Triethylamine → HCID 178520487, compound

HRID 2304916Notes

Reaction equation

HRID 2304916 reaction equation
[F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]([OH:14])=O)=[CH:6][CH:5]=1.C1C=NC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C.Cl.Cl.[NH2:38][CH:39]1[CH2:47][CH2:46][C:42]2[NH:43][CH:44]=[N:45][C:41]=2[CH2:40]1.C(N(CC)CC)C>CC(N(C)C)=O.Cl>[NH:43]1[C:42]2[CH2:46][CH2:47][CH:39]([NH:38][C:12](=[O:14])[CH:11]=[CH:10][C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:16])[F:15])=[CH:9][CH:8]=3)[CH2:40][C:41]=2[N:45]=[CH:44]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 181649HOAtHCID 2777277HCID 2777277, compoundHCID 178478651HCID 178478651, compound

Product 1

HCID 178520487HCID 178520487, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of 3-(4-trifluoromethoxyphenyl)acrylic acid (186 mg, 1.0 mmol) in DMA (5 ml), HOAt (136 mg, 1.0 mmol) and DIC (126 mg, 1.0 mmol) were added and the mixture was stirred for 10 min. A mixture prepared from 5-amino-4,5,6,7-tetrahydro-1H-benzimidazole, dihydrochloride (210 mg, 1.0 mmol), DMA (5 ml) and triethylamine (202 mg, 2 mmol) was added to the activated ester and the mixture was stirred for 16 hours at ambient temperature. The volatiles were evaporated and the residue was stirred with a mixture of H2O (40 ml), 1 N hydrochloric acid (20 ml) and diethyl ether (25 ml). The phases were separated and the aqueous phase was washed with diethyl ether (2×25 ml) and then made alkaline to pH 10-11 with 4 N sodium hydroxide. The alkaline mixture was extracted with ethyl acetate (3×50 ml) and the combined organic extracts were dried (magnesium sulphate). The solvent was evaporated in vacuo to give a residue that was dissolved in 1 N hydrochloric acid (50 ml) and the acidic mixture was evaporated to dryness. The residue was re-evaporated with acetone (2×15 ml), stirred with acetone for 1 hour and the solid was isolated by filtration and dried. This afforded 141 mg (36%) of the title compound.

Workup

  1. stirringthe mixture was stirred for 16 hours at ambient temperature
  2. customThe volatiles were evaporated
  3. stirringthe residue was stirred with a mixture of H2O (40 ml), 1 N hydrochloric acid (20 ml) and diethyl ether (25 ml)
  4. customThe phases were separated
  5. washthe aqueous phase was washed with diethyl ether (2×25 ml)
  6. extractionThe alkaline mixture was extracted with ethyl acetate (3×50 ml)
  7. dry with materialthe combined organic extracts were dried (magnesium sulphate)
  8. customThe solvent was evaporated in vacuo
  9. customto give a residue that
  10. customthe acidic mixture was evaporated to dryness
  11. customThe residue was re-evaporated with acetone (2×15 ml)
  12. stirringstirred with acetone for 1 hour
  13. customthe solid was isolated by filtration
  14. customdried

Sources & evidence

ORD record
ord-fe3faed4d0a14fc9be91100dca805e14
Source dataset
uspto-grants-2002_08
Patent number
US06437147B1

Reaction notes

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