Dimethyl Sulfate → 4-tert-Butyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-[2,2'']bipyrimidinyl-4-yl]-benzenesulfonamide

HRID 2085105Notes

Reaction equation

HRID 2085105 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19](Cl)[N:18]=[C:17]([C:31]3[N:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:37][O:38][CH2:39][C:40]#[C:41][CH2:42][OH:43].C(O)C#CCO.COS(OC)(=O)=O.[H-].[Na+]>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[NH3:14].[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:43][CH2:42][C:41]#[C:40][CH2:39][O:38][CH3:37])[N:18]=[C:17]([C:31]3[N:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 6497Dimethyl SulfateHCID 80662-Butyne-1,4-diolHCID 24758Sodium hydrideHCID 5340554-Methoxy-2-butyn-1-olHCID 111351604-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

Product 2

HCID 222AmmoniaHCID 102819434-tert-Butyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-[2,2'']bipyrimidinyl-4-yl]-benzenesulfonamideYield 82.8%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 250 mg of 4-tert.-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimi-dinyl]benzene sulfonamide (Example 5a) and 1.11 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 THF was added 177 mg of 55% NaH in mineral oil. The suspension was stirred for 16 h at reflux. The reaction mixture was cooled, diluted with 100 ml 10% aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates with ethyl acetate:methanol:sat. aqueous ammonia 8:2:1 to give 116 mg of 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(o-methoxy-phenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide as a slightly yellow foam. LC-MS: tR=5.19 min, [M+1]+=590.40, [M−1]−=588.39

Workup

  1. customprepared
  2. temperatureat reflux
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted 4 times with 50 ml of ethyl acetate
  5. washThe combined organic phases were washed with water
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe crude product was purified by chromatography on prep

Sources & evidence

ORD record
ord-968a72a955414822ac31eedfe878e217
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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