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

HRID 1753880ノート

反応式

HRID 1753880 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
180 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-c6fcdcecafa94f5089ed9b8e24c6dc3b
出典データセット
uspto-grants-2015_10
特許番号
US09168259B2

反応ノート

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