2-Butyne-1,4-diol → HCID 10182534, compound

HRID 2085093Notes

Reaction equation

HRID 2085093 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]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)=[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]([C:28]3[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=3)=[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 22729413HCID 22729413, compound

Product 1

HCID 10182534HCID 10182534, compoundYield 35.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a solution of 21.5 g of 2-butyne-1,4-diol in 200 ml of DMF and 50 ml of DMPU was added in portions 5.5 g of NaH 55% in mineral oil. After the evolution of gas had ceased 5.04 g of 5-isopropyl-N-[6-chloro-5-(p-tolyl)-4-pyrimidinyl]-2-pyridine sulfonamide was added and the resulting mixture was stirred for 80 h at 90° C. The solvent was removed in vacuo and the residue was partitioned between 300 ml of 10% aqueous citric acid and 300 ml of ethyl acetate. The aqueous phase was extracte two more times with ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with hexane:ethyl acetate from 1:1 to 1:4 to give 2.0 g of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-2-pyridine sulfonamide as a brown solid. LC-MS: tR=4.64 min, [M+1]+=453.28, [M−1]−=451.40.

Workup

  1. additionwas added
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between 300 ml of 10% aqueous citric acid and 300 ml of ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe crude product was purified by column chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-9d04f8b0bfbb4181aeb89a7240372c32
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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