Potassium Acetate → Tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)piperazine-1-carboxylate

HRID 1621849Notes

Reaction equation

HRID 1621849 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.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([CH:41]([C:43]2[CH:44]=[C:45](B(O)O)[C:46]([F:49])=[N:47][CH:48]=2)[CH3:42])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C([O-])(=O)C.[K+]>O1CCOCC1.ClCCl.O.[Cl-].[Na+].O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:45]3[CH:44]=[C:43]([CH:41]([N:38]4[CH2:37][CH2:36][N:35]([C:33]([O:32][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:34])[CH2:40][CH2:39]4)[CH3:42])[CH:48]=[N:47][C:46]=3[F:49])[N:3]=2)=[CH:12][CH:13]=1

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 666004735-(1-(4-(Tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid

Product 1

HCID 66611395Tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)piperazine-1-carboxylateYield 99.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

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 (2.140 g, 5.56 mmol) and 5-(1-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (4.12 g, 11.68 mmol) in dioxane (25 mL). Then A-Phos (0.394 g, 0.556 mmol), potassium acetate (1.637 g, 16.68 mmol) and water (3 mL) were added into the reaction mixture. The reaction mixture was stirred and heated in a CEM Voyager Microwave (Large Scale Unit) at 120° C. for 20 min (160 watts, Powermax feature on). The mixture was diluted with dichloromethane (20 mL), water (20 mL) and brine solution (10 mL). The organic layer was collected by extracting with dichloromethane (3×15 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. This gave the crude product as a tan oil. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through silica-gel column (220 g), eluting with 100% ethyl acetate to give tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)piperazine-1-carboxylate (3.65 g, 5.55 mmol, 99% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO) δ 8.47 (dd, J=9.39, 2.35 Hz, 1H) 8.31 (d, J=1.57 Hz, 1H) 7.26 (dd, J=8.61, 3.33 Hz, 4H) 6.90 (dd, J=12.42, 8.71 Hz, 4H) 4.78 (d, J=12.91 Hz, 4H) 3.74 (d, J=8.02 Hz, 6H) 3.70 (d, J=6.85Hz, 1H) 3.28 (d, J=6.06 Hz, 4H) 2.50-2.53 (m, 3H) 2.21-2.39 (m, 4H) 1.37 (d, J=1.76 Hz, H). m/z (ESI, +ve ion) 658.3 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. customThe organic layer was collected
  3. extractionby extracting with dichloromethane (3×15 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThis gave the crude product as a tan oil
  8. custompurified by chromatography through silica-gel column (220 g)
  9. washeluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-a4aefa0bf4404503acc4dfdd80937d7f
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…