Citric Acid → 4-Methyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(p-tolyl)-4-pyrimidinyl]-amide

HRID 1181239Notes

Reaction equation

HRID 1181239 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12](=[O:22])(=[O:21])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:6]=1[C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=1.[H-].[Na+].[Br:32][C:33]1[CH:34]=[N:35][C:36](Cl)=[N:37][CH:38]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Br:32][C:33]1[CH:34]=[N:35][C:36]([O:1][CH2:2][CH2:3][O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12](=[O:21])(=[O:22])[NH:13][C:14]3[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=3)[C:6]=2[C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)=[N:37][CH:38]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 219795764-Methyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(p-tolyl)-4-pyrimidinyl]-amide

Product 1

HCID 219795634-Methyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(p-tolyl)-4-pyrimidinyl]-amideYield 52.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 4-methyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(p-tolyl)-4-pyrimidinyl]-amide (47 mg, Example 11) dissolved in THF (8 ml) was added sodium hydride (14.6 mg, 60% dispersion in mineral oil) and stirring was continued for 15 min followed by the addition of 5-bromo-2-chloro-pyrimidine (39 mg). Stirring was continued for 2 h at 50° C. and 80 h at r.t. The mixture was evaoprated and a 10% citric acid solution was added. The precipitate was filtered off, washed with water and purified by chromatography over silicagel with EtOAc/Hex=1/1 to give 4-methyl-phenyl sulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(p-tolyl)-4-pyrimidinyl]-amide (34 mg). tR=5.34 (LC); [M+H]+=573.02 (ES+).

Workup

  1. stirringStirring
  2. waitwas continued for 2 h at 50° C. and 80 h at r.t
  3. filtrationThe precipitate was filtered off
  4. washwashed with water
  5. custompurified by chromatography over silicagel with EtOAc/Hex=1/1

Sources & evidence

ORD record
ord-3f5e48784c334c908df7593557c1a5c5
Source dataset
uspto-grants-2007_10
Patent number
US07285549B2

Reaction notes

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