1-(2-((2,5-Dichloropyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide → 1-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592377Notes

Reaction equation

HRID 592377 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1>CCN(C(C)C)C(C)C.CO.[Pt]=O>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:17][CH2:18]2)[C:5]([Cl:22])=[CH:4][N:3]=1

Participants

5

Reactant 1

HCID 867122941-(2-((2,5-Dichloropyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

HCID 82844Platinum oxide (PtO)CatalystHCID 887MethanolSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A suspension of 1-(2-((2,5-dichloropyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide (A13) (0.536 g, 1.61 mmol) and platinum oxide (0.110 g, 0.484 mmol) in DIPEA (16 mL) and MeOH (3 mL) was stirred under a hydrogen atmosphere for 58 hours. The resulting mixture was filtered through a pad of Celite and the filtrate concentrated in vacuo. The residue was diluted with water and EtOAc and filtered through a pad of Celite. The filtrate was extracted with EtOAc (2×20 mL) and the combined organic fractions were washed with water (3×20 mL), brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The residue was adsorbed onto silica gel and purified by column chromatography (CombiFlash Rf, 24 g SiO2 Cartridge, 30-60% EtOAc in cyclohexane) to give the title compound A14 as a white solid (375 mg, 69%); 1H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H), 7.43 (d, J=7.2 Hz, 1H), 7.28-7.31 (m, 3H), 5.37 (d, J=17 Hz, 2H), 3.27 (brs, 4H), 1.76 (brs, 2H), 1.16 (brs, 2H). LCMS-B: rt 5.30 min; m/z 337 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through a pad of Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. additionThe residue was diluted with water and EtOAc
  4. filtrationfiltered through a pad of Celite
  5. extractionThe filtrate was extracted with EtOAc (2×20 mL)
  6. washthe combined organic fractions were washed with water (3×20 mL), brine
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by column chromatography (CombiFlash Rf, 24 g SiO2 Cartridge, 30-60% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-00f8c9a557fc4312922ee465647223e9
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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