Trifluoroacetic acid → HCID 54671063, compound

HRID 1522581Notes

Reaction equation

HRID 1522581 reaction equation
[F:1][C:2]1[C:3](I)=[C:4]2[N:10](CCOC)[N:9]=[CH:8][C:5]2=[N:6][CH:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)[C:25]=2[O:24][C:23]2C1=CC=C[C:22]=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].[Cl:64][C:65]1[CH:66]=[CH:67][C:68]([F:79])=[C:69]([C:71]2[CH:76]=[C:75]([NH2:77])[C:74]([CH3:78])=[CH:73][N:72]=2)[CH:70]=1.C(O)(C(F)(F)F)=O>O1CCOCC1.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]>[Cl:64][C:65]1[CH:66]=[CH:67][C:68]([F:79])=[C:69]([C:71]2[CH:76]=[C:75]([NH:77][C:3]3[C:4]4[C:5](=[CH:8][N:9]([CH2:22][CH2:23][O:24][CH3:25])[N:10]=4)[N:6]=[CH:7][C:2]=3[F:1])[C:74]([CH3:78])=[CH:73][N:72]=2)[CH:70]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 67469591HCID 67469591, compoundHCID 67470393HCID 67470393, compound

Product 1

HCID 54671063HCID 54671063, compoundYield 199.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

6-Fluoro-7-iodo-1-(2-methoxyethyl)-1H-pyrazolo[4,3-b]pyridine (45 mg, 0.140 mmol) were combined in dioxane (4 mL) and the following was added sequentially (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.27 mg, 0.035 mmol), Tris(dibenzylideneacetone)dipalladium(0) (32.1 mg, 0.035 mmol), sodium tert-butoxide (40.4 mg, 0.420 mmol) and 2-(5-chloro-2-fluorophenyl)-5-methylpyridin-4-amine (7) (33.2 mg, 0.140 mmol). The reaction vessel was sealed and heated at 110° C. for an hour. The mixture was then cooled, evaporated to dryness, the residue was dissolved in DMF and purified by preparative HPLC (eluting with gradient of 20-45% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column) to give the title compound (30 mg, 49.8% yield) as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H) 3.12 (s, 3H) 3.59-3.81 (m, 2H) 4.57 (t, J=5.18 Hz, 2H) 7.09 (s, 1H) 7.42 (dd, J=10.11, 9.09 Hz, 1H) 7.55-7.70 (m, 1H) 7.77 (dd, J=6.44, 2.65 Hz, 1H) 8.53 (s, 1H) 8.67 (br. s., 1H) 8.80 (s, 1H) 9.70 (br. s., 1H). MS [M+H] found 430.3.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe mixture was then cooled
  3. customevaporated to dryness
  4. dissolutionthe residue was dissolved in DMF
  5. custompurified by preparative HPLC (
  6. washeluting with gradient of 20-45% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-bff5b6e1e0f44d15807ee37af7daf4d5
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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