Acetonitrile → N-[[2-[(3S)-3-Methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]-4-(methylsulfonyl) benzamide

HRID 63409

반응식

HRID 63409 반응식
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:27][CH2:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[C:34](=[O:38])[N:33]([C@@:39]1([CH3:47])[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46])[C:32]2=[O:48].CC#N>CN(C=O)C>[CH3:47][C@:39]1([N:33]2[C:32](=[O:48])[C:31]3[C:35](=[CH:36][CH:37]=[C:29]([CH2:28][NH:27][C:9](=[O:11])[C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:13][CH:12]=4)[CH:30]=3)[C:34]2=[O:38])[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46]

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 682631,1'-CarbonyldiimidazoleHCID 77670p-(Methylsulphonyl)benzoic acidHCID 670196915-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride

생성물 1

HCID 24788309N-[[2-[(3S)-3-Methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]-4-(methylsulfonyl) benzamide수율 32%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
40 °C

실험 절차

A mixture of 4-(methylsulfonyl)benzoic acid (0.40 g, 2.0 mmol) and CDI (0.36 g, 2.2 mmol) in DMF (20 mL) was stirred under nitrogen at 40° C. for 2 hours. Then, 5-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride (0.67 g, 2.0 mmol) was added, and stirring proceeded at this temperature for an additional 2 hours. The mixture was cooled to room temperature, and was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic phase was washed with saturated aqueous sodium bicarbonate solution (2×100 mL) and evaporated. The residue was chromatographed on silica gel using 99:1 methylene chloride-methanol as the mobile phase, providing 0.30 g, in 32% yield. The product was obtained as a white solid; mp 165.5-167.5° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.08 (96.23%); 1H NMR (DMSO-d6) δ 2.09 (s, 3H), 2.22-2.28 (m, 1H), 2.73-2.95 (m, 3H), 3.47 (s, 3H), 4.86 (d, J=5.7 Hz, 2H), 7.98-8.04 (m, 3H), 8.25 (d, J=8.7 Hz, 2H), 8.32 (d, J=8.7 Hz, 2H), 9.58 (t, J=5.7 Hz, 1H), 11.21 (s, 1H); 13C NMR (DMSO-d6) δ 23.0, 30.6, 31.1, 44.8, 45.6, 60.8, 123.7, 125.2, 129.2, 130.3, 131.7, 133.4, 135.5, 140.4, 145.2, 149.0, 167.2, 169.7, 169.9, 174.1, 174.2; Anal. Calcd for C23H21N3O7S+0.3H2O: C, 56.50; H, 4.45; N, 8.59. Found: C, 56.61; H, 4.42; N, 8.30.

후처리

  1. stirringstirring
  2. waitproceeded at this temperature for an additional 2 hours
  3. temperatureThe mixture was cooled to room temperature
  4. customwas partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL)
  5. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution (2×100 mL)
  6. customevaporated
  7. customThe residue was chromatographed on silica gel using 99:1 methylene chloride-methanol as the mobile phase
  8. customproviding 0.30 g
  9. customThe product was obtained as a white solid

출처 및 근거

ORD 기록
ord-24dd3b8a47be40dda6048ba89d9f0f25
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447070B2

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