Diisopropylethylamine → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide

HRID 448497

반응식

HRID 448497 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([F:23])=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 67229011N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide수율 79%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) and 4-fluoro-3-trifluoromethyl-benzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). After stirring at room temperature overnight, the reaction mixture was quenched with methanol (1 mL). The resulting suspension was filtered, and the solid was washed with methyene chloride to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide (0.8 g, 79%) as a white solid: mp 171-173° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=7.5 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.12 (m, 1H), 2.54-2.65 (m, 2H), 2.85-2.98 (m, 1H), 4.97 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5.4 and 12.5 Hz, 1H), 7.68 (t, J=8.9 Hz, 1H), 7.76-7.84 (m, 3H), 8.28-8.35 (m, 2H), 9.43 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.91, 30.86, 38.43, 48.82, 116.20 (116.37, 116.64, 116.80), 117.35 (117.63), 120.50 (124.10), 121.92, 126.51 (126.56), 127.14, 130.65 (130.70), 131.48, 133.22, 134.58, 134.71 (134.77), 138.70, 158.78 (162.21), 164.19, 166.87, 167.44, 169.75, 172.68; Anal. Calcd. for C22H15N3O5F4+0.2H2O: C, 54.94; H, 3.23; N, 8.74; F, 15.80. Found: C, 54.68; H, 3.17; N, 8.63; F, 15.72.

후처리

  1. customthe reaction mixture was quenched with methanol (1 mL)
  2. filtrationThe resulting suspension was filtered
  3. washthe solid was washed with methyene chloride

출처 및 근거

ORD 기록
ord-0a96e7434fec48308601c3accc2a41e0
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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