Sodium Carbonate → HCID 66750305, compound

HRID 75469Notes

Reaction equation

HRID 75469 reaction equation
[CH:1]12[N:8]([C:9]3[N:14]=[C:13](Cl)[N:12]=[C:11]([CH2:16][N:17]([CH3:19])[CH3:18])[CH:10]=3)[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:34]2[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=2)O1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[CH:1]12[N:8]([C:9]3[CH:10]=[C:11]([CH2:16][N:17]([CH3:19])[CH3:18])[N:12]=[C:13]([C:34]4[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=4)[N:14]=3)[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866659081-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine

Product 1

HCID 66750305HCID 66750305, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine (0.400 g, 1.42 mmol) and sodium carbonate (2M in water, 2.12 mL, 4.24 mmol). DME (7 mL) was then added to give a yellow biphasic solution. The solution was degassed with nitrogen for 10 minutes, and tetrakis(triphenylphosphine)palladium(0) (0.098 g, 0.085 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.372 g, 1.697 mmol) were added. The vial was sealed and heated to 120° C. for 40 minutes under microwave irradiation. LCMS indicated that the reaction had not gone to completion. Additional tetrakis(triphenylphosphine)palladium(0) (0.049 g, 0.043 mmol) was added and the reaction was heated to 120° C. for an additional 80 minutes under microwave irradiation. The vessel was then cooled to room temperature and the reaction mixture was filtered through Celite™. The filter cake was washed with ethyl acetate and the filtrate was then concentrated under reduced pressure to provide a brown oil. The crude product was added to a silica gel column and was eluted with 0-10% methanol in methylene chloride to provide 4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((dimethylamino)methyl)pyrimidin-2-yl)aniline (0.365 g, 76%) as a light orange solid. HRMS; [M+H]+ Obs'd=340.2133, [M+H]+ Calc'd=340.2131

Workup

  1. customto give a yellow biphasic solution
  2. customThe solution was degassed with nitrogen for 10 minutes
  3. customThe vial was sealed
  4. temperaturethe reaction was heated to 120° C. for an additional 80 minutes under microwave irradiation
  5. temperatureThe vessel was then cooled to room temperature
  6. filtrationthe reaction mixture was filtered through Celite™
  7. washThe filter cake was washed with ethyl acetate
  8. concentrationthe filtrate was then concentrated under reduced pressure
  9. customto provide a brown oil
  10. washwas eluted with 0-10% methanol in methylene chloride

Sources & evidence

ORD record
ord-a6b6069accb04e3389fe6ce281a0e9e2
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Reaction notes

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