Sodium Carbonate → {3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1846825Notes

Reaction equation

HRID 1846825 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:11][CH:10]([O:12][C:13]2[C:18](Br)=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:36]2[CH2:37][CH2:38][O:39][CH2:40][CH:41]=2)O1>O1CCOCC1.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]>[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:11][CH:10]([O:12][C:13]2[C:18]([C:36]3[CH2:41][CH2:40][O:39][CH2:38][CH:37]=3)=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58548640[3-(5-Bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester

Product 1

HCID 58548678{3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl esterYield 43.3%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of [3-(5-bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester (5.1 g, 13.3 mmol) in dioxane (80 mL) was treated with Na2CO3 (2.8 g, 26.6 mmol) in 15 mL of H2O as a solution, followed by additional of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (3.3 g 16.0 mmol) and Pd(dppf)Cl2 (974 mg, 1.33 mmol). The resulting mixture was heated at refluxing overnight under N2 atmosphere. TLC showed that most of the staring materials were consumed completely. The solution was filtered, and the filter was concentrated. And the residue was purified by silica gel chromatography to give the product (2.2 g, 5.76 mmol, 43%). ESI-MS (M+1): 382 calc. for C18H24ClN3O4 381.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat refluxing overnight under N2 atmosphere
  3. customwere consumed completely
  4. filtrationThe solution was filtered
  5. concentrationthe filter was concentrated
  6. customAnd the residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-95ec245050c34860982a5e95d9e58115
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

Loading…