Hydrogen Peroxide → dibenzyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl phosphate

HRID 1916373ノート

反応式

HRID 1916373 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([OH:29])([CH3:28])[CH3:27])=[C:20]([O:30][CH3:31])[CH:19]=4)[CH:12]=[N:11][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.N1C=NC=N1.C(N(C(C)C)[P:41]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)(C)C.[OH:61]O.O>C(Cl)Cl>[P:41]([O:29][C:26]([CH3:28])([CH3:27])[CH2:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([N:13]2[C:14](=[O:17])[C:15]3[S:16][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[CH:9][C:10]=3[N:11]=[CH:12]2)=[CH:19][C:20]=1[O:30][CH3:31])([O:42][CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)([O:50][CH2:51][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1)=[O:61]

参加物

7

反応物 5

HCID 784Hydrogen PeroxideHCID 962WaterHCID 92571H-1,2,4-TriazoleHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 167186196-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one

生成物 1

HCID 58858116dibenzyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl phosphate収率 80%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A suspension of 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (Example 82) (3.00 g; 6.56 mmol), 1,2,4-triazole (1.36 g; 19.7 mmol) and dibenzyl N,N-diisopropylphosphoramidite (6.62 mL; 19.7 mmol) in 40 mL of CH2Cl2 was heated at reflux for 16 h. The solution was cooled to rt, 30% H2O2 in water (4.00 mL; 35.3 mmol) was added and the solution stirred at rt for 2.5 h. The solution was diluted with CH2Cl2, washed with 1M sodium metabisulfite, 1N HCl, water and brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient) to afford 3.79 g (80%) of the title compound as a white solid. 1H NMR (CDCl3) δ 1.65 (s, 6H), 3.75 (s, 3H), 4.07 (s, 2H), 5.04-5.06 (m, 4H), 6.87-6.96 (m, 3H), 7.29-7.35 (m, 10H), 7.44 (d, J=8.24 Hz, 2H), 7.53 (s, 1H), 7.66 (d, J=8.25 Hz, 2H), 8.10 (s, 1H); 13C NMR (CDCl3) δ 22.56, 25.04, 56.08, 68.98, 69.03, 75.36, 82.87, 111.30, 113.91, 119.15, 120.87, 127.42, 127.67, 127.88, 128.33, 128.48, 129.47, 130.33, 131.54, 135.69, 136.07, 148.19, 149.10, 150.19, 151.63, 156.79, 157.37; HPLC (Method #1) 4.85 min retention time, (100%); MS (ES): m/z 717 [M+H]+.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. washwashed with 1M sodium metabisulfite, 1N HCl, water and brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient)

出典と根拠

ORDレコード
ord-b7f5a93d6a74460a9e5ee988824e7d87
出典データセット
uspto-grants-2013_12
特許番号
US08618115B2

反応ノート

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