Trifluoroacetic acid → HCID 59548462, compound

HRID 1621562Notes

Reaction equation

HRID 1621562 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([C:15]3[C:16]([NH:32][C:33]4[CH:34]=[N:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=4)=[N:17][CH:18]=[C:19]([CH2:21][C:22]4[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=4)[CH:20]=3)[N:12]=[C:11]([CH3:41])[N:10]=2)=CC=1.FC(F)(F)C(O)=O>>[CH3:40][O:39][C:36]1[N:35]=[CH:34][C:33]([NH:32][C:16]2[C:15]([C:13]3[N:12]=[C:11]([CH3:41])[N:10]=[C:9]([NH2:8])[N:14]=3)=[CH:20][C:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=3)=[CH:18][N:17]=2)=[CH:38][CH:37]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 60156086HCID 60156086, compound

Product 1

HCID 59548462HCID 59548462, compoundYield 46%

Conditions

Temperature
75 °C

Procedure

N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (412 mg, 0.574 mmol) was suspended in trifluoroacetic acid (Aldrich redistilled 99+%, 6.0 mL, 78 mmol) and the flask was fitted with a reflux condenser and put in a preheated oil bath (75° C.) and the reaction was stirred overnight. Then, the reaction was cooled to room temperature and concentrated and diluted with saturated sodium bicarbonate and then with 5N NaOH to raise the pH to about 8-9. The suspension was filtered, and the solid was washed with water. The filtrate was discarded, and the solid was collected with DCM and MeOH, concentrated, treated with MeOH, and filtered. The solid was washed with MeOH. The solid was not >95% pure by HPLC, so the filtrate and solid were combined, concentrated, and purified on a silica gel column (30:1 to 20:1 DCM/MeOH). The fractions with product were collected, concentrated, treated with MeOH, and filtered. The yellow solid was washed with MeOH, collected, and dried under high vacuum at room temperature overnight to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (126.1 mg, 46% yield) as a yellow powder. 1H NMR (CDCl3, 400 MHz) δ 11.64 (s, 1H), 8.65 (d, J=2.15 Hz, 1H), 8.36 (d, J=2.35 Hz, 1H), 8.17 (d, J=1.56 Hz, 1H), 8.11 (dd, J=8.90 Hz, 2.25 Hz, 1H), 7.88 (d, J=8.22 Hz, 2H), 7.42 (d, J=7.82 Hz, 2H), 6.78 (d, J=8.80 Hz, 1H), 5.36 (br s, 2H), 4.04 (s, 2H), 3.95 (s, 3H), 3.04 (s, 3H), 2.56 (s, 3H). m/z (ESI, +ve ion) 478 (M+H)+.

Workup

  1. customthe flask was fitted with a reflux condenser
  2. customput in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. concentrationconcentrated
  5. additiondiluted with saturated sodium bicarbonate
  6. temperaturewith 5N NaOH to raise the pH to about 8-9
  7. filtrationThe suspension was filtered
  8. washthe solid was washed with water
  9. customthe solid was collected with DCM and MeOH
  10. concentrationconcentrated
  11. additiontreated with MeOH
  12. filtrationfiltered
  13. washThe solid was washed with MeOH
  14. concentrationconcentrated
  15. custompurified on a silica gel column (30:1 to 20:1 DCM/MeOH)
  16. customThe fractions with product were collected
  17. concentrationconcentrated
  18. additiontreated with MeOH
  19. filtrationfiltered
  20. washThe yellow solid was washed with MeOH
  21. customcollected
  22. customdried under high vacuum at room temperature overnight

Sources & evidence

ORD record
ord-85a9f65f2758444f9706eff4a1137261
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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