5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-N-(6-methoxypyridin-3-YL)-2,3'-bipyridin-6-amine → 4-[6-[(6-Methoxy-3-pyridinyl)amino][2,3'-bipyridin]-5-yl]-6-methyl-1,3,5-triazin-2-amine

HRID 1621766Notes

Reaction equation

HRID 1621766 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[CH:18][C:19]([C:31]4[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=4)=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)[N:10]=2)=CC=1>C(O)(C(F)(F)F)=O.CO>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[CH:18][C:19]([C:31]3[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=3)=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[N:10]=1

Participants

4

Reactant 1

HCID 666113485-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-N-(6-methoxypyridin-3-YL)-2,3'-bipyridin-6-amine

Product 1

HCID 497854384-[6-[(6-Methoxy-3-pyridinyl)amino][2,3'-bipyridin]-5-yl]-6-methyl-1,3,5-triazin-2-amineYield 10.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent2×

Procedure

A solution of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-N-(6-methoxypyridin-3-yl)-2,3′-bipyridin-6-amine (276 mg, 0.440 mmol) in TFA (10 mL) was heated to 75° C. for 15 h. about 80% of the TFA was removed in vacuo and the crude oily residue was pipetted into an ice cooled solution of NaHCO3. The resulting suspension was collected by filtration and was washed with water and MeOH. The solid was then dry-packed on silica gel and purified on the ISCO (12 g column, 1-25% MeOH in DCM) to give partially purified product. This was suspended in MeOH and filtered, and the filtercake was dry-packed with silica gel and purified on the ISCO (12 g column, 3-15% MeOH in DCM) to give 5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(6-methoxypyridin-3-yl)-2,3′-bipyridin-6-amine (17.2 mg, 0.045 mmol, 10.11% yield) as a brown amorphous solid. m/z (ESI, +ve ion) 387.0 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.86 (1H, s); 9.26 (1H, d, J=2.0 Hz); 8.88 (1H, d, J=8.0 Hz); 8.66 (2H, d, J=2.9 Hz); 8.41 (1H, dt, J=8.1, 1.8 Hz); 8.21 (1H, dd, J=8.9, 2.6 Hz); 7.89 (1H, br. s.); 7.74 (1H, br. s.); 7.58 (1H, d, J=8.0 Hz); 7.52-7.56 (1H, m); 6.90 (1H, d, J=9.0 Hz); 3.87 (3H, s); 2.45 (3H, s).

Workup

  1. customwas removed in vacuo
  2. filtrationThe resulting suspension was collected by filtration
  3. washwas washed with water and MeOH
  4. customdry-packed on silica gel and purified on the ISCO (12 g column, 1-25% MeOH in DCM)
  5. customto give partially purified product
  6. filtrationfiltered
  7. custompurified on the ISCO (12 g column, 3-15% MeOH in DCM)

Sources & evidence

ORD record
ord-64ac3dd2f8d949e5b0a6c35ae61804dc
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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