Isonicotinic Acid → HCID 136334030, compound

HRID 2089659Notes

Reaction equation

HRID 2089659 reaction equation
C(N(CC)CC)C.[N:8]1[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=1.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:32][C:33](=[N:67][C:68](=[O:75])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:34]1[CH:39]=[CH:38][C:37]([NH:40][CH:41]([C:54]2[CH:59]=[C:58]([O:60][CH3:61])[CH:57]=[C:56]([O:62][CH2:63][CH2:64]O)[C:55]=2[F:66])[C:42]2[NH:46][C:45](=[O:47])[N:44]([C:48]3[N:53]=[CH:52][CH:51]=[CH:50][N:49]=3)[N:43]=2)=[CH:36][CH:35]=1>CN(C1C=CN=CC=1)C.CN(C=O)C.ClCCl>[NH2:32][C:33](=[N:67][C:68](=[O:75])[C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=1)[C:34]1[CH:39]=[CH:38][C:37]([NH:40][CH:41]([C:42]2[NH:46][C:45](=[O:47])[N:44]([C:48]3[N:49]=[CH:50][CH:51]=[CH:52][N:53]=3)[N:43]=2)[C:54]2[C:55]([F:66])=[C:56]([CH:57]=[C:58]([O:60][CH3:61])[CH:59]=2)[O:62][CH2:63][CH2:64][O:15][C:14](=[O:16])[C:11]2[CH:12]=[CH:13][N:8]=[CH:9][CH:10]=2)=[CH:36][CH:35]=1

Participants

8

Reactant 4

HCID 5922Isonicotinic AcidHCID 8471TriethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 136334022N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide

Product 1

HCID 136334030HCID 136334030, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Under nitrogen atmosphere, triethylamine (0.348 mL) was added under ice-cooling to a mixture of 4-pyridinecarboxylic acid [CAS No. 55-22-1] (61.6 mg), TFFH (132 mg), and dichloromethane (5 mL), and the resulting mixture was stirred for 1 hour. To the mixture, a mixture of N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 1a, 150 mg), DMAP (5 mg), and DMF (2.5 mL) was added dropwise. After stirring the resulting mixture at room temperature for 3 days, the solvent in the mixture was concentrated under reduced pressure. The residue obtained was purified by reverse phase silica gel column chromatography (mixed solvent of acetonitrile-water, containing 0.1% of acetic acid) to obtain the captioned compound (188 mg).

Workup

  1. additionwas added dropwise
  2. concentrationthe solvent in the mixture was concentrated under reduced pressure
  3. customThe residue obtained
  4. customwas purified by reverse phase silica gel column chromatography (mixed solvent of acetonitrile-water, containing 0.1% of acetic acid)

Sources & evidence

ORD record
ord-8b5fdba5c75e4fde9485a7ae91543142
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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