Trifluoroacetic acid → HCID 71543584, compound

HRID 1522533Notes

Reaction equation

HRID 1522533 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH:76]1([NH2:79])[CH2:78][CH2:77]1.C(O)(C(F)(F)F)=O>O1CCOCC1.CS(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(#N)C>[CH:76]1([NH:79][C:2]2[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]3[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])=[O:16])[C:5]3[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=3[N:7]=2)[CH2:78][CH2:77]1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 69828CyclopropylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 565974266-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 71543584HCID 71543584, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (100 mg, 0.258 mmol) was dissolved in 1,4-dioxane (2.6 mL) followed by addition of cesium carbonate (336 mg, 1.031 mmol). After degassing with nitrogen for 5 min, Xantphos (44.8 mg, 0.077 mmol) was added. The mixture was degassed for 2 min, Pd2(dba)3 (35.4 mg, 0.039 mmol) was added, and then degassed for 1 min. Cyclopropanamine (0.090 mL, 1.289 mmol) was added and the contents sealed. The suspension was stirred for 3 h at 100° C. (heat block). The reaction mixture was poured onto water and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to a solid residue. The aq. layer was extracted with 10% MeOH/DCM (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to afford a solid. The combined solid residues were dissolved in DMSO and acetonitrile spiked with TFA, and purified by reverse phase HPLC (Gradient B: 10-70%. A: Water+0.1% TFA. B: CH3CN+0.1% TFA) The title compound was collected as 11 mg (10%); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.39-0.47 (m, 2 H), 0.68-0.76 (m, 2 H), 1.39 (d, J=6.57 Hz, 6 H), 2.11 (s, 3 H), 2.24 (s, 3 H), 2.20 (s, 3 H), 2.64-2.72 (m, 1 H), 4.30 (d, J=4.80 Hz, 2 H), 4.89 (quin, J=6.69 Hz, 1 H), 5.86 (s, 1 H), 6.34 (s, 1 H), 7.25 (d, J=3.03 Hz, 1 H), 8.41 (t, J=4.93 Hz, 1 H), 11.49 (s, 1 H). LCMS(ES) [M+H]+ 409.1

Workup

  1. customAfter degassing with nitrogen for 5 min
  2. customThe mixture was degassed for 2 min
  3. customdegassed for 1 min
  4. customthe contents sealed
  5. temperature(heat block)
  6. additionThe reaction mixture was poured onto water
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a solid residue
  11. extractionThe aq. layer was extracted with 10% MeOH/DCM (2×)
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto afford a solid
  16. custompurified by reverse phase HPLC (Gradient B
  17. customB: CH3CN+0.1% TFA) The title compound was collected as 11 mg (10%)

Sources & evidence

ORD record
ord-2b44796211214446827d3549279d0a23
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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