Dimethylformamide → HCID 68106563, compound

HRID 2403626Notes

Reaction equation

HRID 2403626 reaction equation
[N:1]1([C:7]2[N:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:23]1[CH:24]=[C:25]([CH:40]=[CH:41][CH:42]=1)[CH2:26][N:27]([CH3:39])[C:28](=[O:38])[CH2:29][NH:30]C(=O)OC(C)(C)C.CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+]>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(Cl)(Cl)Cl.O>[CH3:39][N:27]([CH2:26][C:25]1[CH:40]=[CH:41][CH:42]=[C:23]([C:10]2[CH:11]=[N:12][C:7]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[N:8][CH:9]=2)[CH:24]=1)[C:28](=[O:38])[CH2:29][NH2:30]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 164142122-(Piperidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 70570939HCID 70570939, compound

Product 1

HCID 68106563HCID 68106563, compoundYield 44.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 2-(piperidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (14 mg), tert-butyl {2-[(3-bromobenzyl)(methyl)amino]-2-oxoethyl}carbamate (9 mg), and DMF (0.2 ml) were added tetrakis(triphenylphosphine)palladium (3 mg), sodium carbonate (5 mg), and water (0.1 ml), followed by stirring at 60° C. overnight. After cooling to room temperature, to the reaction mixture was added CHCl3 (2 ml), and the reaction mixture was filtered in a column preconditioned by the addition of 0.8 ml of water to a diatomaceous earth column (manufactured by Varian Inc., ChemElute 1 ml). The obtained filtrate was concentrated, and then to the residue were added MeOH (0.5 ml) and a 4 M hydrogen chloride/EtOAc solution (0.5 ml), followed by leaving to stand for 30 minutes. Thereafter, the reaction mixture was concentrated and the compound was purified by preparative liquid chromatography (MeOH/0.1% aqueous formic acid solution) to obtain N-methyl-N-{3-[2-(piperidin-1-yl)pyrimidin-5-yl]benzyl}glycinamide (3.8 mg).

Workup

  1. temperatureAfter cooling to room temperature, to the reaction mixture
  2. filtrationthe reaction mixture was filtered in a column
  3. additionpreconditioned by the addition of 0.8 ml of water to a diatomaceous earth column (manufactured by Varian Inc., ChemElute 1 ml)
  4. concentrationThe obtained filtrate was concentrated
  5. additionto the residue were added MeOH (0.5 ml)
  6. customby leaving
  7. waitto stand for 30 minutes
  8. concentrationThereafter, the reaction mixture was concentrated
  9. customthe compound was purified by preparative liquid chromatography (MeOH/0.1% aqueous formic acid solution)

Sources & evidence

ORD record
ord-0ceb4db2ce9444369a0741e5de4d2b50
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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