Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 4-(6-fluoro-2,3'-bipyridin-5-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621764Notes

Reaction equation

HRID 1621764 reaction equation
[F:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1B(O)O.Cl[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[N:19]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])(=O)C.[K+]>O1CCOCC1.O>[F:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[N:19]=1

Participants

7

Reactant 4

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 517044Potassium AcetateHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 666003126-Fluoro-2,3'-bipyridin-5-ylboronic acid

Product 1

HCID 666114264-(6-fluoro-2,3'-bipyridin-5-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 51.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-fluoro-2,3′-bipyridin-5-ylboronic acid (555 mg, 2.55 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (700 mg, 1.819 mmol), Amphos 2 (64.4 mg, 0.091 mmol) (Aldrich) and potassium acetate (548 mg, 5.58 mmol) (Aldrich) in dioxane (12 mL) and water (3.0 mL) was purged with argon and heated in a microwave reactor at 120° C. for 30 min. The reaction mixture was treated with 1 N NaOH (15 mL) and extracted with EtOAc (50 mL), washed with brine and dried over MgSO4, filtered and concentrated. The crude product was purified on the ISCO (40 g column, 40-100% EtOAc in hexanes) to give 4-(6-fluoro-2,3′-bipyridin-5-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (490.3 mg, 0.938 mmol, 51.6% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 523.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.26 (1H, d, J=1.8 Hz); 8.67-8.72 (2H, m); 8.40 (1H, dt, J=8.0, 2.0 Hz); 7.77 (1H, dd, J=7.8, 1.6 Hz); 7.43 (1H, dd, J=8.0, 5.3 Hz); 7.20-7.25 (4H, m); 6.83-6.90 (4H, m); 4.83 (4H, s); 3.82 (3H, s); 3.80 (3H, s); 2.56 (3H, s).

Workup

  1. customwas purged with argon
  2. additionThe reaction mixture was treated with 1 N NaOH (15 mL)
  3. extractionextracted with EtOAc (50 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified on the ISCO (40 g column, 40-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-121efe6bdd714b9484335fd982d3cda4
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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