Sodium Carbonate → HCID 68781301, compound

HRID 2264442Notes

Reaction equation

HRID 2264442 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[CH:19][C:18](Br)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][CH:31]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[CH:19][C:18]([C:30]3[CH:38]=[CH:37][C:33]([C:34](=[O:35])[NH2:36])=[CH:32][CH:31]=3)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27605884-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 68781024HCID 68781024, compound

Product 1

HCID 68781301HCID 68781301, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a degassed solution of 4-(5-bromo-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.80 mmol, 1.0 equiv; intermediate C13/step 1) in dimethoxyethane (15 mL) was added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (1.38 g, 5.60 mmol, 2.0 equiv; commercially available from CSIRO Molecular Science, Australia), tetrakis(triphenylphosphine)palladium(0) (97.0 mg, 0.08 mmol, 0.03 equiv) and an aqueous solution of 2 M sodium carbonate (5.6 mL) and the reaction mixture heated by microwave irradiation under Ar to 130° C. for 30 min. The crude reaction mixture was extracted with ethyl acetate (3×50 mL) and the combined organic phases washed with a sat. solution of sodium chloride (2×50 mL). The organic phase was dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane/methanol providing 0.31 g (28%) of the title compound. MS (ISP): 398.4 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. extractionwas extracted with ethyl acetate (3×50 mL)
  3. washthe combined organic phases washed with a sat. solution of sodium chloride (2×50 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customthe crude material purified by silica column chromatography
  7. washeluting with a gradient of dichloromethane/methanol providing 0.31 g (28%) of the title compound

Sources & evidence

ORD record
ord-583f96113632448091fe71ec20246841
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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