3-Bromopyridine → 4-Benzothiazol-2-YL-5-pyridin-3-YL-1H-pyrazol-3-ylamine

HRID 407329

Reaction equation

HRID 407329 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([Li])[CH:2]=1.[Li]CCCC.Br[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.S1C2C=CC=CC=2[N:22]=[C:21]1[C:29](=[C:32]([S:35][CH3:36])SC)[C:30]#[N:31].[NH4+:37].[Cl-]>C1COCC1.C1CCCCC1.CCOCC>[S:35]1[C:36]2[CH:2]=[CH:3][CH:4]=[CH:5][C:6]=2[N:1]=[C:32]1[C:29]1[C:30]([NH2:31])=[N:37][NH:22][C:21]=1[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

9

Reactant 5

HCID 122863-BromopyridineHCID 25517Ammonium ChlorideHCID 28077272-Benzothiazol-2-yl-3,3-bis-methylsulfanylacrylonitrileHCID 178418339ButyllithiumHCID 178418470HCID 178418470, compound

Product 1

HCID 667682744-Benzothiazol-2-YL-5-pyridin-3-YL-1H-pyrazol-3-ylamineYield 65%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A yellow suspension of 3-pyridinyl lithium in THF was prepared according to the literature (Cama, L. D.; Wildonger, K. J.; Guthikonda, R.; Ratcliffe, R. W.; Christensen, B. G. Tetrahedron (1983), 39, 2531) by adding n-BuLi (0.25 mL of a 2 M solution in cyclohexane, 0.5 mmol) to a solution of 3-bromopyridine (87 mg, 0.5 mmol) in anhydrous ether (3 mL) at −78° C. To this slurry was rapidly added 2-benzothiazol-2-yl-3,3-bismethylsulfanylacrylonitrile (140 mg, 0.5 mmol) in anhydrous THF (5 mL) under argon. The resulting mixture was stirred at −78° C. for 1 hour, and then slowly warmed up to room temperature and stirred at that temperature for 2 hours. Upon completion of the reaction, the mixture was poured into a saturated NH4Cl aqueous solution. The aqueous phase was extracted with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and evaporated. The crude material was then purified by flash chromatography eluting with CH2Cl2:MeOH=1:0-19:1 to yield 100 mg (65%) of the desired product as a brown oil. MS (m/z, ES+): 310 (M+1, 25%), 263 (M−46, 100%).

Workup

  1. customwas prepared
  2. temperatureslowly warmed up to room temperature
  3. stirringstirred at that temperature for 2 hours
  4. customUpon completion of the reaction
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude material was then purified by flash chromatography
  11. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-2b04432a85644bff9db0ac1ffd348bdf
Source dataset
uspto-grants-2014_06
Patent number
US08754233B2

Linked notes

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