Trifluoroacetic acid → HCID 86679697, compound

HRID 2367701Notes

Reaction equation

HRID 2367701 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][N:9]([CH3:43])[C:10](=[O:42])[NH:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23](C2CCCCO2)[N:22]=[C:21]3[C:33]([NH:35][C:36]2[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=2)=[O:34])[CH:15]=[N:16][CH:17]=1.C([SiH](CC)CC)C>C(Cl)Cl>[CH3:8][N:9]([CH3:43])[C:10](=[O:42])[NH:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][N:22]=[C:21]3[C:33]([NH:35][C:36]2[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=2)=[O:34])[CH:15]=[N:16][CH:17]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86679696HCID 86679696, compound

Product 1

HCID 86679697HCID 86679697, compoundYield 33.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (5 mL) was added to a solution of 5-(5-(3,3-dimethylureido)pyridin-3-yl)-N-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide (CXXVI) (0.134 g, 0.27 mmol) and triethylsilane (0.110 mL, 0.69 mmol) in DCM (5 mL) and stirred 3 h at room temperature. The solvent was removed under vacuum. The residue was treated with water, sonicated briefly to disperse the solids, basified to pH 9.0 with 5 N NH4OH and sonicated again. The solids were filtered, washed with cold water and purified by column chromatography (100% DCM→5:95 MeOH[7N NH3]:DCM) to afford 5-(5-(3,3-dimethylureido)pyridin-3-yl)-N-(pyridin-3-yl)-1H-indazole-3-carboxamide (1) as a white solid (35.8 mg, 0.09 mmol, 33% yield). 1H NMR (DMSO-d6) δ ppm 13.99 (s, 1H), 10.69 (s, 1H), 9.08 (d, J=1.2 Hz, 1H), 8.74 (d, J=1.8 Hz, 1H), 8.63 (s, 1H), 8.51 (d, J=1.5 Hz, 1H), 8.47 (s, 1H), 8.33-8.30 (m, 2H), 8.26 (m, 1H), 7.80 (s, 2H), 7.41 (dd, J=6.6, 3.6 Hz, 1H), 2.98 (s, 6H); ESIMS found for C21H19N7O2 m/z 402.3 (M+H).

Workup

  1. customThe solvent was removed under vacuum
  2. additionThe residue was treated with water
  3. customsonicated briefly
  4. additionto disperse the solids
  5. customsonicated again
  6. filtrationThe solids were filtered
  7. washwashed with cold water
  8. custompurified by column chromatography (100% DCM→5:95 MeOH[7N NH3]:DCM)

Sources & evidence

ORD record
ord-0f1f4be1b216401881396cd8215b1242
Source dataset
uspto-grants-2014_04
Patent number
US08697887B2

Reaction notes

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