Methyl chloroacetate → {3-[4-Methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-phenoxy}-acetic acid methyl ester

HRID 1066500Notes

Reaction equation

HRID 1066500 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)(=[O:17])=[O:16])[C:11]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[C:10]([O:34][CH3:35])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Cl[CH2:39][C:40]([O:42][CH3:43])=[O:41].C(Cl)Cl.CCOC(C)=O>CN(C=O)C>[CH3:43][O:42][C:40](=[O:41])[CH2:39][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[N:9]=[C:10]([O:34][CH3:35])[C:11]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[C:12]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)(=[O:17])=[O:16])[N:13]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 7295Methyl chloroacetateHCID 24758Sodium hydride2×HCID 98485845-Methyl-pyridine-2-sulfonic acid [2-(3-hydroxy-phenyl)-6-methoxy-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amideHCID 21226138Dichloromethane ethylacetate

Product 1

HCID 53666334{3-[4-Methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-phenoxy}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.41 g of 5-methyl-pyridine-2-sulfonic acid [2-(3-hydroxy-phenyl)-6-methoxy-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amide, product of example 1, were dissolved in DMF (30 ml) and treated with NaH (0.061 g of a 65% NaH suspension in oil) under ice cooling. The mixture was stirred for 1 h at RT, treated dropwise with 0.11 g of methyl chloroacetate and was stirred at RT for 20 h until the reaction was completed according to TLC analysis (CH2Cl2/EtOAc: 4/1). The mixture was partitioned between brine and EtOAc the organic layer was dried over Na2SO4 and the solvent removed in vacuo. The residue was purified on a silica gel chromatography column (eluted with Me2Cl2/EtOAc: 7/1). Combination of the purified fractions and evacuation in vacuo afforded {3-[4-methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-phenoxy}-acetic acid methyl ester as a light yellow crystalline solid. ISP mass spectrum, m/e 567.2 (M+1 calculated for C27H26N4O8S: 567).

Workup

  1. stirringwas stirred at RT for 20 h until the reaction
  2. customThe mixture was partitioned between brine and EtOAc the organic layer
  3. dry with materialwas dried over Na2SO4
  4. customthe solvent removed in vacuo
  5. customThe residue was purified on a silica gel chromatography column (eluted with Me2Cl2/EtOAc: 7/1)

Sources & evidence

ORD record
ord-06599323143745c38fe717e8fd98a7c2
Source dataset
uspto-grants-2001_06
Patent number
US06242601B1

Reaction notes

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