Trifluoroacetic acid → HCID 59548292, compound

HRID 1621564Notes

Reaction equation

HRID 1621564 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:18]=3)=[CH:15][C:14]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([S:50]([CH3:53])(=[O:52])=[O:51])=[CH:46][CH:45]=3)=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].FC(F)(F)C(O)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:15][C:14]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([S:50]([CH3:53])(=[O:51])=[O:52])=[CH:46][CH:45]=3)=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66611607HCID 66611607, compound

Product 1

HCID 59548292HCID 59548292, compoundYield 24%

Conditions

Temperature
75 °C

Procedure

4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (384.7 mg, 0.5228 mmol) was dissolved in trifluoroacetic acid (Aldrich redistilled 99+%, 5.0 mL, 65 mmol) and the reaction flask was fitted with a reflux condenser and placed in a preheated oil bath (75° C.) and stirred overnight. Then, the reaction was cooled to room temperature, concentrated, and treated with saturated sodium bicarbonate and 5N NaOH and then with 5N HCl to adjust the pH to 6. Then, DCM was added and the layers were separated. The aqueous phase was filtered, and the collected solid was combined with the organic phase. The aqueous phase was extracted with DCM, and these organic extracts were combined with the organic phase, concentrated, and purified on a silica gel column (30:1 DCM/2N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH). The solvent polarity was increased after most of the product had eluted. The fractions with product were collected, concentrated, treated with MeOH, and filtered. The solid was washed with MeOH, collected, and dried under high vacuum. The material was <95% pure by HPLC, so the solid was washed with EtOAc, filtered, collected, and dried under high vacuum in a water bath (40° C.) and then at room temperature overnight to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (61.3 mg, 24% yield) as a yellow powder. 1H NMR (d6-DMSO, 400 MHz) δ 11.89 (s, 1H), 8.65 (d, J=2.15 Hz, 1H), 8.40 (d, J=2.15 Hz, 1H), 8.38-8.30 (m, 2H), 7.86 (d, J=8.22 Hz, 2H), 7.90-7.84 (m, 1H), 7.74 (br s, 1H), 7.53 (d, J=8.22 Hz, 2H), 4.09 (s, 2H), 3.93 (s, 3H), 3.17 (s, 3H), 2.41 (s, 3H). m/z (ESI, +ve ion) 496 (M+H)+.

Workup

  1. customthe reaction flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. concentrationconcentrated
  5. additiontreated with saturated sodium bicarbonate and 5N NaOH
  6. additionThen, DCM was added
  7. customthe layers were separated
  8. filtrationThe aqueous phase was filtered
  9. extractionThe aqueous phase was extracted with DCM
  10. concentrationconcentrated
  11. custompurified on a silica gel column (30:1 DCM/2N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH)
  12. temperatureThe solvent polarity was increased after most of the product
  13. washhad eluted
  14. customThe fractions with product were collected
  15. concentrationconcentrated
  16. additiontreated with MeOH
  17. filtrationfiltered
  18. washThe solid was washed with MeOH
  19. customcollected
  20. customdried under high vacuum
  21. washso the solid was washed with EtOAc
  22. filtrationfiltered
  23. customcollected
  24. customdried under high vacuum in a water bath (40° C.)

Sources & evidence

ORD record
ord-76abc17eb4e14c5e80c434bb7cf653d8
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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