Potassium Carbonate → 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

HRID 2085097Notes

Reaction equation

HRID 2085097 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH:7]([C:10]1[CH:11]=[CH:12][C:13]([S:16]([NH:19][C:20]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)=[C:24]([O:33][CH2:34][C:35]#[C:36][CH2:37][OH:38])[N:23]=[C:22]([C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)[N:21]=2)(=[O:18])=[O:17])=[N:14][CH:15]=1)([CH3:9])[CH3:8].[CH3:45][O:46][C:47]1[CH:52]=[C:51]([O:53][CH3:54])[N:50]=[C:49](S(C)(=O)=O)[N:48]=1>CN(C=O)C>[CH:7]([C:10]1[CH:11]=[CH:12][C:13]([S:16]([NH:19][C:20]2[C:25]([C:26]3[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=3)=[C:24]([O:33][CH2:34][C:35]#[C:36][CH2:37][O:38][C:49]3[N:50]=[C:51]([O:53][CH3:54])[CH:52]=[C:47]([O:46][CH3:45])[N:48]=3)[N:23]=[C:22]([C:39]3[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=3)[N:21]=2)(=[O:18])=[O:17])=[N:14][CH:15]=1)([CH3:9])[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 8383634,6-Dimethoxy-2-(methylsulfonyl)pyrimidineHCID 98069845-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Product 1

HCID 101899785-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 243 mg of K2CO3 in 15 ml of DMF 450 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 11) was added. After stirring for 0.5 h at 90° C., 192 mg of 4,6-dimethoxy-2-methylsulfonylpyrimidine was added and stirring was continued for 16 h at 90° C. Eventually, the solvent was evaporated and the remaining residue was partitioned between 50 ml of 10% aqueous acetic acid and 50 ml of DCM. The organic layer was separated and the aqueous layer was extracted two more times with 50 ml of DCM. 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 DCM:methanol 20:1 to give 88 mg of 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide as a beige foam. LC-MS: tR=5.54 min, [M+1]+=668.38, [M−1]+=666.39.

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued for 16 h at 90° C
  4. customEventually, the solvent was evaporated
  5. customthe remaining residue was partitioned between 50 ml of 10% aqueous acetic acid and 50 ml of DCM
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted two more times with 50 ml of DCM
  8. washThe combined organic layers were washed with water and brine
  9. dry with materialdried over MgSO4
  10. customevaporated
  11. customThe crude product was purified by column chromatography on silica gel eluting with DCM:methanol 20:1

Sources & evidence

ORD record
ord-96ceb92a765643569ba3caa0dec94f3d
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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