HCID 86712626, compound → HCID 86712627, compound

HRID 1778958Notes

Reaction equation

HRID 1778958 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]#[C:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH:6]=[CH:5][N:4]=1>CN(C=O)C.[Pd]>[CH3:1][S:2][C:3]1[N:8]=[C:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH:6]=[CH:5][N:4]=1

Participants

4

Reactant 1

HCID 86712626HCID 86712626, compound

Product 1

HCID 86712627HCID 86712627, compoundYield 52.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 6228DimethylformamideSolvent3×

Procedure

A suspension of methyl 2-(2-((2-(methylthio)pyrimidin-4-yl)ethynyl)phenyl)acetate (A1) (323 mg, 1.08 mmol) and 10% Pd/C (300 mg) in DMF (15 mL) was stirred under a hydrogen atmosphere at room temperature for 20 hours. The resulting mixture was filtered through Celite, washing with EtOAc (100 mL). The filtrate was evaporated in vacuo to yield a brown oil which was dissolved in DMF (10 mL). A slurry of 10% Pd/C (330 mg) in DMF (5 ml) was added and the resulting suspension was stirred under a hydrogen atmosphere at room temperature for a further 20 hours. The resulting mixture was filtered through Celite, washing with EtOAc (100 mL) then the filtrate was evaporated in vacuo. The resulting residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-20% EtOAc in petroleum benzine 40-60° C.) to yield the title compound A2 as a clear oil (170 mg, 52%); 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J=5.0 Hz, 1H), 7.25-7.14 (m, 4H), 6.75 (d, J=5.1 Hz, 1H), 3.69 (m, 5H), 3.11-3.04 (m, 2H), 2.99-2.91 (m, 2H), 2.57 (s, 3H). LC-MS-A: rt 6.060 min; m/z 303.1 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashing with EtOAc (100 mL)
  3. customThe filtrate was evaporated in vacuo
  4. customto yield a brown oil which
  5. stirringthe resulting suspension was stirred under a hydrogen atmosphere at room temperature for a further 20 hours
  6. filtrationThe resulting mixture was filtered through Celite
  7. washwashing with EtOAc (100 mL)
  8. customthe filtrate was evaporated in vacuo
  9. custompurified by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-20% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-2de4a87a90d74661a27f501c0e7c9118
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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