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 1621753Notes

Reaction equation

HRID 1621753 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 64.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-methoxypyridin-3-amine (354 mg, 2.85 mmol) (Aldrich) and 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (913 mg, 1.902 mmol) in THF (15 mL) was cooled to 0° C. in an ice bath and treated dropwise with 1 M LiHMDS (5.71 mL, 5.71 mmol). After stirring for 1 h at this temperature, 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. Purification on the ISCO (40 g column, 20-100% EtOAc in hexanes) gave 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (717.3 mg, 1.228 mmol, 64.6% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 584.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.65 (1H, s); 8.73 (1H, d, J=2.7 Hz); 8.26 (1H, d, J=2.7 Hz); 8.19 (1H, d, J=2.7 Hz); 7.83 (1H, dd, J=8.8, 2.7 Hz); 7.19 (4H, dd, J=16.2, 8.6Hz); 6.86 (4H, dd, J=10.4, 8.8 Hz); 6.70 (1H, d, J=8.8 Hz); 4.86 (2H, s); 4.81 (2H, s); 3.93 (3H, s); 3.81 (3H, s); 3.79 (3H, s); 2.57 (3H, s).

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. customPurification on the ISCO (40 g column, 20-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dab248ded370426c99d8b477b8ca0595
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…