تفاعل #71703

معادلة التفاعل

(2S)-4-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]piperazine

potassium carbonate

HCl

trimethylboroxin

→

title compound

(2S)-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]-4-{[2-methyl-4-(trifluoromethyl)phenyl]sulfonyl}piperazine hydrochloride

المذيبات

1,4-dioxane

DCM

ether

ظروف التفاعل

المعالجة

1. 1
   تركيزThe reaction mixture was concentrated under vacuum
2. 2
   workup.DISSOLUTIONdissolved in MeOH
3. 3
   ترشيحfiltered through a 5 g SCX column
4. 4
   workup.DISSOLUTIONanother small impurity so the product was dissolved in EtOAc (40 ml)
5. 5
   استخلاصextracted with HCl 2N (40 ml)
6. 6
   workup.ADDITION2 N NaOH was added to the aqueous layer until pH12 and product
7. 7
   استخلاصextracted with EtOAc (100 ml)
8. 8
   أخرىThe organic phase was dried on a phase separation cartridge
9. 9
   تركيزconcentrated under vacuum
10. 10
    استخلاصso was extracted again with 2 N HCl (40 ml)
11. 11
    workup.ADDITION2 N NaOH was added to the aqueous layer until pH12 and product
12. 12
    استخلاصextracted with EtOAc (100 ml)
13. 13
    أخرىThe organic layer was dried on a phase separation cartridge
14. 14
    تركيزconcentrated under vacuum
15. 15
    أخرىto give the free base of the product
16. 16
    أخرىthe solvent was evaporated

الإجراء التجريبي

(2S)-4-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]piperazine (may be prepared as described in Description 31) (216 mg, 0.427 mmol), potassium carbonate (153 mg, 1.109 mmol) in 1,4-dioxane (9 ml) were stirred for 5 min then trimethylboroxin (0.154 ml, 1.109 mmol) and Pd(PPh3)4 (84 mg, 0.073 mmol) were added and the reaction mixture heated at 100° C. for 1 h. The reaction mixture was concentrated under vacuum, dissolved in MeOH and filtered through a 5 g SCX column. LCMS showed still some triphenylphosphine oxide and another small impurity so the product was dissolved in EtOAc (40 ml) and extracted with HCl 2N (40 ml). 2 N NaOH was added to the aqueous layer until pH12 and product extracted with EtOAc (100 ml). The organic phase was dried on a phase separation cartridge and concentrated under vacuum. LCMS of the first EtOAc layer showed it contained some of the product so was extracted again with 2 N HCl (40 ml). 2 N NaOH was added to the aqueous layer until pH12 and product extracted with EtOAc (100 ml). The organic layer was dried on a phase separation cartridge and the two batches were combined and concentrated under vacuum to give the free base of the product. The product was suspended in DCM, 0.5 ml of 1N HCl in ether was added and the solvent was evaporated to give the title compound (193 mg).

المصدر