Cesium carbonate → HCID 178503267, 화합물

HRID 724303

반응식

HRID 724303 반응식
Cl[C:2]1[N:17]=[CH:16][C:15]([F:18])=[CH:14][C:3]=1[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]1)=[O:5].[CH3:19][S:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][C:22]=1[CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:18][C:15]1[CH:16]=[N:17][C:2]([O:27][C:24]2[CH:25]=[CH:26][C:21]([S:20][CH3:19])=[C:22]([CH3:28])[CH:23]=2)=[C:3]([CH:14]=1)[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]1)=[O:5]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 183913-Methyl-4-(methylthio)phenolHCID 178523807HCID 178523807, 화합물

생성물 1

HCID 178503267HCID 178503267, 화합물수율 54.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
55 °C

실험 절차

2-Chloro-5-fluoro-N-(trans-4-hydroxy-cyclohexyl)-nicotinamide (150 mg, 0.55 mmol), 4-methylsulfanyl-3-methyl-phenol (85 mg, 0.55 mmol) and caesium carbonate (358 mg, 1.10 mmol) were suspended in DMF (2 ml) and the reaction was heated to 55° C. and stirred at this temperature under nitrogen for 18 h. The reaction was quenched with sat. ammonium chloride solution (1.5 ml) and water (1.5 ml) and the organic phase was collected by passing the mixture through a chemelute™ cartridge, washing with ethyl acetate. The solvent was removed on a Genevac™ and the residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 changing to 96:4, by volume) to give 5-fluoro-N-(trans-4-hydroxy-cyclohexyl)-2-(4-methylsulfanyl-3-methyl-phenoxy)-nicotinamide (118 mg) as an off-white foam.

후처리

  1. customThe reaction was quenched with sat. ammonium chloride solution (1.5 ml) and water (1.5 ml)
  2. customthe organic phase was collected
  3. washwashing with ethyl acetate
  4. customThe solvent was removed on a Genevac™
  5. customthe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 changing to 96:4, by volume)

출처 및 근거

ORD 기록
ord-d5add661b5a34e4f9f8fda041b6a7238
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141586B2

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