Trimethylsilylacetylene → HCID 73335339, compound

HRID 926281Notes

Reaction equation

HRID 926281 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:29]=[C:14]3[C:15]4[C:20]([CH2:21][CH2:22][N:13]3[C:12](=[O:30])[CH2:11][N:10]=2)=[C:19]([C:23]#[C:24][Si](C)(C)C)[CH:18]=[CH:17][CH:16]=4)[CH:6]=[CH:7][CH:8]=1.BrC1C=CC=C2C=1CCN1C(=O)CN=C(C3C=CC=C(OC)C=3)C=C12.C[Si](C#C)(C)C>N1CCCCC1.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>[CH2:23]([C:19]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:20]=1[CH2:21][CH2:22][N:13]1[C:12](=[O:30])[CH2:11][N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:29]=[C:14]12)[CH3:24]

Participants

8

Reactant 3

HCID 66111Trimethylsilylacetylene2×HCID 73335133HCID 73335133, compoundHCID 86711354HCID 86711354, compound

Product 1

HCID 73335339HCID 73335339, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 8082PiperidineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-(3-methoxyphenyl)-9-((trimethylsilyl)ethynyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one. 37-1. A mixture of 9-bromo-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 20) (1.0 g, 2.52 mmol), Pd(PPh3)2Cl2 (88 mg, 0.13 mmol) and CuI (48 mg, 0.25 mmol) in piperidine (15 mL) was degassed (sonication) with a flux of Ar, and trimethylsilylacetylene (1.06 mL, 7.55 mmol) was then added. The mixture was heated to 80° C. for 18 h. Additional trimethylsilylacetylene (1.00 mL, 7.12 mmol) and Pd(PPh3)2Cl2 (88 mg, 0.13 mmol) were added and the mixture was heated to 80° C. for another 24 h. After cooling to RT, the reaction was diluted with AcOEt, and washed with H2O. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1) afforded the title compound (700 mg) as a brown solid UPLC-MS: MS 415.3 (M+H+); UPLC rt 1.43 min.

Workup

  1. customwas degassed
  2. additionwas then added
  3. temperaturethe mixture was heated to 80° C. for another 24 h
  4. temperatureAfter cooling to RT
  5. washwashed with H2O
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1)

Sources & evidence

ORD record
ord-3aebb81951924866a579604d77c4408c
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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