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

HRID 1893910Notes

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-95d2a0b2bcdd46d9a85ea0c5b59ed549
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513266B2

Reaction notes

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