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Methanesulfonyl chloride → 2-Amino-5-(4-chloromethyl-2-methoxybenzyl)-6-methylpyrimidin-4-yl 2,4,6-triisopropylbenzenesulfonate

HRID 2207105
ノート
印刷プレビュー

反応式

HRID 2207105 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16]O)=[CH:12][C:11]=2[O:18][CH3:19])=[C:4]([CH3:20])[N:3]=1.C(N(CC)C(C)C)(C)C.[CH:30]([C:33]1[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[C:35]([CH:42]([CH3:44])[CH3:43])[C:34]=1[S:45](Cl)(=[O:47])=[O:46])([CH3:32])[CH3:31].[Cl-].[Li+].CS([Cl:55])(=O)=O>O1CCCC1.O>[CH:42]([C:35]1[CH:36]=[C:37]([CH:39]([CH3:40])[CH3:41])[CH:38]=[C:33]([CH:30]([CH3:32])[CH3:31])[C:34]=1[S:45]([O:8][C:6]1[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][Cl:55])=[CH:12][C:11]=2[O:18][CH3:19])=[C:4]([CH3:20])[N:3]=[C:2]([NH2:1])[N:7]=1)(=[O:47])=[O:46])([CH3:43])[CH3:44]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 31297Methanesulfonyl chlorideHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 178492557HCID 178492557、化合物

生成物 1

HCID 1179927752-Amino-5-(4-chloromethyl-2-methoxybenzyl)-6-methylpyrimidin-4-yl 2,4,6-triisopropylbenzenesulfonate
収率 66.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-amino-5-(4-hydroxymethyl-2-methoxybenzyl)-6-methylpyrimidin-4-ol (5.0 g) and N,N-diisopropylethylamine (11.7 g) in tetrahydrofuran (50 g), 2,4,6-triisopropylbenzenesulfonyl chloride (8.3 g) was added and refluxed for 10 h. After cooling to RT, lithium chloride (2.3 g) was added to the reaction mixture and stirred for 0.5 h, methanesulfonyl chloride (4.2 g) was added over 0.25 h dropwise and the reaction mixture was stirred for 4 h at RT. To the reaction mixture, water (25 g) was added and extracted with ethyl acetate (25 g). The organic layer was washed with water (25 mL) and concentrated in vacuo. To the residue, toluene (20 g) was added and concentrated on vacuo to obtain a light brown solid. The solid was precipitated with toluene (30 g) to obtain sub-title compound (6.8 g). 1H-NMR (300 MHz, CDCl3) δ 7.17 (2H, s), 6.90-6.82 (3H, m), 5.16 (2H, brs), 4.55 (2H, s), 4.10 (2H, septet, J=6.8 Hz), 3.82 (3H, s), 3.81 (2H, s), 2.91 (1H, septet, J=6.8 Hz), 2.32 (3H, s), 1.25 (6H, d, J=7.2 Hz), 1.19 (12H, d, J=6.8 Hz)

後処理

  1. temperaturerefluxed for 10 h
  2. stirringthe reaction mixture was stirred for 4 h at RT
  3. extractionextracted with ethyl acetate (25 g)
  4. washThe organic layer was washed with water (25 mL)
  5. concentrationconcentrated in vacuo
  6. additionTo the residue, toluene (20 g) was added
  7. concentrationconcentrated on vacuo
  8. customto obtain a light brown solid
  9. customThe solid was precipitated with toluene (30 g)

出典と根拠

ORDレコード
ord-d2d4a30109c24b33aac73bffec4f2ed0
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09376398B2

反応ノート

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