Sodium Carbonate → 5-(3-Chloropyridin-4-yl)-N4-cyclopentylpyrimidine-2,4-diamine

HRID 79105

Reaction equation

HRID 79105 reaction equation
Br[C:2]1[C:3]([NH:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Cl:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[C:2]1[C:3]([NH:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 38618773-Chloro-4-pyridineboronic acidHCID 582998155-Bromo-N4-cyclopentylpyrimidine-2,4-diamine

Product 1

HCID 582995755-(3-Chloropyridin-4-yl)-N4-cyclopentylpyrimidine-2,4-diamineYield 80%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2 (2.57 g, 10.0 mmol) in dioxane (75 mL) were added 3-chloropyridine-4-boronic acid (4.72 g, 10.0 mmol), trans-dichlorobis(triphenylphosphine)-palladium(II) (702 mg, 1.0 mmol), and sodium carbonate (3.82 g, 36 mmol, in 36 mL of water). The mixture thus obtained was purged with N2 for 10 min and heated at 120° C. in a sealed tube for 22 h. The reaction mixture was diluted with water and the product was extracted with chloroform. The organic layers were dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica gel eluting with 2.5% methanol in dichloromethane to give the title compound (3) as a white solid (2.31 g, 80%). 1H NMR (500 MHz, DMSO-d6) δ 8.64 (1H, s), 8.50 (1H, d, J=4.9 Hz), 7.51 (1H, s), 7.34 (1H, d, 1H, J=4.9 Hz), 6.21 (2H, d, 1H, br s), 5.97 (1H, d, J =7.6 Hz), 4.43 (1H, p, J=7.4 Hz), 1.84 (2H, m), 1.62 (2H, m), 1.40-1.49 (4H, m) ppm; LCMS-ESI (POS), M/Z, M+1: Found 290.0, Calculated 290.1.

Workup

  1. customThe mixture thus obtained
  2. customwas purged with N2 for 10 min
  3. additionThe reaction mixture was diluted with water
  4. extractionthe product was extracted with chloroform
  5. dry with materialThe organic layers were dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel eluting with 2.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-88396905ce1249689de6609c56c357c3
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Linked notes

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