Diethylamine → 2,4-Dimethyl-6-oxo-1-phenyl-5-trimethylsilanylethynyl-1,6-dihydro-pyridine-3-carboxylic acid [(5)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

HRID 222803Notes

Reaction equation

HRID 222803 reaction equation
[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[C:20](Br)[C:19](=[O:24])[N:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH3:31])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C.[CH3:56][Si:57]([C:60]#[CH:61])([CH3:59])[CH3:58]>[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.CN(C)C=O>[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[C:20]([C:61]#[C:60][Si:57]([CH3:59])([CH3:58])[CH3:56])[C:19](=[O:24])[N:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH3:31])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 532387715-Bromo-2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

Product 1

HCID 672458932,4-Dimethyl-6-oxo-1-phenyl-5-trimethylsilanylethynyl-1,6-dihydro-pyridine-3-carboxylic acid [(5)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amideYield 53.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-bromo-2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide (2a, 60.0 mg, 0.124 mmol), N,N-dimethylformamide (0.6 mL), copper(I) iodide (4.5 mg, 0.024 mmol), bis(triphenylphosphine)palladium(II) chloride (9.1 mg, 0.013 mmol), triphenylphosphine (20.0 mg, 0.0762 mmol), N-ethylethanamine (0.6 mL, 6 mmol) and (trimethylsilyl)acetylene (0.052.6 mL, 0.372 mmol) was flushed with Argon and heated under microwave irradiation for 30 min at 120° C. It was evaporated in vacuo, transferred to 20 g silica gel column with 1,2-dichloroethane and separated by flash chromatography with gradient heptane-ethyl acetate to give 2,4-dimethyl-6-oxo-1-phenyl-5-trimethylsilanylethynyl-1,6-dihydro-pyridine-3-carboxylic acid [(S) -cyclobutyl-(3-fluoro-phenyl)-methyl]-amide (33 mg; yield=53%) as a pale yellow-brown solid. LC-MS (m/z) 501.7 (MH+); tR=1.94 (method C).

Workup

  1. customwas flushed with Argon
  2. customIt was evaporated in vacuo
  3. customseparated by flash chromatography with gradient heptane-ethyl acetate

Sources & evidence

ORD record
ord-d7e02b0c5a694131b542a27a669ee6b5
Source dataset
uspto-grants-2012_06
Patent number
US08207347B2

Reaction notes

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