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 1428083Notes

Reaction equation

HRID 1428083 reaction equation
[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

Participants

9

Reactant 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, compoundHCID 867000345-(4-Fluorophenyl)-4-oxo-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1,4-dihydropyridine-3-carboxylic acid

Product 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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)]

Sources & evidence

ORD record
ord-6f356b773e8e4309922bce43fd656b1c
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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