Dimethylformamide → N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

HRID 1753873노트

반응식

HRID 1753873 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10]([C:12]2[C:13]([OH:25])=[N:14][C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:16][C:17]=2[CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.[H-].[Na+].Br[CH2:34][CH2:35][O:36][CH3:37]>CCOC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10]([C:12]2[C:13]([O:25][CH2:34][CH2:35][O:36][CH3:37])=[N:14][C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:16][C:17]=2[CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 178428042N-[(3-Fluorophenyl)-methyl]-2-hydroxy-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

생성물 1

HCID 67286960N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide수율 39%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 200 mg (0.58 mmol) N-[(3-Fluorophenyl)-methyl]-2-hydroxy-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (synthesis is described in section b) of example 19) in DMF (8 ml) 15 mg (0.64 mmol, 60% w/w in mineral oil) NaH were added, followed by stirring at RT for 30 min. Then 88 mg (0.64 mmol) 2-bromoethyl-methylether were added and the RM was heated to 50° C. for 16 h. Subsequently water (10 ml) and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:7) provided 90 mg (0.22 mmol, 39%) N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 21). [M+H]+404.2.

후처리

  1. temperaturethe RM was heated to 50° C. for 16 h
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by CC (hexane/EtOAc 3:7)

출처 및 근거

ORD 기록
ord-8e6f6251548d4274a6b6cb0c5fa71806
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09168259B2

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