2-Bromopyridine → 2-Cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)-4-pyridin-2-ylbutanamide

HRID 561863

반응식

HRID 561863 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([Li])CCC.C(SCCCC)CCC.[C:22](/[C:24](=[CH:40]\[C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][C:51]2[C:56]([Cl:57])=[CH:55][C:54]([CH3:58])=[CH:53][C:52]=2[Cl:59])=[CH:43][CH:42]=1)/[C:25]([N:27]([CH:37]1[CH2:39][CH2:38]1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[CH3:36])=[O:26])#[N:23]>C1COCC1.CCOCC>[C:22]([CH:24]([CH:40]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][C:51]2[C:52]([Cl:59])=[CH:53][C:54]([CH3:58])=[CH:55][C:56]=2[Cl:57])=[CH:43][CH:42]=1)[CH2:8][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[C:25]([N:27]([CH:37]1[CH2:38][CH2:39]1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:30]=1[CH3:36])=[O:26])#[N:23]

참가 물질

7

반응물 4

HCID 79732-BromopyridineHCID 11002Dibutyl sulfideHCID 66761334HCID 66761334, 화합물HCID 178418339Butyllithium

생성물 1

HCID 667612652-Cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)-4-pyridin-2-ylbutanamide

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a THF solution (0.5 M) of 2-bromopyridine (2.8 eq.) was added, at −78° C., n-butyl lithium (1.6 M hexane solution, 2.8 eq.) dropwise over 15 min. The resulting yellow suspension was stirred at −78° C. for a further 15 min before an ether solution (0.5 M) of cuprous iodide (1.4 eq.) and dibutyl sulfide (2.8 eq.) was added over 15 min. The resulting reaction mixture was allowed to stir at −78° C. for 15 min and then at 0° C. for 15 min. Finally, to this was added dropwise at 0° C., a THF solution (0.1 M) of (2E)-2-cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)acrylamide (Example 1, Step 2, 1 eq.). The resulting emerald green suspension was stirred at 0° C. for 15 min and then at RT for 2 h. The reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl:conc. aq. NH4OH solution and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude product thus obtained was purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc). The title compound was isolated as a mixture of diastereomers.

후처리

  1. additionwas added over 15 min
  2. customThe resulting reaction mixture
  3. waitat 0° C. for 15 min
  4. additionFinally, to this was added dropwise at 0° C.
  5. stirringThe resulting emerald green suspension was stirred at 0° C. for 15 min
  6. waitat RT for 2 h
  7. customThe reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl
  8. extractionaq. NH4OH solution and extracted with ether
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated in vacuo
  13. customThe crude product thus obtained
  14. customwas purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc)

출처 및 근거

ORD 기록
ord-1414afcd05de430599c7a232a9ddb81b
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063105B2

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