Diisopropylethylamine → N-{4-[2-Amino-5-(3,4-dimethoxyphenyl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1,4-dihydropyridine-3-carboxamide

HRID 1428083ノート

反応式

HRID 1428083 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:26])[C:10]([C:23]([OH:25])=O)=[CH:11][N:12]([CH2:14][CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[CH:13]=2)=[CH:4][CH:3]=1.C1C=NC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:70][C:71]1[CH:76]=[CH:75][C:74]([C:77]2[C:78]([NH2:93])=[N:79][CH:80]=[C:81]([C:83]3[CH:88]=[CH:87][C:86]([O:89][CH3:90])=[C:85]([O:91][CH3:92])[CH:84]=3)[CH:82]=2)=[CH:73][CH:72]=1>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[NH2:93][C:78]1[C:77]([C:74]2[CH:73]=[CH:72][C:71]([NH:70][C:23]([C:10]3[C:9](=[O:26])[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[CH:13][N:12]([CH2:14][CH2:15][O:16][CH:17]4[CH2:22][CH2:21][CH2:20][CH2:19][O:18]4)[CH:11]=3)=[O:25])=[CH:76][CH:75]=2)=[CH:82][C:81]([C:83]2[CH:88]=[CH:87][C:86]([O:89][CH3:90])=[C:85]([O:91][CH3:92])[CH:84]=2)=[CH:80][N:79]=1

参加物

9

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86700031HCID 86700031、化合物HCID 867000345-(4-Fluorophenyl)-4-oxo-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1,4-dihydropyridine-3-carboxylic acid

生成物 1

HCID 86700033N-{4-[2-Amino-5-(3,4-dimethoxyphenyl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1,4-dihydropyridine-3-carboxamide

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

5-(4-Fluorophenyl)-4-oxo-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1,4-dihydropyridine-3-carboxylic acid was dissolved in DMF (2 ml), and HOAt (41 mg), HATU (170 mg), DMAP (18 mg) and DIPEA (88 μl) were added at room temperature. The reaction mixture was stirred at room temperature for three hours. The compound obtained in Step 2 of Example 1 (96 mg) was added to the reaction mixture at room temperature, followed by stirring overnight. Water was added to the reaction mixture, and the precipitated solid was collected by filtration to give 281 mg of the crude purified title compound as a solid. One hundred forty one mg of the solid was purified by PLC [dichloromethane:methanol=20:1 (v/v)], and the eluate was concentrated under reduced pressure. The residue was purified by PLC [ethyl acetate:methanol=15:1 (v/v)] to give 72 mg of the title compound.

後処理

  1. stirringby stirring overnight
  2. filtrationthe precipitated solid was collected by filtration
  3. customto give 281 mg of the crude
  4. custompurified title compound as a solid
  5. customOne hundred forty one mg of the solid was purified by PLC [dichloromethane:methanol=20:1 (v/v)]
  6. concentrationthe eluate was concentrated under reduced pressure
  7. customThe residue was purified by PLC [ethyl acetate:methanol=15:1 (v/v)]

出典と根拠

ORDレコード
ord-6f356b773e8e4309922bce43fd656b1c
出典データセット
uspto-grants-2015_01
特許番号
US08933103B2

反応ノート

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