Triethylamine → (R)-3-(2,3-Dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 1260444ノート

反応式

HRID 1260444 の反応式
[OH:1][C@@H:2]([CH2:27][OH:28])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22](I)=[CH:21][C:20]=3[F:26])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1.C[Si]([C:33]#[CH:34])(C)C.C(N(CC)CC)C>C1COCC1.[Cu](I)I>[OH:1][C@@H:2]([CH2:27][OH:28])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:33]#[CH:34])=[CH:21][C:20]=3[F:26])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 24966075(R)-3-(2,3-Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

生成物 1

HCID 24963597(R)-3-(2,3-Dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione収率 74.7%

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 8028Tetrahydrofuran溶媒

実験手順

(R)-3-(2,3 Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (200 mg, 0.4 mmol, Example 8), trimethylsilyl acetylene (66 μL, 0.6 mmol), triethylamine (84 μL, 0.6 mmol), copper iodide (14 mg, cat) and dichlorobis(triphenylphoshine) palladium(II) (14 mg, 0.02 mmol) were mixed in THF (2 mL). The mixture was subjected to microwave irradiation at 120° C. for 20 minutes. The solvent was removed in vacuo and the residue dissolved in methanol. Potassium carbonate (50 mg) was added and the solution stirred at RT for 1 hour. After filtration and evaporation the residue was purified by HPLC to give 119 mg of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.79 (s, 3H) 3.11 (s, 1H) 3.54-3.66 (m, 3H) 3.82-3.90 (m, 1H) 3.94-4.02 (m, 1H) 4.30 (dd, J=14.15, 3.79 Hz, 1H) 6.67 (t, J=8.46 Hz, 1H) 7.19 (dd, J=8.21, 0.88 Hz, 1H) 7.21-7.25 (m, 1H) 8.27 (s, 1H) [M+H] calc'd for C20H19FN4O4, 399. found, 399.

後処理

  1. customirradiation at 120° C. for 20 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in methanol
  4. additionPotassium carbonate (50 mg) was added
  5. filtrationAfter filtration and evaporation the residue
  6. customwas purified by HPLC

出典と根拠

ORDレコード
ord-9759262fdfcb40e19608b565f4632a73
出典データセット
uspto-grants-2013_06
特許番号
US08470837B2

反応ノート

読み込み中…