Acryloyl chloride → HCID 86651985, compound

HRID 1615341Notes

Reaction equation

HRID 1615341 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][NH:5][CH3:6].C(N(C(C)C)CC)(C)C.[C:17](Cl)(=[O:20])[CH:18]=[CH2:19].I[C:23]1[C:31]2[C:26](=[CH:27][C:28]([CH:32]=[O:33])=[CH:29][CH:30]=2)[N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:24]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C.C(Cl)Cl>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][N:5]([CH3:6])[C:17](=[O:20])/[CH:18]=[CH:19]/[C:23]1[C:31]2[C:26](=[CH:27][C:28]([CH:32]=[O:33])=[CH:29][CH:30]=2)[N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:24]=1

Participants

9

Reactant 5

HCID 13140Acryloyl chlorideHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 80271Tri-o-tolylphosphineHCID 81531Diisopropylethylamine2×HCID 581896963-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-6-carbaldehyde

Product 1

HCID 86651985HCID 86651985, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A dry round-bottom flask was charged with N1,N1,N2-trimethylethane-1,2-diamine (0.32 mL, 2.50 mmol), diisopropylethylamine (0.87 mL, 5.00 mmol) and CH2Cl2 (12 mL) and the solution cooled with an ice-water bath. Acryloyl chloride (0.20 mL, 2.50 mmol) was added dropwise and the reaction allowed to warm to room temperature. After 3 hours the solvent was removed and the residue purified by column chromatography (silica gel, 88:10:2, CH2Cl2/MeOH/7M NH3 in MeOH) to give 50 mg of a crude oil to which was added 3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-6-carbaldehyde (105 mg, 0.262 mmol), DMF (5 mL) and diisopropylethylamine (0.091 mL, 0.524 mmol). The mixture was degassed by bubbling Argon through the solution for 15 min. Pd(OAc)2 (3.0 mg, 0.013 mmol) and P(o-tolyl)3 (12 mg, 0.039 mmol) were then added and the reaction heated to 110° C. for 18 hours. The mixture was cooled to room temperature, NaHCO3(sat.) (5 mL) was added, and the product extracted (3×) with EtOAc. The organic layer was washed with water (2×) and brine (2×), and then dried over MgSO4. After removal of solvent the residue was purified by column chromatography (silica gel, 93:6:1, CH2Cl2/MeOH/7M NH3 in MeOH) to give 41 mg, 41% of a red-orange oil. MS ESI 431.2 [M+H]+, calcd for [C22H34N4O3Si+H]+ 431.25.

Workup

  1. temperaturethe solution cooled with an ice-water bath
  2. customAfter 3 hours the solvent was removed
  3. customthe residue purified by column chromatography (silica gel, 88:10:2, CH2Cl2/MeOH/7M NH3 in MeOH)
  4. customto give 50 mg of a crude oil to which
  5. customThe mixture was degassed
  6. customby bubbling Argon through the solution for 15 min
  7. temperaturethe reaction heated to 110° C. for 18 hours
  8. temperatureThe mixture was cooled to room temperature
  9. extractionthe product extracted (3×) with EtOAc
  10. washThe organic layer was washed with water (2×) and brine (2×)
  11. dry with materialdried over MgSO4
  12. customAfter removal of solvent the residue
  13. customwas purified by column chromatography (silica gel, 93:6:1, CH2Cl2/MeOH/7M NH3 in MeOH)

Sources & evidence

ORD record
ord-523ff65d56864e11862a8c4707216caf
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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