Water → 4-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621844Notes

Reaction equation

HRID 1621844 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[N:3]=1.[F:28][C:29]1[C:34](B(O)O)=[CH:33][C:32]([CH:38]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH3:39])=[CH:31][N:30]=1.C([O-])(=O)C.[K+].O>C(=O)(O)[O-].[Na+].O1CCOCC1>[F:28][C:29]1[C:34]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[N:3]=2)=[CH:33][C:32]([CH:38]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH3:39])=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 595484562-Fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid

Product 1

HCID 666121034-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 52.5%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.433 g, 1.126 mmol), 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (0.260 g, 1.023 mmol), potassium acetate (0.308 g, 3.14 mmol), Am-Phos (0.051 g, 0.082 mmol), dioxane (3 mL) and water (0.5 mL, 27.8 mmol). The reaction mixture was stirred and heated in a CEM Explorer Microwave Unit for 10 min at 120° C., while 100 Watts of energy was supplied via Powermax® (simultaneous heating while cooling technology). The reaction mixture was diluted with sat. sodium bicarbonate (10 mL) and extracted with chloroform (3×10 mL). The organic extracts were combined and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material as a yellow oil. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (40 gram), eluting with 50% ethyl acetate/hexanes to give 4-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.300 g, 0.537 mmol, 52.5% yield) as a light-yellow oil. 1H NMR (400 MHz, d6-DMSO) δ 8.46 (d, J=9.59 Hz, 1H) 8.31 (d, J=1.57 Hz, 1H) 7.25 (d, J=7.63 Hz, 4H) 6.90 (dd, J=10.27, 8.71 Hz, 4H) 4.77 (d, J=13.30 Hz, 3H) 3.66-3.79 (m, 6H) 3.47-3.61 (m, 5H) 3.36 (s, 4H) 3.18 (d, J=5.09 Hz, 1H) 2.49-2.53 (m, 3H) 2.40 (s, 2H) 2.14-2.34 (m, 2H). m/z (ESI, +ve ion) 559.2 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. temperaturewas supplied via Powermax® (simultaneous heating while cooling technology)
  3. extractionextracted with chloroform (3×10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as a yellow oil
  8. customchromatographed through a silica gel column (40 gram)
  9. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1a43e6244c5a4a89bbef068ae300fc80
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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