참여 물질
| 역할 | 이름 | HCID | 투입량 |
|---|
| 반응물 | Phosphorus pentachloride | HCID 24819 | — |
| 반응물 | Diisopropylethylamine | HCID 81531 | — |
| 반응물 | 2-Cyanopyrimidine | HCID 2757979 | — |
| 반응물 | Sodium Methoxide | HCID 10942334 | — |
| 반응물 | Diethyl (2-methoxyphenoxy)propanedioate | HCID 11140560 | — |
| 반응물 | 5-(2-Methoxyphenoxy)-2-(pyrimidin-2-yl)-tetrahydropyrimidin-4,6-dione | HCID 21979567 | — |
| 반응물 | 2-Amidinopyrimidine hydrochloride | HCID 21983731 | — |
| 반응물 | Sodium methanolate methanol | HCID 23694274 | — |
| 반응물 | Ammonia ammonium chloride | HCID 86743336 | — |
| 생성물 | 4,6-Dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine | HCID 10545706 | — |
반응 단계
The process of the present invention is especially useful for the preparation of 4-tert.butyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidine-2-yl)-pyrimidine-4-yl-benzenesulphonamide (bosentan). For the preparation of this compound 2-cyanopyrimidine is prepared as described above and converted into pyrimidin-2-carboxamidine hydrochloride by means of NH3/NH4Cl in a sodium methanolate/methanol solution. This compound is converted in the presence of sodium methanolate with diethyl (o-methoxy-phenoxy-malonate) into rac-5-(2-methoxy-phenoxy)-2-pyrimidin-2-yl-tetrahydro-pyrimidin-4,6-dione. The obtained product is reacted with N,N-diisopropyl-N-ethylamine and phosphorus pentachloride to give 4,6-dichloro-5-(2-methoxy-phenoxy)-2,2′-bipyrimidine. This substance is then reacted with p-tert.butylbenzenesulphonamide to give 4-tert.butyl-N-6-chloro-5-[2-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl]-benzenesulphonamide and further reacted with sodium ethylene glycolate to give 4-tert.butyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl-benzenesulphonamide (bosentan).
출처 및 근거
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 특허 번호 | US06274734B1 |
|---|
| 출처 데이터셋 | uspto-grants-2001_08 |
|---|
| ORD ID | ord-241e0788f69d4e2f8b251b0f174be803 |
|---|
| 출처 메모 | uspto-grants-2001_08 |
|---|
