Ethylene Glycol → 4-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide

HRID 1181232Notes

Reaction equation

HRID 1181232 reaction equation
[H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].Cl[C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[N:11]=[C:10]([NH:20][S:21](=[O:33])(=[O:32])[NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]([CH3:31])[CH3:30])=[CH:25][CH:24]=2)[C:9]=1[O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[O:41][CH3:42]>C(COC)OC>[OH:5][CH2:4][CH2:3][O:6][C:8]1[N:13]=[C:12]([C:14]2[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=2)[N:11]=[C:10]([NH:20][S:21](=[O:32])(=[O:33])[NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]([CH3:31])[CH3:30])=[CH:25][CH:24]=2)[C:9]=1[O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[O:41][CH3:42]

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 24758Sodium hydrideHCID 102798684-i-Propyl-phenyl sulfamic acid-[6-chloro-5-(o-methoxy-phenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-amide

Product 1

HCID 103028114-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydride (17 mg, 60% dispersion in mineral oil) was added to ethylene glycol (1.2 ml) followed by addition of dimethoxyethane (0.5 ml). Stirring was continued for 30 min, then 4-i-propyl-phenyl sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (45 mg, Referential Example 1e)) was added and the reaction mixture was heated to 80° C. for 48 h. The solvents were evaporated, water (10 ml) and a 10% solution of citric acid was added until the pH was 3 followed by extraction with EtOAc. The organic layers were dried over sodium sulfate and the solvent was evaporated. The crude product was purified by chromatography through silicagel with EtOAc to give 4-i-propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (38 mg). tR=4.56 min, (LC); [M+H]+=552.36 (ES+).

Workup

  1. customThe solvents were evaporated
  2. additionwater (10 ml) and a 10% solution of citric acid was added until the pH was 3
  3. extractionfollowed by extraction with EtOAc
  4. dry with materialThe organic layers were dried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe crude product was purified by chromatography through silicagel with EtOAc

Sources & evidence

ORD record
ord-6848f88555b045c3b3514c7f9ac3e387
Source dataset
uspto-grants-2007_10
Patent number
US07285549B2

Reaction notes

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