Dimethylformamide → 4-i-Propyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(o-methoxy-phenoxy)-2-(4-pyridyl)pyrimidin-4-yl]-amide

HRID 10252

반응식

HRID 10252 반응식
[OH:1][CH2:2][CH2:3][O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)[N:8]=[C:7]([NH:17][S:18](=[O:30])(=[O:29])[NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=2)[C:6]=1[O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[O:38][CH3:39].[H-].[Na+].[Br:42][C:43]1[CH:44]=[N:45][C:46](Cl)=[N:47][CH:48]=1.CN(C=O)C>C1COCC1>[Br:42][C:43]1[CH:44]=[N:45][C:46]([O:1][CH2:2][CH2:3][O:4][C:5]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[N:8]=[C:7]([NH:17][S:18](=[O:30])(=[O:29])[NH:19][C:20]3[CH:21]=[CH:22][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:24][CH:25]=3)[C:6]=2[O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[O:38][CH3:39])=[N:47][CH:48]=1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 103028114-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide

생성물 1

HCID 101228954-i-Propyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(o-methoxy-phenoxy)-2-(4-pyridyl)pyrimidin-4-yl]-amide수율 71.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

4-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (60 mg, Example 3) was dissoved in THF (8 ml). Sodium hydride (14 mg, 60% dispersion in mineral oil) was added and stirring continued for 10 min. 5-Bromo-2-chloro-pyrimidine (37 mg) was added and the mixture was heated to 60° C. for 120 min. DMF (0.5 ml) was added and the solution was stirred at r.t. for 48 h. The solvents were evaporated, water (12 ml) and a 10% solution of citric acid was added until the pH was 3. The precipitate was filtered off and washed with water and purified by chromatography through silica gel with EtOAc/Hex=1:1 to give 4-i-propyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(o-methoxy-phenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (55.4 mg). tR=5.30 min, (LC); [M+H]+=710.35 (ES+).

후처리

  1. stirringthe solution was stirred at r.t. for 48 h
  2. customThe solvents were evaporated
  3. additionwater (12 ml) and a 10% solution of citric acid was added until the pH was 3
  4. filtrationThe precipitate was filtered off
  5. washwashed with water
  6. custompurified by chromatography through silica gel with EtOAc/Hex=1:1

출처 및 근거

ORD 기록
ord-a2a3024b09cf491db1828fcf80ec430e
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094781B2

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