Trifluoromethanesulfonic acid → HCID 59548472, compound

HRID 1621971Notes

Reaction equation

HRID 1621971 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:8]=[C:9]([C:23]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([N:30](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:24]=3)[C:10]([NH:13][C:14]3[CH:15]=[N:16][C:17]([O:21][CH3:22])=[C:18]([F:20])[CH:19]=3)=[N:11][CH:12]=2)[CH2:3][CH2:2]1.FC(F)(F)S(O)(=O)=O>C(O)(C(F)(F)F)=O>[O:1]1[CH2:2][CH:3]=[C:4]([C:7]2[CH:8]=[C:9]([C:23]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([NH2:30])[N:24]=3)[C:10]([NH:13][C:14]3[CH:15]=[N:16][C:17]([O:21][CH3:22])=[C:18]([F:20])[CH:19]=3)=[N:11][CH:12]=2)[CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 68514914HCID 68514914, compound

Product 1

HCID 59548472HCID 59548472, compoundYield 79.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-(5-(3,6-dihydro-2H-pyran-4-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (140 mg, 0.215 mmol) in 3 mL of TFA was treated with 0.15 mL of trifluoromethanesulfonic acid and heated at 80° C. in an oil bath for 3 h. It was concentrated and the dark residue was stirred in 15 mL of EtOAc then treated with 5 mL of 1 N NaOH. The aqueous layer was extracted with 2×10 mL of DCM. The combined EtOAc extracts and DCM extracts were concentrated. The residue was purified on a silica gel column and eluted with 35-100% EtOAc in DCM to give 4-(5-(3,6-dihydro-2H-pyran-4-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (70 mg, 79% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.95 (s, 1H), 8.85 (d, J=2.6 Hz, 1H), 8.49 (d, J=2.5 Hz, 1H), 8.41-8.35 (m, 2H), 7.91 (br., 1H), 7.76 (br., 1H), 6.24 (m, 1H), 4.24 (m, 2H), 3.94 (s, 3H), 3.84 (m, 2H), 2.45 (s, 5H). m/z (ESI, positive ion) 410.0 (M+H)+.

Workup

  1. concentrationIt was concentrated
  2. additionthen treated with 5 mL of 1 N NaOH
  3. extractionThe aqueous layer was extracted with 2×10 mL of DCM
  4. concentrationThe combined EtOAc extracts and DCM extracts were concentrated
  5. customThe residue was purified on a silica gel column
  6. washeluted with 35-100% EtOAc in DCM

Sources & evidence

ORD record
ord-912296163c3844fba3532b389398cedc
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…