1,1'-Carbonyldiimidazole → HCID 25138378, compound

HRID 1880617Notes

Reaction equation

HRID 1880617 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[F:13][C:14]([F:27])([F:26])[C:15]1[N:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[C:23]([OH:25])=O)=[CH:17][CH:16]=1.C1C=CC2N(O)N=NC=2C=1.Br.[Cl:39][C:40]1[C:49]([OH:50])=[C:48]([OH:51])[C:47]([Cl:52])=[C:46]2[C:41]=1[CH2:42][CH2:43][NH:44][CH2:45]2>CCOC(C)=O.O>[Cl:39][C:40]1[C:49]([OH:50])=[C:48]([OH:51])[C:47]([Cl:52])=[C:46]2[C:41]=1[CH2:42][CH2:43][N:44]([C:23](=[O:25])/[CH:22]=[CH:21]/[C:18]1[CH:19]=[N:20][C:15]([C:14]([F:13])([F:27])[F:26])=[CH:16][CH:17]=1)[CH2:45]2

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 757711-HydroxybenzotriazoleHCID 5709645(2E)-3-[6-(Trifluoromethyl)pyridin-3-yl]prop-2-enoic acidHCID 685081725,8-Dichloro-1,2,3,4-tetrahydroisoquinoline-6,7-diol--hydrogen bromide (1/1)

Product 1

HCID 25138378HCID 25138378, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of CDI (83 mg, 0.51 mmol) in EtOAc (2 mL) was added (E)-3-(6-(trifluoromethyl)pyridin-3-yl)acrylic acid (100 mg, 0.46 mmol). The resulting mixture was heated at reflux for 1 h after which HOBt (35 mg, 0.23 mmol) and 5,8-dichloro-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydro bromide (145 mg, 0.46 mmol) were added. Heating at reflux was continued for 3 h before the reaction mixture was allowed to cool to rt. It was then poured into water (15 mL) and the water-phase was extracted with EtOAc (3×15 mL). Combined organics were washed with water (10 mL) and brine (10 mL) and dried (MgSO4). After filtration and evaporation, the crude was purified by column chromatography (SiO2, EtOAc:petroleum ether 50:50) to give a bright yellow solid which was purified further by precipitating the product in EtOAc via addition of petroleum ether. After decantation of the solvent and drying, the title compound (110 mg, 0.25 mmol, 55%) was obtained as a light reddish solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. additionwere added
  3. temperatureHeating
  4. temperatureat reflux
  5. extractionthe water-phase was extracted with EtOAc (3×15 mL)
  6. washCombined organics were washed with water (10 mL) and brine (10 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationAfter filtration and evaporation
  9. customthe crude was purified by column chromatography (SiO2, EtOAc:petroleum ether 50:50)
  10. customto give a bright yellow solid which
  11. customwas purified further
  12. customby precipitating the product in EtOAc
  13. additionvia addition of petroleum ether
  14. customAfter decantation of the solvent and drying

Sources & evidence

ORD record
ord-eaf145bd000042eda80fcef18018cfc6
Source dataset
uspto-grants-2012_11
Patent number
US08318768B2

Reaction notes

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