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

HRID 1621874Notes

Reaction equation

HRID 1621874 reaction equation
[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:22]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29](CC3C=CC(OC)=CC=3)CC3C=CC(OC)=CC=3)[N:23]=2)[C:9]([NH:12][C:13]2[CH:14]=[N:15][C:16]([O:20][CH3:21])=[C:17]([F:19])[CH:18]=2)=[N:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2].FC(F)(F)S(O)(=O)=O.[OH-].[Na+]>C(O)(C(F)(F)F)=O>[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:22]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([NH2:29])[N:23]=2)[C:9]([NH:12][C:13]2[CH:14]=[N:15][C:16]([O:20][CH3:21])=[C:17]([F:19])[CH:18]=2)=[N:10][CH:11]=1)(=[O:4])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 66612048HCID 66612048, compound

Product 1

HCID 497859224-(5-(Ethylsulfonyl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 69%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 4-(5-(ethylsulfonyl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.066 g, 0.100 mmol) in trifluoromethanesulfonic acid (0.089 mL, 1.000 mmol) and 1.5 mL TFA was sealed and heated to 70° C. for 30 min, 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 5 times, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting yellow solid was suspended in 1 mL EtOAc, filtered, rinsing 2× diethyl ether, and dried in vacuo to give 4-(5-(ethylsulfonyl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.029 g, 0.069 mmol, 69% yield) as a yellow solid. m/z (ESI, +ve ion) 420 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.87 (s, 1H), 8.73 (d, J=2.7 Hz, 1H), 8.52 (d, J=2.7 Hz, 1H), 8.41 (d, J=2.5 Hz, 1H), 8.33 (d, J=2.7 Hz, 1H), 7.98 (br. s., 1H), 7.83 (br. s., 1H), 3.95 (s, 3H), 3.06-3.21 (m, 1H), 2.73-2.89 (m, 1H), 2.44 (s, 3H), 1.09 (t, J=7.3 Hz, 3H).

Workup

  1. temperaturecooled
  2. customThe reaction was partitioned between water and DCM
  3. extractionThe aqueous layer was extracted with DCM 5 times
  4. dry with materialthe combined organics were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered
  8. washrinsing 2× diethyl ether
  9. customdried in vacuo

Sources & evidence

ORD record
ord-cd6e4859aabe48e2ac8e16bba2413b80
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…