Trimethylsilylacetylene → 2-amino-8-ethyl-4-methyl-6-((trimethylsilyl)ethynyl)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1666273Notes

Reaction equation

[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[NH2:7][C:8]1[N:9]=[C:10]([CH3:22])[C:11]2[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH2:20][CH3:21])[C:12]=2[N:13]=1.C([O-])(O)=O.[Na+]>C(N(CC)CC)C.[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>[NH2:7][C:8]1[N:9]=[C:10]([CH3:22])[C:11]2[CH:17]=[C:16]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[C:15](=[O:19])[N:14]([CH2:20][CH3:21])[C:12]=2[N:13]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Trimethylsilylethyne (1.44 mL, 10.2 mmol) was added to a pressure tube charged with 2-amino-6-bromo-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one (1.58 g, 5.59 mmol) from above, CuI (0.053 g, 0.279 mmol), and PdCl2(PPh3)2 (0.211 g, 0.279 mmol) in triethylamine (20 mL). The pressure tube was sealed under nitrogen and heated to 50° C. 96 h. The reaction was cooled to room temperature and poured into a saturated solution of NaHCO3 (150 mL), then washed four times with ethyl acetate (50 mL). The organic layers were pooled and dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on SiO2 (2:1, methylene chloride:ethyl acetate) to afford 2-amino-8-ethyl-4-methyl-6-((trimethylsilyl)ethynyl)pyrido[2,3-d]pyrimidin-7(8H)-one (1.09 g, 65% yield) as an off white solid.

Workup

customThe pressure tube was sealed under nitrogen
custom96 h
temperatureThe reaction was cooled to room temperature
washwashed four times with ethyl acetate (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified on SiO2 (2:1, methylene chloride:ethyl acetate)

Sources & evidence

ORD record: ord-338758d6c30849b9961a3f9a4a80e1b7
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044062B2

Reaction notes

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