Fusaric Acid → 5-Butylpyridine-2-carboxylic acid [2-(2,6-dioxo piperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]amide

HRID 448440

反応式

HRID 448440 の反応式
[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=1.S(Cl)(Cl)=O.Cl.[NH2:19][CH2:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:22]=1[C:23](=[O:39])[N:24]([CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38])[C:25]2=[O:30].C(N(CC)CC)C>C1COCC1>[O:38]=[C:32]1[CH:31]([N:24]2[C:23](=[O:39])[C:22]3[C:26](=[CH:27][CH:28]=[CH:29][C:21]=3[CH2:20][NH:19][C:11]([C:8]3[CH:7]=[CH:6][C:5]([CH2:4][CH2:3][CH2:2][CH3:1])=[CH:10][N:9]=3)=[O:13])[C:25]2=[O:30])[CH2:36][CH2:35][C:34](=[O:37])[NH:33]1

参加物

6

反応物 4

HCID 3442Fusaric AcidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 588273525-Butylpyridine-2-carboxylic acid [2-(2,6-dioxo piperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]amide収率 64.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of fusaric acid (0.36 g, 2.0 mmol) and thionyl chloride (10 mL) was heated to reflux for 1 hour. Excess thionyl chloride was removed under vacuum. To the acid chloride, was then added 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), THF (30 mL) and triethylamine (0.61 g, 6.0 mmol), and the resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated, and the crude residue was chromatographed using a methylene chloride-methanol gradient, eluting the product with 95:5 methylene chloride-methanol. This material was further purified by preparative HPLC, eluting with 1:1 acetonitrile-water, providing 0.58 g of the purified product in 64% yield: mp 137-139° C.; 1H NMR (DMSO-d6) δ 0.91 (t, J=7.3 Hz, 3H), 1.24-1.39 (m, 2H), 1.54-1.65 (m, 2H), 2.06-2.10 (m, 2H), 2.51-2.72 (m, 4H), 2.84-2.97 (m, 1H), 4.94 (d, J=6.4 Hz, 2H), 5.17 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.66-7.71 (m, 1H), 7.77-7.86 (m, 3H), 7.97 (d, J=8.0 Hz, 1H), 8.54 (d, J=1.7 Hz, 1H), 9.43 (t, J=6.4 Hz, 1H), 11.16 (s, 1H); 13C NMR (DMSO-d6) δ 13.7, 21.6, 22.0, 31.0, 31.7, 32.6, 38.5, 48.9, 121.8, 121.9, 127.2, 131.6, 133.0, 134.8, 137.3, 139.2, 141.2, 147.5, 148.5, 164.5, 167.0, 167.6, 169.9, 172.8; Anal. calcd for C24H24N4O5.0.3H2O: C, 63.51; H, 5.46; N, 12.34. Found: C, 63.52; H, 5.55; N, 12.05.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 1 hour
  3. customExcess thionyl chloride was removed under vacuum
  4. customThe solvent was evaporated
  5. customthe crude residue was chromatographed
  6. washeluting the product with 95:5 methylene chloride-methanol
  7. customThis material was further purified by preparative HPLC
  8. washeluting with 1:1 acetonitrile-water

出典と根拠

ORDレコード
ord-fafd4deeaeec4d47b531d557a42350ee
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

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