Water → 1-{1-[2-Methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine

HRID 419648노트

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HRID 419648 반응식
[CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[C:6]([CH3:10])=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12].Cl.Cl.[CH3:16][S:17]([N:20]1[CH2:25][CH2:24][N:23]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:22][CH2:21]1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[CH3:10][C:6]1[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:29]1[CH2:28][CH2:27][CH:26]([N:23]2[CH2:24][CH2:25][N:20]([S:17]([CH3:16])(=[O:19])=[O:18])[CH2:21][CH2:22]2)[CH2:31][CH2:30]1

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 184681411-Fluoro-5-methoxy-2-methyl-4-nitrobenzeneHCID 666497911-(Methylsulfonyl)-4-(4-piperidinyl)piperazine dihydrochloride

생성물 1

HCID 594529721-{1-[2-Methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine수율 55%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
100 °C

실험 절차

A mixture of 1-fluoro-2-methyl-5-(methyloxy)-4-nitrobenzene (Example 113, Step B) (0.90 g, 4.9 mmol), 1-(methylsulfonyl)-4-(4-piperidinyl)piperazine (Example 204, step C) (1.20 g, 4.9 mmol) and K2CO3 (0.81 g, 5.8 mmol) in DMSO (15 mL) was heated at 100° C. for 48 h. The reaction was cooled to rt, poured into H2O and extracted exhaustively with DCM. The combined organics were washed with H2O then dried over MgSO4. The resultant solution was concentrated onto silica and purified by flash chromatography to afford 1-{1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine (1.09 g, 55%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (s, 1H), 6.69 (s, 1H), 3.90 (s, 3H), 3.29-3.38 (m, 2H), 3.06-3.15 (m, 4H), 2.87 (s, 3H), 2.68-2.79 (m, 2H), 2.59-2.66 (m, 4H), 2.40-2.48 (m, 1H), 2.20 (s, 3H), 1.80-1.92 (m, 2H), 1.49-1.67 (m, 2H).

후처리

  1. temperatureThe reaction was cooled to rt
  2. extractionextracted exhaustively with DCM
  3. washThe combined organics were washed with H2O
  4. dry with materialthen dried over MgSO4
  5. concentrationThe resultant solution was concentrated onto silica
  6. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-bcd3cb8c572a4bd5a90560cf1469b89e
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

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