Sodium Hydroxide → HCID 59548329, compound

HRID 1621819Notes

Reaction equation

HRID 1621819 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:34][C:35]4[CH:36]=[N:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=4)=[N:17][CH:18]=[C:19]([C:21]([N:24]4[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]4)([CH3:23])[CH3:22])[CH:20]=3)[N:12]=[C:11]([CH3:43])[N:10]=2)=CC=1.OS(C(F)(F)F)(=O)=O.[OH-].[Na+]>FC(F)(F)C(O)=O>[CH3:42][O:41][C:38]1[N:37]=[CH:36][C:35]([NH:34][C:16]2[C:15]([C:13]3[N:12]=[C:11]([CH3:43])[N:10]=[C:9]([NH2:8])[N:14]=3)=[CH:20][C:19]([C:21]([N:24]3[CH2:25][CH2:26][N:27]([S:30]([CH3:33])(=[O:31])=[O:32])[CH2:28][CH2:29]3)([CH3:23])[CH3:22])=[CH:18][N:17]=2)=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 66600572HCID 66600572, compound

Product 1

HCID 59548329HCID 59548329, compoundYield 26.7%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(2-(4-(methylsulfonyl)piperazin-1-yl)propan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.034 g, 0.045 mmol) in trifluoroacetic acid (1 mL) was treated with triflic acid (0.032 mL, 0.361 mmol). The light yellow reaction was sealed and heated at 80° C. After 30 min the reaction was cooled with ice and basified with 10N NaOH, then partitioned between water and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO and purified by prep HPLC (5-70% MeCN/H2O with 0.1% TFA). Product-containing fractions were concentrated, then treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(2-(4-(methylsulfonyl)piperazin-1-yl)propan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.006 g, 0.012 mmol, 25.9% yield) as a yellow solid. m/z (ESI, +ve ion) 514 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.70 (s, 1H); 8.83 (d, J=2.5 Hz, 1H); 8.53 (d, J=2.7 Hz, 1H); 8.45 (d, J=2.5 Hz, 1H); 8.19 (dd, J=8.9, 2.8 Hz, 1H); 7.61-7.93 (m, 2H); 6.81 (d, J=9.0Hz, 1H); 3.84 (s, 3H); 3.01-3.16 (m, 4H); 2.86 (s, 3H); 2.48-2.63 (m, 4H); 2.44 (s, 3H); 1.36 (s, 6H).

Workup

  1. customThe light yellow reaction
  2. customwas sealed
  3. custompartitioned between water and DCM
  4. extractionThe aqueous layer was extracted with DCM (3×)
  5. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThis material was dissolved in DMSO
  9. custompurified by prep HPLC (5-70% MeCN/H2O with 0.1% TFA)
  10. concentrationProduct-containing fractions were concentrated
  11. additiontreated with sat'd aq. NaHCO3 and DCM
  12. extractionThe aq. layer was extracted with DCM (3×)
  13. dry with materialthe combined organic layers were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab8e6b25a7cf4bd685c7215bd59b2828
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…