Trifluoroacetic acid → HCID 178460086, compound

HRID 82080Notes

Reaction equation

HRID 82080 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:22])[CH2:20][CH3:21])[CH:15]=[N:16][CH:17]=3)[CH:10]=2)[N:5](C2CCCCO2)[N:4]=1)=O.[S].[N:30]1[CH:35]=[C:34]([NH2:36])[C:33]([NH2:37])=[C:32]([C:38]2[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=2)[CH:31]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>CN(C=O)C>[N:40]1[CH:41]=[CH:42][CH:43]=[C:38]([C:32]2[C:33]3[N:37]=[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:22])[CH2:20][CH3:21])[CH:15]=[N:16][CH:17]=6)[CH:10]=5)[NH:5][N:4]=4)[NH:36][C:34]=3[CH:35]=[N:30][CH:31]=2)[CH:39]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 5362487SulfurHCID 46315401[3,3'-Bipyridine]-4,5-diamineHCID 58377773N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide

Product 1

HCID 178460086HCID 178460086, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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)propionamide (LX) (1 eq), sulfur (1 eq) and 3,3′-bipyridine-4,5-diamine (XLVIII) (1 eq) in DMF was heated overnight at 140° C. under argon. The solution was cooled and the DMF was distilled under vacuum. The residue was taken in DCM. Triethylsilane (2.5 eq) followed by TFA (30% by volume) was added to the solution and stirred for 2 h at room temperature until TLC showed disappearance of starting material. The solvent was removed under vacuum. Water was added to the residue, sonicated briefly and basified with 5 N NH4OH solution. The solids formed were filtered, washed with cold water and dried at room temperature. The solids were triturated with DCM followed by MeOH to get N-(5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide (47) as a brown solid (49% yield). 1H NMR (DMSO-d6, 400 MHz,): δ 1.67 (t, J=6 Hz, 3H), 2.45 (q, J=6 Hz, 2H), 7.62 (m, 1H), 8.50 (s, 1H), 8.62 (m, 1H), 8.72 (s, 1H), 8.77 (m, 3H), 8.91 (m, 1H), 8.99 (m, 2H), 9.41 (s, 1H), 10.31 (s, 1H), 13.95 (s, 1H), 14.62 (s, 1H). ESIMS found C25H19N9O m/z 462.50 (M+H).

Workup

  1. temperatureThe solution was cooled
  2. distillationthe DMF was distilled under vacuum
  3. additionwas added to the solution
  4. customThe solvent was removed under vacuum
  5. additionWater was added to the residue
  6. customsonicated briefly
  7. customThe solids formed
  8. filtrationwere filtered
  9. washwashed with cold water
  10. customdried at room temperature
  11. customThe solids were triturated with DCM

Sources & evidence

ORD record
ord-0c30cd89305a4f8b9ebcd90ad5f0ea5a
Source dataset
uspto-grants-2014_09
Patent number
US08846714B2

Reaction notes

Loading…