Pivaloyl chloride → HCID 91192837、化合物

HRID 397993ノート

反応式

HRID 397993 の反応式
[CH2:1]([NH:9][C:10]1[N:18]=[C:17]([NH:19][CH2:20][CH2:21][C:22]2[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=2)[N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@H:28]1[C@@H:32]2[O:33]C(C)(C)[O:35][C@@H:31]2[C@@H:30]([C:38]([OH:40])=O)[O:29]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CC(C)(C)[C:52](Cl)=[O:53].O[NH:58][C:59](=[NH:62])[CH2:60][CH3:61].C(Cl)Cl.C1C[O:69][CH2:68]C1>FC(F)(F)C(O)=O.O>[CH:68]([O:33][C@@H:32]1[C@H:31]([O:35][CH:52]=[O:53])[C@@H:30]([C:38]2[O:40][N:62]=[C:59]([CH2:60][CH3:61])[N:58]=2)[O:29][C@H:28]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([NH:19][CH2:20][CH2:21][C:22]1[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=1)=[N:18][C:10]=2[NH:9][CH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:69]

参加物

7

反応物 5

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 21919333Tetrahydrofurane dichloromethaneHCID 70021813HCID 70021813、化合物HCID 178458070HCID 178458070、化合物

生成物 1

HCID 91192837HCID 91192837、化合物

試薬・触媒・溶媒 1

HCID 22392675Trifluoroacetic acid water溶媒

実験手順

Intermediate 34 (0.083 mg, 0.15 mmol) was dissolved in DCM/THF (9:1, 3 ml) using sonication by ultrasound. N,N-diisopropylethylamine (0.057 ml, 3.32 mmol) and trimethylacetyl chloride (0.021 ml, 0.16 mmol) were added at 0° C. with stirring under nitrogen. The reaction was allowed to warm to room temperature over 2 h, cooled again to 0° C. and N-hydroxy-propionamidine (0.015 g, 0.18 mmol in 0.5 ml tetrahydrofuran) added with stirring. The reaction was allowed to warm to room temperature and stirred for 16 h. The solvents were evaporated in vacuo and the reaction mixture dissolved in toluene (10 ml). The reaction was heated to reflux (120° C.) for 8 h. The product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size) eluting with ethyl acetate/methanol (50:1-1:1) to afford crude product as a yellow oil (0.01 g). The product dissolved in trifluoroacetic acid/water (4 ml, 9:1) at 0° C. with stirring under nitrogen for 4 h. The solvents were evaporated in vacuo, azeotroped with toluene (2×50 ml) and purification using Autoprep. HPLC afforded title compound as yellow gum (0.004 g) LCMS SYSTEM C Rt=2.39 min m/z=561 MH+

後処理

  1. customsonication by ultrasound
  2. temperaturecooled again to 0° C.
  3. stirringwith stirring
  4. temperatureto warm to room temperature
  5. stirringstirred for 16 h
  6. customThe solvents were evaporated in vacuo
  7. dissolutionthe reaction mixture dissolved in toluene (10 ml)
  8. temperatureThe reaction was heated
  9. temperatureto reflux (120° C.) for 8 h
  10. customThe product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size)
  11. washeluting with ethyl acetate/methanol (50:1-1:1)
  12. customto afford crude product as a yellow oil (0.01 g)
  13. stirringwith stirring under nitrogen for 4 h
  14. customThe solvents were evaporated in vacuo
  15. customazeotroped with toluene (2×50 ml) and purification

出典と根拠

ORDレコード
ord-9897c69ee8f946ec83c949718f6abc9d
出典データセット
uspto-grants-2003_08
特許番号
US06610665B1

反応ノート

読み込み中…