Water → HCID 66789376, compound

HRID 1672276Notes

Reaction equation

HRID 1672276 reaction equation
[NH2:1][C:2]1[CH:21]=[C:20]([CH2:22][OH:23])[C:5]2[N:6]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:7](=[O:12])[C:8]([CH3:11])([CH3:10])[O:9][C:4]=2[CH:3]=1.N1C=CC=C[CH:25]=1.[CH3:30][S:31](Cl)(=[O:33])=[O:32].O>ClCCl>[F:19][C:16]1[CH:15]=[CH:14][C:13]([N:6]2[C:5]3[C:20]([CH2:22][O:23][CH3:25])=[CH:21][C:2]([NH:1][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:3][C:4]=3[O:9][C:8]([CH3:11])([CH3:10])[C:7]2=[O:12])=[CH:18][CH:17]=1.[F:19][C:16]1[CH:15]=[CH:14][C:13]([N:6]2[C:5]3[C:20]([CH2:22][OH:23])=[CH:21][C:2]([NH:1][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:3][C:4]=3[O:9][C:8]([CH3:11])([CH3:10])[C:7]2=[O:12])=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 66790065HCID 66790065, compound

Product 2

HCID 66789376HCID 66789376, compoundHCID 66790187HCID 66790187, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To solution of 7-amino-4-(4-fluorophenyl)-5-(hydroxymethyl)-2,2-dimethyl-2H -1,4-benzoxazin-3(4H)-one (compound obtained in Reference Example 175(3), 117 mg) and pyridine (0.12 mL) in dichloromethane (5 nm) was added dropwise methanesulfonyl chloride (0.085 mL) under ice-cooling, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in methanol (4 mL) and the solution was refluxed for 15 hours. The reaction mixture was concentrated in vacuo, and the resultant residue was purified by column chromatography on silica gel (Solvent; chloroform→chloroform/methanol=85/15) to give N-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H -1,4-benzoxazin-7-yl]methanesulfonamide as a pale yellow powder (40 mg, MS (APCI) m/z; 409 [M+H]+) and N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide as a pale brown powder (52 mg, MS (APCI) m/z; 409 [M+H]+), respectively.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in methanol (4 mL)
  7. temperaturethe solution was refluxed for 15 hours
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. customthe resultant residue was purified by column chromatography on silica gel (Solvent; chloroform→chloroform/methanol=85/15)

Sources & evidence

ORD record
ord-025932d1e8ed4d578480d1f266e5ee9c
Source dataset
uspto-grants-2011_08
Patent number
US07998956B2

Reaction notes

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