Trifluoroacetic acid → 4-(2-(6-Methoxypyridin-3-ylamino)-5-(1-(3-(methylsulfonyl)azetidin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 2,2,2-trifluoroacetate

HRID 1812299Notes

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:31][C:32]4[CH:33]=[N:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=4)=[N:17][CH:18]=[C:19]([CH:21]([N:23]4[CH2:26][CH:25]([S:27]([CH3:30])(=[O:29])=[O:28])[CH2:24]4)[CH3:22])[CH:20]=3)[N:12]=[C:11]([CH3:40])[N:10]=2)=CC=1.FC(F)(F)S(O)(=O)=O.[C:60]([OH:66])([C:62]([F:65])([F:64])[F:63])=[O:61]>>[F:63][C:62]([F:65])([F:64])[C:60]([OH:66])=[O:61].[CH3:39][O:38][C:35]1[N:34]=[CH:33][C:32]([NH:31][C:16]2[C:15]([C:13]3[N:12]=[C:11]([CH3:40])[N:10]=[C:9]([NH2:8])[N:14]=3)=[CH:20][C:19]([CH:21]([N:23]3[CH2:24][CH:25]([S:27]([CH3:30])(=[O:29])=[O:28])[CH2:26]3)[CH3:22])=[CH:18][N:17]=2)=[CH:37][CH:36]=1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 62406Trifluoromethanesulfonic acid

HCID 66600253N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(3-(methylsulfonyl)azetidin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666111164-(2-(6-Methoxypyridin-3-ylamino)-5-(1-(3-(methylsulfonyl)azetidin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 2,2,2-trifluoroacetateYield 76%

Conditions

Temperature: 25 °C

Procedure

An orange solution of N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(3-(methylsulfonyl)azetidin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (70.0 mg, 0.098 mmol) and trifluoromethanesulfonic acid (0.030 mL, 0.338 mmol) in TFA (1.5 mL) was stirred at 75° C. for 18 h. The resulting mixture was subsequently cooled to 25° C. and concentrated in vacuo. The residue was taken up in DMSO (2.0 mL) and purified by rpHPLC (Phenomenex Luna 5 μm C18 30×150 mm, 35 mL/min, 5 to 100% CH3CN/H2O (plus 0.1% TFA, both solvents) to provide 4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(3-(methylsulfonyl)azetidin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 2,2,2-trifluoroacetate (43.6 mg, 0.075 mmol, 76% yield) as an orange solid. 1H NMR (400 MHz, d4-MeOH) δ 9.10 (d, J=2.5 Hz, 1H), 8.70 (d, J=2.7 Hz, 1H), 8.40 (d, J=2.5 Hz, 1H), 8.19 (dd, J=9.0, 2.7 Hz, 1H), 7.07 (d, J=9.0 Hz, 1H), 4.65 (q, J=6.7 Hz, 1H), 4.54-4.61 (m, 1H), 4.38-4.53 (m, 4H), 4.02 (s, 3H), 3.05 (s, 3H), 2.66 (s, 3H), 2.52 (s, 3H), 1.67 (d, J=6.8 Hz, 3H). 19F NMR (376 MHz, d4-MeOH) δ −79.11 (s, 3F). m/z (ESI, +ve) 471.3 (M+H)+.

Workup

concentrationconcentrated in vacuo
custompurified by rpHPLC (Phenomenex Luna 5 μm C18 30×150 mm, 35 mL/min, 5 to 100% CH3CN/H2O (plus 0.1% TFA

Sources & evidence

ORD record: ord-085204f726904800b3eee4c54c31ce03
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362241B2

Reaction notes

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