Structure of 303994-99-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 303994-99-2 |
Formula : | C8H11N3S |
M.W : | 181.26 |
SMILES Code : | N#CC1=C(C(C)(C)C)N=C(N)S1 |
MDL No. : | MFCD00214700 |
InChI Key : | SDNYSLVRFRAKGO-UHFFFAOYSA-N |
Pubchem ID : | 2768518 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.3% | (2) 2-Amino-5-cyano-4-[(1,1-dimethyl)ethyl]thiazole. Using α-bromo-pivaloylacetonitrile and thiourea as the raw materials, the same operation as the Example 181(1) gave the title compound. Yield: 66.3%. 1H-NMR(CDCl3): δ 1.41(9H, s), 5.32(2H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 80.0℃; for 0.5h;Microwave irradiation; | Example 6b: Synthesis of 2-(l-(9-Pyridin-3-yl)methyl)phthalazin-4-ylamino)-4-tert- butylthiazole-5-carbonitrile[0182] Synthesis of 2-(l-(9-Pyridin-3-yl)methyl)phthalazin-4-ylamino)-4-tert-butylthiazole- 5-carbonitrile (PHT-2) can be synthesized by the following procedure according to Scheme 2b. A mixture of 80 mg (0.44 mmol) of 2-amino-4-tert-butyl-thiazole-5-carbonitrile, 94 mg (0.36 mmol) of l-chloro-4-(3-pyridin-3-ylmethyl)-phthalazine, 40 mg of CuI (0.026 mmol), 53 ml (0.052 mmol, 12 %/substrate) and 112 mg (0.88 mmol) OfK2CO3 in 4 ml of DMF is heated to 8O0C under microwave irradiation for 30 minutes. After cooling, water is added and the solution is extracted with ethyl acetate (EtOAc). The organic layers are combined, washed with water and brine, then dried over MgSO4. Evaporation of the solvents followed by LC-MS purification affords 29 mg (0.104 mmol) of 2-(l-(9-Pyridin-3-yl)methyl)phthalazin-4-ylammo)-4-tert- EPO <DP n="64"/>butylthiazole-5-carbonitrile (PHT-2) and 18.2 mg ( 0.044 mmol) of 4-tert-Butyl-2-[4-(pyridine- 3-carbonyl)-phthalazin-l-ylamino]-thiazole-5-carbonitrile (PHT-5) as a by-product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; In 1,4-dioxane; at 180.0℃; for 0.5h;Microwave irradiation; | Example 6g: Synthesis of 4-tert-Butyl-2-[4-(5-fluoro-pyridm-3-ylmethyl)-phthalazin-l- ylaminol -thiazole-5 -carbonitrile[0187] Synthesis of4-tert-Butyl-2-[4-(5-fluoro-pyridin-3-ylmethyl)-phthalazin-l-ylamino]- thiazole-5 -carbonitrile (PHT-7) can be synthesized by the following procedure according to Scheme 2b. A mixture of 2-amino-4-tert-butyl-thiazole-5-carbonitrile, l-chloro-4-(5-fluoro- pyridin-3-ylmethyl)-phthalazine, CuI (0.1 mol equiv), K3PO4 (3 mol equiv) and N,N,N',N- tetramethyl-ethane-l,2-diamine (5 mol equiv) in dioxane is heated at 180 0C under microwave irradiation for 30 minutes. After cooling, water is added and the solution is extracted with ethyl acetate (EtOAc). The organic layers are combined, washed with water and brine, then dried over MgSO4. Evaporation of the solvents followed by LC-MS purification affords 4-tert-Butyl-2-[4- (5 -fluoro-pyridin-3 -ylmethyl)-phthalazin- 1 -ylamino] -thiazole-5 -carbonitrile (PHT-7) . MS : (ES+) 419 m/z (M+l)+ C22H20FN6S requires 419. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; In 1,4-dioxane; at 180.0℃; for 0.5h;Microwave irradiation; | Example 6i: Synthesis of 4-tert-Butyl-2-[4-(cvano-phenyl-methyl)-phthalazin-l-ylaminol- thiazole-5-carbonitrile.[0189] 4-tert-Butyl-2-[4-(cyano-phenyl-methyl)-phthalazin- 1 -ylamino]-thiazole-5- carbonitrile (PHT-9) can be synthesized by the following the procedure according to Scheme 8. Phenyl-acetonitrile is mixed with dichlorophthalazine and tBuOK and heated. The resulting compound (l-chloro-4-(cyano-phenyl-methyl)-phthalazine) is coupled to 2-amino-4-tert-butyl- thiazole-5-carbonitrile using CuI (0.1 mol equiv), K3PO4 (3 mol equiv) and N,N,N',N'- tetramethyl-ethane-l,2-diamine (5 mol equiv) in dioxane at 180 C under microwave irradiation for 30 minutes. After cooling, water is added and the solution is extracted with ethyl acetate (EtOAc). The organic layers are combined, washed with water and brine, then dried over MgSO4. Evaporation of the solvents followed by LC-MS purification affords 4-tert-Butyl-2-[4- (cyano-phenyl-methyl)-phthalazin-l-ylamino]-thiazole-5-carbonitrile (PHT-9): MS: (ES+) 426 m/z (M+l)+ C24H2IN6S requires 426. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In toluene; at 110.0℃; for 18.0h;Inert atmosphere; | [00194] Example 39C. 4-tert-Butyl-2-(2-(4-chloro-7-methoxy-l'- neopentylspiro [indoline-3 ,4'-piperidine] - 1 -yl)phenylamino)thiazole-5 -carbonitrile : A mixture of Example 39B (100 mg, 0.209 mmol), 2-amino-4-fert-butylthiazole-5- carbonitrile (76 mg, 0.419 mmol), Pd2(dba)3 (38.3 mg, 0.042 mmol), xanthphos (36.3 mg, 0.063 mmol), and sodium carbonate (31.1 mg, 0.293 mmol) in toluene (0.8 mL) was degassed twice under argon. The reaction mixture then was refluxed at 110 C for 18 h, filtered and rinsed with dichloromethane (2 mL x 2). The filtrate was concentrated and purified by flash chromatography (silica gel, eluting with EtOAc/Hexanes) to give Example 39C as yellow oil (53 mg, 0.092 mmol, 44% yield). LC-MS ESI 578.2 (M+H) (Method A, RT = 3.49 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tert.-butylhydroperoxide; 2,2'-azobis(isobutyronitrile); In methanol; at 20.0℃; | General procedure: General procedure: The substrate 1 (1.0 mmol) and thiourea 2(2.0 mmol) were added to solvent (5 mL methanol) at room tem-perature. To the reaction mixture, TBHP (3.0 mmol) and AIBN(0.2 mmol) were added respectively. The reaction mixture wasstirred at room temperature (for substrates 1a-f) or reux tem-perature (for substrates 1g-r) until TLC indicated the total consumption of 1 (for substrates 1p-q, the reaction time is 24 h).The residue was treated with saturated aqueous NaHCO3 (50 mL)and then extracted with EA (30 mL 3). The organic phase waswashed with brine (50 mL 1), dried over anhydrous Na2SO4. Thesolvent was removed and the residue was puried by ash columnchromatography on silica gel (EA/PE) to afford the desired compound 3. |
95% | With tert.-butylhydroperoxide; 2,2'-azobis(isobutyronitrile); In methanol; at 20.0℃; for 2.0h; | 3-carbonyl-3-tert-butylpropionitrile (I-d) (125 mg)And thiourea (II) (152 mg) were added to methanol (5 mL) at room temperature.Add to reactionPeroxy tert-butyl alcohol (288 μL)And azobisisobutyronitrile (33mg),Stir at room temperature for 2 hours.After the reaction was completed, saturated aqueous sodium bicarbonate (50 mL) was added.Extract with ethyl acetate,The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product.The crude product was isolated and purified by column chromatography (ethyl acetate: petroleum ether (v/v) = 3:7).2-amino-4-tert-butyl-5-carbonitrilethiazole (III-d) (173 mg) was obtained as a white solid. Yield: 95%. |
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