HCID 701019, 화합물 → HCID 86664325, 화합물

HRID 922046노트

반응식

HRID 922046 반응식
Cl[C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([Cl:20])[N:3]=1.[CH:21]([Mg]Cl)([CH3:23])[CH3:22]>C1COCC1>[Cl:20][C:4]1[N:3]=[C:2]([CH:21]([CH3:23])[CH3:22])[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=1

참가 물질

4

반응물 2

HCID 701019HCID 701019, 화합물HCID 178418918HCID 178418918, 화합물

생성물 1

HCID 86664325HCID 86664325, 화합물수율 40%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
10 °C

실험 절차

A solution of 6.0 g (18.3 mmol) 2,6-dichloro-N-(4-chlorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesized according to the method described in section a) of example 2) in THF (180 ml) and NMP (60 ml) was degassed for 30 min followed by the addition of 1.3 g (3.7 mmol) Fe(acac)3. This mixture was degassed again for 20 min. At −40° C. 137 ml (2M in THF, 274 mmol) isopropylmagnesiumchloride was added dropwise over 1 h. The reaction mixture was allowed to reach 0° C. and was quenched at this temperature with a sat. aq. NH4Cl sol. followed by stirring at 10° C. for 30 min. Then the mixture was diluted with EtOAc and the organic layer was separated, washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 9:1) provided 2.45 g (7.3 mmol, 40%) 6-chloro-N-(4-chlorobenzyl)-2-isopropyl-4-methyl-pyridine-3-carboxylic amide.

후처리

  1. customNMP (60 ml) was degassed for 30 min
  2. customThis mixture was degassed again for 20 min
  3. customAt −40° C
  4. customto reach 0° C.
  5. customwas quenched at this temperature with a sat. aq. NH4Cl sol.
  6. additionThen the mixture was diluted with EtOAc
  7. customthe organic layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by CC (hexane/EtOAc 9:1)

출처 및 근거

ORD 기록
ord-32e743c9c957411cb332aacb6f13029d
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278103B2

반응 노트

불러오는 중…