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

HRID 2085087Notes

Reaction equation

HRID 2085087 reaction equation
[H-].[Na+].CN1C(=O)N(C)CCC1.[CH2:12]([OH:17])[C:13]#[C:14][CH2:15][OH:16].[CH:18]([C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=3)=[C:35](Cl)[N:34]=[C:33]([C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)[N:32]=2)(=[O:29])=[O:28])=[N:25][CH:26]=1)([CH3:20])[CH3:19]>CN(C=O)C>[CH:18]([C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=3)=[C:35]([O:16][CH2:15][C:14]#[C:13][CH2:12][OH:17])[N:34]=[C:33]([C:45]3[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=3)[N:32]=2)(=[O:28])=[O:29])=[N:25][CH:26]=1)([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 80662-Butyne-1,4-diolHCID 24758Sodium hydrideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 227294005-isopropyl-N-[6-chloro-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Product 1

HCID 98069845-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a slurry of 0.34 g of sodium hydride in 15 ml of DMF and 4 ml of DMPU 2.4 g of 2-butyne-1,4-diol was added at room temperature. The mixture was stirred until no more gas evolved. Then 0.67 g of 5-isopropyl-N-[6-chloro-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide was added and the mixture was stirred at 90° C. for 48 h. The solvent was removed in vacuo and the residue was taken up in 100 ml of 10% aqueous acetic acid. The mixture was extracted three times with 100 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The resulting brown oil was purified by column chromatography on silica gel eluting with DCM containing 4-10% of methanol. This furnished a fraction which after recrystallisation from DCM: ethyl acetate gave 43 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide as pale yellow crystals. A second fraction gave 456 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide with about 90% purity as a brown oil. LC-MS: tR=4.53 min, [M+1]+=530.23, [M−1]−=528.21.

Workup

  1. stirringthe mixture was stirred at 90° C. for 48 h
  2. customThe solvent was removed in vacuo
  3. extractionThe mixture was extracted three times with 100 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 resulting brown oil was purified by column chromatography on silica gel eluting with DCM containing 4-10% of methanol
  8. customThis furnished a fraction which
  9. customafter recrystallisation from DCM

Sources & evidence

ORD record
ord-429a60cb2d9145cdacd26977971e6e2e
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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