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Hydrochloric Acid → 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

HRID 1042273
ノート
印刷プレビュー

反応式

HRID 1042273 の反応式
[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[NH:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.[CH3:22][O:23][C:24]1[CH:46]=[CH:45][C:27]([CH2:28][N:29]2[CH:37]=[N:36][C:35]3[C:30]2=[N:31][CH:32]=[N:33][C:34]=3[C:38]2[C:39](F)=[N:40][CH:41]=[CH:42][CH:43]=2)=[CH:26][CH:25]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl.C([O-])(O)=O.[Na+]>C1COCC1>[CH3:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([CH2:28][N:29]2[CH:37]=[N:36][C:35]3[C:30]2=[N:31][CH:32]=[N:33][C:34]=3[C:38]2[C:39]([NH:1][C:2]3[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]4[C:3]=3[CH:4]=[CH:5][N:6]=[C:7]4[NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)=[N:40][CH:41]=[CH:42][CH:43]=2)=[CH:45][CH:46]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 59627379HCID 59627379、化合物HCID 687254604-(5-Amino-6-methylisoquinolin-1-ylamino)benzonitrile

生成物 1

HCID 687244614-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.250 g, 0.91 mmol) and 9-(4-methoxybenzyl)-6-(2-fluoropyridin-3-yl)-9H-purine (0.34 g, 1.0 mmol) in anhydrous THF (20 mL) was treated dropwise with lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 2.7 mlL, 2.7 mmol) to give a dark suspension. The suspension was sonicated for 2 min and then stirred at RT for 30 min. The reaction mixture was sonicated again for 2 min. The mixture was treated with 1N aq HCl (5 mL) and stirred at RT for 10 min. The reaction mixture was added to satd NaHCO3 (70 mL) and extracted with 3:1 CHCl3:IPA (3×50 mL). The combined organic layers were washed with satd NaCl, dried over Na2SO4, filtered, and concentrated in vacuo to give 840 mg crude product. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (80 g), eluting with a gradient of 10% to 50% EtOAc in CH2Cl2, to give 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 590.2 [M+H]+

後処理

  1. customto give a dark suspension
  2. customThe suspension was sonicated for 2 min
  3. customThe reaction mixture was sonicated again for 2 min
  4. stirringstirred at RT for 10 min
  5. extractionextracted with 3:1 CHCl3
  6. washThe combined organic layers were washed with satd NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give 840 mg crude product
  11. customchromatographed through a Redi-Sep® pre-packed silica gel column (80 g)
  12. washeluting with a gradient of 10% to 50% EtOAc in CH2Cl2

出典と根拠

ORDレコード
ord-6516a53259c5435e9f881a76fbbe0139
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08557830B2

反応ノート

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