Methanol → Avosentan

HRID 2228814Notes

Reaction equation

HRID 2228814 reaction equation
[Na].Cl[C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[N:6]=[C:5]([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=2)(=[O:18])=[O:17])[C:4]=1[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34].[CH3:35][OH:36]>>[CH3:35][O:36][C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[N:6]=[C:5]([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=2)(=[O:18])=[O:17])[C:4]=1[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34]

Participants

4

Reactant 3

HCID 887MethanolHCID 5360545SodiumHCID 11202530HCID 11202530, compound

Product 1

HCID 9912992Avosentan

Procedure

To a solution of 6.9 g sodium in MeOH (300 ml) were added 14.52 g of 5-methyl-pyridine-2-sulfonic acid [6-chloro-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide at RT and the mixture was refluxed for 5 days until completion of the reaction according to TLC analysis. The reaction mixture was concentrated in vacuo to half its volume upon which the crude reaction product precipitated as a sodium salt. It was filtered off by suction and dried in a high vacuum. The solid was dissolved in water, which was then made acidic by addition of acetic acid. The precipitating free sulfonamide was extracted into Me2Cl2. The organic layer was dried over Mg2SO4, concentrated on a rotary evaporator, and the crystalline solid that had formed was filtered off. It was then dried in a high vacuum for 12 h at 120° C. to give the desired 5-methyl-pyridine-2-sulfonic acid [6-methoxy-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide as white crystals. Melting point 225-226° C. ISN mass spectrum, m/e 478.2 (M-1 calculated for C23H21N5O5S1: 478).

Workup

  1. temperaturethe mixture was refluxed for 5 days until completion of the reaction
  2. concentrationThe reaction mixture was concentrated in vacuo to half its volume upon which the crude
  3. customreaction product
  4. customprecipitated as a sodium salt
  5. filtrationIt was filtered off by suction
  6. customdried in a high vacuum
  7. dissolutionThe solid was dissolved in water
  8. additionmade acidic by addition of acetic acid
  9. extractionThe precipitating free sulfonamide was extracted into Me2Cl2
  10. dry with materialThe organic layer was dried over Mg2SO4
  11. concentrationconcentrated on a rotary evaporator
  12. customthe crystalline solid that had formed
  13. filtrationwas filtered off
  14. customIt was then dried in a high vacuum for 12 h at 120° C.

Sources & evidence

ORD record
ord-5bb23e561340450aa28cc4221ec5e11c
Source dataset
uspto-grants-2002_07
Patent number
US06417360B1

Reaction notes

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