Name: 142356-62-5|5,6-Difluoro-1H-1,3-benzodiazol-2-amine|95%
Brand: Ambeed
SKU: A1012400
Price: 61.0 USD
Availability: InStock
Rating: 92 (25 reviews)

1
[ 506-68-3 ]
[ 76179-40-3 ]
[ 142356-62-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	In methanol; water; acetonitrile for 2h; Ambient temperature;
78%	In ethanol at 50℃;	Method D: General procedure: To an appropriate aromatic diamino compound (1 mol. equiv.) in EtOH (4.5 ml/1 mmol starting material) was added cyanogen bromide (1.2 mol. equiv.) and resulting mixture was stirred at 50° C. till disappearance of starting material (TLC control). Then volatiles were removed in vacuo and the solid residue was re-dissolved (or suspended) in H2O. Water mixture was extracted with EtOAc (3×). Organic layer was discarded and water layer was brought to pH 9-10 (according to universal indicator paper) using 25% NH4OH or 1 M aqueous NaOH and it was extracted with EtOAc (3×). Combined organic layers were dried over MgSO4. Drying agent was removed, residue was concentrated to dryness and purified on silica gel column if needed.
59%	Stage #1: bromocyane; 2-amino-4,5-difluoroaniline With sodium hydrogencarbonate In water; acetonitrile at 0 - 20℃; Stage #2: In ethanol for 0.25h; Heating / reflux;	1 Step 1. The procedure used was similar to that reported in J. Med. Chem. 40:811-818, 1997. A solution of 1,2-diamino-4,5-difluorobenzene (500 mg, 3.47 mmol) in water (5 mL) was cooled to 0° C. and then treated with a solution of cyanogen bromide (0.83 mL, 4.16 mmol, 5 M in acetonitrile) and solid sodium bicarbonate (583 mg, 6.94 mmol). The solution was stirred at rt overnight and was then concentrated in vacuo. The dark residue was suspended in ethanol and heated at reflux for 15 minutes. The hot suspension was filtered, rinsing with hot ethanol, and the filtrate was concentrated in vacuo to afford 5,6-difluoro-1H-benzimidazol-2-amine (580 mg, 59%), which was used in the next step without further purification. LC-MS m/z 170.2 (MH+), ret. time 0.85 min; 1H NMR (300 MHz, DMSO-d6) δ 6.30 (br s, 2H), 7.06 (dd, 2H), 10.79 (br s, 1H).

40%	In water; acetonitrile at 0 - 20℃; for 14h;	140 EXAMPLE 140; Synthesis ofN4-(5-bromo-2-methylphenyl)-N5-(5,6-difluoro-lH-benzimidazol-2- yl)-lH-imidazole-4,5-dicarboxamide; Synthesis of 5,6-difluoro-lH-benzo[d]imidazol-2-amine; [00395] 4,5-Diflluorobenzene-l,2-diamine (0.651 g, 0.562 mmol, commercially available from Matrix Scientific) in acetonitrile (10 mL) and water (2 ml) at 0 0C was treated with cyanogen bromide (0.063 g, 0.6 mmol). The reaction mixture was allowed to warm to room temperature, and then stirred for 14 hours. The reaction mixture was then treated with saturated aqueous sodium hydrogen carbonate solution (50 ml) and shaken. The resulting solid was filtered off, washed with water and dried under reduced pressure to give 0.39 g of 5,6-difluoro-lH-benzo[d]imidazol-2-amine (yield, 40%). MS (EI): 186 (MH+).
	In methanol; water

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]
[2]Current Patent Assignee: UNIVERSITY OF BONN; KATHOLIEKE UNIVERSITEIT LEUVEN - US2021/128561, 2021, A1 Location in patent: Paragraph 0277-0279
[3]Current Patent Assignee: BAYER AG - US2004/224997, 2004, A1 Location in patent: Page 34
[4]Current Patent Assignee: EXELIXIS INC - WO2008/42282, 2008, A2 Location in patent: Page/Page column 209-210
[5]Powers, Jay P.; Li, Shyun; Jaen, Juan C.; Liu, Jinqian; Walker, Nigel P.C.; Wang, Zhulun; Wesche, Holger [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2842 - 2845]

2
[ 142356-62-5 ]
[ 142356-63-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With tert.-butylnitrite; copper dichloride In acetone at 20℃; for 0.333333h; Stage #2: 5,6-difluoro-1H-benzo[d]imidazol-2-amine In acetone for 2h; Heating / reflux; Stage #3: With hydrogenchloride In water; acetone at 20℃;	2 Step 2. The procedure used was similar to that reported in J. Med. Chem. 40:811-818, 1997. To a mixture of copper(II) chloride (795 mg, 5.91 mmol) in acetone (20 mL) was added tert-butyl nitrite (0.53 mL, 4.43 mmol). The reaction mixture was stirred at rt for 20 minutes, 5,6-difluoro-1H-benzimidazol-2-amine (500 mg, 2.96 mmol) was then added, and the mixture was heated at reflux for 2 h (with additional portions of tert-butyl nitrite added every 0.5 h). The reaction mixture was then cooled to rt, treated with 2 N HCl, and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated in vacuo to afford 2-chloro-5,6-difluoro-1H-benzimidazole (580 mg, 73%), which was used without further purification in the next step. LC-MS m/z 189.2 (MH+), ret. time 1.96 min; 1H NMR (300 MHz, DMSO-d6) δ 7.62 (t, 2H), 13.5 (br s, 1H).
59%	With copper dichloride; sodium nitrite a) RT, 1 h, b) 100 deg C, 10 min;

Reference： [1]Current Patent Assignee: BAYER AG - US2004/224997, 2004, A1 Location in patent: Page 34
[2]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

3
[ 142356-62-5 ]
[ 121-92-6 ]
<i>N</i>-(5,6-difluoro-1<i>H</i>-benzoimidazol-2-yl)-3-nitro-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In N,N-dimethyl-formamide

Reference： [1]Powers, Jay P.; Li, Shyun; Jaen, Juan C.; Liu, Jinqian; Walker, Nigel P.C.; Wang, Zhulun; Wesche, Holger [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2842 - 2845]

4
[ 78056-39-0 ]
[ 142356-62-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 85 percent / Fe, 1 N aq. HCl / methanol / 3 h / Ambient temperature 2: 91 percent / acetonitrile; H₂O; methanol / 2 h / Ambient temperature

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

5
[ 142356-62-5 ]
5,6-difluoro-1-α-D-ribofuranosylbenzimidazole 2,2'-O-cyclonucleoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 59 percent / aq. CuCl₂, NaNO₂ / a) RT, 1 h, b) 100 deg C, 10 min 2: 1.) BSA, 2.) TMSOTf / 1.) ClCH₂CH₂Cl, 75 deg C, 30 min, 2.) ClCH₂CH₂Cl, 75 deg C, 30 min 3: 55 percent / NH₃ / methanol / 20 h / Ambient temperature

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

6
[ 142356-62-5 ]
2-chloro-5,6-difluoro-1-(β-D-ribofuranosyl)benzimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 59 percent / aq. CuCl₂, NaNO₂ / a) RT, 1 h, b) 100 deg C, 10 min 2: 1.) BSA, 2.) TMSOTf / 1.) ClCH₂CH₂Cl, 75 deg C, 30 min, 2.) ClCH₂CH₂Cl, 75 deg C, 30 min 3: 89 percent / NH₃ / methanol / 3 h / Ambient temperature

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

7
[ 142356-62-5 ]
[ 142371-80-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 59 percent / aq. CuCl₂, NaNO₂ / a) RT, 1 h, b) 100 deg C, 10 min 2: 1.) BSA, 2.) TMSOTf / 1.) ClCH₂CH₂Cl, 75 deg C, 30 min, 2.) ClCH₂CH₂Cl, 75 deg C, 30 min

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

8
[ 142356-62-5 ]
[ 142395-44-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 59 percent / aq. CuCl₂, NaNO₂ / a) RT, 1 h, b) 100 deg C, 10 min 2: 1.) BSA, 2.) TMSOTf / 1.) ClCH₂CH₂Cl, 75 deg C, 30 min, 2.) ClCH₂CH₂Cl, 75 deg C, 30 min

Reference： [1]Zou; Drach; Townsend [Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818]

Yield	Reaction Conditions	Operation in experiment
		2-Amino-5,6-difluorobenzimidazole (11) The filtrate and washings were evaporated to dryness and the procedure was repeated to give an additional 0.355 g of 11. The total yield of 11 was 3.755 g (91%). 1 H NMR (DMSO-d6) d 10.79 (br.s, 1,1-NH), 7.06 (dd, 2,4-H and 7-H, 3 JF-H =11.0 Hz, 4 Jf-H =7.5 Hz), 6.30 (br. s, 2,2-NH2).
		2-Amino-5,6-difluorobenzimidazole (11) The filtrate and washings were evaporated to dryness and the procedure was repeated to give an additional 0.355 g of 11. The total yield of 11 was 3.755 g (91%). 1 H NMR (DMSO-d6) d 10.79 (br. s, 1, 1-NH), 7.06 (dd, 2, 4-H and 7-H, 3 JF-H =11.0 Hz, 4 JF-H =7.5 Hz), 6.30 (br. s, 2, 2-NH2).

10
aqueous CuCl₂ [ No CAS ]
[ 7732-18-5 ]
[ 142356-62-5 ]
[ 142356-63-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium nitrite In methanol; chloroform	2-Chloro-5,6-difulorobenzimidazole (12) 2-Chloro-5,6-difulorobenzimidazole (12) To a stirred mixture of 40 mL of aqueous CuCl2 solution (60% by weight) and 20 mL of H2 O was added a solution of NaNO2 /H2 O (2.08 g/10 mL). Compound 11 (1.69 g, 10 mmole) was then added portionwise over 5 min. The reaction mixture was stirred at room temperature for 1 hr. An additional 30 ml of the aqueous CuCl2 solution (60% by weight) was added and the reaction mixture was heated on a steam bath for 10 min (a small amount of MeOH was added to suppress the formation of foam). The mixture was extracted with EtOAc (150 mL2). The EtOAc solution was washed with sat. NaCl solution (100 mL2), dried (Na2 SO4) and evaporated. The residue was chromatographed on a silica column (315 cm) using 2% and 3% MeOH/CHCl3 as eluants. Evaporation of the appropriate fractions gave a brownish solid. This solid was washed with Et2 O and dried to give 0.962 g of 12. The Et2 O washings were evaporated and the residue was repurified through a silica column (210 cm, eluted successively with 1%, 2% MeOH/CHCl3).
	With sodium nitrite In methanol; chloroform	2-Chloro-5,6-difluorobenzimidazole (12) 2-Chloro-5,6-difluorobenzimidazole (12) To a stirred mixture of 40 mL of aqueous CuCl2 solution (60% by weight) and 20 mL of H2 O was added a solution of NaNO2 /H2 O (2.08 g/10 mL). Compound 11 (1.69 g, 10 mmole) was then added portionwise over 5 min. The reaction mixture was stirred at room temperature for 1 hr. An additional 30 ml of the aqueous CuCl2 solution (60% by weight) was added and the reaction mixture was heated on a steam bath for 10 min (a small amount of MeOH was added to suppress the formation of foam). The mixture was extracted with EtOAc (150 mL2). The EtOAc solution was washed with sat. NaCl solution (100 mL2), dried (Na2 SO4) and evaporated. The residue was chromatographed on a silica column (315 cm) using 2% and 3% MeOH/CHCl3 as eluants. Evaporation of the appropriate fractions gave a brownish solid. This solid was washed with Et2 O and dried to give 0.962 g of 12. The Et2 O washings were evaporated and the residue was repurified through a silica column (210 cm, eluted successively with 1%, 2% MeOH/CHCl3).

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - US5360795, 1994, A
[2]Current Patent Assignee: UNIVERSITY OF MICHIGAN - US5574058, 1996, A

11
[ 76179-40-3 ]
[ 142356-62-5 ]

Yield	Reaction Conditions	Operation in experiment
	With bromocyane In methanol; chloroform; water; acetonitrile	2-Amino-5,6-difluorobenzimidazole (11) 2-Amino-5,6-difluorobenzimidazole (11) To a stirred solution of 4.9 mL of 5M BrCN/MeCN in 50 mL of H2 O, was added dropwise a solution of 3.515 g (24.389 mmole) of 10 in 50 mL of MeOH over 20 min. After the addition, stirring was continued at room temperature for 2 h. The reaction mixture was concentrated to ~50 mL and was extracted with EtOAc (50 mL3). The combined EtOAc solution was back washed with 100 mL of H2 O and then discarded. The combined H2 O phase was basified with sat. NaHCO3 solution (precipitation occurred) and was extracted again with EtOAc (70 mL3). The EtOAc solution was dried (Na2 SO4) and evaporated to dryness. The residue was suspended in 50 mL of CHCl3 and filtered. The yellowish solid was washed with portions of CHCl3 to give 3.40 g of 11.
	With bromocyane In methanol; chloroform; water; acetonitrile	2-Amino-5,6-difluorobenzimidazole (11) 2-Amino-5,6-difluorobenzimidazole (11) To a stirred solution of 4.9 mL of 5M BrCN/MeCN in 50 mL of H2 O, was added dropwise a solution of 3.515 g (24.389 mmole) of 10 in 50 mL of MeOH over 20 min. After the addition, stirring was continued at room temperature for 2 h. The reaction mixture was concentrated to ~ 50 mL and was extracted with EtOAc (50 mL3). The combined EtOAc solution was back washed with 100 mL of H2 O and then discarded. The combined H2 O phase was basified with sat. NaHCO3 solution (precipitation occurred) and was extracted again with EtOAc (70 mL3). The EtOAc solution was dried (Na2 SO4) and evaporated to dryness. The residue was suspended in 50 mL of CHCl3 and filtered. The yellowish solid was washed with portions of CHCl3 to give 3.40 g of 11.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - US5360795, 1994, A
[2]Current Patent Assignee: UNIVERSITY OF MICHIGAN - US5574058, 1996, A

12
[ 142356-62-5 ]
C₁₁H₆BrF₂N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / 4 h / Reflux 2: bromine; trifluoroacetic acid / 2 h / 20 °C