1,8-Diazabicyclo(5.4.0)undec-7-ene → 1,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide

HRID 448451

반응식

HRID 448451 반응식
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[CH3:34][N:35]1[C:39]([CH3:40])=[CH:38][C:37]([C:41](Cl)=[O:42])=[N:36]1>C(#N)C>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:41]([C:37]3[CH:38]=[C:39]([CH3:40])[N:35]([CH3:34])[N:36]=3)=[O:42])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

참가 물질

5

반응물 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27763641,5-Dimethyl-1H-Pyrazole-3-Carbonyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 588273221,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide수율 38%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

1,8-Diazabicyclo[5.4.0]undec-7-ene (1.0 g, 6.6 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) in acetonitrile (40 mL). After stirring for 10 minutes, 1,5-dimethyl-1H-pyrazole-3-carbonyl chloride (0.4 g, 2.6 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was dissolved in CH2Cl2 (80 mL). The CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL), and dried (MgSO4). Solvent was removed, and the residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5) to give 1,5-dimethyl-1H-pyrazole-3-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide (0.3 g, 38%) as a white solid: mp 213-215° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.28 (s, 3H), 2.50-2.64 (m, 2H), 2.84-2.97 (m, 1H), 3.79 (s, 3H), 4.86 (d, J=5.9 Hz, 2H), 5.13-5.20 (dd, J=5.1 and 12.4 Hz, 1H), 6.44 (s, 1H), 7.65-7.79 (m, 3H), 8.69 (t. J=5.9 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 10.66, 21.97, 30.93, 36.39, 37.80, 48.86, 105.53, 121.71, 127.01, 131.51, 132.78, 134.70, 139.60, 140.35, 144.26, 161.91, 167.00, 167.56, 169.83, 172.75; Anal. calcd. for C20H19N5O5+0.4H2O: C, 57.66; H, 4.79; N, 16.81. Found: C, 57.85; H, 4.80; N, 16.64.

후처리

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in CH2Cl2 (80 mL)
  4. washThe CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. customSolvent was removed
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5)

출처 및 근거

ORD 기록
ord-a002226b0c044acc9fdf5735e1af88df
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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