Sodium Carbonate → Tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)piperidine-1-carboxylate

HRID 1621602Notes

Reaction equation

HRID 1621602 reaction equation
[CH2:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.B1C2CCCC1CCC2.Cl[C:25]1[CH:26]=[C:27]([C:40]2[N:45]=[C:44]([CH3:46])[N:43]=[C:42]([N:47]([CH2:57][C:58]3[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=3)[CH2:48][C:49]3[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=3)[N:41]=2)[C:28]([NH:31][C:32]2[CH:33]=[N:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=2)=[N:29][CH:30]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:56][O:55][C:52]1[CH:51]=[CH:50][C:49]([CH2:48][N:47]([CH2:57][C:58]2[CH:59]=[CH:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=2)[C:42]2[N:43]=[C:44]([CH3:46])[N:45]=[C:40]([C:27]3[CH:26]=[C:25]([CH2:1][CH:2]4[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]4)[CH:30]=[N:29][C:28]=3[NH:31][C:32]3[CH:33]=[N:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=3)[N:41]=2)=[CH:54][CH:53]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-MethylenepiperidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 666119674-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 60155885Tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)piperidine-1-carboxylateYield 70.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

tert-Butyl 4-methylenepiperidine-1-carboxylate (0.117 g, 0.592 mmol) was treated with 9-BBN (0.5 M in THF, 1.183 mL, 0.592 mmol) and the mixture was heated at reflux for 4 h. After cooling, the resulting solution was transferred into a stirred mixture of 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.288 g, 0.493 mmol), Pd2(dba)3 (0.023 g, 0.025 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.024 g, 0.049 mmol), and Na2CO3 (0.131 g, 1.233 mmol) in 1,4-dioxane (1.0 mL) and water (0.25 mL). The mixture was sealed and heated under microwave at 140° C. for 30 min. After cooling, the resulting mixture was passed through a short path of Celite® (diatomaceous earth), washing with EtOAc (3×10 mL). The combined organic phases were concentrated and purified by flash chromatography (short column, SiO2, pure hexanes→30% EtOAc in hexanes) to give tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)piperidine-1-carboxylate (0.261 g, 0.349 mmol, 70.9% yield) as a sticky yellow syrup. m/z (ESI, +ve ion) 747.2 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 4 h
  3. temperatureAfter cooling
  4. customThe mixture was sealed
  5. temperatureAfter cooling
  6. washwashing with EtOAc (3×10 mL)
  7. concentrationThe combined organic phases were concentrated
  8. custompurified by flash chromatography (short column, SiO2, pure hexanes→30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d68ed9050814498c87d8ae4b2261a000
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…