Ethyl Acetate → HCID 86608027, compound

HRID 269086Notes

Reaction equation

HRID 269086 reaction equation
C[Zn]C.Cl[C:5]1[CH:10]=[C:9]([C:11]#[C:12][C:13]2[CH:14]=[N:15][N:16]3[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][C:19]([C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=4)=[N:18][C:17]=23)[CH:8]=[CH:7][N:6]=1.[CH3:36]COC(C)=O>C1COCC1.C([O-])(O)=O.[Na+].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>[CH3:36][C:5]1[CH:10]=[C:9]([C:11]#[C:12][C:13]2[CH:14]=[N:15][N:16]3[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][C:19]([C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=4)=[N:18][C:17]=23)[CH:8]=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 86608028HCID 86608028, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 86608027HCID 86608027, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (710 mg, 2.0 mmol) and 2-chloro-4-iodopyridine [CAS 153034-86-7; commercially available] (479 mg, 2.0 mmol) according to general procedure II to produce the intermediate 3-(2-chloro-pyridin-4-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (569 mg, 61%) as a yellow solid. MS (ISP) 467 [(M+H)+] and 469 [(M+2+H)+]; mp 200° C. This material was transformed to the title compound as follows: In a dried flask under argon, dimethylzinc-solution (2M in toluene, 0.16 mL, 0.33 mmol) was added to a solution of the above prepared 3-(2-chloro-pyridin-4-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (233 mg, 0.50 mmol) and Pd(PPh3)4 (17 mg, 3 mol %) in THF (1.7 mL) at 23° C. The reaction mixture was warmed up slowly and refluxed for 2 h. The reaction mixture was poured in sat. NaHCO3-sol., shaken with EtOAc and filtered through Celite. The organic layer was extracted twice with 1N HCl, the combined aqueous layer were made alkaline with 32% NaOH-sol., extracted with EtOAc, the organic washed with sat. NaCl-sol., dried over Na2SO4 and evaporated. The obtained crude product was purified by MPLC with heptane/EtOAc, followed by trituration with ether to give the title 3-(2-methyl-pyridin-4-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (59 mg, 26%) as a yellow solid. MS (ISP) 447 [(M+H)+]; mp 206° C.

Workup

  1. temperatureThe reaction mixture was warmed up slowly
  2. temperaturerefluxed for 2 h
  3. filtrationfiltered through Celite
  4. extractionThe organic layer was extracted twice with 1N HCl
  5. extraction, extracted with EtOAc
  6. washthe organic washed with sat. NaCl-sol
  7. dry with material, dried over Na2SO4
  8. customevaporated
  9. customThe obtained crude product
  10. customwas purified by MPLC with heptane/EtOAc

Sources & evidence

ORD record
ord-875c776a6feb4bdf914dc57b233ad69e
Source dataset
uspto-grants-2008_11
Patent number
US07446113B2

Reaction notes

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