Sodium hydride → US10023592, Example 262

HRID 575751Notes

Reaction equation

HRID 575751 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[H-].[Na+].[F:8][C:9]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:10]=1[O:11][C:12]1[C:13]([C:22]2[C:23]3[CH:32]=[CH:31][O:30][C:24]=3[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=2)=[N:14][C:15](S(C)(=O)=O)=[N:16][CH:17]=1>CN(C=O)C>[F:8][C:9]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:10]=1[O:11][C:12]1[C:13]([C:22]2[C:23]3[CH:32]=[CH:31][O:30][C:24]=3[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=2)=[N:14][C:15]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[N:16][CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 1180220064-[5-(2,4-Difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-6-methylfuro[2,3-c]pyridin-7-one

Product 1

HCID 118020937US10023592, Example 262Yield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of methanesulfonamide (61 mg, 0.65 mmol) in DMF (2 mL) stirred at 0° C. under an atmosphere of nitrogen was treated with NaH (99 mg, 0.7 mmol). After the ice bath was removed, the mixture was stirred at rt for 15 min. The resulting suspension was treated with a solution of 4-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-6-methylfuro[2,3-c]pyridin-7-one (70 mg, 0.16 mmol) in DMF (1 mL). After the nitrogen inlet was removed, the capped mixture was heated to 70° C. for 3 h. After cooling to 0° C., the reaction mixture was stirred vigorously and treated water (500 uL). After 5 min, the cooled mixture was treated with 1N HCl(aq) (1 mL). The resulting suspension was filtered; the filter cake was washed with additional 1N HCl(aq) (1 mL) and isopropyl ether (5 mL) to afford the title compound (50 mg, 70%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.34 (s, 3H) 3.60 (s, 3H) 7.06 (m, 1H) 7.28 (m, 1H) 7.49 (m, 1H) 7.80 (s, 1H) 8.23 (s, 1H) 8.43 (m, 2H) 11.50 (bs, 1H). LCMS (M+H)+=449.

Workup

  1. customAfter the ice bath was removed
  2. customAfter the nitrogen inlet was removed
  3. temperaturethe capped mixture was heated to 70° C. for 3 h
  4. temperatureAfter cooling to 0° C.
  5. stirringthe reaction mixture was stirred vigorously
  6. additiontreated water (500 uL)
  7. waitAfter 5 min
  8. additionthe cooled mixture was treated with 1N HCl(aq) (1 mL)
  9. filtrationThe resulting suspension was filtered
  10. washthe filter cake was washed with additional 1N HCl(aq) (1 mL) and isopropyl ether (5 mL)

Sources & evidence

ORD record
ord-dc1eacfa35d5485f9698254a9589f547
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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