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

HRID 1812014Notes

Reaction equation

HRID 1812014 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[N:19]=2)[C:14](F)=[N:15][CH:16]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=3)[CH2:35][C:36]3[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=3)[N:19]=2)[C:14]([NH:9][C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666119674-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-methoxypyridin-3-amine (Sigma-Aldrich Inc., 1.405 g, 11.31 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.62 g, 7.54 mmol) in THF (15.00 mL) was cooled to 0° C. in an ice bath and treated with 1.0 M LiHMDS in THF (22.63 mL, 22.63 mmol). The reaction mixture was quenched with a saturated solution of NH4Cl at 0° C. and extracted with EtOAc (50 mL), dried over MgSO4, filtered and concentrated. The crude residue was re diluted with DCM and concentrated with SiO2 and chromatographed through a Redi-Sep pre-packed silica gel column on the ISCO (40 g column, 20→100% EtOAc in hexanes) to give 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.77 g, 6.45 mmol, 86% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 584.1 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with a saturated solution of NH4Cl at 0° C.
  2. extractionextracted with EtOAc (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe crude residue was re diluted with DCM
  7. concentrationconcentrated with SiO2
  8. customchromatographed through a Redi-Sep pre-packed silica gel column on the ISCO (40 g column, 20→100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1a80062579fa43daaa12a82e6358d4ab
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…