HCID 66611837, compound → 4-(2-(6-Methoxypyridin-3-ylamino)-5-(pyridazin-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621760Notes

Reaction equation

HRID 1621760 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:27][C:28]4[CH:29]=[N:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=4)=[N:17][CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][N:24]=[N:23][CH:22]=4)[CH:20]=3)[N:12]=[C:11]([CH3:36])[N:10]=2)=CC=1>C(O)(C(F)(F)F)=O>[CH3:35][O:34][C:31]1[N:30]=[CH:29][C:28]([NH:27][C:16]2[C:15]([C:13]3[N:12]=[C:11]([CH3:36])[N:10]=[C:9]([NH2:8])[N:14]=3)=[CH:20][C:19]([C:21]3[CH:26]=[CH:25][N:24]=[N:23][CH:22]=3)=[CH:18][N:17]=2)=[CH:33][CH:32]=1

Participants

3

Reactant 1

HCID 66611837HCID 66611837, compound

Product 1

HCID 595484754-(2-(6-Methoxypyridin-3-ylamino)-5-(pyridazin-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 11.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(pyridazin-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (140 mg, 0.223 mmol) was treated with TFA (10 mL) and fitted with a reflux condenser and heated at 80° C. for 15 h. The TFA was removed in vacuo and the residue was pipetted into an ice-cooled saturated solution of NaHCO3 resulting in a yellow suspension which was collected by filtration on a sintered glass frit. The resulting yellow solid was washed with water and MeOH dry-packed on silica gel and attempted purification on the ISCO (12 g column, 1-40% MeOH in DCM (also tried 25% 2M NH3 in MeOH in DCM)) could not liberate the desired product from silica gel. The silica gel was washed with DMSO (20 mL) and filtered through 0.45 μm acrodiscs and the DMSO removed in a Genevac over the weekend to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(pyridazin-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (9.5 mg, 0.025 mmol, 10.99% yield) as a bright yellow amorphous solid. m/z (ESI, +ve ion) 388.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.99 (1H, s); 9.66 (1H, s); 9.25 (1H, s); 9.21 (1H, d, J=2.3 Hz); 8.91 (1H, d, J=2.3 Hz); 8.55 (1H, d, J=2.7 Hz); 8.16-8.20 (1H, m); 7.98-8.02 (1H, m); 7.92 (1H, s); 7.81 (1H, s); 6.88 (1H, d, J=8.8 Hz); 3.87 (3H, s); 2.54 (3H, s).

Workup

  1. customfitted with a reflux condenser
  2. customThe TFA was removed in vacuo
  3. temperaturecooled saturated solution of NaHCO3 resulting in a yellow suspension which
  4. filtrationwas collected by filtration on a sintered glass frit
  5. washThe resulting yellow solid was washed with water and MeOH dry-packed on silica gel
  6. custompurification on the ISCO (12 g column, 1-40% MeOH in DCM (also tried 25% 2M NH3 in MeOH in DCM)) could not
  7. washThe silica gel was washed with DMSO (20 mL)
  8. filtrationfiltered through 0.45 μm acrodiscs
  9. customthe DMSO removed in a Genevac over the weekend

Sources & evidence

ORD record
ord-66bfa164a9f94edda55a5d056d3f948b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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