Potassium Hydroxide → 6-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide

HRID 1677108노트

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HRID 1677108 반응식
N1([C:7]2[CH:30]=[CH:29][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[O:12])=[CH:9][N:8]=2)CCOCC1.[OH:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1.[OH-].[K+]>CS(C)=O.C(Cl)Cl.O>[CH3:38][N:35]1[CH2:36][CH2:37][CH:32]([O:31][C:7]2[CH:30]=[CH:29][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[O:12])=[CH:9][N:8]=2)[CH2:33][CH2:34]1

참가 물질

7

반응물 3

HCID 14797Potassium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 575716996-Morpholin-4-yl-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide2회

생성물 1

HCID 251820966-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide수율 20.9%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A solution of 6-chloro-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide (130 mg, intermediate from example 23) in DMSO (1.4 ml) was treated with 4-hydroxy-N-methylpiperidine (68 mg) and KOH (93 mg). The reaction mixture was heated for 20 min at 100° C. in the microwave oven. Then it was cooled to r.t. and diluted with CH2Cl2 and water. The aqueous layer was washed with CH2Cl2. The combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 98:2) to give 6-(1-methyl-piperidin-4-yloxy)-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide (29 mg) as off-white solid. MS (ISP): 432.2 ([M+H]+)

후처리

  1. temperatureThen it was cooled to r.t.
  2. washThe aqueous layer was washed with CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 98:2)

출처 및 근거

ORD 기록
ord-933d96172b544c4fa54e4ce18e58dd17
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08008305B2

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