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Product Details of [ 1112982-76-9 ]

CAS No. :1112982-76-9
Formula : C8H6BrN3OS
M.W : 272.12
SMILES Code : BrC2=CC=C1N=C(SC1=N2)NC(C)=O
MDL No. :MFCD18205971
InChI Key :JHGFPKWDFAFFFO-UHFFFAOYSA-N
Pubchem ID :56763853

Safety of [ 1112982-76-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 1112982-76-9 ]

* 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 [ 1112982-76-9 ]

[ 1112982-76-9 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 1112982-76-9 ]
  • [ 30418-59-8 ]
  • [ 1112980-79-6 ]
YieldReaction ConditionsOperation in experiment
78% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90 - 99℃; for 4h; Step 2. N-(5-(3-aminophenyl)thiazolo[5.4-b1pyridin-2-yl)acetamide (Example 156); <strong>[1112982-76-9]N-(5-bromothiazolo[5,4-b]pyridin-2-yl)acetamide</strong> (1.504 g, 5.527 mmol), 3-aminophenylboronic acid monohydrate (1.316 g, 8.493 mmol), Pd(dppf)Cl2-DCM complex (604.4 mg, 0.7401 mmol), and potassium carbonate (2.292 g, 16.58 mmol) were suspended in 1,4-dioxane (45 ml) and water (15 ml) was added. Argon was bubbled through the solution for about 30 seconds, and then the flask was fit with a reflux condensor and placed in a preheated oil bath (90 - 99 C) and stirred under argon for 4 hours. The reaction was cooled to room temperature, filtered, and the solid was washed with DCM and MeOH. The filtrate was concentrated, treated with DCM and MeOH, and filtered. The solid was collected and set aside, and the filtrate was concentrated, treated with Et2O, and filtered. Solid washed with Et2O. This solid was combined with the first batch and dried under high vacuum first at room temperature, anphithen at ~ 50 C. This solid was treated with deionized water and filtered, and the solid was washed with water, collected, and dried under high vacuum in water bath (~ 50 C) to afford N-(5-(3- aminophenyl)thiazolo[5,4-b]pyridin-2-yl)acetamide (1.22 g, 78% yield). MS (ESI pos. ion) m/z: 285. Calculated exact mass for C14H]2N4OS 284.
  • 2
  • [ 39856-57-0 ]
  • [ 13250-46-9 ]
  • [ 1112982-76-9 ]
YieldReaction ConditionsOperation in experiment
100% In acetone; at 65 - 70℃; for 2.5h; Example 146 (Method N); N-(5-(3-(4-methoxyphenylsulfonamido)phenyl)thiazolo[5,4-b]pyridin-2-yl)acetamide; Step 1. N-(5-bromothiazolor5,4-blpyridin-2-yl)acetamide; 2,6-dibromopyridin-3-amine (4.235 g, 16.8 mmol) was dissolved in acetone and acetyl isothiocyanate(1.85 ml, 21.0 mmol) was added. The flask was fit with a reflux condensor and placed in a preheated oil bath (65 - 70 C) and stirred under nitrogen for 2.5 hours. Then, the reaction was cooled to room temperature, poured into water, and filtered. The solid was washed with water, saturated sodium bicarbonate, and water again, and then collected and dried under high vacuum to afford N-(5- bromothiazolo[5,4-b]pyridin-2-yl)acetamide (5.54 g, Yield > 100%).MS (ESI pos. ion) m/z: 272 (MH+, 79Br), 274 (MH+, 81Br). Calculated exact mass for C8H6BrN3OS 271 (79Br), 273 (81Br).
  • 3
  • [ 13250-46-9 ]
  • [ 169833-70-9 ]
  • [ 1112982-76-9 ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol; at 80℃; for 16h; As shown in step 4-i of Scheme 4, acetylisothiocyanate (6.824 g, 67.48 mmol) was added to a solution of 6-bromo-2-chloropyridin-3 -amine (14.0 g, 67.48 mmol) in isopropanol (300 mL). The reaction was heated for 16 hours at 80 0C. LCMS analysis indicated that the resulting mixture contained 85% desired product and 15% intermediate thiourea. The reaction mixture was cooled to RT, filtered, and the filtration cake washed with saturated sodium bicarbonate solution and brine. The solid was air dried to yield N-(5- <n="36"/>bromothiazolo[5,4-6]pyridin-2-yl)acetamide (Compound 1005, 12.0 g): 1H NMR (DMSOd6) delta 8.10(d, IH), 7.68(d, IH), 2.3(s, 3H).
  • 4
  • [ 1112982-76-9 ]
  • [ 934266-82-7 ]
YieldReaction ConditionsOperation in experiment
93% As shown in step 4-ii of Scheme 21, Compound 1005 (5.44 g, 20 mmol) was suspended in 6 N HCl (100 mL). The reaction mixture was heated at reflux for 1 h, at which time all of the material went into solution. The mixture was cooled to RT and the reaction was made basic to a pH of 10, at which time the product precipitated out. The solid was collected on a fritted funnel and dried to afford 5-bromothiazolo[5,4-delta]pyridin-2-amine (Compound 1006, 4.35 g, 93% yield): ESMS (M+H) 230, 232; 1H NMR (DMSO-d6) delta 7.9 (br, 2H), 7.6 (d, IH), 7.4 (d, IH).
  • 5
  • [ 934266-82-7 ]
  • [ 108-24-7 ]
  • [ 1112982-76-9 ]
YieldReaction ConditionsOperation in experiment
100% With pyridine; at 20℃; Example 1; Preparation of 7V-(5-Bromothiazolo[5,4-Z>]pyridin-2-yl)acetamide (1); 1A 1B Example 1[0376] To a 500 ml 3-neck under N2 was added KSCN (42.1 g, 433 mmol), followed by 225 mL of HOAc. It was cooled to -5 0C and 6-bromo-3-aminopyridine (15 g, 86.7 mmol) was added in portions. The mixture was further cooled to -15 0C, and a solution of Br2 (5.7 mL) in 12 mL of HOAc was added dropwise while keeping the bath temperature below 10 0C. It was then allowed to slowly warm up to room temperature and stirred overnight. The small amount of precipitate was filtered off. The mother liquor was cooled to 0 0C, and water was added (200 mL). It was stirred for 5 min, and the precipitate formed was collected and washed with cold MeOH/Et2O (1 :3, 50 mL, 2 times). The solid was dried under vacuum overnight to give 5-bromothiazolo[5,4-b]pyridin-2- amine the titled compound as a yellow solid (10.2 g, 51%). The solvent was stripped from the filtrate to half the volume, and the precipitation was collected, washed with cold MeOH-Et2O, and dried to give another 2 g of product with a combined yield of 12.2 g (61% yield). To the above obtained compound (11.3 g, 40 mmol) in pyridine (88 mL) was slowly added Ac2O (44 mL) at 0 0C. The mixture was then stirred at room temperature for 16 h. Solvent was removed, and the residue was subjected to vacuum for 20 h to give N- (5-bromothiazolo[5,4-b]pyridin-2-yl)acetamide as a light brown solid (13.3 g, 100%). [M+H] calc'd for C8H6BrN3OS, 272; found, 272.
80% With dmap; In dichloromethane; at 20℃;Cooling with ice; Inert atmosphere; In a similar manner as for 5b, started with 4b (0.25 g, 1.09 mmol) to produce 5d (0.23 g, 80%). Mp: 240.0-242.0 C; 1H NMR (DMSO-d6): delta 12.62 (s, 1H, NH), 8.16 (d, J = 8.8 Hz, 1H, Ar-H), 7.57 (d, J = 8.8 Hz, 1H, Ar-H), 2.24 (s, 3H, CH3). ESI-HRMS m/z: calcd for C8H6BrN3NaOS [M+Na]+: 293.9313; found 293.9315.
  • 6
  • [ 1112982-76-9 ]
  • [ 269410-24-4 ]
  • [ 1204741-84-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 130℃; for 0.5h;Microwave irradiation; Example 2; Preparation of iV-(5-(lH-Indol-5-yl)thiazolo [5,4-6] pyridin-2- yl)acetamide (2); PddppfCI2-CEta2CI2 NaHCO3 (sat ), 1 ,4-diotaoxane, microwave, 110-130 0CExample 1 [0377] A mixture of Example 1 (64 mg, 0.23 mmol), 5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-indole (85 mg, 0.35 mmol), PddppfCl2-DCM (cat.), Sat. NaHCO3 (1 mL) and 1,4-dioxane (2 mL) was heated in a microwave at 130 0C for 30 min. The reaction mixture was purified by HPLC to give the titled compound N-(5-(lH-indol-5- yl)thiazolo[5,4-b]pyridin-2-yl)acetamide as a white solid (3.8 mg). 1H NMR (400 MHz, MeOD) delta ppm 8.13 (s, IH), 7.98 (d, J=6 Hz, IH), 7.85 (d, J=6 Hz, IH), 7.72 (d, J=6 Hz, IH), 7.39 (d, J=6 Hz, IH), 7.19 (d, J=4 Hz, IH), 6.46 (d, J=4 Hz, IH), 2.18 (s, 3H); [M+H] calc'd for Ci6H12N4OS, 309; found, 309.
  • 7
  • [ 945863-21-8 ]
  • [ 1112982-76-9 ]
  • [ 1204741-88-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; caesium carbonate;dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In 1,4-dioxane; water; N,N-dimethyl-formamide; at 110 - 120℃; for 2h;Inert atmosphere; Microwave irradiation; Example 6; Preparation of 5-(2-Acetamidothiazolo[5,4-Z>]pyridin-5-yl)-N- methylpicolinamide (6); PcIdPPfCI2-CH2CI2 KOAc, 1 ,4-dioxane microwave, 110 0C Example 1 ditbpfPdCI2, Cs2CO3 NaHCO3(Sat.), DMF, microwave, 110-120 0C[0381] A mixture of 5-bromo-N-methylpicolinamide (320 mg, 1.48 mmol), bispinacolatodiboron (752 mg, 2.96 mmol), PddppfCl2-DCM (cat.), KOAc (436 mg, 4.44 mmol) in 1,4-dioxane (5 mL, degassed) was heated at 110 0C in a microwave for 1 h. To this mixture was then added Example 1 (608 mg, 2.22 mmol), ditbpfPdC12 (cat.), Cs2CO3 (1.45 g, 4.44 mmol), NaHCO3 (sat., 1 mL) and DMF (dry, degassed, 1 mL). It was heated in a microwave at 1100C for 1 h, then at 120 0C for another hour. The reaction mixture was purified by HPLC to give the titled compound as a white solid. 1H NMR (400 MHz, DMSO-rfbeta) delta ppm 12.53 (s, IH), 9.28 (d, J=4 Hz, IH), 8.79 (m, IH), 8.61 (dd, J=8 Hz, IH), 8.18 (m, 2H), 8.08 (d, J=8 Hz, IH), 2.78 (d, J=4 Hz, IH), 2.18 (s, 3H); [M+H] calc'd for Ci5Hi3N5O2S, 328; found, 328.
  • 8
  • [ 1112982-76-9 ]
  • [ 1204742-87-9 ]
  • [ 1204742-26-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.333333h;Microwave irradiation; Example 47; Preparation of 7V-(5-(6-Chloro-5-(ethylsulfonamido)pyridin-3- yl)thiazolo [5,4-6] pyridin-2-yl)acetamide (47); Example 47[0431] A mixture of N-(5-bromo-2-chloropyridin-3-yl)-N-(ethylsulfonyl)ethanesulfonamide (47 A, Ig, 2.55 mmol, prepared following the same procedure for the preparation of 7A), bispinacolatodiboron (0.65 g, 2.76 mmol), PddppfCl2-DCM (0.52 g, 0.637 mmol), and KOAc (0.75 g, 7.65 mmol) in 1,4-dioxane (15 mL) was heated in a microwave at 110 0C for 45 minutes. The crude was used without further purification.[0432] To 2 mL of the above crude reaction mixture was added Example 1 (74 mg, 0.27 mmol), Pd(PPh3)4 (78 mg, 0.067 mmol), K2CO3 (sat., 1 mL). The reaction was heated in a microwave at 120 0C for 20 minutes. The reaction mixture was purified using preparative HPLC to give the titled compound as a yellowish solid (15 mg). 1H NuMR (400 MHz, DMSO-rfbeta) delta ppm 8.98 (s, IH), 8.54 (s, IH), 8.22 (d, J=8.6 Hz, IH), 8.17 (d, J=8.6 Hz, IH), 3.25 (q, J= 7.33 Hz, 2H) 2.25 (s, 3H), 1.31 (t, J= 7.33 Hz, 3H); [M+H] calc'd for Ci5H14ClN5O3S2, 412; found, 412.
  • 9
  • [ 1112982-76-9 ]
  • [ 1204742-71-1 ]
  • [ 1204742-28-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.333333h;Microwave irradiation; Example 49; Preparation of 7V-(5-(6-Chloro-5-(cyclopropanesulfonamido)pyridin-3- yl)thiazolo[5,4-Z>]pyridin-2-yl)acetamide (49); Example 49[0434] 2-Chloro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-3-amine (49A, 100 mg, 0.39 mmol), cyclopropanesulfonyl chloride (221 mg, 1.6 mmol) were mixed in 2 mL pyridine. The mixture was heated at 70 0C overnight. The crude was purified by preparative HPLC (0.05% TFA in mobile phase) to give 6-chloro-5- (cyclopropanesulfonamido)pyridin-3-ylboronic acid (49B, 87 mg), which was mixed with Example 1 (86 mg, 0.32 mmol), Pd(PPh3)4 (91.1 mg, 0.079 mmol), K2CO3 (sat., 1 mL) in 2 mL of 1,4-dioxane. The reaction mixture was heated in a microwave at 120 0C for 20 minutes. The reaction mixture was purified using preparative HPLC to give the titled compound as a yellowish solid (5 mg). 1H NMR (400 MHz, OMSO-Cl6) delta ppm 8.39 (d, J=8.0 Hz, IH), 8.35 (d, J=8.0 Hz, IH), 8.22 (d, J=8.0 Hz, IH), 8.04 (d, J=8.0 Hz, IH), 2.79 (m, IH) 2.25 (s, 3H), 1.02 (m, 2H), 0.94 (m, 2H); [M+H] calc'd for Ci6H14ClN5O3S2,424; found, 424.
  • 10
  • [ 1112982-76-9 ]
  • [ 1204742-84-6 ]
  • [ 1204741-89-8 ]
YieldReaction ConditionsOperation in experiment
Example 7; Preparation of 7V-(5-(6-Chloro-5-(phenylsulf
  • 11
  • [ 1112982-76-9 ]
  • [ 1204742-85-7 ]
  • [ 1204741-90-1 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; caesium carbonate;dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In 1,4-dioxane; water; N,N-dimethyl-formamide; at 110℃; for 1h;Inert atmosphere; Microwave irradiation; Example 8; Preparation of 7V-(5-(6-Chloro-5-(methylsulfonamido)pyridin-3- yl)thiazolo [5,4-6] pyridin-2-yl)acetamide (8); PddppfCI2-CH2CI KOAc, 1 ,4-diotaoxane microwave, 110 0C8A 8Be[0383] To a solution of 5-bromo-2-chloropyridin-3-amine (4 g, 19.28 mmol) in pyridine (50 mL) was added MeSO2Cl (4.5 mL, 57.84 mmol). The mixture was heated at 50 0C for 4 h. The solvent was removed, and the resulting solid was washed with Hexanes-EtOAc (1 : 1, 150 mL) and water, and dried over P2Os for 3 days to give N-(5-bromo-2- chloropyridin-3-yl)-N-(methylsulfonyl)methanesulfonamide as a light brown solid (2.12 g, 30%). The mixture of the bissulfonamide obtained above (263 mg, 0.723 mmol), bispinacolatodiboron (367 mg, 1.45 mmol), PddppfCl2-DCM (cat.), and KOAc (213 mg, 2.17 mmol) in 1,4-dioxane (5 mL, degassed) was heated in a microwave at 110 0C for 1 h. To this mixture was then added Example 1 (329 mg, 1.2 mmol), ditbpfPdCl2 (cat.), Cs2CO3 (707 mg, 2.17 mmol), NaHCO3 (sat., 1 mL) and DMF (dry, degassed, 1 mL). It was heated in a microwave at 1100C for 1 h. The reaction mixture was purified on HPLC to give the titled compound as a white solid (66 mg). 1H NMR (400 MHz, OMSO-d6) delta ppm 12.50 (br s, IH), 8.60 (s, IH), 8.32 (s, IH), 8.13 (d, J=8 Hz, IH), 8.01 (d, J=8 Hz, IH), 2.97 (s, 3H), 2.17 (s, 3H); [M+H] calc'd for Ci4Hi2ClN5O3S2, 398; found, 398.
  • 12
  • [ 1112982-76-9 ]
  • [ 1404227-84-4 ]
  • [ 1616589-57-1 ]
YieldReaction ConditionsOperation in experiment
26% General procedure: To a round bottomed flask were added compound 10 (0.45mmol), bis(pinacolato)diboron (0.54mmol), potassium acetate (1.35mmol), PdCl2(dppf) (0.03mmol) and 1,2-dimethoxyethane (6ml), then the mixture was heated to reflux for 4h under nitrogen atmosphere, cooled to room temperature. Then compound 5a-5e, or 6, or 8a-8b, or 12a-12b, or 14a-14b (0.45mmol), potassium carbonate (1.35mmol), PdCl2(dppf) (0.03mmol) and water (1ml) were added. The resulting mixture was refluxed for another 1-3h under nitrogen atmosphere. The solvent was evaporated off under vacuum and the residue was purified through column chromatography (CHCl3: MeOH=30:1, v/v) to produce 1a-1j, 2a-2f and 3a-3c as white solid. 4.1.11.8 5-(2-Acetamidothiazolo[5,4-b]pyridin-5-yl)-3-(4-fluorophenylsulfonylamino)-2-methoxybenzamide (1h) Yield: 26%; Mp: >270 C; 1H NMR (DMSO-d6): delta 12.56 (s, 1H, NH), 10.05 (s, 1H, NH), 8.16 (d, J = 8.4 Hz, 1H, Ar-H), 8.09 (s, 1H, Ar-H), 7.96 (s, 1H, Ar-H), 7.94 (d, J = 8.4 Hz, 1H, Ar-H), 7.88-7.92 (m, 2H, Ar-H), 7.84 (s, 1H, CONH2), 7.63 (s, 1H, CONH2), 7.42-7.46 (m, 2H, Ar-H), 3.52 (s, 3H, OCH3), 2.25 (s, 3H, CH3). ESI-HRMS m/z: calcd for C22H18FN5NaO5S2 [M+Na]+: 538.0631; found 538.0638.
  • 13
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  • [ 1067877-78-4 ]
  • 14
  • [ 1112982-76-9 ]
  • [ 1190784-15-6 ]
  • 15
  • [ 1112982-76-9 ]
  • [ 1190784-13-4 ]
  • 16
  • [ 1112982-76-9 ]
  • [ 1190783-75-5 ]
 

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