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Sodium hydride → 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

HRID 2085098
ノート
印刷プレビュー

反応式

HRID 2085098 の反応式
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:29][CH2:30][C:31]#[C:32][CH2:33][OH:34])[N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2].[H-].[Na+].[CH3:37][O:38][C:39]1[CH:44]=[C:43]([O:45][CH3:46])[N:42]=[C:41](S(C)(=O)=O)[N:40]=1>C1COCC1>[NH3:8].[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:29][CH2:30][C:31]#[C:32][CH2:33][O:34][C:41]3[N:42]=[C:43]([O:45][CH3:46])[CH:44]=[C:39]([O:38][CH3:37])[N:40]=3)[N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 8383634,6-Dimethoxy-2-(methylsulfonyl)pyrimidineHCID 101408715-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

生成物 2

HCID 222AmmoniaHCID 101458055-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide
収率 44.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 250 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 13) in 15 ml of THF was added 48 mg of NaH. The mixture was stirred for 2 h at room temperature before 120 mg of 4,6-dimethoxy-2-methylsulfonylpyrimidine was added. Stirring was continued for 16 h at reflux. Eventually, the solvent was evaporated and the remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate. The organic layer was separated and the aqueous layer was extracted two more times with 50 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates coated with silica gel with ethyl acetate:methanol: sat. aqueous ammonia 8:2:1 to give 71 mg of 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide as a beige foam. LC-MS: tR=5.50 min, [M+1]+=623.29, [M−1]+=621.40.

後処理

  1. additionwas added
  2. temperatureat reflux
  3. customEventually, the solvent was evaporated
  4. customthe remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted two more times with 50 ml of ethyl acetate
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over MgSO4
  9. customevaporated
  10. customThe crude product was purified by chromatography on prep

出典と根拠

ORDレコード
ord-a4743327dc0a43289390ad90d9a8acd7
出典データセット
uspto-grants-2004_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06720322B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート