Trifluoroacetic acid → HCID 178447236, compound

HRID 1472201Notes

Reaction equation

HRID 1472201 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=[N:16][CH:17]=3)[CH:10]=2)[N:5](C2CCCCO2)[N:4]=1)=O.[S].[F:32][C:33]1[CH:34]=[C:35]([C:39]2[C:40]([NH2:46])=[C:41]([NH2:45])[CH:42]=[N:43][CH:44]=2)[CH:36]=[CH:37][CH:38]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(O)CCC>[F:32][C:33]1[CH:34]=[C:35]([C:39]2[C:40]3[N:46]=[C:1]([C:3]4[C:11]5[C:6](=[N:7][CH:8]=[C:9]([C:12]6[CH:13]=[C:14]([NH:18][C:19](=[O:24])[C:20]([CH3:22])([CH3:21])[CH3:23])[CH:15]=[N:16][CH:17]=6)[CH:10]=5)[NH:5][N:4]=4)[NH:45][C:41]=3[CH:42]=[N:43][CH:44]=2)[CH:36]=[CH:37][CH:38]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 5362487SulfurHCID 463121005-(3-Fluorophenyl)pyridine-3,4-diamineHCID 86701079N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide

Product 1

HCID 178447236HCID 178447236, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide (LXV) (75 mg, 0.18 mmol), sulfur (64 mg, 0.20 mmol) and 5-(3-fluorophenyl)pyridine-3,4-diamine (XL) (41 mg, 0.20 mmol) in n-butanol (10 mL) was refluxed overnight under argon. The solution was cooled and filtered and dried under vacuum for 1 h. The residue was taken in dry DCM (5 mL). Triethylsilane (72 μL, 0.45 mmol) followed by TFA (2.5 mL) was added to the solution and stirred for 2 h at room temperature. The solvent was removed under vacuum. Water was added to the residue, sonicated briefly and basified with a 5N NH4OH solution. The solids formed were filtered, washed with cold water and dried at room temperature. The solids were boiled in DCM, cooled to room temperature and sonicated briefly. The solids were filtered, washed with DCM and dried under vacuum to give N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide (2) as a brown solid (66 mg, 0.13 mmol, 72% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 1.30 (s, 9H), 7.22 (t, 1H), 7.57-7.66 (m, 1H), 8.25 (d, 1H), 8.36 (d, 1H), 8.55 (s, 1H), 8.74 (s, 1H), 8.78 (s, 1H), 8.89 (s, 1H), 8.97 (s, 1H), 9.04 (s, 1H), 9.07 (s, 1H), 9.61 (s, 1H), 13.92 (brs, 1H), 14.63 (brs, 1H); ESIMS found C28H23FN8O m/z 507.5 (M+H).

Workup

  1. temperatureThe solution was cooled
  2. filtrationfiltered
  3. customdried under vacuum for 1 h
  4. additionwas added to the solution
  5. customThe solvent was removed under vacuum
  6. additionWater was added to the residue
  7. customsonicated briefly
  8. customThe solids formed
  9. filtrationwere filtered
  10. washwashed with cold water
  11. customdried at room temperature
  12. temperaturecooled to room temperature
  13. customsonicated briefly
  14. filtrationThe solids were filtered
  15. washwashed with DCM
  16. customdried under vacuum

Sources & evidence

ORD record
ord-5a2fe9f8ba814ee6b841a9b4b451048a
Source dataset
uspto-grants-2015_04
Patent number
US09012472B2

Reaction notes

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