Trifluoroacetic acid → Trifluoroacetic acid

HRID 1522598Notes

Reaction equation

HRID 1522598 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:34])=[C:6]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[N:22][N:23](CC5C=CC(OC)=CC=5)[C:16]=34)[C:11]([CH3:33])=[CH:10][N:9]=2)[CH:7]=1.ClC1C=CC(F)=C(C2C=C(NC3C4C(=CN(CC5C=CC(OC)=CC=5)N=4)N=CC=3)C(C)=CN=2)C=1.[C:69]([OH:75])([C:71]([F:74])([F:73])[F:72])=[O:70]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:34])=[C:6]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[N:22][NH:23][C:16]=34)[C:11]([CH3:33])=[CH:10][N:9]=2)[CH:7]=1.[C:69]([OH:75])([C:71]([F:74])([F:73])[F:72])=[O:70]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67469556HCID 67469556, compoundHCID 67470392HCID 67470392, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 54670128HCID 54670128, compound

Conditions

Temperature
70 °C

Procedure

To the flask containing N-(2-(5-chloro-2-fluorophenyl)-5-methylpyridin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-7-amine and N-(2-(5-chloro-2-fluorophenyl)-5-methylpyridin-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-b]pyridin-7-amine (0.561, 1.184) was added TFA (5.9 mL) and the mixture was stirred at 70° C. for 3 hours. The reaction was cooled to room temperature and concentrated under vacuum to a dark amber residue. To this residue was combined with dichloromethane (25 mL) and saturated sodium carbonate solution (25 mL) resulting in a precipitate which was filtered, rinsed with dichloromethane and water and dissolved in EtOAc, then extracted with water and saturated sodium bicarbonate The organic layer was separated, dried over sodium sulfate, and concentrated to give a yellow solid that was purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 18-25% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give the title compound as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30-2.40 (m, 3H) 7.42 (dd, J=10.86, 8.84 Hz, 1H) 7.53-7.67 (m, 1H) 7.79 (br. s., 1H) 7.94-8.04 (m, 1H) 8.46 (d, J=5.81 Hz, 1H) 8.76 (s, 1H). MS [M+H] found 354.2.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated under vacuum to a dark amber residue
  3. customresulting in a precipitate which
  4. filtrationwas filtered
  5. washrinsed with dichloromethane and water
  6. dissolutiondissolved in EtOAc
  7. extractionextracted with water and saturated sodium bicarbonate The organic layer
  8. customwas separated
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customto give a yellow solid
  12. customthat was purified by preparative HPLC
  13. washeluting with a gradient of 18-25% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-1490e380a204494faf17ee2569effaf7
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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