N-methyl-2-pyrrolidone → 2-chloro-N-(4-fluorobenzyl)-4-methyl-6-[(3R)-3-methylmorpholino]-pyridine-3-carboxylic amide

HRID 922039노트

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HRID 922039 반응식
[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4](Cl)[N:3]=1.Cl.[CH3:22][C@@H:23]1[CH2:28][O:27][CH2:26][CH2:25][NH:24]1.CN1C(=O)CCC1>CCOC(C)=O>[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][C@H:23]2[CH3:22])[N:3]=1

참가 물질

5

반응물 3

HCID 13387N-methyl-2-pyrrolidoneHCID 57356922(3R)-3-Methylmorpholine hydrochlorideHCID 866643232,6-dichloro-N-(4-fluorobenzyl)-4-methyl-pyridine-3-carboxylic amide

생성물 1

HCID 866643222-chloro-N-(4-fluorobenzyl)-4-methyl-6-[(3R)-3-methylmorpholino]-pyridine-3-carboxylic amide수율 20%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
180 °C

실험 절차

A mixture of 6.0 g (19.2 mmol) 2,6-dichloro-N-(4-fluorobenzyl)-4-methyl-pyridine-3-carboxylic amide (synthesized according to the methods described in section a) of example 2), 3.9 g (28.7 mmol) (R)-3-methylmorpholine hydrochloride, 13.0 ml (76.6 mmol) and NMP (18.4 ml) was heated in the MW to 180° C. for 16 h. After cooling to RT the mixture was partiotionated between EtOAc and a 2M aq. NaOH sol. The organic layer was separated, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 1:1) provided 1.4 g (3.7 mmol, 20%) 2-chloro-N-(4-fluorobenzyl)-4-methyl-6-[(3R)-3-methylmorpholino]-pyridine-3-carboxylic amide.

후처리

  1. customsynthesized
  2. temperatureAfter cooling to RT the mixture
  3. customa 2M aq. NaOH sol. The organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by CC (hexane/EtOAc 1:1)

출처 및 근거

ORD 기록
ord-6aae695766e145d1a39a9d526e91c1f0
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278103B2

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