Acetic Acid → HCID 11538495, compound

HRID 2069277Notes

Reaction equation

HRID 2069277 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[C:15]([F:18])([F:17])[F:16])[NH:11][C:10](=[O:19])[N:9]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:8]2=[O:25].C=O.[C:28](O)(=O)C.O1CCCC1>[Pd].C(#N)C.O.O>[OH:1][CH2:2][CH2:3][N:4]([CH3:28])[C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[C:15]([F:18])([F:16])[F:17])[NH:11][C:10](=[O:19])[N:9]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])[C:8]2=[O:25]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712Formaldehyde2×HCID 8028TetrahydrofuranHCID 11717883HCID 11717883, compound

Product 1

HCID 11538495HCID 11538495, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A mixture of 370 mg (0.968 mmol) of N-[6-(2-hydroxy-ethylamino)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide, 0.074 ml (0.912 mmol) of formaldehyde solution (37% in water), 4 ml of acetic acid, 15 ml of tetrahydrofuran and 15 ml of water is hydrogenated in presence of 115 mg of palladium on carbon for 3 days. After day 1 and 2 another portion of formaldehyde (0.074 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 brown oil that is fractionated by medium pressure chromatography on a RP-18 column (20 μm particle size) with acetonitril/water 1:2. The fractions containing the product are combined and extracted with ethyl acetate, the organic phase dried over Na2SO4 and concentrated yielding 165 mg of N-{6-[(2-hydroxy-ethyl)-methyl-amino]-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl}-methanesulfonamide as yellow powder, m.p. 220-224° 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 brown oil 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-b5bc8f4d2214432ea6fb7223f6c640bb
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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