* 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.
To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27mmol) in CHCI3 (10ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5: 1) to give 7-bromobenzo[d]thiazol-6-amine (80mg, 80percent).
75%
With bromine In chloroform at 0℃; for 1 h;
A mixture of benzo[djthiazol-6-amine (2-17, 1 g, 6.6 mmol) and Br2 (1.06 g, 6.6 mmol) in CHC13 (5 mL) was stirred at 0 °C for 1 h. Upon reaction completion, the resulting mixture was concentrated under reduced pressure to provide intermediate 2-18 (yellow solid, 1.2 g, 75percent yield). LCMS (m/z): 229 [M + HI .
67%
at 20℃; for 1 h;
Step A: 7-bromo-benzothiazol-6-ylamineTo a solution of benzothiazol-6-ylamine (6.4 g, 42.6 mmol) in glacial acetic acid (40 mL) was added bromine (2.18 mL) in glacial acetic acid (10 mL) dropwise. The reaction mixture was stirred at RT for 1 h. Water (160 mL) was added to the reaction mixture and the solid formed was extracted with ethyl acetate (3 x 40 mL). The combined organic fractions were washed with saturated aqueous sodium bicarbonate solution (200 mL), water (100 mL), and brine (20 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by column chromatography (20percent ethyl acetate: hexanes) afforded 6.5 g (67percent) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCI3): δ 4.31 (br. s, 2H), 7.02 (d, J=8.4 Hz, 1 H), 7.92 (d, J=8.4 Hz, 1 H), 8.80 (s, 1 H).
34 mmol, 80%
With bromine In acetic acid; ethyl acetate
7-Bromo-6-aminobenzothiazole To a solution of 6-aminobenzothiazole (16 g, 107 mmol) in 100 mL of AcOH was added Br2 (2.0 mL, 43 mmol) dropwise and the resulting reaction mixture was stirred for 1 h at 25° C. Reaction mixture was concentrated in vacuo, yielding a yellow solid which was dissolved in EtOAc and washed with aq. NaHCO3. Organic layer was dried over Na2 SO4 and concentrated in vacuo, yielding an oil which was subjected to column chromatography (10-50percent EtOAc/n-Hexane) to obtain 7.8 g (34 mmol, 80percent) of the desired product.
Reference：
[1] Patent: WO2010/91310, 2010, A1, . Location in patent: Page/Page column 103
[2] Patent: WO2016/161145, 2016, A1, . Location in patent: Paragraph 00693
[3] Patent: WO2011/100502, 2011, A1, . Location in patent: Page/Page column 55
[4] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 18, p. 5919 - 5923
[5] Journal of the Chemical Society, 1949, p. 355,361
[6] Patent: US5677321, 1997, A,
[7] Journal of Molecular Structure, 2010, vol. 975, # 1-3, p. 115 - 127
2
[ 2942-06-5 ]
[ 769-20-0 ]
Reference：
[1] Journal of the Chemical Society, 1949, p. 355,361
3
[ 769-20-0 ]
[ 767-70-4 ]
Yield
Reaction Conditions
Operation in experiment
75%
Stage #1: at 20℃; for 0.333333 h; Stage #2: at 50℃;
Example 30; 7-Bromo-benzothiazoleSodium nitrite (0.229 g, 3.3 mmol) was added to a solution of 7-bromo-benzothiazol-6-ylamine (0.380 g, 1.66 mmol, described in WO 97/31636) in sulfuric acid (10 mL) and the resulting mixture was stirred at room temperature for 20 min. Hypophosphorous acid (10 mL) was added and the mixture was heated at 50° C. overnight. The pH was adjusted to 9-10 by addition of sodium carbonate, and the crude product was removed by filtration and washed with water. Purification by prep-HPLC gave 0.265 g (75percent yield) of the title compound as a white solid: LC-MS (EI) m/z 213 (M++1).
42%
Stage #1: at 20℃; for 1 h; Stage #2: at 0℃; for 1 h;
To 7-bromobenzo[djthiazol-6-amine (2-18, 1 g, 4.4 mmol) in H2S04 (5 ml) was added NaNO2 (605 mg, 8.8 mmol) at 0 °C and the resulting reaction mixture was stirred for 20 mm. H3P02 (5 ml) was then added at 0 °C, and the mixture was stirred for 1 h. Upon reaction completion, the mixture was washed with saturated NaHCO3, extracted with ethyl acetate (50 mL x 3), and the combined organic phases were concentrated under reduced pressure to provide intermediate 2-19 (yellow solid, 400 mg, 42percent yield). LCMS (m/z): 214 [M + HI .
30%
Stage #1: at 0 - 5℃; for 0.25 h; Stage #2: at 20℃;
To a solution of bromobenzo[d]thiazol-6-amine (30 mg, 0.13mmol) was added 50percent H2SO4 (38 mg, 0.39mmol), and then NaNO2 (18 mg, 0.26mmol) was added to the mixture at 0-5 0C. The reaction mixture was stirred about 15 min at 0-5 0C, 50percent H3PO2 (17 mg, 0.26mmol) was added. The mixture was stirred at room temperature overnight, quenched with aq.NaHCO3 solution, extracted with ethyl acetate. The combined organic layer was concentrated under vacuum to give a residue which was purified with chromatography (ethyl acetate/petroleum ether=0.06) to give 7-bromobenzo[d]thiazole (10 mg, 30percent).
To a solution of benzo[d]thiazol-6-amine (100 mg, 0.67mmol) in 6 ml CHCl3 was added Br2 (42 mg, 0.27mmol) in CHCI3 (10ml) dropwise about 15 min. The mixture was concentrated under reduced pressure, and the residue was crystallized from DCM:MeOH (5: 1) to give 7-bromobenzo[d]thiazol-6-amine (80mg, 80%).
75%
With bromine; In chloroform; at 0℃; for 1h;
A mixture of benzo[djthiazol-6-amine (2-17, 1 g, 6.6 mmol) and Br2 (1.06 g, 6.6 mmol) in CHC13 (5 mL) was stirred at 0 C for 1 h. Upon reaction completion, the resulting mixture was concentrated under reduced pressure to provide intermediate 2-18 (yellow solid, 1.2 g, 75% yield). LCMS (m/z): 229 [M + HI .
67%
With bromine; acetic acid; at 20℃; for 1h;
Step A: 7-bromo-benzothiazol-6-ylamineTo a solution of benzothiazol-6-ylamine (6.4 g, 42.6 mmol) in glacial acetic acid (40 mL) was added bromine (2.18 mL) in glacial acetic acid (10 mL) dropwise. The reaction mixture was stirred at RT for 1 h. Water (160 mL) was added to the reaction mixture and the solid formed was extracted with ethyl acetate (3 x 40 mL). The combined organic fractions were washed with saturated aqueous sodium bicarbonate solution (200 mL), water (100 mL), and brine (20 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by column chromatography (20% ethyl acetate: hexanes) afforded 6.5 g (67%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCI3): delta 4.31 (br. s, 2H), 7.02 (d, J=8.4 Hz, 1 H), 7.92 (d, J=8.4 Hz, 1 H), 8.80 (s, 1 H).
7.8 g (34 mmol, 80%)
With bromine; In acetic acid; ethyl acetate;
7-Bromo-6-aminobenzothiazole To a solution of 6-aminobenzothiazole (16 g, 107 mmol) in 100 mL of AcOH was added Br2 (2.0 mL, 43 mmol) dropwise and the resulting reaction mixture was stirred for 1 h at 25 C. Reaction mixture was concentrated in vacuo, yielding a yellow solid which was dissolved in EtOAc and washed with aq. NaHCO3. Organic layer was dried over Na2 SO4 and concentrated in vacuo, yielding an oil which was subjected to column chromatography (10-50% EtOAc/n-Hexane) to obtain 7.8 g (34 mmol, 80%) of the desired product.
Example 30; 7-Bromo-benzothiazoleSodium nitrite (0.229 g, 3.3 mmol) was added to a solution of <strong>[769-20-0]7-bromo-benzothiazol-6-ylamine</strong> (0.380 g, 1.66 mmol, described in WO 97/31636) in sulfuric acid (10 mL) and the resulting mixture was stirred at room temperature for 20 min. Hypophosphorous acid (10 mL) was added and the mixture was heated at 50 C. overnight. The pH was adjusted to 9-10 by addition of sodium carbonate, and the crude product was removed by filtration and washed with water. Purification by prep-HPLC gave 0.265 g (75% yield) of the title compound as a white solid: LC-MS (EI) m/z 213 (M++1).
42%
To 7-bromobenzo[djthiazol-6-amine (2-18, 1 g, 4.4 mmol) in H2S04 (5 ml) was added NaNO2 (605 mg, 8.8 mmol) at 0 C and the resulting reaction mixture was stirred for 20 mm. H3P02 (5 ml) was then added at 0 C, and the mixture was stirred for 1 h. Upon reaction completion, the mixture was washed with saturated NaHCO3, extracted with ethyl acetate (50 mL x 3), and the combined organic phases were concentrated under reduced pressure to provide intermediate 2-19 (yellow solid, 400 mg, 42% yield). LCMS (m/z): 214 [M + HI .
30%
To a solution of bromobenzo[d]thiazol-6-amine (30 mg, 0.13mmol) was added 50% H2SO4 (38 mg, 0.39mmol), and then NaNO2 (18 mg, 0.26mmol) was added to the mixture at 0-5 0C. The reaction mixture was stirred about 15 min at 0-5 0C, 50% H3PO2 (17 mg, 0.26mmol) was added. The mixture was stirred at room temperature overnight, quenched with aq.NaHCO3 solution, extracted with ethyl acetate. The combined organic layer was concentrated under vacuum to give a residue which was purified with chromatography (ethyl acetate/petroleum ether=0.06) to give 7-bromobenzo[d]thiazole (10 mg, 30%).
Step B: 7-bromo-6-iodo-benzothiazole (Title Compound)To a suspension of <strong>[769-20-0]7-bromo-benzothiazol-6-ylamine</strong> (7.6 g, 33.3 mmol) in water (60 mL) was added concentrated hydrochloric acid (6 mL, 72 mmol). The mixture was cooled to 0 C and stirred for 10 min. A cooled (0 C) solution of sodium nitrite (5.0 g, 73 mmol) in water (10 mL) was added dropwise to the reaction mixture keeping the internal temperature below 5 C. The mixture was stirred for further 10 min. A solution of potassium iodide (12.1 g, 73 mmol) in water (15 mL) was added to the reaction mixture and was stirred vigorously for 10 min, and then water (200 mL) and 20% aqueous sodium thiosulfate solution (100 mL) were added. The solid formed was extracted with ethyl acetate (3 x 70 mL). The combined organic fractions were washed with water (100 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by column chromatography (25% ethyl acetate:hexanes) afforded 0.3 g (5%) of the title compound, plus some impure title compound. The impure title compound was recrystallized 2x from 1 :4 DCM:hexanes to afford a further 0.71 g (9%) of the title compound. 1 H NMR (300 MHz, CDCI3): delta 8.99 (s, 1 H), 7.95 (d, J=8.4, 1 H), 7.77 (d, J=8.4 Hz, 1 H).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
