N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}amine → HCID 178428964, compound

HRID 1977954Notes

Reaction equation

HRID 1977954 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([O:16][S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:26]([CH3:29])(=[O:28])=[O:27])(=[O:19])=[O:18])[CH:5]=[C:6]([CH:15]=1)[O:7][CH2:8][C:9]1([CH2:12][O:13][NH2:14])[CH2:11][CH2:10]1.[ClH:30].N1C=CC([C:36]([NH2:38])=[NH:37])=N1>CN(C)C=O>[ClH:30].[CH3:1][C:2]1[CH:3]=[C:4]([O:16][S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:26]([CH3:29])(=[O:28])=[O:27])(=[O:19])=[O:18])[CH:5]=[C:6]([CH:15]=1)[O:7][CH2:8][C:9]1([CH2:12][O:13][NH:14][C:36]([NH2:38])=[NH:37])[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 22722412N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}amineHCID 178479321HCID 178479321, compound

Product 1

HCID 178428964HCID 178428964, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}amine (3.5 g, 8.0 mmol), as prepared in the preceding step, in N,N-dimethylformamide (30 mL) was added 1H-pyrazole-carboxamidine hydrochloride (3.7 g, 25.0 mmol). The reaction mixture was stirred at ambient temperature overnight. N,N-Dimethylformamide was removed under high vacuum. Acetonitrile (50 mL) was added and the solid was removed by filtration. The filtrate was concentrated in vacuo and the residue was dried under high vacuum. The residue was partitioned between water (100 mL plus 5 mL brine) and diethyl ether (50 mL). The water solution was extracted with diethyl ether (50 mL). The combined diethyl ether solution was extracted with pH 5 water (30 mL). The combined water solution was adjusted to pH 8-9 by using 2N NaOH and extracted into ethyl acetate (3×100 mL). The ethyl acetate solution was washed with pH 7 buffer solution (5×60 mL) and brine (50 mL) and dried over Na2SO4. After removing the solvent, 0.6N HCl methanol (50 mL) was added and the solution was concentrated. The residual oil was crystallized from methanol/ethyl acetate (1:50) to give the title compound as white solid (3.6 g, 86%). 1H-NMR (300 MHz, DMSO-d6) δ11.07 (br s, 1H), 8.37 (d, J=7.8 Hz, 1H), 8.09-8.14 (m, 2H), 7.97 (t, J=7.7 Hz, 1H), 7.65 (br s, 4H), 6.76 (s, 1H), 6.52 (s, 1H), 6.51 (s, 1H), 3.86 (s, 2H), 3.78 (s, 2H), 3.48 (s, 3H), 2.21 (s, 3H), 0.69 (m, 2H), 0.62 (m, 2H). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C20H25N3O7S2: 484.1 (M+H), 506.1 (M+Na). Found: 484.0, 506.0.

Workup

  1. customN,N-Dimethylformamide was removed under high vacuum
  2. additionAcetonitrile (50 mL) was added
  3. customthe solid was removed by filtration
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was dried under high vacuum
  6. customThe residue was partitioned between water (100 mL plus 5 mL brine) and diethyl ether (50 mL)
  7. extractionThe water solution was extracted with diethyl ether (50 mL)
  8. extractionThe combined diethyl ether solution was extracted with pH 5 water (30 mL)
  9. extractionextracted into ethyl acetate (3×100 mL)
  10. washThe ethyl acetate solution was washed with pH 7 buffer solution (5×60 mL) and brine (50 mL)
  11. dry with materialdried over Na2SO4
  12. customAfter removing the solvent, 0.6N HCl methanol (50 mL)
  13. additionwas added
  14. concentrationthe solution was concentrated
  15. customThe residual oil was crystallized from methanol/ethyl acetate (1:50)

Sources & evidence

ORD record
ord-e1da6f3b21944a6f859ef1eb6292794f
Source dataset
uspto-grants-2001_05
Patent number
US06235778B1

Reaction notes

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