1,4-Dioxane → HCID 58504799, compound

HRID 2367640Notes

Reaction equation

HRID 2367640 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][C@H:12]([CH3:14])[CH2:11][C@@H:10]([N:15]([CH3:23])[C:16](=[O:22])[CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:9]2)[CH:5]=[C:4](Cl)[N:3]=1.[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[F:36])#[N:26].O1CCOCC1.C([O-])(O)=O.[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.CCOC(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][C@H:12]([CH3:14])[CH2:11][C@@H:10]([N:15]([CH3:23])[C:16](=[O:22])[CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:9]2)[CH:5]=[C:4]([C:30]2[CH:31]=[CH:32][C:27]([C:25]#[N:26])=[C:28]([F:36])[CH:29]=2)[N:3]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 51356287HCID 51356287, compound

Product 1

HCID 58504799HCID 58504799, compoundYield 83.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To N-[(3R,5R)-1-(2-amino-6-chloro-4-pyrimidinyl)-5-methyl-3-piperidinyl]-N,3,3-trimethylbutanamide (80 mg, 0.23 mmol) and (4-cyano-3-fluorophenyl)boronic acid (49 mg, 0.29 mmol) were added 1,4-dioxane (4 mL) and sat. aq. NaHCO3 (2 mL), and the resulting mixture was purged (“degassed”) with N2 into a sealable tube. Pd(Ph3P)4 (26 mg, 0.023 mmol) was added, the tube was sealed, and the reaction mixture was stirred overnight at 100° C. The reaction was allowed to cool down to room temperature and poured onto water and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% Hexanes to 75% EtOAc/Hexanes) afforded the title compound (84 mg) as a solid. LC-MS (ES) m/z=439 [M+H]+.

Workup

  1. customthe resulting mixture was purged
  2. custom(“degassed”) with N2 into a sealable tube
  3. customthe tube was sealed
  4. temperatureto cool down to room temperature
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ac8753b83c0544cc8fa70cd685974ba2
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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