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

HRID 1677108ノート

反応式

HRID 1677108 の反応式
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

参加物

7

反応物 3

HCID 14797Potassium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 575716996-Morpholin-4-yl-N-[2-(4-phenoxy-phenyl)-ethyl]-nicotinamide2 回

生成物 1

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

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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]+)

後処理

  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)

出典と根拠

ORDレコード
ord-933d96172b544c4fa54e4ce18e58dd17
出典データセット
uspto-grants-2011_08
特許番号
US08008305B2

反応ノート

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