2-Butyne-1,4-diol → 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

HRID 2085091

Reaction equation

HRID 2085091 reaction equation
[CH2:1]([OH:6])[C:2]#[C:3][CH2:4][OH:5].[H-].[Na+].[CH:9]([C:12]1[CH:13]=[CH:14][C:15]([S:18]([NH:21][C:22]2[C:27]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[O:35][CH3:36])=[C:26](Cl)[N:25]=[CH:24][N:23]=2)(=[O:20])=[O:19])=[N:16][CH:17]=1)([CH3:11])[CH3:10]>CN(C=O)C.CN1C(=O)N(C)CCC1>[CH:9]([C:12]1[CH:13]=[CH:14][C:15]([S:18]([NH:21][C:22]2[C:27]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[O:35][CH3:36])=[C:26]([O:5][CH2:4][C:3]#[C:2][CH2:1][OH:6])[N:25]=[CH:24][N:23]=2)(=[O:20])=[O:19])=[N:16][CH:17]=1)([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 80662-Butyne-1,4-diolHCID 24758Sodium hydrideHCID 227294075-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

Product 1

HCID 101408715-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamideYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
90 °C

Procedure

To a solution of 11.02 g of 2-butyne-1,4-diol in 100 ml of DMF and 30 ml of DMPU was added 2.8 g sodium hydride in portions. After completion of the addition stirring was continued for 1.5 h followed by the addition of 2.78 g of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide. The mixture was heated to 90° C. and stirred for 65 h. The solvent was removed in vacuo, the residue was taken up in 250 ml of 10% aqueous citric acid and extracted twice with 250 ml of ethyl acetate. The organic phase was washed with water and brine, dried over MgSO4 and evaporated. Column chromatography of the crude product on silica gel eluting with hexane:ethyl acetate 1:1 to 1:4 furnished 1.27 g of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)4-pyrimidinyl]-2-pyridine sulfonamide as a brown solid. Beige crystals were obtained for analytical purposes after crystallisation of a part of the isolated product from 2-propanol. LC-MS: tR=4.50 min, [M+1]+=485.27, [M−1]−=483.41.

Workup

  1. additionAfter completion of the addition
  2. stirringstirred for 65 h
  3. customThe solvent was removed in vacuo
  4. extractionextracted twice with 250 ml of ethyl acetate
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-25e25afe39f6425dbd99c45aca28d71c
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Linked notes

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