Methanol → (1S)-Furan-2-carboxylic acid (2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amide

HRID 913187ノート

反応式

HRID 913187 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:7]2.[O:29]1[CH:33]=[CH:32][CH:31]=[C:30]1[C:34](Cl)=[O:35].C[OH:38]>C1COCC1>[CH2:27]([O:26][C:20]1[CH:19]=[C:18]([C@H:12]([N:8]2[C:9](=[O:11])[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[NH:1][C:34]([C:30]3[O:29][CH:33]=[CH:32][CH:31]=3)=[O:35])[C:7]2=[O:38])[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH:23]=[CH:22][C:21]=1[O:24][CH3:25])[CH3:28]

参加物

5

反応物 3

HCID 887MethanolHCID 682422-Furancarbonyl chlorideHCID 66718531(S)-7-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one

生成物 1

HCID 67417354(1S)-Furan-2-carboxylic acid (2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amide収率 37%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of (1S)-7-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (0.85 g, 2.0 mmol) and 2-furoyl chloride (0.40 mL, 4.1 mmol) in THF (5 mL) was heated to reflux for 17 hours. To the mixture was added methanol (4 mL). The solvent was removed in vacuo to give a solid, which was purified with chromatography (Silica Gel, EtOAc/hexane) to give (1S)-Furan-2-carboxylic acid {2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a solid (380 mg, 37% yield): mp 184-186° C.; 1H NMR (CDCl3) δ 1.45 (t, J=7 Hz, 3H, CH3), 2.86 (s, 3H, CH3), 3.76-3.80 (m, 1H, CHH), 3.83 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 4.56 (dd, J=10, 14 Hz, 1H, CHH), 5.90 (dd, J=5, 10 Hz, 1H, NCH), 6.57-6.58 (m, 1H, Ar), 6.81-6.84 (m, 1H, Ar), 7.10-7.13 (m, 2H, Ar), 7.27-7.28 (m, 1H, Ar), 7.47-7.50 (m, 1H, Ar), 7.63-7.69 (m, 2H, Ar), 8.84 (d, J=9 Hz, 1H, Ar), 10.39 (s, 1H, NH); 13C NMR (CDCl3) δ 14.70, 41.65, 48.74, 54.68, 55.95, 60.37, 64.55, 111.51, 112.51, 112.75, 115.76, 116.47, 118.42, 120.42, 125.03, 129.34, 131.26, 136.15, 137.25, 145.40, 147.05, 148.63, 149.75, 156.49, 167.51, 169.39. Analy, calculated for C25H24N2O8S: C, 58.59; H, 4.72; N, 5.47. Found: C, 58.34; H, 4.86; N, 5.38.

後処理

  1. temperatureto reflux for 17 hours
  2. customThe solvent was removed in vacuo
  3. customto give a solid, which
  4. customwas purified with chromatography (Silica Gel, EtOAc/hexane)

出典と根拠

ORDレコード
ord-0641959565a1458db999bd1b28f1b4dc
出典データセット
uspto-grants-2011_09
特許番号
US08026269B2

反応ノート

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