Tetrahydrofuran → N-(4-(1,3-benzodioxol-5-yl)-3-{2-[(5-chloro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-1H-pyrazol-5-yl)-5-isopropyl-2-pyridinesulfonamide

HRID 397276Notes

Reaction equation

HRID 397276 reaction equation
O1CCCC1.[H-].[Na+].[O:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[C:18]([O:36][CH2:37][CH2:38][OH:39])=[N:19][N:20]([CH3:35])[C:21]=3[NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH:32]([CH3:34])[CH3:33])=[CH:28][N:27]=3)(=[O:25])=[O:24])=[CH:16][C:11]=2[O:10][CH2:9]1.[Cl:40][C:41]1[CH:42]=[N:43][C:44](S(C)(=O)=O)=[N:45][CH:46]=1>CC(N(C)C)=O>[O:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[C:18]([O:36][CH2:37][CH2:38][O:39][C:44]4[N:45]=[CH:46][C:41]([Cl:40])=[CH:42][N:43]=4)=[N:19][N:20]([CH3:35])[C:21]=3[NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH:32]([CH3:34])[CH3:33])=[CH:28][N:27]=3)(=[O:25])=[O:24])=[CH:16][C:11]=2[O:10][CH2:9]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 27277255-Chloro-2-methanesulfonylpyrimidineHCID 22281907HCID 22281907, compound

Product 1

HCID 9808190N-(4-(1,3-benzodioxol-5-yl)-3-{2-[(5-chloro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-1H-pyrazol-5-yl)-5-isopropyl-2-pyridinesulfonamideYield 45%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

In an oven-dried flask a solution of tetrahydrofuran (50 ml) and dimethylacetamide (3 ml) was treated with sodium hydride as a 60% dispersion in oil (460 mg) under an atmosphere of nitrogen. The reaction was stirred for 5 min and then treated with N-[4-(1,3-benzodioxol-5-yl)-3-(2-hydroxyethoxy)-1-methyl-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide (1.0 g) (Preparation 13). The reaction was stirred for 3 h and was then treated with 5-chloro-2(methylsulfonyl)pyrimidine (460 mg). After stirring for a further 3 h the reaction mixture was concentrated and the residue was partitioned between water (100 ml) and ethyl acetate (100 ml). The aqueous was extracted with ethyl acetate (3×75 ml) and the combined organics were dried over sodium sulfate. The solvent was removed and the crude residue was purified on a silica (40 g) column eluting with 20% ether in dichloromethane rising to 45% ether in dichloromethane to yield the title compound as an off-white foam (560 mg).

Workup

  1. stirringThe reaction was stirred for 3 h
  2. stirringAfter stirring for a further 3 h the reaction mixture
  3. concentrationwas concentrated
  4. customthe residue was partitioned between water (100 ml) and ethyl acetate (100 ml)
  5. extractionThe aqueous was extracted with ethyl acetate (3×75 ml)
  6. dry with materialthe combined organics were dried over sodium sulfate
  7. customThe solvent was removed
  8. customthe crude residue was purified on a silica (40 g) column
  9. washeluting with 20% ether in dichloromethane rising to 45% ether in dichloromethane

Sources & evidence

ORD record
ord-8891016ea60343e9b99bea7f39b1854b
Source dataset
uspto-grants-2003_08
Patent number
US06610518B2

Reaction notes

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