Formamide → HCID 25218058, compound

HRID 1929421Notes

Reaction equation

HRID 1929421 reaction equation
S(=O)(=O)(O)O.[CH:6]([NH2:8])=O.N[C:10]1[CH:11]=[C:12]([N:17]2[C:22]3[CH:23]=[CH:24][C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][C:21]=3[O:20][C:19](C)([CH3:32])[C:18]2=O)[CH:13]=[CH:14][C:15]=1[F:16].[BH4-].[Na+].[C:37](=[O:40])([O-])O.[Na+].O1CCC[CH2:43]1>>[CH3:43][N:8]([CH3:6])[C:14]1[CH:13]=[C:12]([N:17]2[C:22]3[CH:23]=[CH:24][C:25]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][C:21]=3[O:20][C:19]([CH3:18])([CH3:32])[C:37]2=[O:40])[CH:11]=[CH:10][C:15]=1[F:16]

Participants

7

Reactant 6

HCID 713FormamideHCID 1118Sulfuric AcidHCID 8028Tetrahydrofuran2×HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 66789441HCID 66789441, compound

Product 1

HCID 25218058HCID 25218058, compound

Procedure

To a solution of 3M sulfuric acid (4 μL) and 36% formamide solution (9.5 mg) in tetrahydrofuran (2 mL) was added a suspension of N-[4-(3-amino-4-fluorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide (compound obtained in Example 44; 20 mg) and sodium borohydride (1 mg) in tetrahydrofuran (3 mL) under cooling in ice/NaCl bath, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added an aqueous saturated sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=7/3→3/7) to give N-{4-[3-(dimethylamino)-4-fluorophenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl}methanesulfonamide (10 mg) as a colorless powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=7/3→3/7)

Sources & evidence

ORD record
ord-c8659dd88e894f468f7b1803fd04519e
Source dataset
uspto-grants-2012_05
Patent number
US08188073B2

Reaction notes

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