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

HRID 1621818Notes

Reaction equation

HRID 1621818 reaction equation
[NH2:1][C:2]([C:5]1[CH:6]=[C:7]([C:20]2[N:25]=[C:24]([CH3:26])[N:23]=[C:22]([N:27](CC3C=CC([O:44][CH3:45])=CC=3)CC3C=CC(OC)=CC=3)[N:21]=2)[C:8]([NH:11][C:12]2[CH:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)=[N:9][CH:10]=1)([CH3:4])[CH3:3].OS([C:50]([F:53])([F:52])[F:51])(=O)=O.[OH-:54].[Na+]>C(O)(C(F)(F)F)=O>[F:51][C:50]([F:53])([F:52])[C:45]([OH:44])=[O:54].[NH2:1][C:2]([C:5]1[CH:6]=[C:7]([C:20]2[N:25]=[C:24]([CH3:26])[N:23]=[C:22]([NH2:27])[N:21]=2)[C:8]([NH:11][C:12]2[CH:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)=[N:9][CH:10]=1)([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 66610862HCID 66610862, compound

Product 1

HCID 666110444-(5-(2-Aminopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 2,2,2-trifluoroacetateYield 45.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-(5-(2-aminopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.025 g, 0.041 mmol) in TFA (1 mL) was treated with triflic acid (0.029 mL, 0.330 mmol), sealed, and heated at 80° C. for 2 h. The reaction was cooled and treated with ice and 10N NaOH until basic. 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 (5-50% MeCN/H2O with 0.1% TFA). Product-containing fractions were concentrated in vacuo to give 4-(5-(2-aminopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 2,2,2-trifluoroacetate (9 mg, 0.019 mmol, 45.5% yield) as an orange solid. m/z (ESI, +ve ion) 367 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.76 (s, 1H); 8.93 (d, J=2.7 Hz, 1H); 8.54 (d, J=2.5 Hz, 1H); 8.50 (d, J=2.7 Hz, 1H); 8.37 (br. s., 3H); 8.13 (dd, J=8.8, 2.7 Hz, 1H); 7.90 (br. s., 1H); 7.80 (br. s., 1H); 6.84 (d, J=9.0 Hz, 1H); 3.85 (s, 3H); 2.45 (s, 3H); 1.68 (s, 6H).

Workup

  1. customsealed
  2. temperatureThe reaction was cooled
  3. customThe reaction was partitioned between water and DCM
  4. extractionThe aqueous layer was extracted with DCM (3×)
  5. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThis material was dissolved in DMSO
  9. custompurified by prep HPLC (5-50% MeCN/H2O with 0.1% TFA)
  10. concentrationProduct-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-3220c4dfa2f544b78bf98f200a33c44a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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