Dimethyl Sulfate → 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide

HRID 2085109Notes

Reaction equation

HRID 2085109 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[C:19](Cl)[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:29][O:30][CH2:31][C:32]#[C:33][CH2:34][OH:35].C(O)C#CCO.COS(OC)(=O)=O.[H-].[Na+]>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[C:19]([O:35][CH2:34][C:33]#[C:32][CH2:31][O:30][CH3:29])[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 6497Dimethyl SulfateHCID 80662-Butyne-1,4-diolHCID 24758Sodium hydride2×HCID 5340554-Methoxy-2-butyn-1-olHCID 227294154-tert.-butyl-N-[6-chloro-5-(p-tolyl)4-pyrimidinyl]-benzene sulfonamide

Product 1

HCID 102994234-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamideYield 61.6%

Reagents, catalysts & solvents 1

HCID 311Citric AcidSolvent

Procedure

To a mixture of 300 mg of 4-tert.-butyl-N-[6-chloro-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide (Example 12c) and 1.8 g of 4-methoxy-2-butyn-1-ol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) was added 288 mg of 55% NaH in mineral oil. After evolution of gas had ceased, the brown suspension was stirred at room temperature for 24 h. Another 288 mg of 55% NaH in mineral oil was added and the mixture was stirred at 60° C. for 18 h. The mixture was cooled, diluted with 50 ml of 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 column chromatography on silica gel eluting with hexane:ethyl acetate 1:1 and precipitated from diethyl ether to give 213 mg of 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide as a white powder. LC-MS: tR=5.61 min, [M+1]+=480.30, [M−1]−=478.39.

Workup

  1. customprepared
  2. stirringthe mixture was stirred at 60° C. for 18 h
  3. temperatureThe 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 column chromatography on silica gel eluting with hexane:ethyl acetate 1:1
  9. customprecipitated from diethyl ether

Sources & evidence

ORD record
ord-f3177699973f44dfa49313132cb6be6b
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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