Dimethylformamide → 6-[(3-[1,3]Dioxolan-2-yl-propoxy)]-N-[4-(5-cyano-3-pyridin-3yl-pyrazol-1-yl)phenyl]nicotinamide

HRID 1634104Notes

Reaction equation

HRID 1634104 reaction equation
C(CCCOC1C=[CH:33][C:10]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[C:24]([C:25]#[N:26])=[CH:23][C:22]([C:27]4[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=4)=[N:21]3)=[CH:16][CH:15]=2)=[O:12])=[CH:9][CH:8]=1)#N.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:42][CH2:43][CH2:44][CH:45]1[O:49][CH2:48][CH2:47][O:46]1.C[N:51]([CH:53]=[O:54])C>>[O:46]1[CH2:47][CH2:48][O:49][CH:45]1[CH2:44][CH2:43][CH2:42][O:54][C:53]1[CH:8]=[CH:9][C:10]([C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([N:20]3[C:24]([C:25]#[N:26])=[CH:23][C:22]([C:27]4[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=4)=[N:21]3)=[CH:18][CH:19]=2)=[O:12])=[CH:33][N:51]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 5520722-(3-Chloropropyl)-1,3-dioxolaneHCID 98037034-(3-cyanopropoxy)-N-[4-(5-cyano-3-pyridin-3-yl-pyrazol-1-yl)phenyl]benzamide

Product 1

HCID 186771106-[(3-[1,3]Dioxolan-2-yl-propoxy)]-N-[4-(5-cyano-3-pyridin-3yl-pyrazol-1-yl)phenyl]nicotinamide

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 6-hydroxynicotinic acid methyl ester (prepared as describrd in Example 25) (10 mmol) in DMF (30 mL) was added cesium carbonate (10 mmol). After 30 minutes, 2-(3-chloropropyl)-1,3-dioxolane (10 mmol) was added and the reaction mixture was heated at 65° C. on an oil bath. After 2 days, the mixture was cooled to room temperature, volatiles were removed, the residue was taken up in water, and extracted with dichloromethane. The organic phase was dried over magnesium sulfate and concentrated. Chromatography of the residue over silica gel (eluent dichloromethane/ethyl acetate 9:1) gave the desired product as the faster eluting product (311 mg, 12%).

Workup

  1. waitAfter 2 days
  2. temperaturethe mixture was cooled to room temperature
  3. customvolatiles were removed
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-90e72c90bb8b4cb9bd67d351b0631128
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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