Isopropylamine → HCID 136344021, compound

HRID 1050756Notes

Reaction equation

HRID 1050756 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:23])=[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:14][S:13][C:9]2=[C:10](Br)[N:11]=1)=[O:5])[CH3:2].[CH3:24][Si:25]([C:28]#[CH:29])([CH3:27])[CH3:26].C(N)(C)C>C1COCC1.CCOC(C)=O.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.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:23])=[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:14][S:13][C:9]2=[C:10]([C:29]#[C:28][Si:25]([CH3:27])([CH3:26])[CH3:24])[N:11]=1)=[O:5])[CH3:2]

Participants

8

Reactant 3

HCID 6363IsopropylamineHCID 66111TrimethylsilylacetyleneHCID 136343982HCID 136343982, compound

Product 1

HCID 136344021HCID 136344021, compoundYield 35.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-Bromo-3-(4-fluoro-phenyl)-4-hydroxy-isothiazolo[5,4-c]pyridine-5-carboxylic acid ethyl ester (124.9 mg, 0.39 mmol) in THF (5.6 mL) was added trimethylsilylacetylene (0.11 mL, 0.78 mmol), PdCl2(PPh3)2 (55.1 mg, 0.078 mmol), CuI (29.9 mg, 0.156 mmol) and isopropylamine (0.34 mL, 2.42 mmol). The reaction mixture refluxed for 16 h with stirring. After cooling to r. t. the mixture was diluted with EtOAc (20 mL), filtered and the filter cake washed with EtOAc (10 mL). The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel. Elution with 0-20% EtOAc/CH2Cl2 gave the title compound as white solid (57 mg): MS (m/z) 415.1 (M+1).

Workup

  1. temperatureThe reaction mixture refluxed for 16 h
  2. temperatureAfter cooling to r
  3. filtrationfiltered
  4. washthe filter cake washed with EtOAc (10 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel
  7. washElution with 0-20% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-e383ae5033274ca69987f88f1502945c
Source dataset
uspto-grants-2016_07
Patent number
US09387200B2

Reaction notes

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