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

HRID 1621698Notes

Reaction equation

HRID 1621698 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[N:6][C:7]=1[F:8].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:40]1[N:45]=[C:44]([CH3:46])[N:43]=[C:42]([N:47]([CH2:57][C:58]2[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=2)[CH2:48][C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=2)[N:41]=1>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[F:8][C:7]1[C:2]([C:40]2[N:45]=[C:44]([CH3:46])[N:43]=[C:42]([N:47]([CH2:48][C:49]3[CH:50]=[CH:51][C:52]([O:55][CH3:56])=[CH:53][CH:54]=3)[CH2:57][C:58]3[CH:59]=[CH:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=3)[N:41]=2)=[CH:3][CH:4]=[C:5]([CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[N:6]=1

Participants

9

Reactant 4

HCID 517044Potassium Acetate2×HCID 2733548Bis(pinacolato)diboraneHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 66600183HCID 66600183, compound

Product 1

HCID 666114074-(2-fluoro-6-(morpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 21%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 4-((5-bromo-6-fluoropyridin-2-yl)methyl)morpholine (277 mg, 1.007 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (49.3 mg, 0.060 mmol), bis(pinacolato)diboron (307 mg, 1.208 mmol) and potassium acetate (198 mg, 2.014 mmol) in 2 mL of dioxane was heated in a microwave at 125° C. for 20 min. Water (0.7 mL), KOAc (100 mg), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (504 mg, 1.309 mmol) and Am-Phos (35 mg) were added and the mixture was heated in a microwave at 102° C. for 35 min. It was diluted with 5 mL of EtOAc and washed with 1 mL of 0.5N NaOH. The EtOAc layer was concentrated and purified on a Redi-Sep pre-packed silica gel column (12 g) eluting with a gradient of 50-75% EtOAc in hexanes to give 4-(2-fluoro-6-(morpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (115 mg, 21% yield) as a brown amorphous solid. 1H NMR (400 MHz, d6-DMSO) δ 8.60 (1H, dd, J=9.8, 1.8 Hz); 7.55 (1H, d, J=7.4 Hz); 7.24 (4H, d, J=8.2 Hz); 6.89 (4H, t, J=8.1Hz); 4.76 (4H, d, J=7.4 Hz); 3.74 (3H, s); 3.72 (3H, s); 3.60 (6H, m); 2.44 (7H, m). m/z (ESI, +ve ion) 545 (M+H)+.

Workup

  1. temperaturethe mixture was heated in a microwave at 102° C. for 35 min
  2. washwashed with 1 mL of 0.5N NaOH
  3. concentrationThe EtOAc layer was concentrated
  4. custompurified on a Redi-Sep pre-packed silica gel column (12 g)
  5. washeluting with a gradient of 50-75% EtOAc in hexanes

Sources & evidence

ORD record
ord-fb987e7063394013841c651238ae0dc6
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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