HCID 24898525, compound → HCID 24898519, compound

HRID 1639671Notes

Reaction equation

HRID 1639671 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][N:8]=2)=[CH:4][C:3]=1[Cl:13].C([Li])(C)(C)C.[CH2:19]([C:23]1[N:28]2[N:29]=[C:30]([CH3:33])[C:31](I)=[C:27]2[N:26]=[C:25]([CH3:34])[CH:24]=1)[CH2:20][CH2:21][CH3:22]>[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[CH2:19]([C:23]1[N:28]2[N:29]=[C:30]([CH3:33])[C:31]([C:2]3[S:6][C:5]([C:7]4[N:11]([CH3:12])[N:10]=[CH:9][N:8]=4)=[CH:4][C:3]=3[Cl:13])=[C:27]2[N:26]=[C:25]([CH3:34])[CH:24]=1)[CH2:20][CH2:21][CH3:22]

Participants

7

Reactant 3

HCID 24898525HCID 24898525, compoundHCID 667214755-(5-Bromo-4-chloro-thiophen-2-yl)-1-methyl-[1,2,4]triazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 24898519HCID 24898519, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Add 5-(5-bromo-4-chloro-thiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (169 mg, 0.61 mmol) to anhydrous THF (5 mL). Cool to −78° C. Add tert-butyl lithium (0.81 mL, 1.37 mmol, 1.7 M in pentane). Stir for 45 min and then add zinc chloride (1.5 mL, 1.76 mmol, 0.5 M in THF) slowly. Stir for 5 min, then warm to room temperature and stir for 15 min. Add bis(tri-t-butylphosphine)palladium (0) (62 mg, 0.12 mmol) and 7-butyl-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (200 mg, 0.61 mmol). Heat to reflux overnight. Filter the reaction through Celite® and concentrate to dryness. Purify using silica gel column chromatography, eluting with 0-50% ethyl acetate in hexane, to give the title compound (36 mg, 15%). ES/MS m/z (35Cl) 401 (M+1)+.

Workup

  1. stirringStir for 5 min
  2. temperaturewarm to room temperature
  3. stirringstir for 15 min
  4. temperatureHeat
  5. temperatureto reflux overnight
  6. filtrationFilter
  7. customthe reaction through Celite®
  8. concentrationconcentrate to dryness
  9. customPurify
  10. washeluting with 0-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-59d838ccea57453aa35fd382c3a3b52d
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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