6-Methoxy-3-pyridinylamine → 3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-N-(6-methoxypyridin-3-YL)quinolin-2-amine

HRID 1621742Notes

Reaction equation

HRID 1621742 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Cl[C:11]1[C:20]([C:21]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]([N:28]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[N:22]=2)=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1.[NH4+].[Cl-]>[CH3:37][O:36][C:33]1[CH:32]=[CH:31][C:30]([CH2:29][N:28]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[C:23]2[N:24]=[C:25]([CH3:27])[N:26]=[C:21]([C:20]3[C:11]([NH:1][C:2]4[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=4)=[N:12][C:13]4[C:18]([CH:19]=3)=[CH:17][CH:16]=[CH:15][CH:14]=4)[N:22]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 866470604-(2-Chloroquinolin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666122093-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-N-(6-methoxypyridin-3-YL)quinolin-2-amineYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 5-amino-2-methoxypyridine (0.08 mL, 0.61 mmol, Aldrich, St. Louis, Mo.) and 4-(2-chloroquinolin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (210 mg, 0.410 mmol) in THF (3 mL) was cooled to 0° C. and LiHMDS (1 M in THF, 1.23 mL, 1.23 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h, diluted with an aqueous satd solution of NH4Cl (5 mL) and extracted with EtOAc (20 mL). The organic extract was washed with water and dried over Na2SO4. The solution was filtered and concentrated in vacuo, and the residue was adsorbed onto a plug of silica gel. Purification by chromatography through a Redi-Sep pre-packed silica gel column (12 g) eluting with a gradient of 2% to 3% 2 M NH3.MeOH in CH2Cl2 gave the title compound as an orange solid (65% pure) that was used without further purification. m/z (ESI, +ve ion) 599.8 (M+H)+.

Workup

  1. extractionextracted with EtOAc (20 mL)
  2. extractionThe organic extract
  3. washwas washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  8. washeluting with a gradient of 2% to 3% 2 M NH3

Sources & evidence

ORD record
ord-05c53a212f6a4781b7984791bf0b536a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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