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Chemical Structure| 61296-22-8 Chemical Structure| 61296-22-8
Chemical Structure| 61296-22-8

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Synonyms: 2-Amino-5-bromothiazole hydrobromide

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Product Details of 2-Amino-5-bromothiazole HBr

CAS No. :61296-22-8
Formula : C3H4Br2N2S
M.W : 259.95
SMILES Code : BrC1=CN=C(N)S1.[H]Br
Synonyms :
2-Amino-5-bromothiazole hydrobromide
MDL No. :MFCD00012712
InChI Key :NUSVDASTCPBUIP-UHFFFAOYSA-N
Pubchem ID :2723848

Safety of 2-Amino-5-bromothiazole HBr

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

Application In Synthesis of 2-Amino-5-bromothiazole HBr

* 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 [ 61296-22-8 ]

[ 61296-22-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 24424-99-5 ]
  • [ 61296-22-8 ]
  • [ 405939-39-1 ]
YieldReaction ConditionsOperation in experiment
91% With dmap; triethylamine; In tetrahydrofuran; at 0℃; Di-tert-butyl dicarbonate [(Boc)20, 100.7 g, 0.461 mol, 1.2 eq] was added to a flask containing a mixture of 2-amino-5-bromothiazole monohydrobromide (la?, 100 g, 0.385 mol, 1.0 eq) and 4-(dimethylamino)pyridine (DMAP, 1.18 g, 9.7 mmol, 0.025 eq) in900 mL of THF and 135 mL of Et3N and cooled to 0 C using an ice bath. The reaction mixture was stirred at r.t. overnight and then concentrated in vacuo. The residue was stirred in EtOAc/Heptane (1:10, 250 ml) at rt overnight and then filtered. The filtrate was washed with brine, dried, filtered, and concentrated in vacuo to furnish intermediate lb? as a yellow solid (91% yield).
78% 4.2 Synthesis of tert-butyl (5-bromo-1,3-thiazol-2-yl)carbamate (506) 5-bromo-1,3-thiazol-2-amine hydrobromide (505, 6.5150 g, 25.062 mmol) and 4-dimethylaminopyridine (69.9 mg, 0.572 mmol) were combined under an atmosphere of dry N2, and tetrahydrofuran (40 mL) and triethylamine (15 mL) were added to form a thick off-white suspension. A solution of di-tert-butyldicarbonate (6.0546 g, 27.742 mmol) in tetrahydrofuran (24 mL) was added to the above suspension, and the resulting slurry was stirred at room temperature for 4 h. The reaction mixture was then poured onto water (100 mL), and the aqueous was extracted with ethyl acetate. The combined organics were washed with saturated NaHCO3 solution, brine, dried over MgSO4, filtered, and the solvent was removed in vacuo. The crude product was adsorbed onto silica gel, and eluted through a plug of silica gel with 9:1 hexanes:ethyl acetate. The eluent was collected, and evaporated to give 506 (5.42 g, 78%) as a colorless crystalline solid. Data for 506: 1H NMR (400 MHz, DMSO-d6) d 12.75 (br s, 1 H), 7.44 (s, 1 H), and 1.48 (s, 9 H) ppm. 13C NMR (100 MHz, DMSO-d6) d 160.1, 152.9 (br), 139.0, 100.5, 81.7, and 27.8 ppm. MS (ESI+) m/z (rel. intensity): 225.1 (100, M81Br-(CH3)2C=CH2+), 223.1 (100, M79Br-(CH3)2C=CH2+).
78% With dmap; triethylamine; In tetrahydrofuran; at 20℃; for 4h;Inert atmosphere; 5-Bromo-1,3-thiazol-2-amine hydrobromide (505, 6.52 g, 25.1 mmol) and 4-dimethylaminopyridine (69.9 mg, 0.572 mmol) were combined under an atmosphere of dry N2, and tetrahydrofuran (40 mL) and triethylamine (15 mL) were added to form a thick off-white suspension. A solution of di-tert-butyldicarbonate (6.06 g, 27.7 mmol) in tetrahydrofuran (24 mL) was added to the above suspension, and the resulting slurry was stirred at room temperature for 4 h. The reaction mixture was then poured onto water (100 mL), and the aqueous was extracted with ethyl acetate. The combined organics were washed with saturated NaHCO3 solution, brine, dried over MgSO4, filtered, and the solvent was removed in vacuo. The crude product was adsorbed onto silica gel, and eluted through a plug of silica gel with 9:1 hexanes:ethyl acetate. The eluent was collected, and evaporated to give 506 (5.42 g, 78%) as a colorless crystalline solid.Data for 506: 1H NMR (400 MHz, DMSO-d6) d 12.75 (br s, 1H), 7.44 (s, 1H), and 1.48 (s, 9H) ppm. 13C NMR (100 MHz, DMSO-d6) d 160.1, 152.9 (br), 139.0, 100.5, 81.7, and 27.8 ppm. MS (ESI+) m/z (rel. intensity): 225.1 (100, M81Br-(CH3)2CCH2+), 223.1 (100, M79Br-(CH3)2CCH2+).
74.9% With pyridine; at 20℃; for 2h; A mixture of 5-bromothiazol-2-amine hydrobromide (LXI) (1.99 g, 7.66 mmol) and Boc2O (2.21 g, 10.1 mmol) in pyridine (6 mL) was stirred at room temperature for 2 h. The solvent was removed, and the residue was purified by silica gel column chromatography (40 g) (0?50% EtOAc/hexanes) to produce tert-butyl (5-bromothiazol-2-yl)carbamate (LXII) as a white solid (1.6 g, 5.73 mmol, 74.9% yield). ESIMS found for C8H11BrN2O2S m/z 222.9 (81BrM+H-tBu).
67% With pyridine; at 20℃; for 16h; Synthesis 39 (5-Bromo-thiazol-2-yl)-carbamic acid tert-butyl ester To a stirred slurry of 2-amino-5-bromothiazole monohydrobromide (18.5 mmol, 4.81 g) in pyridine (50 ml) at room temperature was added, portionwise, di-tert-butyl dicarbonate (20.3 mmol, 4.43 g). The mixture was left to stir at room temperature for 16 hours. The solvent was removed by evaporation under reduced pressure. Water (150 ml_) was added to the slurry and the crude product was extracted with ethyl acetate (2x100 ml_). The organic phase was collected, washed with 1 M hydrochloric acid, then washed with saturated sodium bicarbonate solution. The organic phase was dried over MgSCU, filtered and evaporated under reduced pressure to yield the title compound as a brown/pink powder. Yield: 3.5 g, 67%. LCMS, analytical method 1 , TR=4.82 mins, 100%, MI=222/224 (-tert- Bu). H NMR (300 MHz, CDCI3) delta: 7.23 (1 H, s), 1.58 (9H, s).
63% With pyridine; at 20℃; [00156] Di-tert-butyl dicarbonate (28.90 g, 132.4 mmol) was added portionwise to a suspension of 2-amino-5-bromothiazole monohydrobromide (28.64 g, 110.3 mmol) in pyridine (100 mL) over 20 minutes at room temperature. The mixture was stirred at room temperature overnight. The solvent was evaporated. The residue was extracted between 0.5 N HCl (200 mL) and ethyl acetate (200 mL). The organic layer was separated and concentrated. The residue was filtered through a pad of silica gel using 10% ethyl acetate/hexane as a solvent. The filtrate was concentrated to give tert-butyl-5-bromothiazol-2-ylcarbamate (19.5 g, 63% yield) as a white solid. LCMS (Conditions A): 3.40 min (RT); (M+H)+ = 225.12 (100%), 223.12 (95%). 1H NMR, 400 MHz, CDCl3: delta 7.27 (s, 1 H), 1.60 (s, 9 H).
63% With pyridine; at 20℃; Di-tert-butyl dicarbonate (28.90 g, 132.4 mmol) was added portionwise to a suspension of 2-amino-5-bromothiazole monohydrobromide (28.64 g, 110.3 mmol) in pyridine (100 mL) over 20 minutes at room temperature. The mixture was stirred at room temperature overnight. The solvent was evaporated. The residue was extracted between 0.5 N HCl (200 mL) and ethyl acetate (200 mL). The organic layer was separated and concentrated. The residue was filtered through a pad of silica gel using 10% ethyl acetate/hexane as a solvent. The filtrate was concentrated to give tert-butyl-5-bromothiazol-2-ylcarbamate (19.5 g, 63% yield) as a white solid. LCMS (Conditions A): 3.40 min (RT); (M+H)+ = 225.12 (100%), 223.12 (95%). 1H NMR, 400 MHz, CDCl3: delta 7.27 (s, 1 H), 1.60 (s, 9 H).
62% With pyridine; at 20℃; for 16.25h; Step 1: Preparation 18a; To a slurry of 2-amino-5-bromo-thiazole monohydrobromide (25 g, 96 mmol) in 75 mL of pyridine at rt was added (Boc)2O (23.1 g, 106 mmol) in three portions over 15 min and the resulting mixture was allowed to stir at rt for ?16 h. The mixture was concentrated in vacuo and partitioned between water (200 mL) and ethyl acetate (200 mL). The aqueous layer containing a significant amount of undissolved solids was further extracted with warm ethyl acetate (3×150 mL). The combined organic extracts were then washed with 1 N aq. HCl (3×150 mL), sat'd aq. sodium bicarbonate (2×100 mL), and brine (100 mL), then dried over anhyd sodium sulfate, filtered, and concentrated to afford 16.7 g (62%) of Preparation 18a as a tan solid. HPLC Ret. time: 3.71 min
49% Example 462(S)-tert-butyl (5-[5-([methyl(oxo)phenyl-lambda6-sulfanylidene]amino}carbonyl)pyridin-3- yljethynyl} - 1 ,3-thiazol-2-yl)carbamate Step 1 tert-buiyl (5-bromo-l,3-thiazol-2-yl)carbamate <n="75"/>The title compound was prepared by a modification of the procedure described in J. Med. Chem. 2005, 48, 1886-1900. A mixture of 2-amino-6-bromothiazole monohydrobromide (390 mg, 1.5 mmol) and NaHCO3 (441 mg, 5.3 mmol) in 6.0 mL tert-butyl alcohol was heated for 1 minute at near reflux, then cooled to room temperature. To this mixture was added DMAP (18 mg, 0.15 mmol) and di-tert-butyl dicarbonate (1.0 M in THF, 1.65 mL) and the reaction stirred at room temperature for 16 hours. In order to drive reaction to completion, additional di-tert-butyl dicarbonate (1.0 M in THF, 0.5 mL) was added, the reaction heated at 50 0C for 2 hours, then di- tert-butyl dicarbonate (1.0 M in THF, 1.0 mL) and 100 mg NaHCO3 added and continued heating at 50 0C an additional 2 hours. The mixture was filtered and rinsed with EtOAc, then the EtOAc filtrate washed with H2O, dilute aqueous HCl, saturated NaHCO3 solution, brine, dried with anhydrous anhydrous Na2SO4 and rotary evaporated. The brown solid was chromatographed eluting with hexane/EtOAc and the product triturated with hexane to give the title compound as a cream solid (204 mg, 49%).
46% With pyridine; In acetonitrile; at 22℃; for 22h; tert- Butyl 5-bromothiazol-2-ylcarbamate: A suspension of 5- bromothiazol-2-amine hydrobromide (325 g, 1250 mmol) in acetonitrile (3.0 L) was stirred at room temperature (22 0C) and treated with pyridine (506 mL, 6251 mmol) followed by di-tert-butyl dicarbonate (435 mL, 1875 mmol, Aldrich). The reaction mixture was stirred at room temperature for 22 hours. The solvent was reduced in vacuo and the mixture was partitioned between EtOAc and 1 N HCl. The aqueous layer was extracted again with EtOAc and the combined organic phases were washed with 1 N HCl, saturated NaHCtheta3, and saturated NaCl. The organic layer was then dried over Na2Stheta4 and filtered. The reaction mixture was concentrated, loaded onto silica, and purified by flash chromatography (0 - 25 %, EtOAc in hexanes). The fractions were concentrated in vacuo to provide tert-butyl 5-bromothiazol-2-ylcarbamate (160 g, 46 %) as a white crystalline solid.
40% With dmap; In tetrahydrofuran; for 48h; 5-bromothiazol-2-amine hydrobromide (105 g, 403 mmol) was suspended in 500 mL of tetrahydrofuran, and dimethylaminopyridine (2.41 g, 20 mmol) was added to form a white turbidity. A solution of di-tert-butyl dicarbonate (105.6 g, 484.6 mmol) in tetrahydrofuran was slowly added dropwise. The mixture was reacted for two days. Then the reaction solution was concentrated, dissolved in dichloromethane (300mL), mixed with silica gel and isolated by column (eluted with petroleum ether / ethyl acetate = 10/1 - 6/1 gradient) to give 45 g of tert-butyl 5-bromothiazol-2-ylcarbamate as an off-white solid, yield 40%, MS(ESI): m/z 278.98 (M + H)+.
With pyridine; at 20℃; for 1h; To a stirred suspension of 2-amino-5-bromothiazole hydrobromide (2.5 g, 9.617 mmol) in pyridine (7.5 ml) was added Di-tert-butyl dicarbonate (2.31 g, 10.584 mmol) and the reaction was stirred for 1 hr at room temperature. Pyridine was removed under reduced pressure and the residue was pardoned between water (100 ml) and ethyl acetate (100 ml). The layers were separated, the organic layer was washed with 1N HCl followed by Sat. sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to get (5-bromo-thiazol-2-yl)-carbamic acid tert-butyl ester (1.8 g). 1H NMR (400 MHz, CDCl3): delta 1.58 (s, 9H), 7.24 (s, 1H), 10.94(bs, 1H). MS (El) m/z: 279.0 (M+1).
5-bromothiazol-2-amine hydrobromide (8.58 g, 33 mmol) was shaken with saturated aqueous solution of NaHCCh (50 mL) and EtOAc (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over MgSCE, filtered, concentrated under reduced pressure and dried under high vacuum. The residue was dissolved in CH2CI2 (40 mL). To the solution were added DMAP (40 mg, 0,33 mmol) and di- tert-butyl dicarbonate (8.0 g, 36.0 mmol). The mixture was stirred at 25 C for 24 hours. The solvent was evaporated and the resulting /^/7-butyl (5-bromothiazol-2-yl)carbamate was directly used in the next step without purification.

 

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