Cesium carbonate → 2-chloro-N-(3-fluorobenzyl)-4-methyl-6-thiomorpholino-pyridine-3-carboxylic acid amide

HRID 1039774노트

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HRID 1039774 반응식
[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4](Cl)[N:3]=1.[NH:21]1[CH2:26][CH2:25][S:24][CH2:23][CH2:22]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:21]2[CH2:26][CH2:25][S:24][CH2:23][CH2:22]2)[N:3]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 67164ThiomorpholineHCID 866643132,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide

생성물 1

HCID 866643262-chloro-N-(3-fluorobenzyl)-4-methyl-6-thiomorpholino-pyridine-3-carboxylic acid amide수율 49.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A solution of 700 mg (2.24 mmol) 2,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesis is described in section a) of example 2), 280 μl (2.9 mmol) thiomorpholine and 3.95 g (12.1 mmol) Cs2CO3 in dioxane (60 ml) was degassed for 30 min followed by the addition of 285 mg (0.25 mmol) Pd(PPh3)4. Subsequently the reaction solution was heated to 120° C. for 16 h. Then the mixture was filtered through celite and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 19:1) provided 420 mg (1.1 mmol, 49%) 2-chloro-N-(3-fluorobenzyl)-4-methyl-6-thiomorpholino-pyridine-3-carboxylic acid amide.

후처리

  1. customwas degassed for 30 min
  2. filtrationThen the mixture was filtered through celite and
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by CC (hexane/EtOAc 19:1)

출처 및 근거

ORD 기록
ord-d38e801c9a6d4d15bdcd99fb28652960
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552200B2

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