Triethylamine → HCID 57780716, compound

HRID 2076100Notes

Reaction equation

HRID 2076100 reaction equation
CN(C)/[CH:3]=[C:4]1\[CH2:5][CH2:6][CH2:7][C:8]([OH:17])(C2C=NC=CC=2)[C:9]\1=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH:41][C:42]([NH2:44])=[NH:43])[CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1.C(N(CC)CC)C>C(O)C.O1CCCC1>[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH:41][C:42]2[N:44]=[CH:3][C:4]3[CH2:5][CH2:6][CH2:7][CH:8]([OH:17])[C:9]=3[N:43]=2)[CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 67096114HCID 67096114, compoundHCID 178493228HCID 178493228, compound

Product 1

HCID 57780716HCID 57780716, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of crude 6-[1-dimethylamino-meth-(E)-ylidene]-2-hydroxy-2-pyridin-3-yl-cyclohexanone (1002 mg, 2.7 mmol), N-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-guanidine dinitrate (948 mg, 3.3 mmol) and triethyl amine (546 mg, 5.4 mmol) in ethanol (13.5 mL) was heated to 160° C. for 30 minutes in a microwave oven. The reaction was concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and the solvent was removed under reduced pressure to yield 1340 mg of crude intermediate. This was dissolve in tetrahydrofurane (13.5 mL) and under nitrogen 1M TBAF solution in tetrahydrofurane (4.0 mL) was added. The reaction was stirred at room temperature over night and was concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was purified on silica gel using dichloromethane/methanol (9:1 v/v) as eluent to yield the title compound (765 mg, 81%) as a brown foam. MS ISP (m/e): 352.3 (100) [(M+H)+]. 1H NMR (DMSO-D6, 300 MHz): δ (ppm)=9.67 (s, 1H), 8.30 (s, 1H), 7.98 (s, 1H), 7.65 (s, 1H), 7.38 (d, 1H), 7.20 (d, 1H), 7.03 (s, 1H), 5.24 (d, 1H), 4.44 (m, 1H), 3.79 (s, 3H), 2.55-2.65 (m, 2H), 2.14 (s, 3H), 1.65-1.95 (m, 4H).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customThe residue was partitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto yield 1340 mg of crude intermediate
  9. additionwas added
  10. concentrationwas concentrated under reduced pressure
  11. customThe residue was partitioned between water and ethyl acetate
  12. extractionThe aqueous layer was extracted twice with ethyl acetate
  13. washThe combined organic layers were washed with brine
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. customthe solvent was removed under reduced pressure
  17. customThe residue was purified on silica gel

Sources & evidence

ORD record
ord-9e8badb42cfb468eb89c9afcf48b55a9
Source dataset
uspto-grants-2011_04
Patent number
US07923450B2

Reaction notes

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