Trimethylsilyl iodide → 2-(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid

HRID 2167651ノート

反応式

HRID 2167651 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]([C:27](=[O:39])[C:28]([P:31](=[O:38])([O:35]CC)[O:32]CC)([F:30])[F:29])=[CH:26][C:4]=2[N:3]=1.[Si](I)(C)(C)C>C(Cl)Cl>[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](=[O:39])[C:28]([P:31](=[O:32])([OH:35])[OH:38])([F:29])[F:30])=[CH:26][C:4]=2[N:3]=1

参加物

4

反応物 2

HCID 85247Trimethylsilyl iodide2 回HCID 86651452Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate

生成物 1

HCID 498383852-(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate (2-4) (1.0 equiv.) in DCM (0.05 M) at 0° C. was added TMSI (5.0 equiv.). The reaction was warmed to room temperature over 2 hours, and more TMSI was added (2.5 equiv.). The reaction was stirred for another 30 minutes, and then quenched with small amounts of water. The DCM was removed by evaporation, and then added DMSO/water. The mixture was adjusted to pH 9 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 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid (9) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 8.82 (s, 1H), 8.5 (br, 1H), 8.44 (s, 1H), 8.2 (br, 1H), 7.98 (d, 1H, J=8.2 Hz), 7.2 (br, 2H), 7.05 (d, 1H, J=8.3 Hz), 6.73 (s, 1H), 6.67 (d, 1H, J=8.3 Hz), 3.70 (s, 3H), 2.99-2.87 (m, 4H), 2.25 (s, 3H). LRMS [M+H]=502.2

後処理

  1. customquenched with small amounts of water
  2. customThe DCM was removed by evaporation
  3. customdirectly purified on RP-HPLC
  4. washeluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient
  5. additionThe fractions containing the product
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ccdd8d443e324ecdb5570d0a6d6afb90
出典データセット
uspto-grants-2015_06
特許番号
US09045470B2

反応ノート

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