Water → HCID 22221610, compound

HRID 1836055Notes

Reaction equation

HRID 1836055 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:18]([OH:20])=O)[C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=3)=[CH:7][C:6]=2[CH:17]=1.O.[NH2:22]N.Cl.C[N:26]([CH3:35])CCCN=C=NCC.O>CN(C=O)C>[OH:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]2[O:9][C:5]3[C:4]([C:18]4[O:20][CH:35]=[N:26][N:22]=4)=[CH:3][C:2]([OH:1])=[CH:17][C:6]=3[CH:7]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22221627HCID 22221627, compound

Product 1

HCID 22221610HCID 22221610, compoundYield 2.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 24 (0.6 g, 2.2 mmol) in DMF (3-5 mL) and hydrazine monohydrate (0.25 mL, 5 mmol) was treated with EDCl (1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (0.64 g, 3.3 mmol) and the reaction allowed to stir at rt for several hours. The reaction was worked up by adding water and extracting twice with EtOAc. The combined EtOAc extracts were washed with brine and dried over MgSO4. The EtOAc was concentrated to render 125 mg of the crude acyl hydrazide which was used as is for the next step. The crude acyl hydrazide from the previous step was treated with 3-5 mL of triethyl orthoformate and catalytic p-toluenesulfonic acid and heated to reflux for 30 minutes. The reaction mixture was allowed to cool to rt and was poured into 2 N HCl aq, extracted with EtOAc, washed with 2 N HCl aq, saturated NaHCO3 aq, brine, and dried over MgSO4. Filtration and concentration followed by chromatography on silica gel (1:19 MeOH/CH2Cl2) gave 15 mgs of 138: MP=260-266° C.; 1H NMR (DMSO-d6) δ 9.94 (br s, 1 H), 9.75 (br s, 1 H), 9.45 (s, 1 H), 7.79 (d, 2 H, J=8.7 Hz), 7.33 (d, 1 H, J=2.4 Hz), 7.20 (s, 1 H), 7.18 (d, 1 H, J=2.4 Hz), 6.92 (d, 2 H, J=8.7 Hz); MS 295 (M+H)+.

Workup

  1. extractionextracting twice with EtOAc
  2. washThe combined EtOAc extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationThe EtOAc was concentrated
  5. additionThe crude acyl hydrazide from the previous step was treated with 3-5 mL of triethyl orthoformate and catalytic p-toluenesulfonic acid
  6. temperatureheated
  7. temperatureto reflux for 30 minutes
  8. temperatureto cool to rt
  9. additionwas poured into 2 N HCl aq
  10. extractionextracted with EtOAc
  11. washwashed with 2 N HCl aq, saturated NaHCO3 aq, brine
  12. dry with materialdried over MgSO4
  13. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-6bf53d888035489c931e0edb5f11a20e
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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