Sodium Hydroxide → 4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621822Notes

Reaction equation

HRID 1621822 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]([C:43]([N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)([CH3:45])[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].FC(F)(F)S(O)(=O)=O.[OH-].[Na+]>C(O)(C(F)(F)F)=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]([C:43]([N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)([CH3:45])[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 666111624-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595483214-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 29.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.363 g, 0.522 mmol) in TFA (3 mL) was treated with trifluoromethanesulfonic acid (0.232 mL, 2.61 mmol). The reaction was sealed and heated at 80° C. for 30 min, cooled, and poured onto ice. The mixture was basified with 10N NaOH and the reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO and purified by prep HPLC (10-55% MeCN/H2O with 0.1% TFA). Product-containing fractions were treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×) and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.069 g, 0.152 mmol, 29.1% yield). m/z (ESI, +ve ion) 455 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.91 (s, 1H); 8.90 (d, J=2.5 Hz, 1H); 8.48 (d, J=2.5 Hz, 1H); 8.33-8.44 (m, 2H); 7.88 (br. s., 1H); 7.73 (br. s., 1H); 3.93 (s, 3H); 3.57 (br. s., 4H); 2.44 (s, 3H); 2.36-2.43 (m, 4H); 1.35 (s, 6H).

Workup

  1. customThe reaction was sealed
  2. temperaturecooled
  3. additionpoured onto ice
  4. customthe reaction was partitioned between water and DCM
  5. extractionThe aqueous layer was extracted with DCM (3×)
  6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThis material was dissolved in DMSO
  10. custompurified by prep HPLC (10-55% MeCN/H2O with 0.1% TFA)
  11. additionProduct-containing fractions were treated with sat'd aq. NaHCO3 and DCM
  12. extractionThe aq. layer was extracted with DCM (3×)
  13. dry with materialthe combined organic extracts were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4111ce05a15e4068ad00ae0ac654ae65
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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