Tris(trimethylsilyl) phosphite → 5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid

HRID 2167660

反応式

HRID 2167660 の反応式
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH:27]=[O:28])=[CH:26][C:4]=2[N:3]=1.[P:29]([O:40][Si](C)(C)C)([O:35][Si](C)(C)C)[O:30][Si](C)(C)C>C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([C:27]([P:29](=[O:30])([OH:40])[OH:35])=[O:28])=[CH:26][C:4]=2[N:3]=1

参加物

4

反応物 2

HCID 137213Tris(trimethylsilyl) phosphiteHCID 581665185-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde

生成物 1

HCID 498385115-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

To a stirred suspension of 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (2-2) (Example 9—Step 1) (1.0 equiv.) in toluene (0.27 M) was added tris(trimethylsilyl) phosphite (1.0 equiv.). The reaction was stirred at 80° C. for 60 minutes, then solvents were removed, and the resulting residue was taken up in DMSO (0.27 M), and IBX (1.5 equiv.) was added. The reaction was stirred at room temperature for 2.5 hour, and was filtered and directly purified on RP-HPLC using a C18 column, eluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient. The fractions containing the product were combined and concentrated in vacuo to give 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid (14) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 9.84 (s, 1H), 9.35 (s, 1H), 9.09 (s, 1 H), 8.89 (s, 1 H), 8.76 (d, 1H, J=8.4 Hz), 8.60 (s, 1H), 8.19 (d, 1H, J=8.8 Hz), 7.04 (d, J=8.8 Hz, 1H), 6.70 (d, 1H, J=2.8 Hz), 6.62 (dd, 1H, J=2.8, 8.4 Hz), 3.64 (s, 3H), 3.15-3.09 (m, 2H), 2.97-2.91 (m, 2H), 2.23 (s, 3H). LRMS [M+H]=452.1

後処理

  1. customsolvents were removed
  2. additionIBX (1.5 equiv.) was added
  3. stirringThe reaction was stirred at room temperature for 2.5 hour
  4. filtrationwas filtered
  5. customdirectly purified on RP-HPLC
  6. washeluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient
  7. additionThe fractions containing the product
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-97ced71f170d495caa500d1cb43e93f2
出典データセット
uspto-grants-2015_06
特許番号
US09045470B2

関連ノート

読み込み中…