Nitrogen → HCID 11442512, compound

HRID 2216532Notes

Reaction equation

HRID 2216532 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:17]=[C:18](Br)[N:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:30])[CH:28]=[CH2:29].N#N.C(N(CC)CC)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:17]=[C:18](/[CH:29]=[CH:28]/[C:27]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[N:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 8471Triethylamine2×HCID 15458tert-Butyl acrylateHCID 21943316HCID 21943316, compound

Product 1

HCID 11442512HCID 11442512, compoundYield 60.1%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 12.4 (100 mg, 0.243 mmol) in DMF (1.5 ml) was added tert-butyl acrylate (0.045 ml, 0.304 mmol) and tri-o-tolylphosphine (3.7 mg, 0.0122 mmol). After the 5 min degass with N2, triethylamine (0.068 ml, 0.486 mmol) and Pd(OAc)2 (2.7 mg, 0.0122 mmol) were added, and the reaction mixture stirred at 80° C. for 17 h. Additional reagents (same molar equivalents except triethylamine (0.034 ml, 0.243 mmol) and the mixture was stirred at 100° C. for an additional 3 h. Reagent addition was repeated and the mixture again stirred at 100° C. for 17 h. The solution was partitioned between EtOAc and H2O and the organic phase washed with brine, dried (Na2SO4), concentrated, and the crude product purified by SiO2 chromatography (stepwise gradient: 30 to 50% Et2O/hexanes) to afford 67 mg (60%) of 12.5. MS (ESI) 459.4 (MH+).

Workup

  1. additionwere added
  2. additionReagent addition
  3. stirringthe mixture again stirred at 100° C. for 17 h
  4. customThe solution was partitioned between EtOAc and H2O
  5. washthe organic phase washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customthe crude product purified by SiO2 chromatography (stepwise gradient

Sources & evidence

ORD record
ord-e6bd02abae544c8d8675d785c2e1eecf
Source dataset
uspto-grants-2006_09
Patent number
US07112601B2

Reaction notes

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