Dimethyl Sulfate → 5-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide

HRID 2085103Notes

Reaction equation

HRID 2085103 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18](Cl)[N:17]=[C:16]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2].[CH3:36][O:37][CH2:38][C:39]#[C:40][CH2:41][OH:42].C(O)C#CCO.COS(OC)(=O)=O.[H-].[Na+]>CN(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:42][CH2:41][C:40]#[C:39][CH2:38][O:37][CH3:36])[N:17]=[C:16]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6497Dimethyl SulfateHCID 80662-Butyne-1,4-diolHCID 24758Sodium hydride2×HCID 5340554-Methoxy-2-butyn-1-olHCID 227294115-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Product 1

HCID 101447365-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamideYield 45.7%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 300 mg of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)4-pyrimidinyl]-2-pyridine sulfonamide (Example 1f) and 1.47 g of 4-methoxy-2-butynol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) in 15 ml of DMF was carefully added 234 mg of 55% NaH in mineral oil. The brown solution stirred for 24 h at room temperature before further 120 mg of 55% NaH in mineral oil was added. Stirring was continued for 24 h. The mixture was diluted with 100 ml of 10% aqueous citric acid and extracted four times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 50 ml of water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with ethyl acetate to give 154 mg of 5-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide as a yellow solid. LC-MS: tR=4.84 min, [M+1]+=576.42, [M−1]−=574.37.

Workup

  1. additionwas added
  2. extractionextracted four times with 50 ml of ethyl acetate
  3. washThe combined organic phases were washed twice with 50 ml of water
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe crude product was purified by column chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-78b65cc80d8c48108c41b3254d1d3502
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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