Potassium Carbonate → 4-tert.-butyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-benzene sulfonamide

HRID 2085094Notes

Reaction equation

HRID 2085094 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][C:32]#[C:33][CH2:34][OH:35])[N:18]=[C:17]([C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:42][O:43][CH:44]1[C:49](=S(=O)=O)[C:48]([O:53][CH3:54])=[N:47][C:46](C)=[N:45]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][C:32]#[C:33][CH2:34][O:35][C:46]3[N:47]=[C:48]([O:53][CH3:54])[CH:49]=[C:44]([O:43][CH3:42])[N:45]=3)[N:18]=[C:17]([C:36]3[CH:37]=[CH:38][N:39]=[CH:40][CH:41]=3)[N:16]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 102815734-tert-Butyl-N-[6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-benzenesulfonamideHCID 771347914,6-Dimethoxy-2-methyl-sulfonylpyrimidine2×

Product 1

HCID 102836504-tert.-butyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-benzene sulfonamideYield 20.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 400 mg of 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-benzene sulfonamide (Example 2c), 116 mg of 4,6-dimethoxy-2-methyl-sulfonylpyrimidine and 147 mg of potassium carbonate in 15 ml of DMF was stirred at 90° C. for 16 h. Further 42 mg of 4,6-dimethoxy-2-methyl-sulfonylpyrimidine was added and stirring was continued at 90° C. for 24 h. Eventually, the solvent was removed in vacuo, and the resulting residue partitioned between 50 ml of 5% 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, dried over MgSO4 and evaporated. The remaining oil was purified by column chromatography on silica gel eluting with toluene: ethyl acetate 4:1 to 1:1. The product obtained was recrystallised from ethyl acetate:diethyl ether to give 76 mg of 4-tert.-butyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-benzene sulfonamide as white crystals. LC-MS: tR=5.84 min, [M+1]+=713.35, [M−1]−=711.45.

Workup

  1. stirringstirring
  2. waitwas continued at 90° C. for 24 h
  3. customEventually, the solvent was removed in vacuo
  4. customthe resulting residue partitioned between 50 ml of 5% aqueous acetic acid and 50 ml of DCM
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted two more times with 50 ml of DCM
  7. washThe combined organic layers were washed with water
  8. dry with materialdried over MgSO4
  9. customevaporated
  10. customThe remaining oil was purified by column chromatography on silica gel eluting with toluene: ethyl acetate 4:1 to 1:1
  11. customThe product obtained
  12. customwas recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-bfecddc9fc384e3ea9fb20765b81999d
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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