, 0.42 mol) was added slowly and the reaction mixture was warmed to room temperature. After 2 hours HPLC showed complete conversion of the dibromide to the monobromide. Water (1.2 L) was added and the resulting precipitate was filtered. Washing with water (2*200 mL) and drying provided 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (135 g, 92% yield).
		Method D: Sodium bromate Bromination (Two Step Procedure Using Reduction of dibromide); A solution of 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole (20.0 g, 112.2 mmol) in dichloromethane (200 mL) was added to a solution of NaBrO3 (50.8 g, 336.7 mmol) in water (200 mL) at rt. The resulting two-phase mixture was cooled to 0 C. The solution of NaHSO3 (35.7 g, 336.7 mmol) in water (160 mL) was added dropwise to maintain the batch temperature below 20 C. (1 h). The resulting red solution was stirred at rt until 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole was below 1.0 AP by HPLC (2 h). The organic layer (bottom layer) was separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane solution was washed with 10% aqueous Na2S2O3 solution (200 mL), water (200 mL) and 15% brine (200 mL). A white solid (a mixture of monobromide and dibromide) was obtained after concentrating under vacuum. This solid was dissolved in wet MeCN (200 mL, KF: 1.5-4%), and the solution was cooled to -5 C. to 0 C. N,N-diisopropylethylamine (6.0 g, 8.1 mL, 46.4 mmol) was added, followed by dropwise addition of diethyl phosphite (6.0 g, 46.1 mmol) over 15 minute. The mixture was stirred at -5 C. to 0 C. until 3-(4-(dibromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole was <0.5 AP (1.5-2 h). Water (500 mL) was added over 30 min, resulting in a white slurry. This slurry was stirred at rt for 1-3 h, and then filtered. The cake was washed with water (2×200 mL), and then dried under vacuum at 45 C. for 20 h.Anal. Calcd. for C9H6BrFN2O: Calc. C, 42.05; H, 2.35; N, 10.89; Br, 31.08; F, 7.39. Found: C, 42.10; H, 2.24; N, 10.90; Br, 31.18; F, 7.00.

Reference： [1]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 18
[2]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 18

4
[ 1146699-65-1 ]
[ 1146699-64-0 ]

Yield	Reaction Conditions	Operation in experiment
94%		A 200 mL round bottom flask was charged with 3-(4-(dibromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (8.37 g, 25 mmol) and THF (60 mL). The mixture was cooled to 0 C. and diisopropyl ethyl amine (3.48 g, 27 mmol) was added dropwise over 15 minutes, followed by diethyl phosphite (3.7 g, 26.8 mmol). The mixture was stirred at room temperature for 60 minutes and quenched with 40 mL of water. The aqueous layer was extracted with ether (2*80 mL). The combined organic layer was washed with 20 mL of sat aq. NH4Cl and 20 mL of saturated sodium chloride solution. The organic layer was dried over sodium sulfate, filtered and concentrated on a rotovap to give a crude solid which was purified by a short silica pad to afford 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (6.03 g, 94%). mp 87.3 C. 1H-NMR (CDCl3, 400 MHz) delta 8.80 (s, 1H), 7.94 (dd, 1H), 7.87 (dd, 1H), 7.58 (t, 1H), 4.57 (s, 2H); 13C-NMR (CDCl3, 400 MHz) delta 166.97, 166.95, 165.45, 162.29, 159.73, 132.34, 132.30, 128.99, 128.90, 128.81, 124.04, 124.01, 115.56, 115.32, 25.22, 25.18; 19F-NMR (CDCl3, 400 MHz) delta -115.81, -115.84, -115.86. Anal. Calcd for C9H6BrFN2O: C, 42.05; H, 2.35; N, 10.90. Found: C, 42.17; H, 2.17; N, 10.63.
		Method D: Sodium bromate Bromination (Two Step Procedure Using Reduction of dibromide); A solution of 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole (20.0 g, 112.2 mmol) in dichloromethane (200 mL) was added to a solution of NaBrO3 (50.8 g, 336.7 mmol) in water (200 mL) at rt. The resulting two-phase mixture was cooled to 0 C. The solution of NaHSO3 (35.7 g, 336.7 mmol) in water (160 mL) was added dropwise to maintain the batch temperature below 20 C. (1 h). The resulting red solution was stirred at rt until 3-(3-fluoro-4-methylphenyl)-1,2,4-oxadiazole was below 1.0 AP by HPLC (2 h). The organic layer (bottom layer) was separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane solution was washed with 10% aqueous Na2S2O3 solution (200 mL), water (200 mL) and 15% brine (200 mL). A white solid (a mixture of monobromide and dibromide) was obtained after concentrating under vacuum. This solid was dissolved in wet MeCN (200 mL, KF: 1.5-4%), and the solution was cooled to -5 C. to 0 C. N,N-diisopropylethylamine (6.0 g, 8.1 mL, 46.4 mmol) was added, followed by dropwise addition of diethyl phosphite (6.0 g, 46.1 mmol) over 15 minute. The mixture was stirred at -5 C. to 0 C. until 3-(4-(dibromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole was <0.5 AP (1.5-2 h). Water (500 mL) was added over 30 min, resulting in a white slurry. This slurry was stirred at rt for 1-3 h, and then filtered. The cake was washed with water (2×200 mL), and then dried under vacuum at 45 C. for 20 h.Anal. Calcd. for C9H6BrFN2O: Calc. C, 42.05; H, 2.35; N, 10.89; Br, 31.08; F, 7.39. Found: C, 42.10; H, 2.24; N, 10.90; Br, 31.18; F, 7.00.
		Method B. Alternative One-Pot Bromination 3-(3-Fluoro-4-methylphenyl)-1,2,4-oxadiazole (101.8 g, 0.57 mol) and N-bromosuccinimide (206 g, 1.16 mol) were dissolved in acetonitrile (~1 L) and azobisisobutyronitrile (4.2 g, 26 mmol) was added at room temperature. The mixture was heated to 70 C. for 2 hours at which point HPLC showed complete conversion of the starting material to a mixture of the monobromide and dibromide. The mixture was cooled to 0 C. and diisopropyl ethyl amine (73 mL, 54.2 g, 0.42 mol) was added while maintaining the reaction temperature below 5 C. Diethyl phosphite (54.7 mL, 58.6 g, 0.42 mol) was added slowly and the reaction mixture was warmed to room temperature. After 2 hours HPLC showed complete conversion of the dibromide to the monobromide. Water (1.2 L) was added and the resulting precipitate was filtered. Washing with water (2*200 mL) and drying provided 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (135 g, 92% yield).

Reference： [1]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 6; 18
[2]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 18
[3]Patent: US2009/111858,2009,A1 .Location in patent: Page/Page column 18

5
[ 1146699-64-0 ]
(R)-2-(4-chloro-[¹³C₆]-phenylsulfonamido)-5,5,5-trifluoropentanamide [ No CAS ]
(R)-2-(4-chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-[¹³C₆]-phenylsulfonamido)-5,5,5-trifluoropentanamide [ No CAS ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2014,vol. 57,p. 600 - 605

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Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
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P308	IF exposed or concerned:
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P314	Get medical advice/attention if you feel unwell.
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P321
P322
P330	Rinse mouth.
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P332	IF SKIN irritation occurs:
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P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
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P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
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P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
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P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
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P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
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P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
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P406	Store in corrosive resistant/ container with a resistant inner liner.
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P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
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P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1146699-64-0 ]

Quality Control of [ 1146699-64-0 ]

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Product Details of [ 1146699-64-0 ]

Calculated chemistry of [ 1146699-64-0 ]

Physicochemical Properties

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Lipophilicity

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Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 1146699-64-0 ]

[ 1146699-64-0 ] Synthesis Path-Upstream 1~4

[ 1146699-64-0 ] Synthesis Path-Downstream 1~5

Related Functional Groups of [ 1146699-64-0 ]

Fluorinated Building Blocks

Aryls

Bromides

Related Parent Nucleus of [ 1146699-64-0 ]

Oxadiazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1146699-64-0 ]

Related Parent Nucleus of
[ 1146699-64-0 ]