Formaldehyde → 5-isopropyl-N-[6-(4-phenoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyrid in-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide

HRID 2085104Notes

Reaction equation

HRID 2085104 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18](Cl)[N:17]=[C:16]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2].[O:36]([CH2:43][C:44]#[C:45][CH2:46][OH:47])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1(OCC#C)C=CC=CC=1.C=O.[H-].[Na+]>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[NH3:8].[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:47][CH2:46][C:45]#[C:44][CH2:43][O:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:17]=[C:16]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 712FormaldehydeHCID 24758Sodium hydrideHCID 83613(Prop-2-ynyloxy)benzeneHCID 160466794-Phenoxybut-2-yn-1-olHCID 227294115-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide

Product 2

HCID 222AmmoniaHCID 102115145-isopropyl-N-[6-(4-phenoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyrid in-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamideYield 129%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 300 mg of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 1f) and 502 mg of 4-phenoxy-2-butyn-1-ol (prepared starting from phenyl-propargylether and para-formaldehyde following the procedure given in J. Chem. Soc. Perkin Trans. 1, 1991, 1721-1727) in 15 ml of THF was added 228 mg of 55% NaH in mineral oil. The orange suspension was stirred at room temperature for 1 h before it was diluted with 100 ml of 10% aqueous citric acid. The mixture was extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed with 50 ml of water, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates with ethyl acetate:methanol:sat. aqueous ammonia 8:2:1 to give 241 mg of 5-isopropyl-N-[6-(4-phenoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyrid in-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide as a slightly yellow foam. LC-MS: tR=5.95 min, [M+1]+=666.58, [M−1]−=664.62

Workup

  1. extractionThe mixture was extracted three times with 50 ml of ethyl acetate
  2. washThe combined organic phases were washed with 50 ml of water
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe crude product was purified by chromatography on prep

Sources & evidence

ORD record
ord-6ec2f64db1c444419b3d32176712f9c1
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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