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

HRID 1039766노트

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HRID 1039766 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-19be471eebf047fe9387aa2c61627d3a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552200B2

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