Реакция #69596

Уравнение реакции

(3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

HATU

4-chloro-2-pyridinecarboxylic acid

DIPEA

→

title compound

Выход 39.4%

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

Выход 39.4%

Растворители

DMF

Условия реакции

Обработка

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 1.5 h
3. 3
   ДругоеThe reaction mixture was partitioned between DCM
4. 4
   ДругоеThe layers were separated
5. 5
   Промывкаthe aqueous was washed with further DCM (2×20 ml)
6. 6
   КонцентрированиеThe combined organics were concentrated
7. 7
   Другоеto leave a dark brown gum
8. 8
   ДругоеPurification by silica chromatography (Biotage SP4, 25S cartridge)
9. 9
   Промывкаeluting with 12-100% ethyl acetate in isohexane
10. 10
    Другоеgave a pale yellow gum
11. 11
    ДругоеFurther purification by MDAP

Методика

HATU (411 mg, 1.08 mmol) was added to a solution of 4-chloro-2-pyridinecarboxylic acid (142 mg, 0.90 mmol) in DMF (4 ml) and the mixture was treated with DIPEA (0.394 ml, 2.25 mmol). This mixture was stirred for ca. 10 min at ambient temperature. (3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (Description 2) (333 mg, 1.082 mmol) was then added and stirring was continued for 1.5 h. The reaction mixture was partitioned between DCM and sat aq. NaHCO3 solution (20 ml each). The layers were separated and the aqueous was washed with further DCM (2×20 ml). The combined organics were concentrated to leave a dark brown gum. Purification by silica chromatography (Biotage SP4, 25S cartridge), eluting with 12-100% ethyl acetate in isohexane, gave a pale yellow gum, shown to be impure by LCMS and NMR analysis. Further purification by MDAP gave the title compound as a colourless glass (159 mg).

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