Pyrimidine, 2,4-dichloro-5-methyl- → Methyl 1-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxylate

HRID 592436Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([C:12]([O:14][CH3:15])=[O:13])[CH2:11][CH2:10]1)#[CH:2].[Cl:16][C:17]1[N:22]=[C:21](Cl)[C:20]([CH3:24])=[CH:19][N:18]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.CCN(C(C)C)C(C)C>O1CCOCC1.[Cu]I.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:16][C:17]1[N:22]=[C:21]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:9]2([C:12]([O:14][CH3:15])=[O:13])[CH2:11][CH2:10]2)[C:20]([CH3:24])=[CH:19][N:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of methyl 1-(2-ethynylphenyl)cyclopropanecarboxylate K2 (1.34 g, 6.67 mmol), 2,4,-dichloro-5-methylpyrimidine (1.41 g, 8.67 mmol), CuI (0.063 g, 0.33 mmol), PdCl2(PPh3)2 (0.234 g, 0.333 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.097 g, 0.33 mmol) in 1,4-dioxane (15 mL) was bubbled with N2 for 10 minutes. DIPEA (3.48 mL, 20.0 mmol) was added and the reaction mixture was stirred under N2 at 80° C. for 3 hours. The reaction mixture was cooled and the volatiles were removed in vacuo to give a black residue that was purified by column chromatography (Biotage Isolera, 2×40 g SiO2 cartridges, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the impure title compound A41 as a yellow oil (estimated 80% purity, 1.352 g, 50%). LCMS-A: rt 6.79 min; m/z 327 [M+H]+.

Workup

customwas bubbled with N2 for 10 minutes
temperatureThe reaction mixture was cooled
customthe volatiles were removed in vacuo
customto give a black residue that
customwas purified by column chromatography (Biotage Isolera, 2×40 g SiO2 cartridges, 0-50% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record: ord-8277781481c44da5a8b0ef2645848a9a
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

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