3-Aminopyridine → HCID 86679696, compound

HRID 1507118Notes

Reaction equation

HRID 1507118 reaction equation
CN(C(ON1N=[N:16][C:11]2[CH:12]=[CH:13][CH:14]=[N:15][C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][N:26]([CH3:54])[C:27](=[O:53])[NH:28][C:29]1[CH:30]=[C:31]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[N:40]([CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[N:39]=[C:38]3[C:50](O)=[O:51])[CH:32]=[N:33][CH:34]=1.C(N(C(C)C)CC)(C)C.NC1C=NC=CC=1>CN(C=O)C>[CH3:25][N:26]([CH3:54])[C:27](=[O:53])[NH:28][C:29]1[CH:30]=[C:31]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[N:40]([CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[N:39]=[C:38]3[C:50]([NH:16][C:11]2[CH:10]=[N:15][CH:14]=[CH:13][CH:12]=2)=[O:51])[CH:32]=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 100093-AminopyridineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86679694HCID 86679694, compound

Product 1

HCID 86679696HCID 86679696, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.190 g, 0.5 mmol) was added to a solution of 5-(5-(3,3-dimethylureido)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (CXXIV) (0.39 g, 1.21 mmol) and diisopropylethylamine (0.174 mL, 1.0 mmol) in DMF stirred at room temperature under argon. After stirring 5 min, the solution was added with 3-aminopyridine (CXXV) (0.047 g, 0.5 mmol). The solution was stirred overnight at room temperature under argon. The DMF was removed under reduced pressure, and the residue was treated with water, sonicated briefly and filtered. The solids were washed with cold water and dried at room temperature. The product was purified by column chromatography using a 4 g Thomson normal phase silica gel cartridge (100% DCM→5:95 MeOH:DCM) to afford 5-(5-(3,3-dimethylureido)pyridin-3-yl)-N-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide (CXXVI) as an off white solid (323 mg, 0.67 mmol, 55% yield). 1H NMR (DMSO-d6) δ ppm 10.56 (s, 1H), 9.06 (d, J=2.0 Hz, 1H), 8.75 (d, J=1.6 Hz, 1H), 8.64 (s, 1H), 8.53 (d, J=1.6 Hz, 1H), 8.46 (s, 1H), 8.34-8.29 (m, 2H), 8.26 (m, 1H), 8.03 (d, J=7.0 Hz, 1H), 7.88 (dd, J=7.0, 1.2 Hz, 1H), 7.43 (dd, J=6.64, 3.84 Hz, 1H), 6.07 (dd, J=8.0, 1.8 Hz, 1H), 3.98 (m, 1H), 3.82 (m, 1H), 2.98 (s, 6H), 2.63-2.60 (m, 1H), 2.11-2.06 (m, 2H), 1.83-1.81 (m, 1H) 1.52 (m, 2H); ESIMS found for C21H23N5O4 m/z 410.0 (M+H).

Workup

  1. stirringAfter stirring 5 min
  2. stirringThe solution was stirred overnight at room temperature under argon
  3. customThe DMF was removed under reduced pressure
  4. additionthe residue was treated with water
  5. customsonicated briefly
  6. filtrationfiltered
  7. washThe solids were washed with cold water
  8. customdried at room temperature
  9. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-33dee1f140bd4899840d62bb11fd264f
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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