1,4-Dioxane → N,N-bis(4-methoxybenzyl)-4-(3-(6-methoxypyridin-3-ylamino)pyridin-4-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1811919Notes

Reaction equation

HRID 1811919 reaction equation
Cl[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[N:9]=1.[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[N:39][CH:40]=1.CC([O-])(C)C.[Na+].O1CCOCC1>[NH4+].[Cl-]>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:10]2[N:9]=[C:8]([C:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[NH:34][C:35]3[CH:40]=[N:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[N:13]=[C:12]([CH3:14])[N:11]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 811216-Methoxy-3-pyridinylamineHCID 23676156Sodium t-butoxideHCID 666002154-(3-Chloropyridin-4-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66600265N,N-bis(4-methoxybenzyl)-4-(3-(6-methoxypyridin-3-ylamino)pyridin-4-yl)-6-methyl-1,3,5-triazin-2-amineYield 24%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-chloropyridin-4-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (32 mg, 0.069 mmol), 5-amino-2-methoxypyridine (0.017 mL, 0.139 mmol), Brett precatalyst ((SP-4-4)-[2-[2-(amino-κN)ethyl]phenyl-κC]chloro[dicyclohexyl[3,6-dimethoxy-2′,4′,6′-tris(1-methylethyl)[1,1′-biphenyl]-2-yl]phosphine-κP]palladium) (2 mg) and sodium 2-methylpropan-2-olate (16.64 mg, 0.173 mmol) and dioxane (1 mL). The reaction mixture was stirred and heated in an oil bath at 100° C. for 16 h. The reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (2×20 mL). The organic extract was washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange oil. The crude product was purified by silica gel chromatography eluting with 20% THF/CH2Cl2 to give N,N-bis(4-methoxybenzyl)-4-(3-(6-methoxypyridin-3-ylamino)pyridin-4-yl)-6-methyl-1,3,5-triazin-2-amine (9 mg, 0.016 mmol, 24% yield). 1H NMR (300 MHz, CDCl3) δ 10.32 (s, 1H); 8.49-8.68 (m, 1H); 8.33 (s, 1H); 8.24 (d, J=5.12 Hz, 2H); 8.03 (d, J=5.12 Hz, 2H); 7.95 (d, J=1.61 Hz, 1H); 7.38 (dd, J=8.70, 2.41 Hz, 2H); 7.21 (d, J=8.33 Hz, 2H); 7.14 (d, J=8.33 Hz, 2H); 6.98 (s, 1H); 6.87 (d, J=8.33 Hz, 2H); 6.79 (d, J=8.33 Hz, 2H); 6.72 (d, J=8.77 Hz, 1H); 4.86 (s, 2H); 4.79 (s, 2H); 3.81 (s, 3H); 3.76 (s, 3H); 2.56 (s, 3H). m/z (ESI, +ve ion) 550.0 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×20 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as orange oil
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 20% THF/CH2Cl2

Sources & evidence

ORD record
ord-199539ea27ad463b8f3cda0f04fff253
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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