Formaldehyde → N-(6-dimethylamino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide

HRID 2069276Notes

Reaction equation

HRID 2069276 reaction equation
NC1C=C2[C:9](=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13])[NH:8][C:7](=[O:16])[N:6]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])C2=O.[CH2:23]=O.[O:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1.[C:30](#[N:32])C.O>[Pd].C(O)(=O)C.O>[CH3:23][N:32]([CH3:30])[C:26]1[CH:27]=[C:28]2[C:9](=[CH:10][C:11]=1[C:12]([F:13])([F:14])[F:15])[NH:8][C:7](=[O:16])[N:6]([NH:17][S:18]([CH3:21])(=[O:19])=[O:20])[C:29]2=[O:25]

Participants

8

Reactant 4

HCID 712Formaldehyde2×HCID 8028TetrahydrofuranHCID 11964604N-(6-amino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamideHCID 18373917Acetonitrile--water (1/1)

Product 1

HCID 11632005N-(6-dimethylamino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent

Procedure

A mixture of 370 mg (1.094 mmol) of N-(6-amino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide, 0.083 ml (1.02 mmol) of formaldehyde solution (37% in water), 0.0033 ml of acetic acid, 21 ml of tetrahydrofuran and 21 ml of water is hydrogenated in presence of 100 mg of palladium on carbon for 10 days. After day 1, 3, 4, 5 and 6 another portion of formaldehyde (0.083 ml) and acetic acid (0.0033 ml) is added. After filtration of the reaction mixture the tetrahydrofuran is evaporated and the remaining aqueous phase extracted with ethyl acetate. The organic phase is washed with brine, dried over Na2SO4 and concentrated to dryness leaving a yellow powder that is fractionated by medium pressure chromatography on a RP-18 column (20 μm particle size) with acetonitril/water 3:4. The fractions containing the product are combined and extracted with ethyl acetate, the organic phase dried over Na2SO4 and concentrated yielding 277 mg of N-(6-dimethylamino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide as yellow powder, m.p. 254-272° C.

Workup

  1. filtrationAfter filtration of the reaction mixture the tetrahydrofuran
  2. customis evaporated
  3. extractionthe remaining aqueous phase extracted with ethyl acetate
  4. washThe organic phase is washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customleaving a yellow powder that
  8. additionThe fractions containing the product
  9. extractionextracted with ethyl acetate
  10. dry with materialthe organic phase dried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-43c6fb453b574bb4bc67b11250dfdd63
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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