1,1,3,3-Tetramethylguanidine → 4-[4-Methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid 1-acetoxy-ethyl ester

HRID 1066524Notes

Reaction equation

HRID 1066524 reaction equation
[CH3:1][O:2][C:3]1[C:8]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[C:7]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=2)(=[O:21])=[O:20])[N:6]=[C:5]([C:29]2[CH:34]=[CH:33][N:32]=[C:31]([C:35]([OH:37])=[O:36])[CH:30]=2)[N:4]=1.CN(C)C(N(C)C)=N.Cl[CH:47]([O:49][C:50](=[O:52])[CH3:51])[CH3:48]>CN(C=O)C>[C:50]([O:49][CH:47]([O:36][C:35]([C:31]1[CH:30]=[C:29]([C:5]2[N:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[O:16][CH3:17])=[C:7]([NH:18][S:19]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=3)(=[O:21])=[O:20])[N:6]=2)[CH:34]=[CH:33][N:32]=1)=[O:37])[CH3:48])(=[O:52])[CH3:51]

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 5218651-Chloroethyl acetateHCID 98929854-[4-Methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid2×

Product 1

HCID 536759234-[4-Methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid 1-acetoxy-ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.52 g of 4-[4-methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid, product of example 21, in DMF (10 ml) were added at RT 0.23 g of 1,1,3,3-tetramethylguanidine followed by 0,245 g of acetic acid 1-chloroethyl ester (preparation described by M. Ertan et al., Arzneim. Forsch. 1992, Vol. 42, 70). The reaction mixture was then heated at 60° C. for 20 h, cooled to RT and partitioned between ice water and EtOAc. The organic layer was washed with water, dried over Na2SO4 and the organic layer was removed in vacuo. The residue was purified on a silica gel chromatography column (eluted with tert-butyl methyl ether). Combinations of the purified fractions and evacuation in vacuo afforded 4-[4-methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid 1-acetoxy-ethyl ester as a white solid. ISN mass spectrum, m/e 608 (M−1 calculated for C28H27N5O9S: 608).

Workup

  1. temperaturecooled to RT
  2. custompartitioned between ice water and EtOAc
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. customthe organic layer was removed in vacuo
  6. customThe residue was purified on a silica gel chromatography column (eluted with tert-butyl methyl ether)

Sources & evidence

ORD record
ord-662a365c4ffa4922b718df7d3082241d
Source dataset
uspto-grants-2001_06
Patent number
US06242601B1

Reaction notes

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