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Diisopropylamine → 2-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(3-hydroxy-3-methylbut-1-yn-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one

HRID 510135
ノート
印刷プレビュー

反応式

HRID 510135 の反応式
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)=[C:16](I)[N:15]=2)=[N:6]1.[CH3:30][C:31]([OH:35])([C:33]#[CH:34])[CH3:32].C(NC(C)C)(C)C.C(OCC)(=O)C>O1CCCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1CCCCC1>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)=[C:16]([C:34]#[C:33][C:31]([OH:35])([CH3:32])[CH3:30])[N:15]=2)=[N:6]1
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 7912DiisopropylamineHCID 82582-Methyl-3-butyn-2-olHCID 8857Ethyl AcetateHCID 867200522-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-iodo-7-methyl-7,9-dihydro-8H-purin-8-one

生成物 1

HCID 867200562-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(3-hydroxy-3-methylbut-1-yn-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one収率 24.1%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 8028Tetrahydrofuran溶媒HCID 8078Cyclohexane溶媒

実験手順

0.5 g (0.997 mmol) of the compound obtained in example 107 in tetrahydrofuran (10 ml) was admixed under argon with 251 mg (2.992 mmol) of 2-methyl-3-butyn-2-ol, 0.419 ml (2.992 mmol) of diisopropylamine, 57 mg (0.299 mmol) of copper(I) iodide and 140 mg (0.199 mmol) of dichlorobis(triphenylphosphine)palladium(II). Subsequently, the mixture was stirred at RT overnight and then heated to reflux for 10 h. After cooling, the mixture was filtered. The filtrate was concentrated, slurried in acetonitrile, water and a small amount of dimethylformamide, and filtered once again. The filtrate thus obtained was admixed with ethyl acetate and cyclohexane and stirred briefly, the precipitated residue was filtered off, and the filtrate was concentrated and purified by means of preparative HPLC (acetonitrile: water+5% trifluoroacetic acid)−gradient. 110 mg of the title compound were obtained (23% of theory).

後処理

  1. temperatureheated
  2. temperatureto reflux for 10 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. concentrationThe filtrate was concentrated
  6. filtrationwater and a small amount of dimethylformamide, and filtered once again
  7. customThe filtrate thus obtained
  8. stirringstirred briefly
  9. filtrationthe precipitated residue was filtered off
  10. concentrationthe filtrate was concentrated
  11. custompurified by means of preparative HPLC (acetonitrile: water+5% trifluoroacetic acid)−gradient

出典と根拠

ORDレコード
ord-8ac39b4be23e44a08cedc94f34f43a57
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09096592B2

反応ノート

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