Triethylamine → 2,5-Dichloro-N-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]nicotinamide

HRID 448446

반응식

HRID 448446 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].[Cl:23][C:24]1[C:29]([C:30](Cl)=[O:31])=[CH:28][C:27]([Cl:33])=[CH:26][N:25]=1.C(N(CC)CC)C>C1COCC1>[Cl:23][C:24]1[N:25]=[CH:26][C:27]([Cl:33])=[CH:28][C:29]=1[C:30]([NH: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])=[O:31]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27999962,5-Dichloro-nicotinoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 588272942,5-Dichloro-N-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]nicotinamide수율 54.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), 2,5-dichloropyridine-3-carbonyl chloride (0.42 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) in THF (30 mL) was stirred at ambient temperature under nitrogen for 18 hours. The mixture was evaporated, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting with 95:5 methylene chloride-methanol, providing 0.50 g of the product (54% yield): mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.53-2.58 (m, 2H), 2.83-2.97 (m, 1H), 4.93 (d, J=5.7 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.3 Hz, 1H), 7.82-7.91 (m, 3H), 8.28 (d, J=2.5 Hz, 1H), 8.61 (d, J=2.5 Hz, 1H), 9.35 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.3, 48.9, 122.1, 127.3, 130.3, 131.6, 133.4, 134.9, 137.8, 138.0, 145.0, 148.8, 164.1, 166.9, 167.5, 169.8, 172.8; Anal. calcd for C20H14Cl2N4O5.0.2H2O: C, 51.68; H, 3.12; N, 12.05. Found: C, 51.64; H, 3.05; N, 11.98.

후처리

  1. customThe mixture was evaporated
  2. customthe residue was chromatographed
  3. washeluting with 95:5 methylene chloride-methanol

출처 및 근거

ORD 기록
ord-c9f3b6e06413422babd0d9b1b45c254e
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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