Potassium Carbonate → 4-(5-(3,6-Dihydro-2H-pyran-4-YL)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812341Notes

Reaction equation

HRID 1812341 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Cl[C:17]1[CH:18]=[C:19]([C:24]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([N:31]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=3)[CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)[N:25]=2)[C:20]([F:23])=[N:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.Cl[Pd]Cl>[O:1]1[CH2:6][CH:5]=[C:4]([C:17]2[CH:18]=[C:19]([C:24]3[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([N:31]([CH2:32][C:33]4[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=4)[CH2:41][C:42]4[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=4)[N:25]=3)[C:20]([F:23])=[N:21][CH:22]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666004024-(5-(3,6-Dihydro-2H-pyran-4-YL)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Reagents, catalysts & solvents 2

HCID 131730193HCID 131730193, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (320 mg, 1.523 mmol) (Frontier Scientific), 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (600 mg, 1.250 mmol), potassium carbonate (400 mg, 2.89 mmol), and Amphos-PdCl2 (50 mg, 0.071 mmol) in dioxane (8 mL) was sparged with argon for 5 min. The mixture was heated at 110° C. under nitrogen. After 14 h, x-phos and Pd2dba3 (40 mg each) were added. After 3 h, more x-phos, Pd2dba3 and boronic ester were added. After 16 h, the mixture was cooled to room temperature, and partitioned between EtOAc (40 mL) and water (20 mL). The aqueous phase was extracted with EtOAc once. The combined organic phase was washed with water (3×), dried over Na2SO4 and concentrated. The residue was purified on silica gel (5 to 30% EtOAc). The dechlorinated fraction came out as the first major peak, followed by the product as the next major peak. The product was collected as a pink solid (130 mg). m/z (ESI, positive ion): 528.2 (M+H)+. 1H NMR (400 MHz, CDCl3-d) δ ppm 2.49-2.58 (m, 5H) 3.79 (s, 3H) 3.91 (s, 3H) 3.95 (t, J=5.38 Hz, 2H) 4.31-4.36 (m, 2H) 4.82 (d, J=8.61 Hz, 4H) 6.20 (br. s., 1H) 6.86 (dd, J=11.15, 8.61 Hz, 4H) 7.22 (d, J=6.85 Hz, 4H) 8.31 (d, J=1.96 Hz, 1H) 8.50 (dd, J=9.00, 2.54 Hz, 1H).

Workup

  1. customwas sparged with argon for 5 min
  2. additionx-phos and Pd2dba3 (40 mg each) were added
  3. waitAfter 3 h
  4. additionmore x-phos, Pd2dba3 and boronic ester were added
  5. waitAfter 16 h
  6. temperaturethe mixture was cooled to room temperature
  7. custompartitioned between EtOAc (40 mL) and water (20 mL)
  8. extractionThe aqueous phase was extracted with EtOAc once
  9. washThe combined organic phase was washed with water (3×)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified on silica gel (5 to 30% EtOAc)
  13. customThe product was collected as a pink solid (130 mg)

Sources & evidence

ORD record
ord-9953a271909c4ef38f8bf7728851560a
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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