Trifluoroacetic acid → HCID 59548292, compound

HRID 1811977Notes

Reaction equation

HRID 1811977 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 5 N NaOH and then with 5 N 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/2 N ammonia in MeOH to 10:1 DCM/2 N 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 5 N 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/2 N ammonia in MeOH to 10:1 DCM/2 N 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-76eec01b64db499381c84efd82745455
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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