N-methyl-2-pyrrolidone → 6-(3-fluorophenyl)-N-{1-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]piperidin-4-yl}nicotinamide

HRID 602076노트

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HRID 602076 반응식
[F-].[Cs+].CN1CCCC1=O.Cl.[F:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:32]=[CH:31][C:21]([C:22]([NH:24][CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[O:23])=[CH:20][N:19]=2)[CH:15]=[CH:16][CH:17]=1.Cl[C:34]1[N:39]=[CH:38][C:37]([C:40]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:41])=[CH:36][CH:35]=1>O>[F:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:32]=[CH:31][C:21]([C:22]([NH:24][CH:25]3[CH2:26][CH2:27][N:28]([C:34]4[CH:35]=[CH:36][C:37]([C:40]([N:42]5[CH2:43][CH2:44][O:45][CH2:46][CH2:47]5)=[O:41])=[CH:38][N:39]=4)[CH2:29][CH2:30]3)=[O:23])=[CH:20][N:19]=2)[CH:15]=[CH:16][CH:17]=1

참가 물질

6

반응물 4

HCID 13387N-methyl-2-pyrrolidoneHCID 25953Cesium fluorideHCID 8574994-(6-Chloropyridine-3-carbonyl)morpholineHCID 672680466-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide hydrochloride

생성물 1

HCID 249910436-(3-fluorophenyl)-N-{1-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]piperidin-4-yl}nicotinamide수율 15.3%

시약·촉매·용매 1

HCID 962Water용매

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온도
96 °C

실험 절차

To a vial containing CsF (684 mg, 4.50 mmol) and 1-methyl-2-pyrrolidinone (NMP, 2 mL) was added 6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide hydrochloride (247 mg) and (6-chloropyridin-3-yl)(morpholino)methanone (170 mg, 0.750 mmol). The reaction mixture was heated to 96° C. for 24 hrs. After allowing the reaction to cool to room temperature the reaction was diluted with H2O (3 mL) and the mixture extracted with ethyl acetate (3×10 mL). The organics were combined, dried (MgSO4) and the solvent removed to give an oil, which after chromatography (silica, 5% MeOH: DCM) gave 6-(3-fluorophenyl)-N-{1-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]piperidin-4-yl}nicotinamide (55 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.09 (1H, s), 8.53 (1H, d, J=7.7 Hz), 8.30 (1H, dd, J=8.4, 1.6 Hz), 8.23 (2 H, d, J=11.9 Hz), 8.15 (1H, d, J=8.4 Hz), 8.02 (1H, d, J=7.9 Hz), 7.98 (1H, br. s.), 7.53-7.61 (1H, m), 7.26-7.37 (1H, m), 5.02 (1H, br. s.), 4.45 (1H, br. s.), 4.24 (1H, br. s.), 3.86 (1H, br. s.) 3.73 (1H, br. s.), 3.30 (3H, br. s.), 1.87-2.05 (5H, m), 1.61 (2H, br. s.), 0.75 (3H, t, J=7.3 Hz)

후처리

  1. customthe reaction
  2. temperatureto cool to room temperature the reaction
  3. extractionthe mixture extracted with ethyl acetate (3×10 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed
  6. customto give an oil, which after chromatography (silica, 5% MeOH: DCM)

출처 및 근거

ORD 기록
ord-bbf95462c7624be7a150a40b18607720
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902373B2

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